High-accuracy temperature measurement plays a vital role in biomedical, oceanographic, and photovoltaic industries. Here, a highly sensitive temperature sensor is proposed and demonstrated based on cascaded polymer-infiltrated Mach–Zehnder interferometers (MZIs), operating near the dispersion turning point. The MZI was constructed by splicing a half-pitch graded index fiber (GIF) and two sections of single-mode fiber and creating an inner air cavity based on femtosecond laser micromachining. The UV-curable polymer-infiltrated air cavity functioned as one of the interference arms of MZI, and the residual GIF core functioned as the other. Two MZIs with different cavity lengths and infiltrated with the UV-curable polymers, having the refractive indexes on the different sides of the turning point, were created. Moreover, the effects of the length and the bending way of transmission SMF between the first and the second MZI were studied. As a result, the cascaded MZI temperature sensor exhibits a greatly enhanced temperature sensitivity of −24.86 nm/°C based on wavelength differential detection. The aforementioned result makes it promising for high-accuracy temperature measurements in biomedical, oceanographic, and photovoltaic applications. Temperature is one of the most common indicators used for condition monitoring in biomedical, oceanographic, and photovoltaic industries ,2,3,4. T−6 RIU/°C) [Fiber Bragg grating sensors are the most typical fiber-optic temperature sensors; however, the temperature sensitivity of them is usually very low ~10 pm/°C) . To date pm/°C .  RIU/°C) . Hence,  RIU/°C) . Very re RIU/°C) . Additio RIU/°C) . HoweverIn this paper, we propose and demonstrate a highly sensitive temperature sensor by cascading two UV-curable polymer-infiltrated Mach–Zehnder interferometers (MZIs) operating near the dispersion turning point (DTP). The single MZI consists of two single-mode fiber (SMF) pigtails, a half-pitch graded index fiber (GIF) that serves as an in-fiber collimator, and an inner air cavity created by femtosecond laser micromachining. A cascaded MZI temperature sensor with cavity lengths of 60 and 80 μm in the first and the second MZI was created. Moreover, two types of UV-curable polymers with the refractive indexes of 1.460 and 1.540 were employed to infiltrate these two MZIs, respectively. The UV-curable polymer-infiltrated air cavity functioned as one of the interference arms of MZI and the residual GIF core functioned as the other. Moreover, the effects of the length and the bending way of transmission SMF between the first and the second MZI were studied. The temperature response results showed that such a cascaded MZI temperature sensor exhibited a greatly enhanced temperature sensitivity of −24.86 nm/°C based on wavelength differential detection. The aforementioned result makes it promising for high-accuracy temperature measurements in biomedical, oceanographic, and photovoltaic applications.Generally speaking, refractive index (RI)-matching liquid is the typical thermo-sensitive liquid material for the infiltration of in-fiber microstructures to obtain highly sensitive MZI temperature sensors . However1 and SMF2) of the first MZI  serve as a lead-in and lead-out fiber, respectively. A half-pitch GIF with a length of 490 μm serves as a collimator, which can reduce insertion loss of MZI [2 can be described as [1 and I2 represent the beam power of the two interference arms, L1 is the air cavity length, λs is the wavelength, Δn1 = npolymer1 − ncore is the RI difference between the UV-curable polymer (npolymer1) and GIF core (ncore = 1.491), and L1Δn1 is the optical path difference (OPD) between two interference beams of the MZI1. The resonance dip wavelength can be expressed as:m is the wavelength of the mth order interference dip. The free spectral range (FSR) of the interference fringe dip is determined by OPD, as:As illustrated in s of MZI . The ligribed as :(1)I=I1+2) is the same as MZI1 and λL is the dip wavelength of MZI2. When the transmission light is injected into the MZI2, the interference signals are combined into the whole spectrum. Using a curved transmission SMF  can further suppress the multimode interference noise. Moreover, the RI sensitivity can be derived from Equation (2) as dλm/d(Δn1) = λm/Δn1 and the calculated results are shown in the inset of 1(T) = npolymer1(T) − ncore(T) is the RI difference between the UV-curable polymer and GIF core under temperature T, δpolymer1 is the TOC of UV-curable polymer (~−2 × 10−4 RIU/°C) [core is the TOC of silica (~8.3 × 10−6 RIU/°C) [1 and MZI2 are designed to be 60 μm and 80 μm, respectively. Moreover, the RI of the UV-curable polymers used in MZI1 and MZI2 are chosen to be 1.460 and 1.540, respectively.The working principle of the second MZI   and δcor RIU/°C) . As a re1 are shown in 2. In step 4, as shown in 1 and MZI2 were cascaded by splicing the two SMF pigtails together. Furthermore, the SMF  between MZI1 and MZI2 of 200, 80, 50, and 20 cm, respectively. The effect of air cavity lengths on the performance of MZIs has been well studied in the previous work [1 and MZI2 of these cascaded MZI samples are designed to be 60 μm and 80 μm, respectively. As shown in 2  that the positive temperature sensitivity of MZI1 results from the RI difference Δn1 < 0, and the TOC of the UV-curable polymer is negative (~−2 × 10−4 RIU/°C) [2 results from the RI difference Δn2 > 0.Subsequently, we investigated the temperature response of a cascaded MZI temperature sensor by putting it into a high-precision oven (accuracy: up to 0.1 °C). The temperature was varied from 22 to 29 °C and was maintained for 20 min at each measurement point. As shown in L − λS) of the cascaded MZI temperature sensor as a function of the temperature in the case of temperature cycling from 22 to 29 °C. It can be seen that the data could be well fitted by linear functions. It is obvious that the cascaded MZI temperature sensor exhibits greatly enhanced temperature sensitivities of −24.86 nm/°C and −24.74 nm/°C in the heating and cooling processes, respectively, based on wavelength differential detection. The temperature sensitivities are almost twice that of a single MZI temperature sensor [e sensor ,26. Hence sensor .We have proposed and demonstrated a highly sensitive temperature sensor by cascading two UV-curable polymer-infiltrated MZIs operating near the DTP. The effects of the length and the bending way of transmission SMF between the first and the second MZI were studied. After optimizing these parameters, a cascaded MZI temperature sensor without multimode interference noises in the transmission spectrum was obtained. The temperature test showed such a cascaded MZI temperature sensor has a greatly enhanced temperature sensitivity of −24.86 nm/°C, based on wavelength differential detection. Hence, the simple fabrication process, compact size, and ultrahigh temperature sensitivity of the proposed cascaded MZI-based temperature sensor would make it eminently suitable for utilization for high-accuracy temperature measurements in biomedical, oceanographic, and photovoltaic applications.


The compressive strength of concrete is further enhanced, and the pore structure is refined. The introduction of LC3 also promotes the formation of Friedel’s salt, which could improve the chloride binding capacity of concrete using SWSS. Furthermore, the stress-strain relationship of sustainable concrete is analyzed, and the experimental results are compared with the commonly used constitutive models. The predictive constitutive models are proposed to effectively describe the mechanical performance of sustainable concrete.To promote the sustainable development of the construction industry, concrete incorporating polyethylene (PE) fiber-strengthened recycled coarse aggregate (SRCA) and seawater and sea sand (SWSS) is prepared. The usage of SRCA significantly improves the mechanical performance of concrete. The strength is improved, and the failure mode of concrete cylinders is also remarkably altered. The incorporation of SWSS that alleviates the shortage of freshwater and river sand slightly reduces the mechanical strength of concrete at 28 and 90 days, while the replacement of cement by 35% limestone calcined clay cement (LC Mukharjee et al. [With the rapid development of urbanization, the process of urban construction renewal is accelerating. On the one hand, natural coarse aggregates are excessively consumed. on the other hand, a large amount of construction and demolition (C&D) waste is generated. The rampant stacking as well as the landfilling of a huge amount of C&D waste not only causes environmental pressure, but also occupies land resources. From the perspective of sustainable development, the recycling of waste concrete is an effective way to solve the above mentioned problems ,2,3,4. Ee et al.  have ince et al. ,20,21. Te et al.  to enhane et al. . The hyde et al. . This st− in SWSS [Many countries and regions today are facing fresh water shortages, and by 2025, 5.5 billion people in the world will be under water pressure . The wor in SWSS ,35,36.3) concrete exhibits comparable mechanical strength and even shows superior durability performance compared with ordinary concrete [3 with a total substitution ratio of 45% (a combination of 30% metakaolin and 15% limestone) to replace ordinary Portland cement (OPC), the 7d compressive strength of LC3 cement mortar was increased by 10%, the compressive strength of 28d was increased by 15%, and when LC3 with a total substitution ratio of 60%, its 28d compressive strength could also reach 93% of OPC. Dhandapani et al. [3 had better compressive strength than OPC concrete at all the studied ages including 2, 7, 28, 90 and 365 days. It can be seen that LC3, a low carbon cementitious material, has obvious advantages for improving the properties of SWSSC.The usage of SCMs to replace one part of cement is an effective way to improve the chloride binding capacity of SWSS concrete ,37. The concrete ,41,42. Aconcrete  used LC3i et al.  found th3 is investigated. The usage of untreated SWSS will facilitate the engineering construction in coastal area and remote island, and the sustainable concrete could be used in combination with corrosion resistant reinforcement. Thus, it is necessary to investigate the mechanical performance and the microstructural characteristics of this new type of concrete. The stress-strain behavior of concrete is discussed in detail, and the constitutive relationship is also investigated. Additionally, the predictive constitutive models are proposed by considering the influence of concrete age.In this paper, the sustainable concrete prepared with SRCA, SWSS and LCRCA was obtained by crushing unknown waste concrete collected from a local C&D waste site in Shenzhen, China. The particle size range of RCA is 5~20 mm, as shown in After strengthening, the crushing index of SRCA is reduced to be 12.21% with the reduction ratio being 37.35%; the water absorption ratio of SRCA being 6.02% kept almost unchanged, as shown in 3 is composed of OPC, calcined clay and limestone. The chemical composition and physical properties of the cementitious materials is presented in 3S, 15.08% C2S, 9.31% C3A, and 12.46% C4AF. Two replacement ratios of OPC by LC3, 35% and 50%, were investigated. Fine aggregates used in this work are sea sand and desalted sea sand. The detailed properties of fine aggregates are illustrated in The cement used is OPC 42.5R. LC3 on the performance of concrete, L(35) SSRC, representing the concrete prepared with SRCA, seawater, sea sand and 35% substitution ratio of OPC by LC3, and L(50) SSRC, representing the concrete prepared with SRCA, seawater, sea sand and 50% substitution ratio of OPC by LC3 were investigated. The mixture proportions of the five concrete types are illustrated in In order to evaluate the influence of the strengthening method of RCA on the properties of concrete, RC, the reference concrete prepared with untreated RCA, tap water and desalted sea sand, and SRC, the concrete made with SRCA, tap water and desalted sea sand were investigated. To characterize the effect of seawater and sea sand on the properties