Natural rubber (NR) exhibits good elasticity, flexural resistance, wear resistance, and excellent mechanical properties, and it has been widely used in aerospace, transportation, medical, and health fields. For NR, however, the resistance to thermal-oxidation and ozone aging is fairly poor. Although aging properties of NR can be significantly improved with the incorporation of chloroprene rubber (CR) according to some references, the miscibility between NR and CR, the morphologies of the binary blends, and so on are revealed ambiguously. In this work, molecular dynamics simulation (MD) and dissipative particle dynamics (DPD) simulation were carried out to predict the compatibility between natural rubber and chloroprene rubber in view of Flory–Huggins parameters. The morphologies of the blends were obtained with the use of the DPD method. The simulation results were furtherly examined by means of Fourier transform infrared spectroscopy (FT-IR) and dynamic mechanical analysis (DMA). It was found that the miscibility between NR and CR is poor. Nevertheless, the miscibility could be improved when the content of CR is 50% or 90%. In addition, spinodal decomposition with a critical temperature of 390 K would take place according to the phase diagram. Microphase structure such as spherical, lamellar, and bicontinuous phases can be found with different contents of CR in the blends with the results of morphologies analysis. Hevea brasiliensis, is conspicuous for its excellent mechanical properties and high insulation. It is widely recognized that dynamic flexibility originated from the double-bond structure endows NR marvelous toughness. The unsaturated structure also affords NR versatile chemical modification strategies. On the other hand, NR is very susceptible to oxidation due to the highly unsaturated structure, which results in poor thermal-oxidative aging resistance and ozone resistance [With the rapid development of society, the performance requirements of polymers have been more and more stringent. To meet this need, enormous effects have been devoted for the purpose of polymer modification. Of them, polymer blending has become an effective and cost-saving methodology ,2. Natursistance ,4,5,6. Nsistance ,8,9,10. sistance  et al. dsistance  investigsistance  exploredIt is well known that properties of polymer materials are considerably governed by their morphology. As for NR and CR, the former is a typical nonpolar polymer while the other is a polymer with characteristic of polarity. The compatibility between them plays an important role in the morphology, phase structure, and properties of the blends’ inevitably. Homogeneous phase structure due to good compatibility and macroscopic phase separation owing to complete incompatibility are not desirable for polymer blending . In contFortunately, with the development of computer technology, molecular simulation has been widely used in various materials fields and is favored by scientific researchers. Molecular simulation can not only predict information of structure together with properties of polymers, but also provide explanations of experimental observations at different length and time scales. Many computational methods have been applied for exploration of polymer materials, which should be well chosen according to object scale. For example, molecular dynamics or Monte Carlo methods have often been adopted to investigate polymers at molecular scale. Dissipative particle dynamics (DPD), Brownian dynamics, dynamic density functional theory method, and so on have been widely used to probe polymers at mesoscale scale. In addition, some methods such as micromechanics have been employed at the level of macroscale. To achieve materials for meeting the needs of engineering, NR/CR blends were furtherly modified with other components. It is worthy of expectation that morphologies of the blends could be explored beforehand in depth with the help of molecular simulation to turn the properties desired. With the aid of molecular simulation, morphological evolution, phase separation, and so on, it can be elucidated in polymer blending systems. Structure and properties of the blends can also be predicted with the results of molecular and atomic scales analysis ,16.Although molecular simulations are widely used in polymer blending systems, most of them have focused on plastic blending systems or other composite material systems, but there are not many molecular simulation studies on rubber blend systems. Yang Jinmeng et al.  used molRecently, functional polymer materials in constitution of NR and CR have been fabricated and investigated. For instance, sensing characteristics of conductive chloroprene rubber/natural rubber composites were examined in consideration of a coblending process . The morIn this work, we investigated the compatibility between NR and CR by calculating the solubility parameters and the Flory–Huggins parameter using the method of molecular dynamics. Then we constructed the phase diagram of the NR/CR blends. The morphologies of the blends were visualized by using the DPD method. In addition, FT-IR and DMA experiments were carried out to support the results of molecular simulation.Materials studio (MS) is a commercial molecular simulation software developed by Accelrys Company, which includes functions of modeling, structure