Infant mortality remains a major developmental challenge in many low-income countries. Epidemiological evidence suggests that infant acquisition of maternal microbiome is essential for programming of immunity and metabolism. As such, irrational maternal antibiotic use may affect infant health.The aim of the study was to determine the effects of prenatal antibiotic use on early postnatal life (90 days) in a low-income community in Ghana.The study was a retrospective study of 412 mother-baby pair medical records in a low-income community in rural Ghana.During the ninety-day period, the prevalence and relative risk of neonatal sepsis, respiratory disorders, and dermatitis were significantly higher in infants treated prenatally with antibiotics compared to untreated infants. Prenatal antibiotic treatment was not significantly associated with the risk of developing neonatal jaundice and conjunctivitis. However, prenatally antibiotic exposed infants were three times likely to visit the hospital for a non-scheduled/non-review treatment within the first 90 days compared to unexposed babies.Intrapartum antibiotic treatment is associated with poor early infant health. Rationalizing antibiotic use during pregnancy may contribute to reducing infant mortality. Although there has been a steady decline in recent years, maternal and infant mortality remain a major developmental challenge in many low-income countriesTo protect both maternal and foetal health, several anti-infective medicines are employed. In many sub-Saharan Africa countries, very few laboratories are equipped to isolate and identify causative organisms often leading to irrational antibiotic prescription patterns in pregnancy resulting in possible foetal exposure to antibiotics in utero Infectious diseases are a leading cause of early infant mortality. A compromised immunity predisposes the infant to infectious diseases. Unfortunately, over 99% of infant mortality occur in areas where less than 1% of research into infant mortality is carried out The study site, National Health Insurance, is located within the Bekwai Municipality near the Greater Kumasi Area of the Ashanti Region of Ghana. The area is rural and the majority of inhabitants engage in peasant farming and/or petty trading. The hospital is a 45-bed capacity district hospital. It runs an ante-natal and post-natal clinic. It has a resident Gynaecologist, Pharmacist, several Midwives and Nurses. Most patients access health through the capitation program of the National Health Insurance. The area was chosen because it was rural with no pharmacy and many of the people used National health insurance, this was supposed to help check out of hospital antibiotic usage which is a major confounding factor for the study.Based on the fertility rate of the municipality (110.5 per 1000 women) and applying Cochran 1977) equation, a minimum of 325 respondents were required 77 equatiThe Inclusion criteria were as follows:Mother should have attended at least three Antenatal Clinics, delivered at the hospital and attended postnatal clinic at the facility.The baby should have attended all scheduled reviewsThe exclusion criteria were as follows:Mother-baby pairs with no records or scanty postnatal recordsBabies who were not breastfed or who missed scheduled review visitsTwin births, births by referrals were also excluded.In this study, impetigo, dermatitis and eczema were all categorized as dermatitis.Rhinitis, chest infection, pneumonia, bronchiolitis and any other condition related to the respiratory tract were accepted us Respiratory tract disease.The mean number of hospital visits was obtained using the count of the number of times the child was brought to the hospital to seek medical treatment or attention. Normal post-natal review visits or scheduled visits were excluded from the count of visits.The term “neonatal conjunctivitis” was chosen to represent any diagnosis of a prescriber listed as follows; neonatal conjunctivitis, septic or bacterial conjunctivitis, allergic conjunctivitis and ophthalmia neonatorum.Ethical approval for the study was given by the Committee on Human Research, Publications and Ethics, Kwame Nkrumah University of Science and Technology, School of Medical Sciences and Komfo Anokye Teaching Hospital, Kumasi (CHRPE/AP/347/16). Permission to carry out the research was given by the hospital management committee of Seventh-Day Adventist Hospital, Dominase . Individual permission and consent were not possible as mother/baby pair medical records were the principal source of data. For confidentiality, patient's name and address were also excluded.Data from mother/baby pair folders were first captured with a special questionnaire and transferred unto IBM Statistical Package for Social Sciences (SPSS) version 21 for analysis. Categorical variables such as the presence or absence of a neonatal condition were analysed with Pearson Chi-square. P value less than or equal to 0.05 at 95% confidence interval was considered statistically significant. Relative risk was used as an indicator of the degree of association between a condition and comparable groups.The choice of low-income deprived rural community without a community pharmacy limited the impact of potential out-of-hospital antibiotic use. Secondly, the “capitation policy” of the National Health Insurance Scheme of Ghana encouraged mother/baby to seek health at the hospital instead of elsewhere where they have to pay out of pocket. This made respondents more likely to seek treatment from the hospital. Nonetheless, the study cannot completely rule out the possibility of some out-of-hospital antibiotic use. The study could not account for the effects of diet, herbs sometimes used for lactation on the study outcome P<0.001, K=55.47, DF=1). Fifty-five percent (55%) of babies delivered vaginally were treated prenatally with antibiotics, whereas 94.5% of babies who born by Caesarean were exposed to antibiotics intrapartum  was compared with infants whose mothers were not treated with antibiotics during pregnancy. Four hundred and twelve (412) mother-baby pairs met the inclusion criteria for the study. Of the 412 infants involved in the study, 271 children were exposed to intrapartum antibiotics at some stage of pregnancy. One hundred and forty-one (141) infants who were not exposed to intrapartum antibiotics served as controls . Three hrapartum There was no statistically significant difference in terms of mean birth weight, mean APGAR scores, birth defects  between neonates exposed to intrapartum antibiotics and unexposed neonates at birth (Day 0). There was also no statistically significant difference in mean appearance, pulse, grimace, activity, and respiration (APGAR) scores, weight at birth and birth defects between babies delivered by Caesarean or delivered vaginallyP<0.001, Cl=95%, K=20.6, DF=1). After adjusting for the influence of method of delivery, the adjusted relative risk was 2.1 . The risk of neonatal sepsis was higher in third trimester antibiotic usage and perinatal (24 hours to delivery) antibiotic use  (P = 0.134), age (P = 0.85), gravida (P = 0.65), religion did not significantly affect the risk of an infant developing sepsis within the first 90 days of life.The prevalence of neonatal sepsis was 22.1 % within the general study population with the first 90 days of postnatal life. However, the prevalence of neonatal sepsis was significantly higher in infants whose mothers were treated with antibiotics prenatally than in infants born to untreated mothers (28.8% VRS 9.2%). The relative risk was 4 times higher amongst intrapartum antibiotic treated babies than infants whose mothers were not treated with antibiotics  . Maternap<0.001). The relative risk was still high even after adjusting for the mode of delivery . Unlike neonatal sepsis, the period of pregnancy within which the antibiotic was administered to the mother had minimal effects on the relative risk of developing respiratory tract disorders i.e. 3.3, 2.1, 3.4 for each trimester respectively. However, infants who were exposed to antibiotics in all trimesters had six to seven times the relative risk of developing a respiratory tract disorder compared to children who were not treated with antibiotics at all. Maternal socio-demographic factors such as marital status, gravida, age did not influence the relative risk of developing respiratory tract diseases  in the intrapartum antibiotic exposed and unexposed group was 18.5 % (50) versus 5.0 % (7). Infants exposed to antibiotics intrapartum were four times more likely to develop respiratory tract disease than unexposed children  babies were diagnosed with dermatitis within the first 3 months of post -natal life . Out of The prevalence of conjunctivitis within the general study population of neonates was 8.98 % (n=37). The prevalence of conjunctivitis in infants exposed prenatally to antibiotics was 11.8% (n=32) as against 5.0 % (n=7) non exposed group. The relative risk of neonates developing conjunctivitis was 2.56 . However, after adjusting for the effects of mode of delivery, the risk of neonatal conjunctivitis was not statistically significant 2.0 . There was no statistically significant association between Mother's age (p = 0.189), religion (p = 0.628), marital status (p= 0.976), gravida (p= 0.538) and occupation (p= 0.729) and the relative risk of neonatal conjunctivitis The prevalence of neonatal jaundice in the study population was 6.8 % (28). The prevalence of jaundice in the antibiotic exposed infants was 23(8.5%) compared to 5(3.5%) in the non-antibiotic exposed group. The relative risk of neonatal jaundice in infants exposed to antibiotic at any point in pregnancy was 2.5 . After adjusting for mode of delivery, the relative risk was 0.924 . Maternal factors such as gravida, age, marital status did not significantly affect the risk of neonates developing dermatitis p<0.001, F = 13.92). There was no statistically significant association between the number of visits and other socio-economic factors of the mother . After adjusting for method of delivery, the association between antibiotic exposure and mean visits was still significant, 0.53±0.86 days as against 0.20±0.52 days  born to antibiotic exposed mothers at a rural hospital in Ghana were evaluated. Infants treated prenatally with antibiotics had higher prevalence of dermatitis, respiratory disorders, sepsis and subsequently made more non-scheduled visits to the hospital compared to unexposed cohorts. There was a strong association between the prenatal antibiotic use and the risk of developing neonatal sepsis and neonatal respiratory disorder. The relative risk for neonatal sepsis was six to seven times higher when antibiotics were administered within 24 hours of delivery. There was also a moderate association between neonatal dermatitis and maternal prenatal antibiotic use. Similar reports and trends have been noted in similar studies in other parts of the world by other authors. It has been reported by other authors that intrapartum antibiotic is a significant risk factor for not only asthma and other allergic diseases but infectious diseases in later life The development of the infant immune system and metabolism depends partly on the quality of microbiota inherited from the mother Epigenetic factors have been known to affect the expression of transcription genes needed to regulate the population of T cells. Bacterial metabolites and short fatty acid chains have been implicated in modification of histone bodies Infants prenatally treated with antibiotics had higher risk of developing neonatal sepsis, neonatal respiratory disorder, and dermatitis. The infants were 3.5 times likely to visit the hospital for non-scheduled or non-review treatment.