of concrete, SSRC, the concrete prepared with SRCA, seawater and sea sand was studied. To explore the influence of LCCylindrical specimen with a diameter of 150 mm and a height of 300 mm was used for the axial compression test. Two curing ages including 28 days and 90 days were considered. The 3000 kN MTS-YAW6306 pressure testing machine (MTS Systems (China), Shenzhen, China) was applied for loading. The displacement-controlled load was applied at the rate of 0.3 mm/min until the failure of the specimen. The linear variable displacement transducers (LVDTs) were used to measure the axial displacement of the specimen. The Dewesoft dynamic collection box  Measurement and Control Technology, Beijing, China) was used to collect the load and displacement data during the loading process.3 and SWSS on the microstructural characteristics of concrete using SRCA, mercury intrusion porosimetry (MIP) test was performed. The samples were cut off from the ruptured concrete, and the coarse aggregates were eliminated. The hydration process was terminated by immersing the specimens in absolute ethyl alcohol. Then, the specimens were vacuum dried at 60 °C for 24 h before testing. Poromaster GT-60 Mercury Intrusion Porosimeter, Quantachromre , was used for MIP testing.To explore the influence of LC3 and SWSS on the microstructure of concrete using SRCA, X-ray diffraction (XRD) analysis was performed to identify the hydration phase assemblages of the four paste types of SRC, SSRC, L(35)SSRC and L(50)SSRC. The pastes were prepared in parallel with the concrete cylinders and cured to 28 days. After the termination of hydration process, the paste was vacuum dried at 60 °C for 24 h. Then, the paste samples were ground into powder before XRD testing. During the test, Cu Kα radiation (λ = 1.54 Å) at 40 kV and 40 mA was applied, and the scanning was performed at a speed of 0.02°/step from 5° to 65°.To further investigate the influence of LCThe average stress-strain curves of various concrete cylinders at the age of 28 and 90 days are shown in 3, the strength of concrete L(35)SSRC is further improved at the two studied ages, as shown in 3 is incorporated in concrete, the mechanical performance is deteriorated. The strength reduction ratios of L(50)SSRC attain 10.56% at 28 days and 16.24% at 90 days compared to L(35)SSRC. The failure mode of L(50)SSRC is also altered with the main splitting cracks formed. However, the cylinder still keeps complete with few blocks peeling off from the specimen. It could be concluded that the fiber reinforced strengthening layer limits the interlinking of cracks, and thus the falling off of broken fragments is avoided, regardless of cement types, water types and fine aggregate types.When seawater and sea sand are introduced in concrete, the mechanical behavior is slightly deteriorated. The compressive strengths of SSRC are slightly lower than those of SRC at both 28 and 90 days. The failure mode of SSRC is similar to that of SRC, as shown in 3. The reactive silica and alumina in calcined clay could react with the hydration product Ca(OH)2, and lead to the formation of C-A-S-H [3 from limestone to form mono- (Mc) and hemi-carboaluminates (Hc), and the carboaluminates transfer to Friedel’s salt when chloride ion exists in the hydration system [3 is impaired when the replacement ratio rising to 50%. The effective water/binder ratio is significantly reduced when 50% LC3 is used, and the decrease of clinker content lowers the build-up of hydration phases. Especially, the content of available Ca(OH)2 is reduced, and thus the pozzolanic reaction between calcined clay and Ca(OH)2 is limited. This phenomenon results in the adverse impact on the strength of concrete. According to Krishnan [3 is 55%, only a small fraction (45.6%) of MK is reacted, and about 50% of MK is not involved in the hydration process. C-A-S-H . The alun system . This phKrishnan , when th3 also demonstrates slight influence on the value of elastic modulus. However, the elastic modulus of L(35)SSRC and L(50)SSRC are still comparable to those of SSRC. Furthermore, for each concrete type, the elastic modulus of concrete rises with the increase of curing age. As for the peak strain, the usage of SRCA slightly decreases the value, while the incorporation of seawater, sea sand and 35% LC3 further enhance the strain value 24(CO3)Cl2(H2O)1.6(H2O)8), the latter of which is a solid solution between carboaluminates and Friedel’s salts. Additionally, calcium hydroxide (CH) content was significantly reduced due to the pozzolanic reaction with the reactive components in calcined clay [3 system. Furthermore, since the excess calcium carbonate present in the LC3 system prevents the converting of ettringite to monosulfate [The XRD patterns of the four studied paste types are demonstrated in d cement ,57,58,59d cement ,60. Somed cement ,40,54 haned clay ,34,36. Tned clay  and decrosulfate ,56, the The stress-strain relationship of concrete is the basis of concrete structure design and is crucial for the application of concrete. In this study, the existing constitutive models were analyzed in combination with the experimental data, and the optimum constitutive models that fit well with the mechanical behavior of the studied concrete types were selected.σ and ε are the stress and strain of concrete, respectively; σ0 and ε0 represent the peak stress and the corresponding strain of concrete, respectively; cuσ is the ultimate strain of concrete; E0 is the initial elastic modulus of concrete, and sE = σ0/ε0, is the secant modulus between peak point  and the origin point.Various researchers reported extensive experimental and theoretical studies on the constitutive relationship of concrete, and proposed the relevant constitutive models based on the experimental results. Details of the several commonly used constitutive models of concrete are shown in D is used to adjust the softening characteristics of the stress-strain curve. Parameter C in Zhou et al. [a and b in Guo [R2 are determined, as shown in In Sargin  model, pu et al.  model isb in Guo  model coIt is remarked that all the models could effectively predict the rising phase of the stress-strain curve. However, neither Hognestad ,62 modelIn order to establish the constitutive models of RC, SRC, SSRC, L(35)SSRC, and L(50)SSRC, Sargin  model, Z3, SWSS and strengthened recycled coarse aggregate, and the constitutive relationships of various concrete types were established based on the experimental results. The following conclusions are drawn:(1)3 is added. The compressive strength of L(35)SSRC is the highest at both 28 and 90 days. Moreover, the failure mode of concrete cylinders is altered with the usage of SRCA. More cracks are generated, and the cylinders keep almost intact without concrete blocks peeling off from the cylinders.The mechanical performance of concrete using SRCA is remarkably improved, and the increasing ratio of 28-day compressive strength attains 19.34%. Slight reduction of compressive strength is observed when SWSS is incorporated, while, the situation is alleviated when 35% LC(2)3 and SWSS refines the pore structure of concrete matrix. Although the total porosity is increased, the increment is mainly attributed to the rising of the volume of gel pores, which exhibit negligible influence on the strength of concrete.The incorporation of both LC(3)3 and SWSS further promotes the formation of Friedel’s salt owing to the high content of aluminate phases in calcined clay. The content of Ca(OH)2 is reduced due to the pozzolanic reaction with the reactive components in calcined clay, while the content of CaCO3 is increased with the incorporation of limestone.SWSS leads to the formation of Friedel’s salt and additional ettringite, and the combination of LC(4)Based on the comparison analyses between the commonly used stress-strain models and the experimental results, the predictive constitutive models of the sustainable concretes are proposed by considering the influence of concrete age.The main objective of this study is to explore the mechanical performance of sustainable concrete incorporating LC


In the last 10 years, several literature reports supported radioligand therapy (RLT) in neoadjuvant settings for pancreatic neuroendocrine tumors (PanNETs). Indeed, primary tumor shrinkage has been frequently reported following RLT in unresectable or borderline resectable PanNETs. Moreover, RLT-induced intratumoral modifications facilitate surgery, both on primary tumor and metastasis, having a great impact on progression free survival (PFS), overall survival (OS) and quality of life (QoL). However, prospective controlled investigations are necessary to confirm preliminary data and to define the best RLT scheme and the ideal patient that, in a multidisciplinary approach, should be referred to neoadjuvant RLT. Pancreatic neuroendocrine tumors (PanNETs) account for ~10% of all neuroendocrine tumors (NETs). Approximately 70% of these neoplasms are non-functioning and frequently present as relatively indolent and slow-growing masses. Therefore, diagnosis is frequently delayed, occurring when the disease has already spread to lymph nodes, liver, or bone .PanNETs are currently classified according to the 2017 WHO classification. Grading has a strong impact on both clinical behavior and prognosis of patients affected by PanNETs, being a crucial parameter to take into consideration in the global therapeutic strategy .Currently, surgery is potentially the only curative treatment for PanNETs . Convers111I) or Gallium-68 (68Ga). Likewise, in the settings of radioligand therapy (RLT), SSA can bind high energy beta emitters, such as Yttrium-90 (90Y) or Lutetium-177 (177Lu) -labeled radiopeptides. On the other hand, very different schemes were employed concerning cycles number and injected activity. Therefore, a better standardization of neoadjuvant RLT is desirable and should be investigated in future trials. Although RLT is currently mainly performed with [177Lu]-based radiopharmaceuticals, [90Y]-radiolabeled peptides might still play an important role. Indeed, the greater tissue penetrance of the beta radiations emitted by 90Y, compared to 177Lu, enhances the cross-fire effect that damages even those cellular clones with lower SSTR expression and potentially more undifferentiated. This feature, combined with the higher linear energy transfer (LET), candidates [90Y]-radiopeptides as potentially more effective in the treatment of large and biologically aggressive lesions [177Lu]-based RLT has proven to be safer than 90Y. 177Lu could be more effective on small lesions, also in relation to its longer half-life, allowing a prolonged dose delivery [177Lu]-DOTATOC and [90Y]-DOTATOC, but not in neoadjuvant settings. A dual-isotope approach could allow a better risk-benefit ratio in neoadjuvant setting in PanNETs, representing a challenge for planning future multicentre randomized trials in this subset of patients.The available results derive from studies with heterogeneous neoadjuvant RLT schemes. Indeed, different isotopes have been employed:  studies , 25, 34,7Lu in 6 , 28, 29 7Lu in 6 , 27, alw lesions . On the delivery . Baum et177Lu]-DOTATATE, followed by surgery for PanNETs,  is ongoing [On the basis of available evidence, a phase II single-arm multicentric trial on neoadjuvant RLT with [ ongoing . The maiFurther ongoing trials proposing neoadjuvant RLT for PanNETS or for NETs of different primary origin are not available at present. Likewise, other trials aiming to compare the efficacy of different RLT schemes in this subset of patients are lacking.The present mini-review summarizes the available data in the literature. However, most of the studies on neoadjuvant RLT are single case reports or small sample size studies –29, 34. RLT could represent a safe and effective neoadjuvant therapy in unresectable or border line resectable PanNETs. Further prospective controlled investigations are necessary to confirm these preliminary data and to define the ideal therapeutic scheme. In addition, the multidisciplinary approach is preferable to identify patients who could benefit from neoadjuvant RLT to become eligible for second-line surgery.