optimization, performance calculation, and so on. The software contains many functional modules to perform molecular dynamics, molecular mechanics, quantum mechanics, and other computational simulation methods, which can realize the simulation of materials from microscopic to mesoscopic scales. At present, Materials studio is widely used in petrochemical, food and pharmaceutical, biochemistry, and other fields, and is often used in the research of polymer material properties, surface chemistry, surface catalysis, and other issues.Molecular dynamics simulation (MD) is based on Newtonian mechanics, simulates the motion of particles by applying forces and torques, extracts relevant information from the system, and analyzes the performance of the system. The motion law of particles in the system follows Newton’s equation of motion:i is:The acceleration of particle i after time t can be obtained:By integrating Lagrange’s equation of motion over time, the acceleration, velocity, and position of particle i is subjected to, respectively; i, respectively; and the superscript “0” is the initial value of each physical parameter.In the formula, MD simulations themselves have become more powerful and accessible over the past few years . Ndoro eIn this study, the Materials Visualizer module of Materials Studio (MS) software was used to construct the NR/CR blends with different mass ratios, and molecular dynamics methods were used to optimize the model and calculate the performance of blends; the miscibility of the NR/CR blends was analyzed with Flory–Huggins interaction parameters and phase diagrams.The modeling process of the NR/CR blends is depicted in fs.The models were furtherly annealed with a temperature gradient of 50 K, rising from 300 K to 500 K, and then decreased from 500 K to 300 K. Five cycles were performed to eliminate unreasonable configurations. The annealed models were then balanced for 100 ps of NVT together with 200 ps of NPT. Every trajectory was saved per ps. The last 50 ps trajectories were used for performance analysis. The whole molecular dynamics simulation process adopted the COMPASS force field , Nosé–HoDissipative particle dynamics (DPD) is a simulation method at the mesoscopic scale proposed by Hoogerbrugge and Koelman in 1992 . Unlike I, and The starting point of the dissipative particle dynamics simulation formula is the integral Newton equation, and the dynamic behavior between the beads can be described by the Newtonian equation of motion:.ijε is a random number that averages to zero, indicating each interacting pair of beads is selected randomly at each time step And the three forces can be given by:NDPD is the number of beads in the molecular chain for the DPD simulation; C∞ is the limiting characteristic ratio, which is an inherent property of the molecular chain.Whether a model is reasonable or not plays a key role in the results of dissipative particle dynamics simulations. DPD simulation uses a series of beads to represent the atomic clusters in the system, which makes use of the flexible potential function to calculate the system energy and describes the movement of beads through the equation of motion and three kinds of forces . TherefoC∞ of NR and CR. The C∞ of NR and CR are found to be 5.45 and 5.44, respectively. As a consequence, the NR and CR coarse-grained models could be obtained by using 1 bead to replace 5 repeating units of NR and CR molecular chains, as shown in The Synthia module of Materials Studio was used to calculate the limit characteristic ratio The natural rubber/chloroprene rubber blends were prepared with a mechanical blending method. Firstly, NR was masticated in an open-roll mixing mill for 2 min, and then CR was added, and stearic acid, zinc oxide, promoter, sulfur, and other additives were gradually added according to the formula. The mixing process required repeated cutting knives operating, and the process was kept for 10 min. Secondly, the mixed compounds needed to be triangulated 4 times and crimped 4 times. Thirdly, the compounds were stored for 24 h to eliminate internal stress. Lastly, no rotor vulcanizer  was used to test the vulcanization performance of the compounds, and then the compounds were vulcanized at 140 °C × 13.5 MPa on a platen vulcanizer to obtain the NR/CR blending vulcanizates.A DMA test of the samples  was carried out on a dynamic thermomechanical analyzer  in a film-stretching mode. The scanning temperature ranged from −130 °C to 60 °C, and the heating rate was 3 K/min. The frequency was 1 Hz, and the strain amplitude was 25 μm.