In this paper, the thermal-related stress–strain behavior of alkali-activated slag (AAS) concretes, with different alkali concentrations and moduli, was studied under compression. After exposure to high temperatures , a compression test was carried out on the specimens. The stress–strain relationship, axial compressive strength, and elastic modulus were expressed using both a displacement extensometer and the digital image correlation (DIC) technique. It was mainly determined that: (1) With the increase in temperature, the stress–strain curves of the AAS concretes tended to be flattened, indicating reductions in both axial compressive strength and elastic modulus. After 1000 °C, only 2.5–3.7% axial compressive strength and 1.4–3.9% elastic modulus remained, respectively. (2) The DIC technique was used for thermal strain measurements of the AAS concrete. Compared to the traditional extensometer, DIC yielded a small error of 4.5% and 7.2% for axial compressive strength and elastic modulus measurements, respectively. The strain cloud chart obtained from DIC was helpful for monitoring the damage process of the specimens. The findings of this paper refined scientific systems of AAS concrete under thermal action, and also provided a newly non-contact approach for thermal strain measurements of AAS concrete under compression. Alkali-activated slag (AAS) is made by activating granulated blast furnace slag (GGBS) with an alkaline activator  . As it dFires have frequently occurred in buildings in recent years. In this context, as a potential cementitious material with which to construct buildings, the fire (high temperature)-related performance, and mechanical properties in particular, of AAS should be fully understood before its extensive application. Compared to a compressive strength test, which is usually applied to evaluate the mechanical properties of concrete after high-temperature treatments, the stress–strain behavior could reflect its bearing capacity and deformation more comprehensively. Researchers have discussed the thermal stress–strain behavior of normal concrete ,26,27, f2O% of slag, 4, 6, 8) and moduli . The stress–strain relationship, axial compressive strength, and the elastic modulus of the concretes was studied. In this paper, after exposure to high temperatures, uniaxial compression was carried out on AAS concretes (sodium silicate solution was used as an activator) with different alkali concentrations  produced by Fuchen chemical reagent Co., Ltd. in Tianjin, China, was used to adjust the Ms of the WG to the values required. Manufactured sand with a modulus of 2.81 was used as fine aggregates. Before mixing, the sand was sieved sufficiently to remove any stone powder that might exist. Crushed limestone with a continuous gradation in a range of 5–25 mm was used as coarse aggregate. Tap water was used for mixing and curing. Slag from Qujing, Yunnan province, China, was used to manufacture AAS concrete. The activity index of the slag was 83% at 28 days. Its chemical compositions and X-ray diffraction (XRD) pattern are shown in 2O% of 4, 6 and 8, and Ms of sodium silicate solution of 1.0, 1.5 and 2.0 were produced. For all the mixes, the binder content, water binder ratio (W/B), and sand ratio were kept same at 400 kg/m3, 0.45 and 40%, respectively. Binder content was a sum of slag content, NaOH content and solid content in WG. Water content in WG was considered in the calculation of W/B. The mix proportions of the concretes are given in AAS concretes with NaA muffle furnace was used to heat the concrete specimens to 200 °C, 400 °C, 600 °C, 800 °C, and 1000 °C, respectively, with a heating velocity of 5 °C/min. After maintaining 2 h at the target temperatures, the power of the furnace was shut down and the specimens were cooled with the furnace to room temperature. The regime described above is shown in An axial compression test was carried out on the concrete specimens at room temperature and after high-temperature exposures according to the Chinese standard GB/T50081-2019 . The expAxial compressive strength The elastic modulus F is the maximum force the specimens could withstand, kN; F0 is the initial force when reference stress is 0.5 MPa, kN; aF is the force when stress is 1/3 of the A is the loading area, 100 mm × 100 mm;L is the measure distance, 100 mm;ε0 is the deformation value recorded in the last 30 s while maintaining F0 for 60 s, mm; aε is the deformation value recorded in the last 30 s while maintaining aF for 60 s, mm.Simultaneously, DIC technology was also used to test and analyze the stress–strain behavior of the concretes under axial compression, and the results were compared to the ones obtained from displacement extensometers. Before the testing, white paint was sprayed onto the surface of the two sides of the specimens with no displacement extensometers, followed by black paint spraying, to artificially produce random speckles see  for defoFurthermore, VIC-2D was also used to calculate the strain field of the region, where the step size and sub-region were assigned to 5 pixels and 151 pixels × 151 pixels, respectively. p, axial compressive strength), gradient of the curve , and the strain corresponding to the stress peak (ε) are summarized in The stress–strain relationship of the concrete specimens at room temperature and after exposure to high temperatures is shown in af is the axial compressive strength of the concrete after exposure to high temperatures, MPa; af0 is the axial compressive strength of the concrete at room temperature, MPa;T is the temperature, °C.E is the elastic modulus of the concrete after exposure to high temperatures, GPa;E0 is the elastic modulus of the concrete at room temperature, GPa;T is the temperature, °C.2O% on the stress–strain relationship of the concrete specimens at room temperature and after exposure to high temperatures is shown in 2O% was kept at 6%. From 2O% of 6% could ensure a relatively higher residual axial compressive strength. This is in agreement with the results reported by Nasr et al. [2O% could provide AAS with sufficient hydration and then a dense matrix structure [2O% on the residual axial compressive strength of the concrete specimens was not significant. However, unlike axial compressive strength, the concrete specimen with Na2O% of 6% did not exhibit much advantage when the residual elastic modulus was considered before 600 °C, as shown in 2O% had no significant influence on the elastic modulus of the concrete after 600 °C. When Ms of 2.0 was applied, the concrete specimen always yielded a relatively lower residual axial compressive strength as a result of the less hydrated matrix [The influence of Nar et al. . The reatructure  to resisd matrix . MeanwhiThe thermal stress–strain relationship obtained using DIC technology is shown in Since the strain value in the cracked area is greater than that in the non-cracked area, the cracks could be easily identified according to the strain on the concrete surface. After high-temperature exposure, the damage process of the concrete specimens under axial compression was monitored using the DIC technique in situ, and the result (6%-2.0 as an example) is shown in (1)Generally, with the increase in temperature, stress–strain curves of the AAS concrete specimens tend to be flattened, indicating reductions in both stress peak  and gradient of the curve (elastic modulus), as well as an increase in the strain corresponding to the stress peak. After 1000 °C, only 2.5–3.7% axial compressive strength and 1.4–3.9% elastic modulus remained, respectively.(2)2O% of 6% could ensure a relatively higher residual axial compressive strength. However, the concrete specimen with Na2O% of 6% did not exhibit much advantage when residual elastic modulus was considered. After reaching 600 °C, the influence of Na2O% on both axial compressive strength and elastic modulus was not significant. When Ms of 2.0 was applied, the concrete specimen always yielded a relatively lower residual axial compressive strength. Meanwhile, when residual elastic modulus was considered, such mixes performed well to a certain extent.Before 600 °C, Na(3)The DIC technique is feasible for thermal strain measurement of the AAS concrete. Compared to a traditional extensometer, DIC has yielded a small error of 4.5% and 7.2%, respectively, for axial compressive strength and elastic modulus measurement. The strain cloud chart obtained using DIC has confirmed that in general, the stress corresponding to the first cracking of the specimens reduced with the increase in temperature, as a result of thermal damage. After the initial cracking, with the further increase in stress, more severe cracking occurred on the specimens. When cracks went through the section of the specimens, the specimens were completely damaged.This paper focuses on the axial compression performance of AAS concrete exposed to high temperatures. In particularly, the effect of high temperature, different alkali concentration, and modulus on the residual axial compressive strength, elastic, modulus, and stress–strain behavior have been analyzed in detail. Based on the experimental program used in this paper, the following conclusions could be drawn:Overall, the findings of this study have refined the scientific system of AAS concrete under thermal action, and also have provided a newly non-contact approach for thermal strain measurement of AAS concrete under compression.