TG-DTA shows that Na2SiO3 is enhancing the early strength of the ISD system by promoting the consumption of Ca(OH)2 in the ISD system to produce C-S-H. However, in the late reaction of the ISD system, Na2SiO3 inhibits the late strength development of the ISD system by suppressing Ca(OH)2 production. Concrete with ISD dosing of 30% or less meets the C40 requirement. MIP and BSE show that ISD provides a filling effect to concrete, but also causes a reduction in the active reactants of concrete and the combined effect of microfilling and active effects affects the strength development of ISD concrete. This study provides a theoretical and scientific basis for the preparation of iron tailings-based ternary solid waste dopants, and, in addition, the study promotes the consumption of iron tailings solid waste and the development of multiple solid waste dopants.Iron tailing solid waste not only has a high annual output but also has a low comprehensive utilization rate. Low utilization rate of iron tailings seriously restricts the development of comprehensive utilization of solid waste. In order to prepare an iron tailings-based ternary solid waste admixture and to verify its application to concrete, first, the effect of solid waste synergy on the strength of an iron tailings-steel slag-desulfurization ash admixture (ISD) system was investigated. Second, the effect of chemical activator dosing on the strength of an ISD system was studied and the mechanism of chemical activator action on the ISD system was investigated by thermogravimetric analysis (TG-DTA) Then, the effect of this admixture on the strength of concrete was studied. Finally, the mechanism of the effect of this admixture on the strength of concrete was clarified by mercury intrusion porosimetry (MIP) and backscattering electron tests (BSE). The results showed that the 7 d and 28 d compressive strengths of the ISD admixture were significantly higher than those of iron tailings single admixture. The 7 d and 28 d compressive strengths of the ISD system reached 24.9 MPa and 36.1 Mpa, respectively, when the ratio of iron tailings:steel slag:desulfurization ash = 1:1:1. Na In recent years, the massive accumulation of solid waste, such as iron tailings and red mud, has caused serious problems to the ecological environment ,2,3. StuIn addition, many scholars have conducted research not only on concrete properties, but also on the direction of iron tailings activation. Gu et al., studied the effect of mechanical activation and iron tailings content on ultra-high-performance concrete, and it was found that mechanically activated iron tailings are suitable for concrete admixtures . Yao et 3S and C2S in it, which has potential cementing activity [As a by-product of steelmaking, the annual production of steel slag in China amounts to more than 100 million tons . Steel sactivity . Howeveractivity . The uti2 and other unstable components, limiting its resourcefulness [Desulfurization ash, a semi-dry flue gas desulfurization product, has an annual production of several billion tons in China . Desulfuefulness .In conclusion, it is potentially feasible to apply iron tailings, steel slag and desulfurization ash to composite admixtures. Systematic studies to prepare an ISD admixture, to investigate the effect of chemical activators on the strength of an ISD admixture and to verify the feasibility of an ISD admixture applied to concrete have not been carried out in depth, hindering the development of ISD systems in the direction of admixture and limiting the utilization rate of iron tailings.2SiO3 activator on the mechanical properties of the ISD admixture system was investigated by adjusting the Na2SiO3 activator dose on the basis of the suitable ratio and the mechanism of the effect of Na2SiO3 activator on the mechanical properties of the ISD admixture system was investigated by means of TG-DTA microscopic techniques. Finally, the ISD cement admixture was applied to concrete to verify its feasibility and analyze its mechanism of action by microscopic means.The objective of this paper is to prepare a cement admixture from iron tailings–steel slag–desulfurization ash ternary solid waste. Firstly, the synergistic effect of the ternary solid waste was investigated by adjusting the ratio of each solid waste in the ISD system and determining the suitable ratio. Secondly, the effect of Na2SiO3 produced by Tianjin Science and Trade was used as the chemical activator. Standard sand: China ISO standard sand produced by Xiamen Aisiou Standard Sand Co, China. Water: tap water is taken. Iron tailing waste rock and iron tailing sand are provided by Liaoning One Cube Sand Industry Co, China. Water reducing agent: P-II type air-entraining water reducing agent produced by Shenyang Sheng Xinyuan Building Materials Co, China.Iron tailing powder: iron tailing powder from Crooked Head Mountain, Benxi, China. Steel slag: steel slag from Shanghai Baowu Iron and Steel Group, China. Desulfurization ash: desulfurization ash from Aoda Refractories Processing Plant, Lingshou County, Shijiazhuang City, China. Cement: P·O 42.5 benchmark cement from Shanshui Group, China. Activator: the NaThe chemical compositions and mass fractions of iron tailings, steel slag and desulfurization ash determined by X-ray fluorescence (XRF) are shown in This test is designed to replace 30% of cement with solid waste dopants, such as iron tailings. Referring to the “Test Method for Cementitious Sand Strength (ISO Method)” (GB/T17671-1999) and the specific test ratios shown in Referring to the experimental proportioning scheme shown in The compressive strength and flexural strength of the admixture specimens were determined concerning the “Test Method for Cementitious Sand Strength (ISO Method)” (GB/T17671-1999), and the average value of three parallel values was taken for each group of test results.The compressive strength test of concrete specimens was carried out with reference to the standard for “Test Methods of Physical and Mechanical Properties of Concrete” (GB/T50081-2019). First, the 7 d, 14 d and 28 d compressive strengths of the concrete were tested using a Shenzhen brand universal testing machine (2000 kN) with a loading rate of 0.7 MPa/s. The compressive strength results are then converted using the conversion factor, which is taken as 0.95. The average value of compressive strength of three specimens was taken as the test result.2 contents of 7 d and 28 d admixture specimens were determined by means of TG-DTA microanalysis. The specimens were heated to 812 °C for thermogravimetric analysis in a nitrogen atmosphere using a comprehensive thermal analyzer with a heating rate of 20 °C/min. The gel water and Ca(OH)2 contents at each hydration age were calculated from the following Equations (1) and (2):2; and where 18, 74 are the molecular weights of H2O and Ca(OH)2, respectively.The gel water and Ca(OH)The concrete test samples were analyzed for mercury compression by mercury intrusion porosimetry (MIP) testing. First, the concrete pieces were cut parallel to the surface of the specimen using a cutter at a position 15 mm from the surface of the concrete block. Then, core samples (without drilling for aggregate) were drilled on the cut surface of the concrete test blocks using an electric drill and hollow core bit (8–14 mm inner diameter of the drill bit). After sampling, the samples were soaked in anhydrous ethanol for 7 days to terminate hydration, then dried for 3 days and tested for mercury compression (drying temperature of 50 ± 2 °C). Porosity and pore size distribution of the samples were measured at a maximum pressure of 414 MPa using an AutoPore IV 9510 fully automated mercury manometer in Shanghai, China.Interfacial transition zone analysis was performed on concrete test samples by backscattering electron tests (BSE). Firstly, test pieces with a thickness of about 3–5 mm were cut from the concrete specimens. When cutting, the concrete pieces were cut parallel to the surface of the specimen with a cutter at 15 mm and 18–20 mm from the surface of the specimen, respectively. Then, core samples (including aggregates) were drilled on the cut surface of the concrete test blocks using an electric drill and hollow core bit (8–14 mm inner diameter of the drill bit). After sampling, the samples were soaked in anhydrous ethanol for 7 days to terminate hydration, and then dried for 3 days (drying temperature of 50 ± 2 °C). The dried samples were immersed in epoxy resin for 24 h. The sample to be tested is then prepared by grinding, shaping, ultrasonic cleaning and drying (drying temperature of 50 ± 2 °C). The magnification of the test image is 500 times, the resolution is 1024 × 768 pixels. Image J 1.8.0 image processing software was used to perform quantitative analysis and calculations on the images.In order to clarify the effect of steel slag admixture on the strength of the ISD system, three cement mortar specimens with 1:3, 1:1 and 3:1 steel slag–desulfurization ash ratios were prepared, and the specimens were maintained for 7 d and 28 d before strength testing. The test results are shown in 2 in the iron tailings in a volcanic ash reaction to form CSH [2S and C3S, which can provide cementing materials, such as Ca(OH)2 and C-S-H, for the iron tailing dopant system [2S and C3S, which can make the ISD system produce more gelling materials, such as C-S-H 32. However, the continued substitution of steel slag for desulfurization ash will cause a reduction in the pre-strength of ISD. This is due to the inhibition of the early hydration of the cement by steel slag, and the higher the amount of steel slag, the more obvious the effect [The results in form CSH . In addit system ,32. Moree effect . The late effect .To further clarify the effect of iron tailings doping ratio on the strength of the ISD admixture, the test was set up by 1:1, 1:2 and 1:4 of three kinds of iron tailing and steel slag–desulfurization ash ratio doping cement preparation of the colloidal sand specimens, and the strength test was carried out after 7 d and 28 d of specimen maintenance. The test results are shown in The compressive strength of the ISD system gradually increased with the increase in the iron tailings admixture, which is contrary to the results of Cheng et al. . This ca2SiO3 activator on the strength of the ISD admixture. Five Na2SiO3 doping amounts  of ISD admixture sand specimens were prepared, and the strength test was carried out after 7 d and 28 d of specimen maintenance. The test results are shown in On the basis of iron tailings–steel slag–desulfurization ash doping ratio of 1:2:2, an attempt was made to further investigate the effect of an Na2SiO3 will react with Ca(OH)2 to form C-S-H and NaOH [2SiO3 will also promote the rapid hydration reaction of C3A in the ISD system, so Na2SiO3 can promote the pre-strength growth of the ISD system. However, with the gradual increase in Na2SiO3 incorporation, more Na2SiO3 reacts with Ca(OH)2 to generate C-S-H, causing many cementitious materials in the ISD system to wrap around the surface of solid waste and cement particles, which inhibits the hydration of cement and the volcanic ash effect of solid waste; in addition, Na2SiO3 will cause the porosity of the ISD system to rise, thus reducing the overall density of the ISD system [2SiO3 will not only inhibit the late compressive strength of the ISD system, but also the early strength of the ISD system.Naand NaOH ,39, and and NaOH , which pD system . Therefo2 in the gelling material products, to realize the quantitative analysis of the degree of volcanic ash reaction in the ISD system, and then to determine the mechanism of the action of Na2SiO3 activator on the mechanical properties of the ISD admixture system.TG-DTA can be used to analyze the generation of gel water and Ca(OH)2SiO3, respectively, after 7 d and 28 d of standard maintenance for comparative analysis; the experimental results are represented by In the experiment, iron tailings: steel slag: desulfurization ash = 1:2:2, the ratio of the total mass of solid waste admixture to the total mass of cement is 3:7, the water-to-binder ratio is 0.5, the ratio of binder-to-sand is 1:3 (mass ratio), the activator is 0% and 0.6% doping of Na2SiO3 doping are similar, with three heat losses occurring in three heat absorption peaks for each specimen. The first occurred at about 100 °C, when the C-S-H and Aft dehydroxylation of the gel water mainly occurred; the second occurred at about 450 °C, when the dehydroxylation of Ca(OH)2 followed by water loss mainly occurred; and the third occurred at about 670 °C, when the decomposition of calcium carbonate mainly occurred [2 contents of 7 d and 28 d ISD admixture specimens determined by TG-DTA microanalysis are represented by occurred . The gel2 content in the reaction of the 7 d ISD system without Na2SiO3 is greater than that of the ISD system with Na2SiO3, while the gel water content is less than that of the ISD system with Na2SiO3, and the experimental results of Ca(OH)2 and gel water content fully demonstrate that Na2SiO3 improves the precompressive force of the ISD system by reacting with Ca(OH)2 to produce gels, such as C-S-H. The Ca(OH)2 content in the reaction of the 28 d ISD system without Na2SiO3 is lower than that of the ISD system with Na2SiO3, while the gel water content is greater than that of the ISD system with Na2SiO3, which fully indicates that due to the reaction of a large amount of Na2SiO3 with Ca(OH)2 to generate C-S-H, which causes many cementitious materials in the ISD system to wrap around the surface of solid waste and cement particles, inhibiting the hydration of cement and the volcanic ash effect of solid waste, thus reducing the late strength of the ISD system.In order to test the effect of the ISD admixture in concrete and to determine the effect of ISD admixture dosage on the compressive strength of concrete, in the experiment, four ISD doping amounts of 0, 10%, 20% and 30%  were set; the water–cement ratio was 0.44, and the doping ratio was iron tailings:steel slag:desulfurization ash = 1:2:2, and the comparative analysis was carried out after 7 d, 14 d and 28 d of standard maintenance. The experimental results are represented by 2, which leads to the ISD admixture mainly causing a volcanic ash reaction, but the volcanic ash reaction rate is much lower than the hydrolytic hydration reaction of cement [f cement , thus caIn order to further explain the mechanism of the effect of the variation of the ISD admixture on the compressive strength of concrete in the direction of total and harmful pore volume, the concrete with three ISD admixture levels of 0, 20% and 30% and cured for 28 d in The interfacial transition zone is a weak region of concrete, which has a large influence on the mechanical properties of concrete . In ordeIt can be seen from The BSE test results further confirm the results of the mercury compression test in The 7 d and 28 d compressive strengths of an ISD admixture are significantly higher than those of an iron tailings single admixture. With the increase in the proportion of steel slag admixture, the pre-strength of the ISD admixture grows first and then decreases. The 7 d and 28 d compressive strengths of the ISD admixture showed a trend of increasing and then decreasing with the increase in the proportion of iron tailings. The 7 d and 28 d compressive strengths of the ISD system reached 24.9 MPa and 36.1 MPa, respectively, when the ratio of iron tailings:steel slag:desulfurization ash = 1:1:1.2SiO3 can promote the early strength growth of an ISD admixture and also inhibit the later strength of an ISD admixture. Na2SiO3 is suitable for the early strength agent of an ISD admixture, but the amount of admixture should not exceed 0.6% of the admixture. Na2SiO3 is used to improve the early strength of the ISD system by promoting the consumption of Ca(OH)2 in the ISD system to produce C-S-H. However, in the late reaction of the ISD system, Na2SiO3 inhibits the late strength development of the ISD system by inhibiting Ca(OH)2 production.The appropriate amount of NaAn ISD admixture will cause the early strength of concrete to decrease. The late strength of concrete can also be reduced when ISD is mixed in excessive amounts. Concrete with ISD dosing of 30% or less meets C40 requirements.The strength of ISD concrete is influenced by the total pore volume, and the total pore volume of ISD concrete increases with the increase in ISD admixture. ISD will provide a filler effect to concrete, but it will also cause a reduction in the active reactants of concrete, and the combined effect of a microfill effect and an active effect affects the strength development of ISD concrete.In this study, a ternary solid waste admixture was prepared using iron tailings, steel slag and desulfurization ash and its application to concrete was verified. The effects of dopant type and chemical activator on the mechanical properties of ISD were investigated, and the mechanism of chemical activators on ISD was analyzed by TG-DTA. The strength, porosity, and interfacial transition zone of ISD concrete were tested by concrete compressive test, MIP, and BSE. This study provides a scientific basis for the preparation of ISD dopants and promotes the consumption of bulk solid waste iron tailings. The main test findings are as follows:Since the water-to-cement ratio can seriously affect the workability of cement mortar and the performance of concrete, further studies on the effect of water-to-cement ratio on the performance of ISD concrete are needed.If increasing the amount of ISD in concrete will further improve the economic value of ISD concrete, it is necessary to further investigate the performance of high-dosage ISD concrete.Durability is an important property of concrete, and it is necessary to study the durability of ISD concrete, such as impermeability and resistance to sulfate attack.Admixtures can significantly improve the performance of concrete, and further research is needed to investigate the admixtures suitable for ISD concrete.In this paper, although the compressive strength of concrete with ISD admixture of 30% or less meets the C40 requirement, the mechanical properties of ISD mixes need to be further investigated, as follows:


Braided composite stent (BCS), woven with nitinol wires and polyethylene terephthalate (PET) strips, provides a hybrid design of stent. The mechanical performance of this novel stent has not been fully investigated yet. In this work, the influence of five main design factors  on the surface coverage, radial strength, and flexibility of the BCS were systematically studied using computational models. The orthogonal experimental design was adopted to quantitatively analyze the sensitivity of multiple factors using the minimal number of study cases. Results have shown that the nitinol wire diameter and the braiding angle are two most important factors determining the mechanical performance of the BCS. A larger nitinol wire diameter led to a larger radial strength and less flexibility of the BCS. A larger braiding angle could provide a larger radial strength and better flexibility. In addition, the impact of the braiding angle decreased when the stent underwent a large deformation. At the same time, the impact of the PET strips increased due to the interaction with nitinol wires. Moreover, the number of PET strips played an important role in the surface coverage. This study could help understand the mechanical performance of BCS stent and provides guidance on the optimal design of the stent targeting less complications. The sMuch efforts have been made to optimize the stent design ,8 since Recently, a novel braided composite stent (BCS) was proposed to combine the merits of both braided stent and covered stent for achieving the desirable radial strength, flexibility, and increased surface coverage . It was 22.1The BCS, braided with 32 strands of nitinol wires and PET strips, has a length of 15 mm and an outer diameter of 7 mm . The steβ is the angle between the helical wire and the axial direction of the stent. The width of the PET strip w could be calculated by:l is the distance of the two intersection points along the circumferential direction /sin2β with N1 as the number of intersections between polyester strip and nitinol wire, N2 as the number of intersections between nitinol wires, and N3 as the number of intersections between polyester strips. L is the length of stent, which can be expressed as L = πD cot β; d is the diameter of the nitinol wire; w is the width of the polyester strip; Lwire and Lstrip are the total length of the nitinol wire and polyester strip, respectively. Both can be calculated based on the number of nitinol wire n1 or polyester strips n2, and the braiding angle β [The surface coverage  angle β  as(3)2.2Three-dimensional models of the BCSs were constructed on the aforementioned geometrical design. The nitinol wire was adopted as a superelastic material, which was implemented through a built-in Abaqus User Material Subroutine (VUMAT) . The PETCompression tests were carried out to investigate the influence of stent design parameters on the radial strength of the stent . The steX and Y directions, (2) restrained rotation about Y and Z axes, (3) X deflection of RP1 + X deflection of RP2 = 0. (4) Rotation about X axes of RP1 and RP2 reached at 60° [The stent flexibility was characterized by the pure bending tests  Figure . A fixedd at 60° , respectThe stent wires were meshed with two-node linear beam element (B31) and the PET strips were meshed with reduced 4-node doubly curved shell elements (S4R). The nitinol wire was meshed with 192 elements and 240 elements for the braiding angle of 55° and 65°, respectively. The PET strip was meshed with 2,176 elements and 2,160 elements for the braiding angle of 55° and 65°, respectively. The rigid compressor foot and supporting plate were meshed with 1,645 and 4,622 rigid quadrilateral R3D4 elements, respectively. Mesh-sensitivity analyses were conducted to insure that all results are convergent. A general contact algorithm was adopted among all contact surfaces with a friction coefficient of 0.3 . The kin2.3qt) was applied to identify the sensitivity of multiple factors with minimal experiments, where L is the orthogonal array, n is the number of study cases, t is the level of factors, and q is the number of factors [8(25) was designed to systematically evaluate the sensitivities of five input factors to the mechanical performance of the stent. The modulus of the PET strip and four geometrical design parameters  levels of each input factor are shown in 8(25) orthogonal table are shown in An orthogonal experimental design Ln was the most sensitive one to the compression load among the five factors during the loading process no matter at the small or large deformation  reduced from 22% to 10% at the large deformation, and the value of the factor A (PET strip modulus) becomes prominent from 18% to 25%. The reason is that the radial strength is mainly borne by nitinol wires during the whole compression process, while with the increase of compression deformation, the braiding angle under the presser foot becomes smaller, the PET strips enforced more constrain on the nitinol wires and enhanced the radial strength of the stent.The compression load at the deformation of 30% and 50% of its original diameter during the loading process for all eight cases is summarized in ormation , and theC  and factor D (nitinol diameter). Bigger initial braiding angle can achieve better flexibility of the stent, while the increase of the nitinol diameter can reduce the flexibility of the stent. In detail, the initial braiding angle is more sensitive to the bending moment at the bending angle of 30° (36%), while this sensitivity decreases (27%) when the bending angle is up to 60°. By contrast, the influence of the nitinol wire diameter on the bending moment becomes more prominent with the bending angle increase from 30° (25%) to 60° (33%)  . It can 0° (33%) . It is cTo comprehensively evaluate the mechanical properties of the stents in this article, the bending moment as the abscissa axis and radial strength as the ordinate axis were combined, as shown in 4For peripheral artery stenosis, the implanted stent will be exposed to various “dynamic” loads, such as radial compression, bending, and torsion ,39. The The radial strength is the primary consideration of the stent conceptual design to scaffold the narrow lumen . The nitThe longitudinal flexibility of stent was associated with the risk of kinking and incidence of limb thrombosis in tortuous anatomy . Without5The BCS has advantages of good flexibility and high radial strength. To optimize the stent design in different physiological environments is urgently needed based on the understanding the sensitivity of stent parameters. In this study, the orthogonal experimental design was adopted to quantify the influence of five input factors on the surface coverage, radial strength, and flexibility of the stent. Our results show that nitinol diameter and initial braiding angle are two most sensitive factors that affect the mechanical performance of BCS. The influence of the nitinol diameter increased when the stent underwent a large deformation, while the influence of the initial braiding angle was the opposite. At the same time, the impact of PET strips increased due to the interaction with nitinol wires. The surface coverage of BCS mainly depends on the number of the PET strips. In addition, the interaction between stent and a torturous artery in a complex mechanical environment should also be carried out simultaneously to better evaluate the mechanical properties of the stent.