The high rates of industrial and agricultural wastes and byproduct production produced several environmental concerns in addition to increasing the risks of contaminating natural resources. The amount of organic waste has been rising over the past few decades, but it has been poorly managed, especially in smaller countries where it is either burned, improperly disposed, or thrown in landfills. Moreover, the production of concrete generates a large amount of waste that has a negative impact on our planet even though it is an extremely significant building material. The potential of developing another plain concrete mixture sample with date palm mesh addition to create more environmentally friendly concrete with better qualities. In addition to using experimental quantitative research to measure the effectiveness of various concrete mixes after adding palm tree residues that underwent biological, chemical, & mechanical treatments, a theoretical qualitative method was also employed in this study to evaluate and identify the ideal mixture design. The prototypes' strength, density, thermal conductivity, slump, and absorption rate were all measured during the experiments. Having a lower heat conductivity and greater strength, the mechanically treated fibers with a 0.6% addition provided the best prototype, according to the research findings. Several researchers have studied various methods of using agricultural waste to develop environmentally friendly concrete mixtures with adequate strength and better mechanical qualities while having minimal environmental impact. Researchers have experimented methods of partially replacing cement content with palm wastes in order to manufacture environmentally friendly concrete to reduce the waste generated by cement production. The goal of this study is to reduce the environmental impact of palm wastes by using them as a component to the mixture of plain concrete, while also figuring out how to properly dispose and recycle organic wastes and byproducts and enhancing the qualities of plain concrete. In order to create the best sample, which has greater strengths and properties compared to the standard plain concrete but with a reduced thermal conductivity, a detailed assessment of organic wastes, cement, and plain concrete will be presented in this study, along with recommendations for combining them to reduce their environmental impact. The findings and results will help create a prototype sample that will be examined and contrasted with the control concrete mixture2.The increasing human population, consumption rate and human actions in countries all over the world resulted in the production an average of 38 billion metric tons of organic wastes per year3. The projection study of the solid waste generation in Fig. 4. The improper discarding and burning of organic waste resulted in various environmental & health problems5.Despite the existing 66 composting plants less than 25% of the organic waste in Egypt are being recycled6.There are three types of organic wastes which are the household organic waste, the agriculture organic waste, and the Industrial organic waste, studies show that 50% of organic wastes consists of agricultural wastes7.The most important agriculture crops that are produced in Egypt are listed in Fig. 9. A single adult date palm tree when trimmed regularly can produce approximately 25 kg of waste per year9. In 2012 Egypt produced 1.47 million tons of dates which makes it the major date producer in the world since it presented one-fifth of the world’s production. The date palm rachis has a long history of being used in the handmade arts, ornaments, baskets, crates, and furniture10. The industrialized wooden strips that are made from the date palm rachis are used to make floorings that is an alternative to the timber floorings, and in the countryside, housings use the palm rachis as a covering material for their roofs.Egypt is the world's biggest producer of date palm fruit. Egypt's yearly date production increased by 70% in 2019, accounting for nearly 30,000 tons11.Figure 12. MDPSF can be obtained from the thin tissue that covers the top of the male plant and works as an insulator to protect the palm from the vagaries of weather14. Date palm fibers are usually treated to reduce the limitations and to improve their performance as shown in Fig. Comparing with the other date palm fiber species, male date palm surface fiber (MDPSF) has the best tensile strength which range between 170 and 300 MPa13. The amount and properties of the materials used, as well as the method placing, finishing, and curing the concrete, all have a direct impact on its quality. Concrete is a versatile building material that can be used for a wide range of agricultural and residential purposes. It can withstand many acids, silage, milk, manure, fertilizers, water, fire, and abrasion with the right materials and techniques. Due to the usage of concrete as a structural material, strength is considered a very important property to have. Concrete's compressive strengths typically range from 2000 to 5000 pounds per square inch (psi), however for sometimes, concrete can be produced to withstand over 10,000 psi14.Concrete is a composite material composed of Portland cement, water, aggregates, and, in some cases, admixtures. The cement and water combine to form a paste that solidifies and bonds the aggregates14.Concrete is well known for its abilities to withstand compression; however, it is very week in tension which makes it very likely to shrink or crack since it becomes more fragile the more its strength increases. Accordingly, to increases its ability to withstand tensions stress steel reinforcement was used However, it is not preferred since it is very expensive, and its tremendous permeability can cause corrosions in it. Recently researchers proposed that polyvinyl alcohol (PVA) and polypropylene fibers can be used instead of steel fibers. However, the production of these fibers requires the use of unsustainable chemical compoundsThere are variety of factors that can affect and control the properties of concrete such as the mix proportions that has a huge effect on the concrete's strength. Such as: Workability of Concrete,Segregation of concrete, Bleeding in Concrete, Compressive Strength/Concrete grades, Tensile strength of concrete, and Shrinkage of concrete:15. The heavy dependence on coal in industry contributes to extremely high emissions of CO2 and Sulphur, among other pollutants15.The main component of any concrete mixture is the concrete which is known to have major environmental impacts such as: Energy consumption which is the most serious environmental issue associated with cement and concrete production. Cement production is one of the most energy-intensive industries in the world. The manufacture of cement and the subsequent use of fuel for mining and transportations consumes around 1.758 kWh per ton of cement2 emissions that are produced during the cement manufacturing process are generated from two different sources. The primary source is fossil fuels, which is around 3/4 tons CO2 per ton of cement and calcined into the cement kiln by lime process. The combustion of rotary kilns is the main cause. Around 5% of overall CO2 emissions are accountable to the cement industry. Apart from CO2, both cement and concrete production emit significant amounts of air pollution, with dust being the most visible pollutant which accounts for 360 pounds per ton of cement produced.16. Another environmental problem associated with cement and concrete production is water pollution. Water used for cleaning equipment is sometimes disposed through placing ponds at the batch plant, where the solids settle out16.COThe research methodology is classified into two main categories based on the nature of this study: data gathering and data analysis approaches, as indicated in Fig. The experiment in this study was divided into 2 phases, phase one is the fibers treatments, and phase two is the concrete mixing. The IUCN Policy Statement on Research Involving Species at Risk of Extinction and the Convention on the Trade in Endangered Species of Wild Fauna and Flora were both complied with, in the collection and use of plant samples for this study. In specifically, a non-lethal harvest of palm mesh fibers was carried out in a farm located in Ismailia, Egypt; this species is classified as having "least concern" status in the IUCN Red List Assessment.The male date palm mesh was collected during the harvesting season of the date palm trees form a farm in Ismailia, Egypt all the fibers were gathered from Sukkari date palms as shown in Fig. Mechanical treatment: the date palm mesh was soaked in water for 24 h to ensure saturation, then hand-separated and dried at room temperature for another 24 h before being cut into 60 mm pieces. The chemical treatment: the date palm mesh was soaked for 1 h in 1% NaOh at 100 °C, then it was chopped to 60 mm pieces which is the most common size used in literature. While the Biological treatment: the retting process was used to extract the fibers through which the mesh was soaked in water for 20 days to rot, after that it was cleaned, and the fiber was separated and dried under sunlight. Then the fiber was kept at 100 °C for 24 h for partial removal of moisture.Ten M30 mixtures of plain concrete were created with the addition of male date palm fibre with a 0%, 0.4% (30 gm), 0.6% (45g m), & 0.8% (60 gm) respectively for each type of treatment to create a total of 150 samples. There sample sizes varied to suit the different type of tests, there were 30 cylindrical samples that measured 10 × 10 × 20 cm and was used for the split cylinder tests, 30 cuboid samples that measured 10 × 10 × 50 cm and were used for the flexural strength tests, while 90 cube samples that measured 10 × 10 × 10 cm and was used for the rest of the tests. The material properties of the components used in the concrete mixtures are listed in Table The concrete mixtures were designed according to the Egyptian standard guidelines by using the materials listed in Fig. The slump test: The concrete slump test indicates the consistency of a concrete mixture. This test is done on the fresh concrete after the mixing and is presented in Fig. The unit weight: The weight of concrete required to fill a container of a defined volume is referred to as the unit weight, the unit weight was measured for a 10 × 10 × 10cm cube.The absorption rate: was measured at the age of 7 and 28 days, through measuring the sample weight before curing then after 7 days, and after 28 days.The Compressive strength: Concrete’s ability to withstand loads before failing. It was measured for the samples at the age of 7 and 28 days using compression testing machine.Flexural strength test: Flexural strength is a form of measuring concrete tensile strength since it measures the ability of a plain concrete beams and slabs to withstand bending failure. It was measured for the samples at the age of 28 days using bend test machine.Split cylinder test: This test is used to determine the lateral tensile stress of concrete; it was measured for the samples at the age of 28 days using compression testing machine.The box method was used to calculate the heat transition as shown in Fig. The findings will be presented into two different levels; the experiment conducted, and the observational results noted during the experiment. Slump, absorption, unit weight, compressive strength, flexural strength, tensile strength, and thermal conductivity are the experimental tests of the concrete’s samples with different treatments and percentages of fibres, while comparing them to the control samples. The maximum, average, and minimum experimental results of the tests are illustrated in Table Table According to this experimental study, The M6 samples has successfully reduced the human health impact and environmental impact while providing lower thermal conductivity and better strength.15 work that stated that with increasing fiber percentage and length, the compressive strength decreased while the flexural strength increased. The research finding proved that the best properties were of the samples that included 0.6% mechanical treated fibers, while highlighting that the chemical treatment produced the worst physio-mechanical properties of the concrete samples.This study investigated the possibility of using different treatment methods to treat male date palm fibers in order to utilize them in the plain concrete mixtures in order to improve it physical and mechanical properties and produce ecofriendly concrete through minimizing the harmful effects of improper disposal of organic waste such as the date palm residues, while decreasing the use of cement content since adding the fibers helps in combining the plain concrete’s components and slightly increase the volume of the total mixture. The research experiment added three different percentages of date palm fibers to identify the best combination of treatment and percentages to achieve the ideal prototype with the best physio-mechanical properties. Unlike Alatshan et al.


Hospital medicine physicians providing coverage during evening and night shifts are often responsible for higher patient volumes during these busy shifts. Data on decisions to start or broaden antibiotic therapy by covering physicians are limited.We evaluated antibiotic administration data from Duke University Health System between July 1, 2021 and March 31, 2023 to identify antibiotic “starts” and “escalations” attributed to hospitalists. Starts were defined as the first administration per patient encounter without antibiotics on the preceding calendar day. Escalations were defined as an increase in cumulative spectrum score  in the 48 hours following administration compared to the score in the 48 hours prior. Shifts from intravenous to only oral antibiotics were not counted as an escalation. We visualized these data as a heat map based on weekday-hour combinations and then compared the median number of starts and escalations between daytime shifts , evening, “cross cover,” coverage shifts , and overnight shifts (remaining times), using the Mann-Whitney U nonparametric test with daytime shifts as the comparator group.The analysis included 7,045 antibiotic starts and 4,879 escalations across 78,845 unique patient admissions. Heat maps  revealed specific practice patterns. Median starts for night shift were significantly lower than day shift starts, but cross cover starts were significantly higher . Night shift escalations were significantly lower than day shift while cross coverage showed no difference .Antibiotic starts and escalations by hour and day of weekHeat maps of counts of antibiotic (A) starts and (B) escalations by hour and day of weekHourly starts and escalations of antibiotics by hospitalist shiftBox-and-whisker plots of counts of antibiotic (A) starts and (B) escalations per hour by hospitalist shift.Antibiotic escalations differed across work shifts; visualization of these patterns aids in antimicrobial prescribing pattern recognition and may assist in finding opportunities for supportive antimicrobial stewardship strategies.Rebekah W. Moehring, MD, MPH, FIDSA, FSHEA, UpToDate, Inc.: Author Royalties


This work practices biomimetic nanosystem in targeted imaging and immunotherapy, paving the way for strategy designing for tumor inhibition.Anti-tumor M1-like and pro-tumor M2-like tumor-associated macrophages (TAMs) coexist in tumor microenvironments (TME). The adverse effects of these M1/M2 subsets on tumors directly affect the current strategies to improve anti-tumor immune response. Therefore, it has attracted great attention to change the tumor immunosuppressive microenvironment by reprogramming TAMs. In this paper, we constructed biomimetic nanoparticles (HMMDN-Met@PM) targeting M2-like TAMs for macrophage re-polarization. In detail, the core of the biomimetic nanoparticles is metformin-loaded hollow mesoporous manganese dioxide nanoparticles (HMMDN-Met). Benefited from the hollow and porous structure of HMMDN, metformin, the regulator of M1/M2 adopted in this work, can be easily and widely loaded into HMMDN. Moreover, macrophage membranes were utilized for HMMDN-Met coating (HMMDN-Met@MM) to prevent the premature drug leakage and provide specific molecular recognition/TME targeting. In addition, M2 macrophage targeting peptide (M2pep) was modified on the surface of macrophage membrane to specifically deliver the drug to M2-like TAMs to promote the polarization of M2 to M1 macrophages. Through in vitro and in vivo studies, we found that the expression of surface markers and inflammatory factors CD206, Arg-1 and IL-10 of type M2 macrophages decreased, while the surface markers of type M1 macrophages and the expression of inflammatory factors CD80, TNF-α and iNOS increased, indicating the successful re-polarization of M2 macrophages and finally realizing the inhibition of tumor growth. At the same time, under the acidic and GSH conditions of tumor, HMMDN was decomposed into MnThe online version contains supplementary material available at 10.1186/s12951-023-02122-8. Cancer has become a main cause of death in China. Since 2000, the morbidity and mortality of cancer in China have been increasing . TraditiIt is known that the main pathways involved in macrophage polarization such as notch, interferon regulatory factor (IRF), Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT), phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) and Toll-like receptor agonists have been used to convert pro-tumor M2 TAMs into anti-tumor M1 macrophages . Resiqui2O2 to reduce Mn4+ to Mn2+. The resulting Mn2+ enhances the ability of T1-weighted MRI  [20 [202O2 thted MRI  22]. Th. Th2O2 thted MRI . Using Hhted MRI . If it ihted MRI . The orihted MRI . Then pehted MRI  28] . In. In2). AHMMDN (1 mg) was dispersed in 1 mL DI water, and metformin solution (2 mg/mL) was introduced. The mixture was stirred overnight at room temperature. Then the solution was centrifuged, and the supernatant was collected. The absorbance of Met in supernatant was determined at 232 nm by a UV–vis spectrometer, and the content of Met in the supernatant was calculated according to the standard curve. The drug loading capacity (LC) and entrapment efficiency (EE) were determined by the following formula.Macrophage membrane was obtained according to the previously reported method  35]. Th. Th35]. In order to obtain HMMDN-Met@MM, the macrophage membrane vesicles and nanoparticles were mixed by ultrasonication for 2 min with the weight ratio of macrophage membrane protein to nanoparticles at 1:1. Then the mixture was extruded by an Avestin Mini-extruder for 10 times to obtain HMMDN-Met@MM solution. Finally, the uncoated membrane was removed through centrifugation . The macrophage-biomimetic nanoparticles were stored at 4 °C.DSPE-PEG-M2pep  and HMMDN-Met@MM (1 mg/mL) were mixed and stirred at 4 °C for 2 h following reported protocol . DSPE-PE2, SiO2@mMnO2, HMMDN, HMMDN-Met@MM and HMMDN-Met@PM were characterized by transmission electron microscopy . The structure of HMMDN nanoparticles was confirmed by HAADF-STEM imaging and element mapping of HMMDN. The specific surface area and pore size distribution of HMMDN were measured with the nitrogen adsorption/desorption isotherms calculated by Brunauer-Emmett-Teller (BET) method . The size and zeta potential of SiO2, SiO2@mMnO2, HMMDN, HMMDN-Met@MM and HMMDN-Met@PM were measured on a Zetasizer . To validate the successful synthesis of HMMDN-Met@MM, the UV–vis absorption spectra of Met, HMMDN, HMMDN-Met, MM vesicles and HMMDN-Met@MM were measured by UV–vis spectrometry. For the connection of DSPE-PEG-M2pep, we used Fourier transform infrared (FT-IR) spectrometer to collect the infrared spectra of HMMDN, DSPE-PEG-M2pep, HMMDN-Met@MM and HMMDN-Met@PM. Finally, dynamic light scattering was used to monitor the stability of HMMDN-Met@PM in PBS.The morphology and size of SiOThe HMMDN-Met, HMMDN-Met@MM or HMMDN-Met@PM suspensions present at distinct experimental conditions (PBS (pH 7.4), PBS (pH 5.5) and PBS (pH 5.5) containing 10 mM GSH) were picked out at pre-determined time points. The amount of metformin released from the tested NPs was analyzed by UV–vis spectrometry.1-weighed magnetic resonance signal was measured on a 3.0 T MR imaging system (GE 750 W). Due to MDN can respond to tumor microenvironments (TME), such as pH or GSH [2+ solution  for further detection. After 6 h, the T1-weighed signal of the obtained sample was collected. The T1 relaxation time in the same region of interest  in each hole was measured. The abscissa was the concentration of Mn, and the ordinate was the reciprocal of the T1 relaxation time of the sample. The slope of the corresponding linear regression equation represented the T1 relaxation rate.The aqueous TH or GSH , therefo2.Mouse macrophages (RAW 264.7), mouse embryonic fibroblasts (3T3) and mouse breast cancer cells (4T1) were provided by the Cell Bank of the Chinese Academy of Sciences. Dulbecco’s modified Eagle medium (DMEM) containing fetal bovine serum (10%), penicillin (100 U/mL) and streptomycin (0.1 mg/mL) was used for cell culture. The cells were cultured in an incubator at 37 °C in a humidified atmosphere containing 5% CO4 cells/well) and cultured for 24 h. Then, the original culture medium was discarded and M1 macrophages were induced by fresh medium containing 100 ng/mL LPS and 25 ng/mL IFN-γ, and M2 macrophages were induced by 25 ng/mL IL-4. The harvested macrophages were used for the experiment of cell function in vitro.RAW 264.7 cells in culture medium were inoculated in 6-well plates  to determine the macrophage phenotype. In short, after the macrophages were polarized according to the above method, the cells experienced immobilization of 4% paraformaldehyde for 15 min, followed by the treatment of 0.3% TritonX-100 for 30 min. After PBS washing, 10% bovine serum albumin solution were used to block the cells for 1 h at room temperature. Then, the cells were incubated with an anti-CD80 and CD206 antibody at 4 °C overnight. After incubated with fluorescent secondary antibody for 2 h, the anti-fluorescence quenching agent (including DAPI staining solution) were adopted for nuclei imaging. Finally, the cells were observed and photographed under confocal laser scanning microscope (CLSM).4/well. After 24 h of attachment, the fresh DMEM medium containing different concentrations of HMMDN-Met@PM  was incubated with cells. After 24 h, 100 µL 1 mg/mL MTT solution was added to each well and incubated in the dark at 37 °C for 4 h to form formazan crystals. Then, 100 µL dimethyl sulfoxide (DMSO) was added into each well to dissolve formazan crystals. The absorbance of the dissolved crystals was recorded at 490 nm with a microplate photometer for the determination of cell viability. The cytotoxicity on RAW 264.7 cells of other nanoparticles/Met including HMMDN, Met, HMMDN-Met and HMMDN-Met@MM  were tested with similar procedures. In addition, the cytotoxicity of HMMDN-Met@PM  on 3T3 cells was also measured.We evaluated the cytotoxicity of HMMDN@PM and HMMDN-Met@PM in vitro with different phenotypes of RAW 264.7 cells and 4T1 cells with MTT assay. Cells were mainly inoculated in a 96-well plate at a concentration of 1 × 104/well. Then, it is induced to M2 macrophages with above-mentioned method. After that, different nano-complexes were incubated with M2 macrophages for 24 h. Finally, the cells in different groups were imaged by CLSM.The expression of CD80 and CD206 was measured by CLSM to determine the macrophage re-polarization. RAW264.7 macrophages were inoculated and cultured for adhering to the wall in 6-well plates at a concentration of 1 × 105/well and cultured overnight. 12 h later, different macrophage phenotypes  were induced with different cytokines, and further cultured for 24 h. Then, different nanocomplexes were incubated with M2 macrophages for 24 h. Untreated M2 macrophages were served as control. Before detection, the cells were digested from 6-well plate and collected in a centrifuge tube. The supernatant was discarded by 2,000 rpm centrifugation for 5 min and cells were re-suspended in 4% paraformaldehyde solution for 10 min. After discarding the supernatant, blocked with 10% bovine serum albumin for 30 min, the obtained cells were followed by incubated with 0.3% TritonX-100 for 5 min at room temperature. Finally, 5 µL FITC anti-mouse CD80 or FITC anti-mouse CD206 was added and incubated for 1 h at 4 °C. After centrifugation, the cells were re-suspended in 500 µL 4% paraformaldehyde solution. The fluorescence expression in each sample was analyzed by flow cytometry.For flow cytometry test, RAW 264.7 cells were inoculated in 6-well plates at the concentration of 2 × 10To investigate the specific signaling pathways related to M1/M2 polarization, we conducted western blotting assay to evaluate the AMPK and the phosphorylation of AMPK (pAMPK) in macrophages with different treatments. Protein samples from macrophages left untreated (Control) or treated with HMMDN, HMMDN@PM, Met, HMMDN-Met, HMMDN-Met@MM or HMMDN-Met@PM  were prepared in a RIPA buffer supplemented with protease inhibitor and quantified by the BCA Protein Assay . Then, the samples were mixed with 5 × loading buffer before heating at 100 °C for 5 min. The extracted proteins ran on a 12.5% Bis-Tris 10-well minigel in running buffer using a Bio-Rad electrophoresis system at 80 V for 0.5 h and then at 100 V for 1 h. Furthermore, the proteins were transferred from the gel to the poly (vinylidene difl-fluoride) membranes followed by blocking for 1 h with 5% skimmed milk powder in tris-buffered saline after the electrophoresis. Then, the membranes