Clinical trials completed in the last two decades have contributed significantly to the improved overall survival of children with cancer. In spite of these advancements, disease relapse still remains a significant cause of death in this patient population. Often, increasing the intensity of current protocols is not feasible because of cumulative toxicity and development of drug resistance. Therefore, the identification and clinical validation of novel targets in high-risk and refractory childhood malignancies are essential to develop effective new generation treatment protocols. A number of recent studies have shown that the hepatocyte growth factor (HGF) and its receptor Mesenchymal epithelial transition factor (c-MET) influence the growth, survival, angiogenesis, and metastasis of cancer cells. Therefore, the c-MET receptor tyrosine kinase and HGF have been identified as potential targets for cancer therapeutics and recent years have seen a race to synthesize molecules to block their expression and function. In this review we aim to summarize the literature that explores the potential and biological rationale for targeting the HGF/c-MET pathway in common and high-risk pediatric solid tumors. We also discuss selected recent and ongoing clinical trials with these agents in relapsed pediatric tumors that may provide applicable future treatments for these patients. Mesenchymal epithelial transition factor (c-MET) is a cell-surface receptor tyrosine kinase that is widely expressed throughout many organ systems. c-MET is predominantly expressed in epithelial cells, while its ligand (hepatocyte growth factor–HGF) is largely expressed by cells of mesenchymal origin , 2. UndeMET or HGF gene is mutated do not survive in utero. Disruption of the HGF/c-MET pathway results in impaired placentation, liver development, and development of the skeletal muscles of the limbs , Src homology-2-containing (SHC), Src, Src homology 2 domain-containing phosphatase-2 (SHP2), signal transducer and activator of transcription 3 (STAT3), growth factor receptor-bound protein 2 (GRB2), and GRB2-associated binding protein 1 (GAB1) –29. NotaIn addition to the “main” HGF/c-MET signaling pathway, there is evidence for significant crosstalk between c-MET and other cell surface proteins, including integrins, plexins, CD44, and other receptor tyrosine kinases, notably the epidermal growth factor receptor (EGFR) , 33. TheFinally, c-MET can be downregulated by degradation after activation. The c-MET receptor is internalized through clathrin-mediated endocytosis and is either ubiquitinated and degraded or recycled back to the cell surface. Ubiquitination is mediated by binding of Cbl (an E3 ubiquitin ligase) to the phosphorylated tail of c-MET, and disruption of this interaction can lead to increased activity of c-MET –39. OtheA more thorough discussion of the molecular signaling underpinning the HGF/c-MET pathway is beyond the scope of this review, and is summarized schematically in , 46.MET gene have been identified in a wide range of human cancers, increased activity of the HGF/c-MET pathway is often seen in cancer as a result of physical and chemical changes in the tumor stroma, leading to upregulation of c-MET, or clonal selection of c-MET-expressing cancer cells. The result is often a subset of invasive cancer cells resistant to chemotherapy, and prone to dissemination  was sufficient to lead to the development of RMS tumors with a similar molecular signature to human RMS tumors (Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in pediatric patients . The majS tumors .In vitro studies of the relationship between c-MET and the PAX3-FOXO1 fusion protein have shown that while expression of c-MET is upregulated by PAX3-FOXO1, PAX3-FOXO1 expression is not necessary for c-MET expression and activity. Ginsberg et al. found that in myogenic cells transfected with PAX3-FOXO1 and fusion-positive ARMS cells, c-MET expression correlated with levels of PAX3-FOXO1. However, high levels of c-MET expression were also found in some samples of ERMS, suggesting that PAX3-FOXO1 is not necessary for c-MET expression , tumor growth stopped and subsequently regressed , the infiltrating cells had greater levels of c-MET expression than did cells from the corresponding primary tumors  is the most common primary bone tumor, and occurs in a bimodal age distribution with a peak in the pediatric age range. Survival in OS has plateaued since the 1980’s, and new treatments are needed, especially for those with advanced disease . The c-MPatane et al. showed that overexpression of c-MET could transform osteoblasts (with undetectable c-MET levels at baseline) to an OS-like phenotype, capable of anchorage-independent growth, and increased basement membrane and 3-D invasion. Development of this OS-like phenotype was inhibited by blockade of c-MET receptor dimerization or with c-MET targeting shRNA . A more MET gene. Re-expression of these suppressed miRNAs has been shown to lead to reduced OS growth and invasion (A number of similar reports have suggested a role for c-MET in the development of OS through suppression or downregulation of microRNAs (miRNAs). Specifically, studies have shown that a range of cancer-related miRNAs are decreased in OS, inversely correlated with increased c-MET expression, and directly target the wild-type 3′-UTR of the invasion –84.in vivo xenograft tumor growth  is the second most common primary pediatric bone tumor. Fleuren et al. found that a majority of samples of ES  had medium to high levels of cytoplasmic c-MET expression. More specifically, however, they found that expression of c-MET localized to the plasma membrane (and not cytoplasmic c-MET) was associated with worse overall survival. ES cell lines were susceptible to treatment with (non-selective) c-MET inhibitors cabozantinib and crizotinib . A recenne model .Gliomas are the most common pediatric CNS tumors, which after leukemia are responsible for the most cancer deaths in this population . Few effin vitro and in vivo experiments with anti-HGF agents, have suggested that both autocrine and paracrine signaling of HGF occurs in gliomas (in vivo xenograft glioma tumors by decreasing cell proliferation and increasing apoptosis (and through effects on angiogenesis which will be addressed separately). Notably, Kim et al. showed in a murine model that glioma xenografts which express c-MET without co-secreting HGF are completely resistant to treatment with an anti-HGF mAb. However, the authors indicated that these results do not necessarily preclude successful therapy in humans, as any native murine HGF in this model  would not have been targeted by the anti-HGF mAb  –94. Micr gliomas , 95–97.  gliomas , 91, 94. gliomas , 98, or  gliomas  decreaseStudies comparing HGF/c-MET expression in pathological specimens to clinical outcomes have indicated that greater presence of HGF/c-MET is associated with poorer prognosis and outcomes (though this data is largely from adult patients) –103. IntIn vitro stimulation with HGF promoted chemotactic migration and increased DNA synthesis in neuro microvascular endothelial cells, suggesting a direct pro-angiogenic role for HGF  (the MET promoter is known to have HIF-1 binding sites), and was more pronounced in cell lines that had relatively low basal c-MET expression  of pediatric high-grade gliomas analyzed  is the most common brain malignancy in pediatrics. Due to the risk of leptomeningeal dissemination, current therapy of MB generally includes surgical resection, chemotherapy and radiation of the neuraxis–an aggressive treatment approach which can result in significant morbidity including endocrinological and neurocognitive deficits. MB develops from neural progenitor cells in the posterior fossa, most commonly in the cerebellum—the HGF/c-MET pathway is crucial for normal cerebellar development , and dysMET in 38.5% of tumor samples analyzed , and inhibition or overexpression of c-Myc in MB modulated the effects of HGF on cell cycle progression and proliferation . AdditioMB can be classified into molecular subgroups: wingless/integrated (WNT), sonic Hedgehog (SHH), and groups 3 and 4. Genetic analysis has revealed an association between increased c-MET expression and the SHH subgroup of MB, though increased c-MET expression is also seen in a subset of tumors classified in groups 3 and 4 –130. HigNeuroblastoma (NB) is a malignancy derived from primitive cells of the sympathetic nervous system and is the most common extracranial pediatric solid tumor . The cliin vitro , and decreased tumor growth and metastasis in vivo -degrading factors. Pre-stimulation of NB cells with HGF in a model of NB in chick embryos  led to the increased formation of well vascularized tumors . A furth in vivo .MET gene amplification, and only one example of increased c-MET expression by IHC. The rest of the samples analyzed did not show any c-MET overexpression, though the authors did identify some alternatively spliced MET isoforms , also known as nephroblastoma, is the most common renal malignancy in children. It is an embryonal malignancy and is thought to derive from aberrant differentiation and development in early nephrogenesis. HGF/c-MET autocrine and paracrine signaling has been shown to play a part in early kidney development , and so es of WT . In 2002es of WT . In contes of WT . To dateWhile rare overall, hepatoblastoma (HB) is the most common pediatric liver malignancy , particularly in younger children and infants. HB is thought to arise from early hepatic progenitor cells, and owing to their pluripotent nature, histological subtypes of HB include both epithelial and mixed epithelial-mesenchymal variants . As prevn = 5) and c-MET mRNA levels were found to be upregulated in HB tumor samples compared to healthy liver tissue  increased proliferation of established HB cell lines, while higher (non-physiologic) concentrations of HGF had the opposite effect . HGF was shown to be produced by stromal cells in co-culture with HB cells, suggesting a paracrine mechanism of HGF stimulation, while analysis of tumor sections revealed high expression of c-MET by epithelial tumor cells. In a subset of patients, HB tumors were compared to normal liver tissue  affecting β-catenin accumulation in HB. Purcell et al. studied clinical samples of HB, and while 87% (85/98) of tumors showed aberrant β-catenin accumulation, the frequency of CTNNB1 mutations in their patient cohort was substantially lower [at most 20% (20/98) of samples], suggesting an alternative mechanism for β-catenin accumulation. Significant levels of c-MET activated β-catenin  were found to have undetectable levels of c-MET .n = 27). The majority of tumors evaluated were either highly or focally positive for c-MET [74% (14/19)], but no correlation with c-MET staining and best response was observed. Of note, the one patient with clear cell sarcoma who had a PR was negative for c-MET staining  with advanced microphthalmic transcription factor (MITF)-associated tumors . The best response in the study was a partial response (PR) in a patient with clear cell sarcoma. Baseline tumor expression of c-MET was evaluated by IHC for 19 patients  investigated the effects of cabozantinib in ES and OS. Though the trial was primarily conducted in adult patients (the median age of OS patients was 34), the results showed that in patients with OS, treatment with cabozantinib gave rise to a 12% objective response rate and 33% of patients had 6 months of non-progression (meeting the study’s primary efficacy criterion). Moreover, a biomarker analysis indicated that an increased soluble (plasma) c-MET level at baseline was correlated with improved progression free survival, suggesting that this subpopulation of OS patients with high c-MET expression was responding to the anti-c-MET therapy . In a hen = 29), ES, RMS, non-RMS soft tissue sarcoma, WT , and other rare