were treated with primary antibodies, including anti-pAMPK, followed by the incubation of horseradish peroxidase-labeled goat/anti-rabbit IgG(H + L). The protein signals were measured by an enhanced chemiluminescent detection kit  using a chemilumines-cence/fluorescence image analysis system .4 cells/well) and cultured for 24 h followed by the induction to M2 macrophages. Then the cells were co-treated with HMMDN (0.34 mM Mn), HMMDN@PM (0.34 mM Mn), Met (30 µg/mL), HMMDN-Met (0.34 mM Mn), HMMDN-Met@MM (0.34 mM Mn) and HMMDN-Met@PM (0.34 mM Mn). After another 24 h, the content of proinflammatory cytokines including IL-10, Arg-1, iNOS and TNF-α in the supernatant were quantified with ELISA kits. All experiments were performed in triplicate.RAW 264.7 cells were inoculated in 24-well plates , and induced into M1 and M2 after adherent. Then, after incubating for 2 h with HMMDN-Met, HMMDN-Met@MM or HMMDN-Met@PM, the cells were washed 3 times using PBS and immobilized in 4% paraformaldehyde. The nucleus was counterstained with anti-fluorescence quenching agents (including DAPI staining solution). Finally, cells were observed and photographed with CLSM. The obtained images were analyzed by ImageJ software.For CLSM, 1 wt% coumarin-6 (C6) was loaded into HMMDN-Met, HMMDN-Met@MM and HMDMN-Met@PM. RAW 264.7 cells were inoculated in a 6-well plate  was used to mark M2 macrophages, while coumarin-6  loaded in HMMDN-C6@PM was utilized for nanoparticle tracing. Mixed macrophages were incubated with APC-anti CD206 and/or HMMDN-C6@PM and analyzed by flow cytometry.M2 macrophages and 4T1 cell were cultured on a Transwell culture plate with a pore diameter of 0.4 μm, establishing a non-contact co-culture model. M2 macrophages were seeded in 24-well Transwell plates (upper compartment) and cultured for 24 h. 4T1 cells were seeded in the lower compartment of each Transwell plate for 24 h. Then, different nano-complexes  were incubated with M2 macrophages for 24 h, respectively. Untreated M2 macrophages were served as control. The cell viability of 4T1 was detected by MTT assay.Due to the damage of the membrane structure of dead cells, intracellular lactate dehydrogenase (LDH) will be leaked into the culture medium. Thus, the cytotoxicity was further evaluated by measuring the release of LDH from 4T1 cells in the lower compartment. Establish a non-contact co-culture model of M2 macrophages and 4T1 cell as described above. In addition, a control model containing M2 macrophages seeded in the upper compartment, and only DMEM in the lower chamber was developed to eliminate the effect of LDH released by M2 macrophages of upper compartment. Then the supernatant was collected after incubating with different nanomaterials . The supernatant was detected according to the instructions. The specific lysis of 4T1 cells was calculated by the following formula:Female C57BL/6 mice and Balb/c mice aged 6 weeks were obtained from the Animal Center of Xuzhou Medical University. All animals were maintained under standard housing conditions and all animals were acclimatized for at least 3 days before the experiments started. All animal protocols were approved by the Ethics Committee of Xuzhou Medical University (202209S101).6 4T1 cells was subcutaneously injected into the right back of BALB/c mice. Further treatment began when the tumor volume reached approximately 75 mm3. Mice were randomly divided into 5 groups (n = 5 per group): PBS (control), Met, HMMDN-Met, HMMDN-Met@MM and HMMDN-Met@PM (tail intravenous injection). The Met dose is 10 mg/kg body weight (150 µL with a Met concentration of 1.0 mg/mL). The materials were given once every three days, for a total of 4 times. The weight of mice and the tumor volume were measured every two days. The volume is calculated as V = d2 × L/2 . The tumor growth inhibition (TGI) (%) = (V-V0)/V0 × 100%. On the 16th day, all tumors were separated and weighted, major organs  and tumors were sectioned and stained with hematoxylin and eosin (H&E), followed by observation with microscopy. In addition, TNF-α, IL-10, Arg-1 and iNOS in the sera of mice were also determined using ELISA assay.To construct the subcutaneous breast tumor model, 100 µL PBS containing 1 × 10Immunohistochemistry staining was performed to evaluate effect of macrophages polarization of each therapy group. M1 macrophage phenotypic marker CD80 and M2 phenotypic marker CD206 were investigated by immunohistochemistry staining. The images were collected with an optical microscope.3, the mice were anesthetized by intraperitoneal injection of 4% chloralhydrate and fixed on a special coil for magnetic resonance imaging. The whole body images of mice were performed on 3.0 T MR imaging system (GE 750 W). Before the materials injection, the plain scan images of the whole body of the mice were obtained for comparison. Subsequently, 150 µL HMMDN-Met@PM, HMMDN-Met@MM or HMMDN-Met were injected via the tail vein (the dose of Met of each group of samples was 10 mg/kg body weight). The mice were scanned by MRI at 15, 30, 45 min and 1, 2, 4, 6, 12, 24 h after injection, in which the region of interest (ROI) was tumor area and metabolic organ. The T1 signal intensity at each time point was measured on the AW4.6 post-processing workstation.When the subcutaneous tumor volume grew to 75 mmThe in vivo toxicity of HMMDN-Met@PM nanocomplex was evaluated by monitoring the blood and histological changes. The blood samples were collected for further biochemical analysis, and histological changes of several organs  were evaluated post-injection of HMMDN-Met@PM nanocomplex. Twelve C57BL/6 were divided into 4 groups with 3 mice in each group. Mice were injected with normal saline or HMMDN-Met@PM (10 mg/kg Met) via tail vein. At 0, 1, 7 and 21 days after administration, the blood was collected for blood routine and blood biochemical tests. The obtained organs were fixed in 10% formalin, sectioned and stained with hematoxylin and eosin (H&E) and observed under optical microscope, respectively.As reported in the literature , hemolysThe data measured in the experiments were expressed as mean ± standard deviation. A single factor analysis of variance (ANOVA) analysis and least significant difference (LSD) were performed to compare the significant differences between the data. *p < 0.05, **p < 0.01, and ***p < 0.001 were used to indicate the significance of the difference.2 nanoparticles were first synthesized. TEM images showed that SiO2 nanoparticles have a uniform spherical structure with the diameter of about 181.3 ± 2.2 nm  [2+ might exhibit excellent MRI effect.It is reported that Mniagnosis . Thus, weduction . As show− 1s− 1) . This reBefore the evaluation of HMMDN-Met@PM to re-polarize M2 macrophages, their cytotoxicity on normal healthy cells was first evaluated with MTT assay. Results in Fig. Then, to confirm the re-polarization effect of HMMDN-Met@PM, M2 macrophages were hatched with HMMDN, HMMDN@PM, Met, HMMDN-Met, HMMDN-Met@MM and HMMDN-Met@PM. CLSM and flow cytometry were utilized to detect the macrophage phenotype after treatments. As expected, the red fluorescence emissions from CD80 increased obviously in HMMDN-Met, HMMDN-Met@MM and HMMDN-Met@PM group, and HMMDN-Met@PM displayed the best re-polarization effect of M2 macrophages to M1 macrophages. The green fluorescence emissions from CD206 presented similar phenomena and almost no green fluorescence emission could be observed in HMMDN-Met@PM group Fig. A–C. FlowTo further verify re-polarization effect of M2 macrophages, the changes of cytokines associated with M1 and M2 macrophages were also monitored by enzyme-linked immunosorbent assay (ELISA). Consistent with the flow cytometry results, Met, HMMDN-Met, HMMDN-Met@MM and HMMDN-Met@PM could all reduce the M2 macrophage related immunosuppressive cytokines, Arg-1 and IL-10, and improve the M1 macrophage related cytokines, iNOS and TNF-α. Compared with untreated M2 macrophages, the releases of iNOS and TNF-α increased to 152.2% and 218.7%, respectively, and the releases of Arg-1 and IL-10 decreased to 61.9% and 59.5%, respectively after treatment with HMMDN-Met@PM Fig. F. Thus, Furthermore, it is reported that metformin can activate AMPK signaling pathway, and the metformin-triggered increase of AMPK phosphorylation (pAMPK) provides inhibition on the M2-like polarization induced by IL-13 . Chiang To evaluate the targeting ability of HMMDN-Met@PM to M2-like TAMs, MRI and fluorescence imaging were performed in vitro. In Fig. M2-like TAMs in tumor microenvironment are the main accomplices of tumor occurrence and development, and play an important role in tumor angiogenesis, metastasis and inhibition of anti-tumor immune response . HMMDN-MDue to the damage of the membrane structure of dead cells, intracellular lactate dehydrogenase (LDH) will be leaked into the culture medium. Therefore, we further collected the supernatant of 4T1 cells in the lower chamber, and evaluated the viability of 4T1 cells by LDH Kit. The results in Fig. 1-weighted MRI scans were conducted at various time points pre- and post-injection of different nanomaterials. When the tumor volume reached about 100 mm3, the mice were randomly divided into 3 groups and treated with HMMDN-Met, HMMDN-Met@MM, or HMMDN-Met@PM via the tail vein injection. As shown in Fig. 1 signal in tumor gradually became stronger at the first 4 h, and then turned weaker with the time. However, compared with HMMDN-Met and HMMDN-Met@MM group, T1 signal gradually became brighter at the first 15 min and kept stronger at the same time point in HMMDN-Met@PM group  agonists, transcriptional signal modulators, microRNAs, and other compounds, have been widely adopted for repolarization . HoweverBelow is the link to the electronic supplementary material.Supplementary Material 1


The bonding strength increased as the ratio of the non-interfacial failure area to the total area increased, ensuring a stronger attachment to the concrete surface. Overall, the results showed that the bonding strength was significantly affected by the metal type.Exterior finishes protect reinforced concrete buildings against environmental factors, improve their durability, and enhance their exterior design. In this study, the influence of different metal types used in arc thermal metal spraying on the adhesion between concrete and metal coatings was analyzed. Five metals with different melting points were tested, and the differences between their melting points and surface temperatures immediately after thermal spraying were measured. The bonding strength of each metal was evaluated. Additionally, the interface between the concrete surface and metal coating was analyzed using image analysis and optical microscopy. The results demonstrated that Zn achieved the highest bonding strength (1.84 MPa), which had the lowest melting point and surface temperature immediately after spraying, while Cu/Sn achieved the lowest strength (1.38 MPa), which had the highest temperatures. The bonding strength had a closer relationship (R The exterior finishes of reinforced concrete buildings provide an important protective element against environmental factors, such as temperature, snow, wind, rain, and external disasters. Furthermore, they can improve the durability and exterior design of buildings. Therefore, sufficient considerations are required for appropriately selecting the exterior finishing materials and methods ,2,3.The finishing methods currently applied to building structures include the wet method of directly applying paint and plaster materials to the structure and the dry method of attaching stone materials and panels . The wetRecently, metal-film finishing methods have been developed to apply arc thermal metal spraying (ATMS) to water treatment and electromagnetic wave shielding facilities ,9,10,11.Therefore, this study aims to evaluate the influence of the metal used as a wire material in ATMS on the concrete bonding strength. Metal coatings were formed on the concrete surface using various metals. The surface temperature of the coatings was measured immediately after spraying, as well as the bonding strength. In addition, the interface between the concrete surface and metal coating was evaluated through image analysis of the fracture sections and optical microscopy (OM).In this study, various experiments were performed to examine the bonding strength between the metal coating and concrete based on the metal type. Typically, concrete with a strength of 27 MPa is used as the substrate. The most efficient surface treatment methods in terms of the bonding strength determined in previous studies (sand blasting → surface hardener (SH) → surface roughness agent (SRA)) were used in this study . In the After surface treatment, metal spraying was performed using five metals. A commonly used metal spray coating thickness of 200 μm was adopted . The bonFor the appropriate application of ATMS to concrete surfaces, metals with a low melting point, unique color, and high durability are chosen from the metals that can be sprayed ,3,4. The3 was used. For Al, 100% pure white Al with a melting point of 660 °C and density of 2.70 g/cm3 was used. In the case of the Zn/Al alloy, a gray alloy (Zn 85% and Al 15%) with a melting point of 540 °C and density of 4.91 g/cm3 was used in the experiment. Cu/Zn and Cu/Sn with melting points of 914 and 1018 °C, densities of 8.60 and 8.75 g/cm3, and metal ratios of 8:2 and 9:1, respectively, were used.The cement used in the substrate concrete was ordinary Portland cement , adhering to the KS L 5201 regulations . Table 3ATMS is a technology that forms a porous, strong, and stable film on the material surface by melting wire or powder metals using gas or electric arcs and spraying the molten metals under a high-pressure environment with six bars or higher ,22,23,24The concrete cured for 28 days was dried at 100 °C for two days and subjected to sand blasting for surface cleaning. Subsequently, SH  was applied to increase the concrete surface strength, which is expected to affect the bonding strength as well ,25. SRA Immediately after metal spraying, the surface temperature was measured using an infrared thermometer (FLUKE-62 Mini) on three points at a distance of 300 mm, as shown in The bonding strength was evaluated according to the KS F 4716  and ASTMAfter the bonding strength measurements were completed, image analysis was conducted on the fracture sections to examine the failure pattern between the metal spraying coating and concrete surface and quantitatively calculate the non-interfacial failure area. An OM  was used to observe the cross-sectional area of the specimen, as shown in Visual inspection of the failure pattern revealed that the non-interfacial or partial non-interfacial failures of Zn, Zn/Al, and Al met the performance criterion of KS F 9001, as shown in 2 = 0.9946) with the difference between the melting point and surface temperature immediately after metal spraying compared to its correlation (R2 = 0.9589) with the surface temperature immediately after metal spraying, the difference between the melting point and surface temperature immediately after metal spraying was assessed to have a more significant effect on the bonding strength. Voids are generated in the metal spraying coating because of the shrinkage between the metal particles as the sprayed metal rapidly cools. Furthermore, the bonding strength is decreased by the voids between the concrete surface and metal spraying coating [ coating .2 = 0.99), as mentioned in the previous section. In other words, the significant difference between the melting point of the metal and surface temperature immediately after metal spraying had a negative impact on the bonding strength because it induced more failures at the interface between the concrete surface and metal coating  than that of the concrete .As shown in Concrete surface treatment was conducted for the application of ATMS (SHA and SRA were applied). Metal coatings were generated on the concrete surface by applying ATMS. In this instance, only the metal type differed, whereas the distance between the concrete and metal spraying gun (300 mm) and the ambient temperature (20 ± 2 °C) were kept constant. Therefore, the adhesion between the concrete surface and metal coating was only affected by the metal type. During the application of ATMS, rapid cooling occurred because of the temperature difference between the ambient environment and metal particles when the metal particles collided with the concrete surface, causing the deposited metal particles to contract . TherefoIn addition, a close look at the metal coating revealed that the metal coating with Zn had a more compact cross-sectional geometry than that with Cu/Sn. In particular, voids of various sizes are observed in the red dotted circle depicted in The surface temperature varied depending on the type of metal used. Zn showed the lowest surface temperature, while Cu/Sn exhibited the highest. The surface temperature immediately after metal spraying increased with the metal’s melting point.The strength of the bond between the concrete and metal coatings also differed depending on the type of metal used. Zn exhibited the highest bonding strength (1.84 MPa), while Cu/Sn showed the lowest (1.38 MPa). Upon examining the failure modes, non-interfacial failure occurred mostly with Zn, whereas interfacial failure occurred mostly with Cu/Sn.2 = 0.9946) with the difference between the melting point of the metal and surface temperature immediately after metal spraying compared to its relationship (R2 = 0.9589) with the surface temperature immediately after metal spraying, the difference between the melting point and surface temperature immediately after metal spraying was assessed to have a greater impact on the bonding strength between the sprayed metal coating and concrete.Because the bonding strength exhibited a close relationship , whereas Cu/Sn exhibited the lowest RN value.The metal coating was found to be closely attached to the concrete surface with Zn; however, there was a gap between the metal coating and the concrete surface with Cu/Sn. This gap induces interfacial failure and ultimately has a negative impact on the bonding strength.The metal type  was found to have a significant influence on the bonding strength. For the application of metals with a high melting point to the concrete surface, further research on surface treatment methods is required to ensure adequate bonding strength.


Antibiotic residues in livestock farming have been identified as a potential cause of antimicrobial resistance in humans and animals. This study aimed to determine whether antibiotic residues were present in the chicken meat, eggs, feces, and feed collected from all four districts in the Mymensingh division of Bangladesh.To detect antibiotic residues in the collected samples, qualitative thin-layer chromatography (TLC) and quantitative high-performance liquid chromatography (HPLC) were used. A total of 230 samples were analyzed for antibiotic residues of commonly used 11 antibiotics. Out of these, 40 meat and 40 feces samples were collected from broilers and layers, 30 egg samples from ducks and layers, and 120 feed samples from broilers and layers from the study area. Thin-layer chromatography was used to screen the presence of antibiotic residues; TLC-positive samples were then subjected to further HPLC analysis to determine the residue concentrations.Thin-layer chromatography analysis revealed that 23.5% of the tested samples contained residues from six different antibiotic classes . Thin-layer chromatography analysis showed that 35% and 25% of the meat samples were positive for residues from the broiler and layer, respectively. About 15% and 30% of layer and duck egg samples had positive residues, respectively. Out of 120 feed samples analyzed, about 15.8% had various antibiotic residues. In addition, feces samples from broilers and layers had 50% and 35% antibiotic residues, respectively. A total of 2.5% meat and 3.3% egg samples had antibiotic residues above the maximum residue limit (MRL). Based on the findings of this study, the highest percentage of oxytetracycline, followed by doxycycline and ciprofloxacin, were detected in feed samples, and oxytetracycline was detected in meat and egg samples.This study clearly showed the misuse of antibiotics in the poultry sector in Bangladesh. Although antibiotic residues below the MRL level are suitable for human consumption, they may result in antimicrobial drug resistance to pathogens. All reaTwo (2 mg/mL) of five antibiotic-free blank samples were spiked using 100 μL of different working standards, thoroughly mixed and allowed for 15 min . FortifiTo study the recovery rates and linearity of samples, 2 mg/2 mL of free from any antibiotic were spiked with 100 mL of five working standards that were evenly mixed and allowed to stand at room temperature (25°C to 30°C) for 15 min. Samples were injected into the HPLC system according to previously published work with modifications where possible .As stated earlier, the following equation was used to calculate the recovery rate :y = mx + b; where y = peak area, x = antibiotic concentration (ppb), and the correlation coefficient (r²).A standard solution of ciprofloxacin, oxytetracycline, and doxycycline was prepared in five different concentrations and injected into the HPLC system to obtain linear calibration curves using five points. Calibration curves were obtained using the equation f value was analyzed using SPSS software version 26.0 . The distance the compound moved from the baseline (where it was first spotted) divided by the distance the solvent moved from the baseline is the Rf factor, which was calculated and compared to the distance traveled by the standard. The data were, then, inserted into an MS Excel spreadsheet  for cleaning, processing, and analysis.The percentage of RA total of 230 samples were qualitatively analyzed by TLC for the presence of different antimicrobial residues, out of which 54 (23.5%) were confirmed to be positive. Among all TLC-positive samples, fecal samples from broiler and layer had the highest percentage of residues with 50% and 35%, respectively . FollowiThe presence of different specific antibiotic residues in various samples is shown in Samples that were positive for antibiotic residues in TLC were further analyzed by HPLC for their concentration. The concentration of antibiotic residues in poultry feed and feces samples is shown in The study aimed to identify and quantify the presence of specific antibiotic residues in poultry industry of Mymensingh Division. Thin-layer chromatography was used to detect the presence of residues from various samples, which were further quantified using HPLC. This study is crucial because antibiotic residues or metabolites can remain in animal proteins such as meat, egg, and milk after a prior drug use  and evenPoultry meat is a good substitute for red meat due to its nutritional value, price, and availability. However, a decrease in poultry meat quality has recently been observed due to uncontrolled drug use, inaccurate biosafety measures, and lack of maintenance of the withdrawal period . When stet al. [Since practically everyone consumes poultry eggs worldwide, the presence of antibiotic residues in eggs is a serious public health concern. In this study, 6 (20%) of the total eggs were residue positive from duck and layer birds . Oxytetret al. , who detet al. . Other set al. –36, someIndiscriminate use of antibiotics in poultry feed is another big problem that we face nowadays. In Bangladesh, antibiotics are regularly used as feed additives at sub-therapeutic dose for growth promotion and prophylaxis , 37. HowAnother threat of using random antibiotics in poultry sector is their excretion through feces. Unmetabolized residues passing through feces could generate antimicrobial resistance to the organisms living in soil and surfaces. In this study, 17 42.5%) out of 40 fecal samples from broiler and layer were positive for residues, where oxytetracycline was the highest (12.5%) . In anot.5% out oThe study was limited to some selected parts and not all of the Mymensingh Division. The sample size was also small because we were led by volunteers and government representatives rather than being familiar with all farms in the study area.The findings of this study, point out a high threat posed by the use and misuse of antimicrobials in poultry production, even though most of them were below the MRL values. There is an obvious trend of use and misuse of antibiotics in the poultry sector, contributing to the menace of antimicrobial resistance. Policymakers should take proper measures and ensure compliance through surveillance and testing of poultry products regularly throughout the country.KR, MTH, and AAS: Conceptualized and supervised the study. KR, AAS, MTH, SS, and AM: Performed all the experiments, and prepared the manuscript draft. KR, FA, and MMA: Designed and supervised the study and revised and finalized the manuscript draft. AAS, AH, MIH, FA, and MZI: Performed the statistical analysis and prepared the graphs and tables. KR, AAS, and FA: Revised the manuscript. All authors have read, reviewed, and approved the final manuscript.