tumors (n = 23). Overall, in OS 10/29 patients (34%) had disease control after 4 months (2 PR and 8 SD), while no partial or complete responses were seen in patients with EWS, RMS, or WT (though some PRs were seen in other rare tumors). The study showed potential for cabozantinib in treatment of OS, but limited efficacy in other sarcomas or WT  , a phaseas or WT .A recent single-institution case series reported on the use of cabozantinib in four pediatric patients with relapsed NB. All four patients had extended disease control after treatment with cabozantinib for at least 6 months, while two patients had complete responses (>12 months) and remained in clinical remission at the time of publication . It is, ALK.Crizotinib is another non-selective TKI targeting c-MET, though many of the clinical studies of crizotinib have focused primarily on its role targeting anaplastic lymphoma kinase (ALK). In the adult population, crizotinib is approved for treatment of NSCLC with altered ALK aberrations . From this cohort, 11 patients with genetic alterations were enrolled and received crizotinib (results from only eight patients were available at the time of abstract publication). The tumor analysis found one MET translocation, and three instances of MET amplification. Notably the single patient with a MET translocation (glioma) had progressive disease with crizotinib therapy  (The European Organization for Research and Treatment of Cancer (EORTC) “CREATE” trial was designed as a multi-center multi-tumor trial to evaluate crizotinib in a range of cancer types known to harbor alterations in the targets of crizotinib (d ROS-1) . The triIn advanced ARMS (positive for MET fusion protein), crizotinib (as a single agent) did not have meaningful clinical activity, with just one patient achieving a PR as the best outcome. As only eight patients out of 13 were evaluable for the primary end-point due to the aggressive course of their disease, the authors suggest that targeted therapeutics like crizotinib might be better trialed in aggressive cancers as an earlier treatment (in combination with standard chemotherapy). Given the lack of disease response to anti-c-MET therapy, the authors postulate that c-MET activation is likely not a key driver of disease progression at this advanced stage in ARMS, but may play a role in earlier differentiation .MET amplification  of cases available for molecular analysis revealed fication .MET, treatment of tumors with anti-HGF/c-MET agents will likely be most impactful in preventing disease progression or relapse after treatment or resection, and when used in combination with cytotoxic therapies. Multiple pre-clinical studies reviewed above suggest that the HGF/c-MET pathway is important for protecting cancer cells from insult, and so it follows that anti-HGF/c-MET therapy could be effective as an adjuvant to other cytotoxic therapies. One of the key hurdles in cancer therapy is overcoming drug resistance developed within heavily pre-treated refractory tumors and targeting the HGF/c-MET pathway could be a promising tool for addressing this.Clearly, the HGF/c-MET pathway contributes to a wide variety of pediatric malignancies. Given its crucial role in development, proliferation, cell motility, and regeneration this is perhaps unsurprising, as aberrations in these cellular functions are commonly identified as drivers of oncogenesis and metastatic spread. There is ample evidence in the literature reviewed above to suggest that targeting the HGF/c-MET pathway could be an effective anti-cancer strategy across a range of tumor types. This promise has not, however, been fully borne out in the limited number of pediatric clinical trials that have been completed to date. Overall, the HGF/c- MET pathway is an exciting target and has shown early promise in cancers such as osteosarcoma. However, in many of the tumor types reviewed here, the principal effects of dysregulated HGF/c-MET signaling have largely been shown to be an increase in invasive/metastatic behavior, resistance to chemo- or radiotherapy, and a promotion of poorly differentiated “stem-like” cells, as opposed to driving cell proliferation and growth. This is likely reflected in the relative paucity of objective clinical responses seen in pediatric clinical trials to date. With the potential exception of tumors containing growth-sustaining genetic alterations in in vitro models generally do not reflect the diversity seen across tumors in patients. Many of the studies reviewed above included analysis of HGF/c-MET expression in patient samples, though there existed considerable variability in the methods for quantification, and the “normal” controls used between reports. Biomarker analysis for appropriate patient selection is crucial for any targeted therapy to achieve its predicted potential from pre-clinical data, although in early stages of development it is important to include open Phase I/II studies as to not exclude any groups who might potentially benefit from the therapy for reasons not yet fully elucidated. There are currently multiple ongoing or recruiting trials of anti-c-MET agents including pediatric patients, hence it is expected that additional key data will become available regarding the safety and efficacy of these agents for childhood cancers in the near future.It is also important to acknowledge that, while invaluable for pre-clinical research and drug development, MG and AN contributed to the review of the literature and writing of the manuscript. Both authors contributed to the article and approved the submitted version.


Objectives: Early-onset pancreatic cancer (EOPC) – defined as pancreatic cancer diagnosed before the age of 50 years – is associated with a poor prognosis as compared to later-onset pancreatic cancer (LOPC). Emerging evidence suggests that EOPC may exhibit a genetic signature and tumor biology that is distinct from that of LOPC. We review genetic mutations that are more prevalent in EOPC relative to LOPC and discuss the potential impact of these mutations on treatment and survival.Materials and Methods: Using PubMed and Medline, the following terms were searched and relevant citations assessed: “early onset pancreatic cancer,” “late onset pancreatic cancer,” “pancreatic cancer,” “pancreatic cancer genes,” and “pancreatic cancer targeted therapy.”CDKN2, FOXC2, and SMAD4 are significantly more common in EOPC as compared to LOPC. In addition, limited data suggest that PI3KCA mutations are more frequently observed in EOPC as compared to LOPC. KRAS mutations are relatively rare in EOPC.Results: Mutations in Conclusions: Genetic mutations associated with EOPC are distinct from those of LOPC. The preponderance of the evidence suggest that poor outcomes in EOPC are related both to advanced stage of presentation and unique tumor biology. The molecular and genetic features of EOPC warrant further investigation in order to optimize management. Indeed, although relatively rare, pancreatic cancer represents the third most common cause of cancer-related death nationwide (dex.htm) . Incidendex.htm) –4. The rdex.htm) , 6, the dex.htm) . Survivadex.htm) .KRAS and high rate of SMAD4 mutations [There are no established data that definitively distinguish the tumor biology of EOPC from (LOPC). Previous studies have identified many genetic mutations that are shared between EOPC and LOPC –12. Howeutations . Based oSimilar to early-onset lung and breast cancer, EOPC is associated with inferior survival relative to LOPC . AlthougThe purpose of this review is to identify genetic mutations that are more prevalent in EOPC as compared to LOPC and discuss the potential impact of these mutations on tumor biology, treatment, and survival.The median age of diagnosis of pancreatic cancer in the United States is 71 years . Risk faThe clinical presentation of EOPC and LOPC is identical and characterized by weight loss, jaundice, pruritus, nausea, and vomiting . EOPC haNext generation sequencing (NGS) is a “massive-parallel” or “high-throughput” sequencing technique used to determine the precise order of nucleotides within a strand of DNA/RNA. The first generation sequencing was developed by Frederick Sangers , who useLKB1/STK11), Li-Fraumeni syndrome (TP53), familial atypical mole-multiple melanoma (FAMMM) syndrome (CDKN2A), Fanconi anemia, and mutations in BRCA1/2, CFTR, KRAS, SMAD4, and FOXC2 [BRCA1/2, may be influenced by modifiable risk factors such as smoking and should be thought of in the context of the multistage theory of carcinogenesis.Although numerous studies have examined modifiable risk factors associated with EOPC , only rend FOXC2 , 25–27. nd FOXC2 . SeveralCDKN2A, FOXC2, SMAD4, and PI3KCA [There are only a few genetic mutations that have been linked specifically to EOPC in population studies, including d PI3KCA –30. Limid PI3KCA . Howeverd PI3KCA .The mechanism of pancreatic carcinogenesis involves a complex interplay of multiple related genetic and molecular factors . Other gKRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma [KRAS mutations are relatively rare in EOPC. In one recent study, authors found that only 42.8% of patients with EOPC expressed a KRAS mutation [arcinoma , 34. Howmutation . The commutation , 36 and mutation , 38. TheKRAS mutant pancreatic cancers could be considered EOPC if detected via early screening. Screening for early detection in high-risk individuals such as familial pancreatic cancer could potentially identify more patients with pancreatic cancer at an early stage and age [KRAS mutation-associated carcinogenesis is illustrated in Interestingly, mathematical models have shown that it takes nearly twelve years from the oncogenic event that initiates pancreatic carcinogenesis until the development of the parental clone and an additional seven years for the development of metastatic subclones within the primary cancer , 40. The and age . The mecMLH1, MSH2, MSH3, MSH6, PMS1, and PMS2, which repair DNA replication errors, result in MSI [Mutations or epigenetic changes of mismatch repair genes such as t in MSI . The pret in MSI , gastrict in MSI , and cant in MSI . Howevert in MSI , 47 and t in MSI . The pret in MSI –53; simit in MSI , 54. Thet in MSI . There aCKDN2A, which normally functions as a tumor suppressor gene involved in the pathway that inhibits the cell cycle at the G1 checkpoint. Mutations in CDKN2A are found in 95% of pancreatic cancers [CKDN2A encodes the protein p16inka, which acts as a cell cycle regulator. Previous studies have shown that loss of the p16inka protein may increase progression of cells that have a pre-existing KRAS mutation [KRAS mutations prevalence appear to be less common in EOPC as compared to LOPC [CDKN2A mutation was significantly increased in EOPC patients [One of the recently studied genes associated with EOPC is  cancers , 56. CKDmutation . Notably to LOPC , 30. TsaFOXC2 is an oncogenic transcription factor associated with many different cancers, including hepatocellular carcinoma and breast cancer. The true prevalence of FOXC2 mutations in pancreatic cancer remains to be established. It is upregulated in pancreatic ductal adenocarcinoma and enhances growth and migration of cancer cells [FOXC2 upregulation was associated with EOPC and potentially early epithelial-to-mesenchymal transition [er cells . It inteer cells , 59. Tsaansition .SMAD4 is an important tumor suppressor gene that is found to be inactivated in approximately 50% of pancreatic cancers and has been associated with a more aggressive clinical course [SMAD4 serves as part of this pathway, where it forms as complex with specific sequences of DNA in the cell nucleus after it is activated by a TGF-β protein. When SMAD4 is mutated, the cell proliferation process is left unchecked and rapid cell growth follows. Previous analyses have demonstrated that patients with EOPC had higher mutations rates of SMAD4 than those