Hydrogel + T8IC + Laser + BMP-2 + H2O2 incorporated with mild PTT (45 °C), enhanced PDT and sustained release of BMP-2. It was present with excellent bactericidal effect, osteogenic induction and biosafety both in vitro and in vivo. Besides, immunohistochemistry staining and micro-CT analyses had confirmed that PTT and PDT could promote bone regeneration through alleviating inflammation state. Altogether, this novel approach with synergistic antibacterial effect, anti-inflammation and bone regeneration has a great potential for the treatment of periodontitis in the future.Periodontitis is a common public health problem worldwide and an inflammatory disease with irregular defect of alveolar bone caused by periodontal pathogens. Both antibacterial therapy and bone regeneration are of great importance in the treatment of periodontitis. In this study, injectable and thermosensitive hydrogels with 3D networks were used as carriers for controlled release of osteo-inductive agent (BMP-2) and Near Infrared Region-II (NIR-II) phototherapy agents (T8IC nano-particles). T8IC nano-particles were prepared by reprecipitation and acted as photosensitizer under 808 nm laser irradiation. Besides, we promoted photodynamic therapy (PDT) through adding HThe online version contains supplementary material available at 10.1186/s12951-023-02124-6. P. gingivalis) is the most dominant bacteria in periodontal disease, especially in chronic periodontitis [Periodontitis is a common public health problem worldwide and carries with substantial morbidity, seriously affecting the patient’s chewing, pronunciation and aesthetics –3. It isdontitis . At presdontitis –10. The dontitis –14, or pdontitis , neglectPhototherapy is kind of method relying on the sunlight or artificial light  to prevent and treat diseases –20, whicIn recent years, Bone tissue engineering has brought new hope for the repair of alveolar bone defects in patients with periodontitis, which has three key factors including seed cells, scaffolds and bioactive factors , 30. Par2O2). Hydrogel + T8IC + Laser + BMP-2 + H2O2 incorporated with mild PTT (45 °C), enhanced PDT and sustained release of BMP-2, which exhibited excellent bactericidal effect, osteogenic induction and biosafety in vitro and in vivo. Besides, it was confirmed that PTT and PDT could promote bone regeneration through alleviating inflammation state. Altogether, this novel approach with synergistic antibacterial effect, anti-inflammation and bone regeneration has a great potential for the treatment of periodontitis in the future  was dissolved in 1 ml tetrahydrofuran (THF) and 1.5 mg DSPE-mPEG2000 was dissolved in 5 ml phosphate buffer saline (PBS). Then, the T8IC solution was dripped into DSPE-mPEG2000 solution under magnetic stirring (800 rpm) at room temperature. After stirring for 5 min, the mixed solution was removed to rotary evaporation. When the solution was dried, 5 mL PBS was added and T8IC nano-particles (T8IC NPs) were obtained by reprecipitation under ultrasonic shaking for 10 min. The size and morphology of T8IC NPs were detected by dynamic light scattering (DLS) and transmission electron microscope (TEM). UV-visible light absorption, NIR-II fluorescence emission were tested by the UV-Vis spectrophotometer.1.5 mg T8IC (C2) and different concentrates of T8IC NPs  and photostability  were characterized and recorded by an infrared camera.After 3 min UV irradiation, 0.8 g chitosan was dissolved in 40 mL of sterile 0.1 mol/L HCl solution. 5 mg gelatin was dissolved in 1mL of deionized water at room temperature and filtered through a 0.22 μm filter. Subsequently, 2 g β-glutamine was dissolved in 8 mL deionized water and filtered through a 0.22 μm filter. Then, 40 mL of chitosan solution was mixed with 1 mL of gelatin solution and 8 mL of β-glutamine solution under magnetic stirring (800 rpm). 0.1 mol/L NaOH solution was added into the mixture by drop until the pH was 7.0. Finally, T8IC NPs (40 µg/ml) obtained by reprecipitation  and BMP-MC3T3-E1 cell line, a mouse skull osteoblast precursor cell line, was purchased from Shanghai Zhongqiao Xinzhou Biotechnology Co. LTD. The effects of different concentrations of T8IC NPs without laser irradiation and different temperatures  on the proliferation of MC3T3-E1 cells were detected through CCK-8 kit. The actin of MC3T3-E1 cells was labeled with Rhodamine-Phalloidin and the nucleus was labeled with DAPI to observe the effect of different treatments on the cytoskeleton of MC3T3-E1 cells.2O2 was monitored by the oxidation of DPBF at 418 nm in dichloromethane.The generation of ROS in the two groups: Hydrogel + T8IC + Laser + BMP-2, Hydrogel + T8IC + Laser + BMP-2 + HP. gingivalis  was cultured in brain heart infusion (BHI) medium with yeast extract (50 mg/L), hemin (1 mg/L) and vitamin K3 (1 mg/L) in a humidified incubator at 37 °C anaerobically. P. gingivalis was inoculated in the lower chamber of a 96-well plate  and the hydrogel was placed in the upper chamber of a transwell 96-well plate and irradiated with an 808 nm laser (1.5 W/cm2) for 4 min: Control, Hydrogel, Hydrogel + H2O2 (0.15%), Hydrogel + BMP-2 (100 ng/ mL), Hydrogel + T8IC + Laser , Hydrogel + T8IC + Laser + BMP-2 + H2O2 . The proliferation of P. gingivalis was detected by the optical density (OD) at 600 nm and 1 was corresponding to 109 CFU/ml. At the same time, the bacterial of each group was diluted 2 × 104 times and one drop of the bacteria solution was evenly spread on the blood plate for colony culture. After 10 days, the colony forming units (CFU) of each group were counted. The biofilm live/dead staining in each group was also observed via confocal laser scanning microscopy. The live bacteria were stained with SYT09 dye  and the dead bacteria was labeled with PI .5/well) and cells in each group , Hydrogel + BMP-2 (100 ng/mL), Hydrogel + T8IC + Laser , Hydrogel + T8IC + Laser + BMP-2 + H2O2  were separately cultured in osteogenic induction medium for 4 days. MC3T3-E1 cells were inoculated in the lower chamber of a 6-well plate and the hydrogel was placed in the upper chamber of a transwell 6-well plate.MC3T3-E1 cells were seeded in a 6-well plate . The mRNA expression of osteogenesis related genes  in each group was detected by quantitative real-time PCR using SYBR Green Master MIX . GAPDH was used as internal reference for mRNA level and x = 2The osteogenic differentiation ability of MC3T3-E1 cells was detected by alkaline phosphatase (ALP) activity kit (4 days and 7 days), ALP staining kit (4 days) and alizarin red staining kit (21 days), respectively.2O2 and T8IC NPs in the body of BALB/C nude mice  was observed by an in vivo fluorescence detector with near-infrared second-window fluorescence scanner. After 3 weeks, the mice in each group were euthanized.All animals were kept in a pathogen-free environment and fed ad lib. The procedures for care and use of animals were approved by the Ethics Committee of Nanjing University and all applicable institutional and governmental regulations concerning the ethical use of animals were followed. After subcutaneous injection in the back and 808 nm laser irradiation for 4 min were applied, the distribution and degradation of Hydrogel + T8IC + Laser + BMP-2 + HP. gingivalis bacterial suspension for 12 h) to establish a periodontitis model [2), Hydrogel + BMP-2 (100 ng/ml BMP-2), Hydrogel + T8IC + Laser + BMP-2 + H2O2 . Drugs in each group were slowly injected into the periodontal pocket of the maxillary second molars.The maxillary second molars of female C57BL/6J mice were ligated with 5 − 0 silk thread , liver function  and renal function  were detected.3) and bone volume fraction  were also performed.Micro-CT was used to detect alveolar bone defect repair of C57BL/6J mice. After euthanized, the maxilla with molars were fixed in 4% paraformaldehyde overnight and then were examined by a viva CT micro-computed tomography scanner  at 10.5 μm resolution. The 3D images of the maxilla were reconstructed. The distance between cemento-enamel junction and the alveolar bone crest (CEJ-ABC) was measured to evaluate the periodontal defect. Volumetric and morphometric analyses including bone mineral density  in the periodontal tissue of C57BL/6J mice. After treatment, the main organs  were dissected from the mice. HE staining was performed to observe the inflammatory status of the tissues and the changes of cell morphology.All the quantitative results were reported as mean ± standard deviation from at least three independent studies. The statistical analysis was performed by using the statistical software . Multiple comparisons of data were performed by two-tailed Student’s t tests or one-way analysis of variance. Probability value of P < 0.05 was considered statistically significant.T8IC