with LOPC [l course , 60, 61.ith LOPC .PI3KCA is a gene that encodes the p110 alpha protein which is involved in the phosphatidylinositol 3-kinase (PI3K) pathway. Mutations are present in 3–5% of patients with pancreatic cancers [PTEN tumor suppressor gene that normally inhibits this pathway. Previous studies have shown mutations to PTEN result in accelerated mutated pancreatic cell growth but have so far not been linked to EOPC [ cancers –64. This cancers . However cancers . Further to EOPC .CFTR) is a transmembrane chloride channel that helps maintain fluid homeostasis in the body. Mutations in the form of phenylalanine 508 deletion (ΔF508) are the most commonly seen alteration. The prevalence of CFTR mutations in pancreatic cancer is estimated range between 5 and 8% [CFTR mutations and EOPC was proposed over a decade ago. In 2005, McWilliams and colleagues found that 8.4% of EOPC patients had CFTR mutations as compared to 4.1% in the control group [n = 33) with only two patients found to have a CFTR mutation; these patients were 42 and 50 years of age. A follow up study by the McWilliams group again found a significant increase in pancreatic cancer in carriers of the CFTR gene (5.3% versus 3.8%) along with a younger average onset (62 versus 67 years) [CFTR mutations in early pancreatic cancer, including a recent analysis in which investigators found no significant difference in the rate of EPOC among patients with the most common CFTR variants  as compared to a control group [Cystic fibrosis transmembrane conductance regulator  examining management strategies and survival differences between EOPC and LOPC; data from existing studies can only be extrapolated to provide insight into the potential effect of available therapeutics on EOPC. For example, gemcitabine was compared to FOLFIRINOX in one RCT involving 342 patients aged 65 years or younger with metastatic pancreatic cancer and good performance status . The FOLBRCA-mutated metastatic pancreatic cancer that had not progressed during platinum-based chemotherapy. Subjects included in the study were relatively young, with median age of 57 years. Authors concluded that maintenance therapy with Olaparaib increased progression-free survival as compared to placebo [BRCA-mutated EOPC as a first-line treatment for metastatic disease warrants further exploration.Approximately 10% of pancreatic cancers have familial inheritance , 86. Scr placebo . MoreoveBRCA1/2 and PALB2 (gBRCA/PALB2+) mutation. In a phase II trial comparing cisplatin and gemcitabine with or without veliparib in gBRCA/PALB2+ in patients with stage III or stage IV pancreatic adenocarcinoma, cisplatin and gemcitabine were shown to be the more effective regimen and concurrent veliparib did not improve response rate [The response to treatment may vary in patients with both a germline nse rate . Howevernse rate –92 may lnse rate . In subgMolecular targets, such as human epidermal growth factor receptor type 1 (HER1/EGFR), which are overexpressed in many pancreatic cancers have also been targeted clinically with mixed outcomes. Moore et al. first demonstrated a statistically significantly improvement in survival in advanced pancreatic cancer by adding erlotinib to gemcitabine . In the Circulating tumor DNA (ctDNA) can be used to determine pancreatic adenocarcinoma prognosis and can conceivably help select targeted therapeutic agents . Indeed,Immune checkpoint inhibitors (ICIs) have historically been ineffective for the management of pancreatic adenocarcinoma. However, emerging evidence suggests that ICIs may play an important role in the management of both EOPC and LOPC. In a 2021 study by Lenzo et al., authors described several subsets of patients who may benefit from ICI therapy, including those with a PD-L1-driven phenotype or PD-1 axis-driven immunosuppression . A subseThere are no established treatment guidelines tailored toward EOPC. In advanced or metastatic disease, treatment for EOPC and LOPC is similar and based predominantly on performance status and comorbidities . The firChallenges in medical management of pancreatic cancer are vast and are related to metabolism of therapeutic agents , managemPancreatic cancer is increasing in incidence and will become second leading cause of cancer death by 2030. Unfortunately, the prognosis of pancreatic cancer remains dismal. Individuals with EOPC tend to have fewer comorbidities and are more likely to undergo chemo- and radiation therapy as compared to their counterparts with LOPC, but nevertheless face a worse prognosis. Poor outcomes in EOPC patients may be multifactorial and related to advanced stage of presentation at diagnosis and unique tumor biology. The genomic basis of EOPC warrants further investigation and consideration as a distinct clinical entity. Future studies and trials may lead to the identification of genetic mutations distinct to EOPC and the development of new targeted interventions.


On Mars, structural loads and the low tensile strength of in-place Martian binders make existing solutions for Martian structures uneconomical because they are based on the terrestrial sources like inflatable units. Here we address this issue by introducing and analyzing three innovative structural forms in accordance with the structural engineering point of view using symmetric optimum parabolic rotated arch shapes and in-place waterless sulfur-based concrete. These forms minimize the tensile stresses under Martian structural loads. Probable Martian structural loads, including gravity, wind, marsquakes, asteroid and meteoroid impact loads and their effects have been investigated and calculated. The proposed models were analyzed under Martian structural loads using the implicit finite element method and the results were compared to two concrete structural forms from previous studies. The proposed models could tolerate Martian structural loads with complete elastic behavior and would significantly decrease the Martian colonization cost due to using Martian resources and reduce element importing from Earth. Due to these reasons, multiplanetary life has received a lot of attention since the beginning of the twenty-first century. Also, with the increasing demand for energy (beyond the capacity of the Earth) in parallel with the passing of type 1 Kardashev scale, multi-planetary life seems inevitable4.Because of the economic opportunities, discovery of a new world, new energy sources and preserve our species, multiplanetary life is of interest5. The Martian colonization solutions should be appropriate with today’s Martian harsh environment. Environmental factors affecting structural loads such as atmospheric pressure, marsquakes, wind, and asteroid and meteoroid impacts can be calculated using data from landers and orbiters such as InSight and Odyssey9. NASA has studied suitable structural forms for human settlement on Mars for a total mission time of 919 days10. The envisioned structural form is a cylindrical metal shape with a height and diameter of 8 m that is able to tolerate the difference between the internal and external pressure. However, shuttles (~ 110 to 120 tons) would carry these habitats (~ 50 tons) from Earth, increasing the costs dramatically, including vehicle development, fuel, management, increasing the number of shuttle launch and so on.Some ideas have been proposed for terraforming Mars but there is a long way to go with this notion11. The design of a human-friendly Martian base is envisioned to consist of five structural units based on the terrestrial sources for structures by Kozicki and Kozicka12, who proposed the suitable design, size and area for the intended structures.It is not feasible to transport all the structures required to create a settlement on Mars from Earth. However, because of the low tensile strength of Martian binders, building Martian structures with these in-place binders would be very challenging. The design of an optimum Martian base on the regolith using inflatable and tensile resistance materials has been assessed for covered and uncovered structural elements13. In this regard, structures below and near the surface are options but would require remarkable energy for construction15. It is possible to produce a durable, fast curing and stable concrete with high compressive strength (more than 100 MPa) using the Martian regolith. Sulfur-based concrete is one of the best options for use in a 3D structural printer17. A hybrid dome shape printable Martian structure that consists of a thin inflatable shell and printed regolith was proposed by Troemner et al.18. This structure that was a part of NASA’s habitat challenge could tolerate Martian structural loads as well as environmental loads.The structural components for creation of an outpost using a 3D printer were investigated using inflatable structural elements  and the regolith as the binder  13 and Kozicki and Kozicka12. The amount of concrete required for the construction of the models was investigated to determine which model would require the least energy to build.In this paper the effect of the gravity load, difference in the interior and exterior pressures, wind loads, and marsquake loads were studied and calculated using data from Viking 1 and 2 and the InSight mission SEIS data to develop a design load map with which to design a Martian structure. The effects of asteroid and meteoroid impact loads also were assessed. Three innovative structural forms for a Martian settlement are proposed that use symmetric rotated optimum parabolic arches. These forms have been designed to minimize the tensile stress and maximize the compressive stress under Martian structural loading to meet the requirements of Martian concrete and eliminate the import of structural elements from Earth. The models were analyzed under Martian structural loading using the implicit finite element model (FEM) and the structural behavior of the models was compared with concrete structural forms from the studies of Cesaretti et al.Because Mars experiences less gravity acceleration than Earth, the self-weight of the Martian structural system would be much less than a terrestrial structure. The habitats should be designed to tolerate the 1 atm pressure difference between interior and exterior to satisfy human comfort. In addition to the structural self-weight, 1 atm of pressure would be applied as a constant distributed load inside the habitat.9. Figure 19. As on Earth, the wind speed on Mars varies according to the season. For better accuracy, a longer time span should be considered to determine the wind speed. Figure 19. The maximum wind speed occurred on sol 214 with a speed of 25.9 m/s. The InSight wind speed observations during the first 220 sols showed a maximum wind speed of almost 25 m/s20, confirming good agreement between the Viking 1 and InSight wind speed observations.Maximum wind speeds of 9.5 m/s have been recorded by Viking 1 and 7.1 m/s by Viking 2 during the first 44 and 50 solar days (sols), respectively2, 342.52 N/m2, and 5,9917.02 N, respectively21. Wind is a fundamental atmospheric quantity caused by air movement. The wind force or pressure depends on the air density (ρ) or its mass per volume. At the surface at an average temperature, Mars air density is about 0.016 that of the Earth, which is 1.22 kg/m3 at 15 °C. The fluid dynamic pressure or wind stagnation pressure at the envisioned speed considering Mars air density was calculated as 6.70 N/m2  were calculated using Eqs. –3 as bei.24 km/h 7. The seismometer was capable of detecting seismic motion of magnitude of 5 within an 0.021 area (1000 km) of the red planet. Up to September 2019, the InSight lander recorded 174 events, including 24 deep events (mantle origin) of a relatively high magnitude and low frequency content22. No marsquake with a magnitude greater than 3.8 Richter was recorded.During the 640 h mission of Viking 2, high-quality seismic