is a novel organic semiconducting material, mainly used in high performance organic photovoltaic device. T8IC nano-particles (T8IC NPs) were synthesized through reprecipitation. The Zeta potential of T8IC NPs was 21.9 ± 1.12 mV. It was homogeneously distributed and kept stable in PBS and DMEM for 14 days Figure A. The abThe translucent chitosan/β-glutamine/gelatin pre-gel was injectable and flowed like a viscous liquid. Interestingly, the sol-gel transition occurred when the temperature was around 45 ℃ within 2 minutes Fig. A-1B. ScaThe hydrogel has been widely used as the scaffold and drug carrier for controlled drug release in craniofacial tissue engineering, contributing to delivering antibiotics, growth factors, chemotherapy drugs, vaccines and anti-inflammatory agents to aim tissues and cells –53. DualA good photothermal conversion ability of Hydrogel + T8IC + Laser + BMP-2 was detected under different concentrations of T8IC NPs and different laser power (808 nm) Fig. J K. The 2) when the temperature was over 45 ℃. The cell viability decreased to 73%, 45%, 6% after temperature reached to 45 ℃, 50 ℃ and 55 ℃, respectively , H2O2 manifested better antibacterial efficiency [2O2 and enhanced antibacterial efficiency was designed. DBPF probe was used to assess changes of ROS content in Hydrogel + T8IC + Laser + BMP-2 and Hydrogel + T8IC + Laser + BMP-2 + H2O2 under 808 nm laser irradiation. As shown in Fig. 2O2, implying more ROS generated and a better PDT effect. Other studies had shown that the combination of PDT and PTT could destroy the bacterial membranes and enhance bacterial eradication [2O2 (45 ℃) group compared to the Hydrogel + T8IC + Laser (45 ℃) group  had significantly less P. gingivalis colonies, while the pathogens in the Hydrogel + T8IC + Laser + BMP-2 + H2O2 (45 ℃) were nearly entirely eliminated. In addition, P. gingivalis suspended within the BHI medium, so 3D images of the live/dead (green/red) bacterial fluorescence staining were built up to detect the biofilm viability of P. gingivalis  and the biofilms were almost stained red in Hydrogel + T8IC + Laser + BMP-2 + H2O2 (45 ℃), consistent with the colony forming unit assay. In general, the phototherapy generated from Hydrogel + T8IC + Laser + BMP-2 + H2O2 including enhanced PDT and mild PTT, exhibited a superior bactericidal effect. Therefore, we finally selected 45 ℃ as a mild temperature in the following study.Firstly, we assessed the temperature on the bacterial inhibition. The hydrogel and Hydrogel + BMP-2 had no effect on the ion Fig. A. The baficiency , 56. Thedication , 58, 59.oup Fig. C, suggessay Fig. D. Both H2O2 and Hydrogel + BMP-2 had less effect on the actin filaments labelled by phalloidine (red), while cell shrinkage and detachment in the Hydrogel + T8IC + Laser (45 ℃) and Hydrogel + T8IC + Laser + BMP-2 + H2O2 (45℃) were observed due to the combined effects of PTT and PDT. Delightfully, the cell regained the bioactivity, cell spreading and attachment after another 24-hour culture. Besides, although the proliferation of MC3T3-E1 cells was inhibited in Hydrogel + T8IC + Laser and Hydrogel + T8IC + Laser + BMP-2 + H2O2 1 day after treatment, the cell viability had resuscitated 3 days after treatment , quantitative analysis of ALP activity, ALP staining and alizarin red staining. After 4 days culture, gene expression of osteogenic mRNAs  was much higher in the Hydrogel + BMP-2 and Hydrogel + T8IC + Laser + BMP-2 + H2O2 , indicating that PTT could induce the release of BMP-2 and promote osteogenic gene expression, as shown in Fig. Osteoblast differentiation was assessed by mRNA expression  and alizarin red staining  were consistent with the results of PCR. Hydrogel + BMP-2 and Hydrogel + T8IC + Laser + BMP-2 + H2O2 exhibited intensified staining of ALP and mineralized nodules. In addition, the ALP activity of Hydrogel + BMP-2 and Hydrogel + T8IC + Laser + BMP-2 + H2O2 was much higher than other groups after both 4 days and 7 days culture . All those results proved that the mild PTT and enhanced PDT generated by Hydrogel + T8IC + Laser + BMP-2 + H2O2 may not affect the release and bioactivity of BMP-2. On the contrary, as shown in Fig. The ALP staining Fig. A and aliing Fig. B were co2O2 Fig. D. All th2O2 in the body of BALB/C nude mice, an in vivo fluorescence detector with NIR-II fluorescence scanner  was designed and assembled. The emission spectrum of T8IC NPs belongs to NIR-II window, so the fluorescence scanner could detect the residual content of T8IC NPs to monitor the metabolism of Hydrogel + T8IC + Laser + BMP-2 + H2O2in vivo. The sol-gel transition of chitosan/β-glutamine/gelatin hydrogel occurred in 5 min when the temperature reached to 37 ℃ [2O2) and laser irradiation in the present study, the effect of PTT made the sol-gel transition time shorten to 2 min (45 ℃). Thus, when the hydrogel was applied in vivo, it wouldn’t go back to solution if temperature goes down from 45 ℃ to the body temperature and it is able to perform controlled release of the drugs. As shown in Fig. 2O2 and T8IC NPs . The blood routing test and biochemical examination after treatment was conducted to explore the effect on peripheral blood cells index. WBC, RBC, Hb, HCT and all the indexes representing hepatorenal function  had no significant difference between the experimental and control groups  and bone volume fraction  was detected after establishment of the periodontitis model in the experimental groups. Both BMD and BV/TV were significantly highest in the Hydrogel + T8IC + Laser + BMP-2 + H2O2 among the other four experimental groups  was measured to evaluate the periodontal regeneration . The quaInflammation is a kind of important immune defense. When the tissue is threated by toxins or bacteria, the inflammatory response is initiated and it is a normal state of self-protection and beneficial to human health. However, inflammation is also potentially harmful, if not dealt with in a timely manner, and will cause cytokine storm and other physical dysfunction . The pat2O2 exhibited a better osteogenic effect than Hydrogel + BMP-2 and Hydrogel + T8IC + Laser. Furthermore, even without the application of BMP-2, there was bone regeneration in the Hydrogel + T8IC + Laser, implying enhanced PDT and mild PTT may induce bone regeneration through enhancing the anti-inflammation performance, as had been reported [). The cytokines in the Hydrogel + T8IC + Laser was lower than that of Hydrogel + BMP-2 and there was a least inflammatory state in the Hydrogel + T8IC + Laser + BMP-2 + H2O2 (P < 0.05). All those results above implied that PTT and PDT generated by Hydrogel + T8IC + Laser and Hydrogel + T8IC + Laser + BMP-2 + H2O2 may promote bone regeneration through alleviating the inflammation state.As shown in Fig. reported , 59. To Figure S4), which validated its biocompatibility. The body weight of mice, blood routing test and biochemical examination were also conducted above to confirmed its biosafety. To further verify their potential toxicity, H&E staining of major organs  was also conducted. The results demonstrated that the cell morphology of major organs was intact and there was no obvious infiltration of inflammatory cells . All results above indicated the excellent biosafety and histocompatibility of Hydrogel + T8IC + Laser + BMP-2 + H2O2.The hemolysis assay was performed to detect the biosafety of T8IC NPs in vitro. No hemolysis of red blood cells from mice incubated with different concentrations of T8IC NPs was observed (2O2). T8IC NPs was prepared by reprecipitation and acted as NIR-II phototherapy agents under 808 nm laser irradiation. To avoid the damage of hyperthermia to surrounding tissues, we promoted PDT through adding H2O2 to facilitate the antibacterial effect instead of increasing the temperature of PTT. Hydrogel + T8IC + Laser + BMP-2 + H2O2 incorporated with mild temperature PTT (45 °C), enhanced PDT and sustained release of BMP-2. It was presented with excellent bactericidal effect, osteogenic induction and biosafety both in vitro and in vivo. Even without the application of BMP-2, there was bone regeneration and less expression of the proinflammatory cytokines  in the Hydrogel + T8IC + Laser group, implying that PTT and PDT could promote bone regeneration through alleviating inflammation state. In general, this novel approach with synergistic antibacterial effect, anti-inflammation and bone regeneration has a great potential for the treatment of periodontitis in the future.In summary, an injectable and thermosensitive hydrogel with 3D networks was used as drug carrier for controlled release of osteo-inductive agent (BMP-2) and NIR-II phototherapy agents (T8IC NPs and HBelow is the link to the electronic supplementary material.Supplementary Material 1