data recorded in ambient silence, detected a possible marsquake at sol 80 with a probable magnitude of 3 on the Richter scale with a high-frequency content24. Three frequencies of 2.6, 4.2 and 6.9 Hz continuously exist , the probability of an asteroid hitting the surface of Mars is much higher than for Earth. Studies have shown that, on average, 200 asteroids having an average length of 1.5 m hit Mars annually.26 Eqs.  calculat28. However, particles with diameters of 60–1200 µm could reach the surface of Mars29. A density of 1000 kg/m3 has been considered for such particles30. Considering the characteristics of the planet, the terminal velocity for a particle of 125 µm in size with a roughly spherical shape has been calculated to be 9.07 m/s  compared to Mars (5030 m/s) can prevent the passage of these bodies. By comparison, a meteoroid influx on Mars could be about four times that on Earth. Surprisingly, the thin atmosphere of Mars works as a shelter against meteoroid impacts0 m/s com33. Even a particle of 1264 µm in diameter, which is less likely to impact the structure because of the very low influx, will have an impact penetration of about Because of the high influx, meteoroids would impact Martian structures. However, because of the pressure difference between the interior and exterior of the structure, structural sealing and permeability are of importance. This means that the amount of penetration due to the impact of such particles on Martian structures should be calculated. This amount was calculated using Eqs. –17 as beTable Figure The total height and base radius of Model-2 are 9.01 m and 10.00 m, respectively Fig. a,b. this2 and 10 m. respectively. A constant thickness of 20 cm has been considered for the walls. Table As Fig. 12 and Cesaretti et al.13 models, respectively. For plastic strain which is related to the damage and cracks, under 50% of atmospheric pressure, Model-1 shows 54.63% and 17.22% fewer MPLS than the concrete structural forms of Kozicki and Kozicka12 and Cesaretti et al.13, respectively (Model-1 shows no plastic strain). The proposed models are the only ones that show complete elastic behavior under 1 atm of internal pressure.The maximum principal logarithmic strain (MPLS) and the plastic strain magnitude (PSM) of the models under 0% (only gravity load), 50% , and 100%  of atmospheric pressure as internal pressure and the gravity load, at the same time  behavior. For example, at 50% of atmospheric pressure, the MPS of the Model-1 was 0.35 and 1.92 MPa less than for the Cesaretti et al.13 and Kozicki and Kozicka12 concrete structural forms, respectively.Figure The MPS contours of the models under 50% of atmospheric pressure are shown in Fig. In-place Martian concretes and binders such as plaster of Paris (POP), ordinary Portland cement (OPC), alkali-activated cement, sulfur concrete, Geopolymer cement, and Mg-based cement show brittle behavior under loads with very low tensile strength and relatively suitable compressive strength. The proposed structures (chiefly Model-1) were designed to minimize the tensile stress and maximize compressive stress to enable the use of in-place concretes to show appropriate and linear behavior under Martian structural loads using only Martian concretes. Thus, these structural systems can be constructed using concretes other than sulfur concrete.12.The energy available is a concern on Mars. Less concrete for construction reduces required energy. Because of the distance of Mars from the Sun (negative effect) and the thin and clear atmosphere (positive effect), the amount of solar energy which reaches the surface of Mars is around 41% lower than the Earth Fig. . Figure 13 and Kozicki and Kozicka12. This means it requires less energy for mining sulfur from the regolith, melting sulfur, finding suitable aggregate and the 3D printing process. In addition, there will be lower costs because the import structural elements from Earth is not required, which will mean a significant reduction in cost, energy, and time spent, which are major consideration for Martian colonization. Another advantage of this model is the possibility of optimization of the weight of the roof (due to gravity) and the lifting force (due to 1 atm of pressure).Model-1 requires about 2% less concrete material during construction than the models of Cesaretti et al.The need to explore an unknown environment is an inherent characteristic of human beings. Multiplanetary life will happen for future generations. It could occur relatively soon and Mars will likely be the first destination. Mars colonization requires low-cost, low-energy, reliable and stable structures for its first settlement. Our study addressed these issues by proposing innovative structural forms. Investigation and calculation of the lateral loads of wind and marsquakes using recorded data from the landers (Viking 1 and 2 and InSight), gravity, internal pressure, and role of asteroid and micro-meteoroids indicate that the self-weight load from gravity and the pressure difference between the interior and exterior are crucial loads for Martian structures. The proposed models show completely elastic behavior under Martian structural loads, which is essential for the permeability of Martian structures. While the concrete structural forms of previous studies showed plastic behavior under 50% to 100% of internal atmospheric pressure, Model-1 requires less concrete and less construction energy. Besides the better structural behavior and less concrete requirement for construction, Model-1 has a simpler geometry than Model-2 and Model-3 that makes construction and printing process easier. The results showed that the proposed models eliminate the need for costly importation of terrestrial structural units such as inflatable elements from the Earth. Additionally, because of the similar behavior of the Martian in-place concretes, very limited tensile strength and almost suitable compressive strength, and linear behavior of the proposed Martian structures it is possible to use these structural forms for different kinds of in-place Martian concretes such as POP, OPC, alkali-activated cement, sulfur concrete, Geopolymer cement, Mg-based cement, etc.Of note, this study only proposed a new generation of Martian structural forms. Other challenges that should be considered for a Martian building such as radiation shield, required thermal energy, internal human-friendly design, mechanical equipment, etc. should be studied by relevant experts.35.The general structural stability, geometric combability, and adequation of a structure in the short- and long-term should be assessed using valid and appropriate analysis methods. Although these loads can be categorized as being live or dead loads, in this study, the structural loads were assessed as being either vertical or lateral loads21:z, Equations –3 were u37:In climatology, wind is the motion of gases relative to the surface. The wind force or pressure depends on the air density (ρ) or its mass per volume. Therefore, a heavier atmosphere applies more wind pressure on the structure. The atmospheric conditions of Mars are completely different from that of Earth. The fluid dynamic pressure can be calculated using Eq.  by consi40. However, all the remarkable (low frequency) marsquakes that have been recorded (24 numbers) originated in the mantle22. Of note, by considering the size of the two planets, that the crust of Mars has an average depth of 50 km, which is about three times that of Earth. Therefore, marsquake waves should travel for longer distances (from the mantel to the surface) in comparison with shallow earthquakes and this would strongly dampen the motion components. A magnitude 4 Richter marsquake would be much less dangerous than a 4 Richter earthquake, which is not sensible for human.Tectonic plates are the main causes of shallow strong ground motions. On Earth, shallow ground motions comprise the most numerous earthquakes at depths of 0–70 km. Destructive earthquakes usually occur at depths of less than 15 km on the crust. The closer to the surface that an earthquake occurs, the greater the chance for destruction (higher PGA). However, there is no clear evidence for plate tectonics on any planet except Earth. This is no exception for Mars. Some researchers have proposed that the crust of Mars could have been seismically active millions of years ago40. Assuming wave propagation that is similar to that of the Earth, empirical predictive Eq. , Equations –17 were 43. Because of the low tensile strength and relatively high compressive strength of available Martian binders and concretes, arch elements are suitable forms for Martian structures. The current study proposed and analyzed suitable Martian structure forms using rotated arches. Figure 45. The optimum arch shape can be calculated according to Eq.  planet. Observations show that on average, 6.8 wt% of Martian dust (2.7 wt% S) and 6.2 wt% of the soil (2.48 wt% S) are composed of SO48. A low temperature will actually increase curing of this type of concrete. Furthermore, sulfur is in a rhombic phase in the Martian environment and atmospheric conditions. The current study used the average stress–strain curve for sulfur concrete from Wendner et al.33. The average strain–stress curves of the intended Martian sulfur concrete were shown in Fig. Sulfur concrete is waterless, can be used in 3D printers and workable in the temperatures and atmosphere of Mars. Additionally, its production requires less energy than other binders, including Martian OPC and basalt concrete. Studies have shown that the highly varied temperature of Mars from day to night and season to season does not affect the durability of sulfur concrete (intra-stress envelope)It should be noted that in the presence of moisture, sulfur may produce toxic gases. To prevent this, an appropriate thin layer of plaster is proposed for the internal wall and roof. This layer is not a structural component and would tolerate no structural loads. It only decreases the permeability and prevents the production of toxic gases.13 and the residual dome (RD) of Kozicki and Kozicka12 which also have been built using sulfur concrete. For the purposes of comparison, the volumes of all five models were chosen to be almost similar to one another. The volume of the RD dome from the Kozicki and Kozicka model was considered as the reference volume. The models showed a maximum volume difference of 2.08%. Table The behavior of the proposed models was compared to the concrete structural forms from Cesaretti et al.50.Abaqus software was used to perform non-linear dynamic FE implicit analysis. This software has a good ability to analyze models with concrete-like behavior like this study including initial damage, damage evolution, strength and stiffness deterioration51. The plastic magnitude strain (PMS), the MPLS and the MPS were considered as the control criteria. The concrete damage plasticity model was chosen for modeling sulfur concrete behavior based on the sulfur concrete stress–strain behavior50. The analysis method was the implicit Hilber-Hughes-Taylor method with a full Newton–Raphson solution for greater accuracy52. Table The strain parameter is more sensitive than displacement as the structural damage control criteria53. Outside the atmosphere of Earth, the amount of the power per unit area (W/m2) received from the Sun at noon is about 1300 W/m2. On a clear sunny day (spring or summer), the maximum solar irradiance that reaches the Earth’s surface at noon is 950–1000 W/m2. This value is 430–590 W/m2 for a sunny day on Mars; therefore, the amount of solar energy is much lower.Energy and time are some of the greatest concerns in deep space exploration and for Martian colonization55. However, many will not be available in the early stages of colonization.The concrete volume required for construction is determinative. Figure