−1.FT-IR spectra of the NR/CR blends were analyzed using a Fourier Transform Infrared Spectroscopy . The specimens were scanned with attenuated total reflection (ATR) model in the range of 400–4000 cmV are solubility parameter, cohesive energy, and volume, respectively. For a molecular simulation, the more molecules and the longer chain length in the system, the more simulation time will be needed, and the higher the requirements of the calculation will be.Solubility parameter , 1430 cm−1 (deformation vibration of methylene antisymmetric plane with chlorine atom in the adjacent position), 1117 cm−1 (vibration of carbon chain skeleton), and 824 cm−1 (corresponds to the C-H out-of-plane deformation vibration on the triple substitution C=C). The red curve is the NR IR curve, and the main characteristic band is 1375 cm−1 corresponding to the symmetric stretching vibration of methyl group, 838 cm−1 for the C-H out-of-plane deformation vibration of the cis-disubstituted carbon–carbon double bond, and 1450 cm−1 for the antisymmetric deformation vibration of methylene group.It can be seen from NR-CR and the critical interaction parameter χc showed that the compatibility of the NR/CR blends with different mass ratios was poor. The maximum critical co-dissolution temperature of the NR/CR blends was calculated to be about 375 K according to phase diagram. The results of DPD simulation, FT-IR, and DMA also showed that the compatibility between NR and CR was poor. However, the miscibility could be improved when the content of CR was 50% or 90%. Furthermore, the diameters of the dispersed phase were calculated to be nanoscale according to the results of density variation along the x-axis of the simulation box. This work would be helpful for design of rubbery polymers with the guidance of molecular simulation.In this work, molecular dynamics simulation and the DPD method were used to investigate the compatibility of the NR/CR blends system from interaction parameters, phase diagram, and morphologies of the blends. The results of the Flory–Huggins interaction parameter χ


Then, ABS composed of polymers, salts and ionic liquids were evaluated to optimize the laccase confinement in one phase while PDA is recovered in the opposite phase. The most promising ABS allowing the separation of laccase from the reaction product is composed of polypropylene glycol (400 g mol−1) and K2HPO4. The polymerization of dopamine in ABS leads to a remarkable improvement of polymerization of 3.9-fold in comparison to the conventional chemical PDA polymerization. The phase containing the confined laccase was reused for four consecutive reaction cycles, with a relative polymerization of 68.9% in the last cycle. The results of this work proved that ABS are a promising approach to create a liquid support for enzyme reuse allowing the process intensification efforts. The use of biocatalysts in ABS emerges as sustainable and alternative platforms from environmental and techno-economic points of view.Polydopamine (PDA), a bioinspired polymer from mussel adhesive proteins, has attracted impressive attention as a novel coating for (nano) materials with an adequate conformal layer and adjustable thickness. Currently, PDA is obtained from dopamine chemical oxidation under alkaline conditions, limiting its use in materials sensible to alkaline environments. Envisaging a widespread use of PDA, the polymerization of dopamine by enzymatic catalysis allows the dopamine polymerization in a large range of pHs, overcoming thus the limitations of conventional chemical oxidation. Moreover, the conventional method of polymerization is a time-consuming process and produces PDA films with poor stability, which restricts its applications. On the other hand, the main bottleneck of enzyme-based biocatalytic processes is the high cost of the single use of the enzyme. In this work, laccase was used to catalyse dopamine polymerization. To improve its performance, a liquid support for integrating the laccase and its reuse together with the PDA production and recovery was developed using aqueous biphasic systems (ABS). Firstly, dopamine polymerization by laccase was optimized in terms of pH, temperature and initial dopamine concentration. It was demonstrated that the highest enzymatic polymerization of dopamine was achieved at pH 5.5, 30°C and 2 mg ml Polydopamine (PDA) is a bioinspired polymer from mussel adhesive proteins, and has attracted relevant attention as a novel coating for (nano) materials with adequate conformational layer and adjustable thickness . PDA was2, NaIO4 or KClO3   that leads to spontaneously dopamine self-polymerization. However, it is a time-consuming process requiring a long reaction time, 24 h, and oxidant agents such as Oor KClO3 . These hor KClO3 . In addior KClO3 . To overor KClO3 . Laccaseor KClO3 . Moreoveor KClO3 . Therefoor KClO3 . For exaditions) . Howeverditions) . To boosditions) . In thisditions) . Neverthditions) . Therefoditions) . Recentlditions) . Anotherditions) , while mditions) . Therebyi), and the reuse of the enzyme. The potential of laccase in polymerization is herein exploited and compared with the non-enzymatic method. Several parameters including the temperature, pH of the medium and initial dopamine concentrations on the dopamine polymerization were also investigated and optimized.This work aims the development of an integrated and sustainable platform for the enzymatic production and recovery of PDA and biocatalyst reuse using ABS. The biocatalytic process for the polymerization of dopamine was carried out using laccase as the biocatalyst and ABS composed of polymers, salts, and ILs. ABS was used for the first time as reaction media and liquid support for laccase allowing the simultaneous separation of product, soluble PDA intermediate species (PDA−1 (PPG 400), polyethylene glycol with a molecular weight of 400 g mol−1 (PEG 400), ABTS (≥ 98 wt% purity) and dopamine hydrochloride (98 wt% purity) were acquired from Sigma-Aldrich. The ILs, cholinium dihydrogen phosphate  and cholinium acetate  were both purchased from IoLiTec, and cholinium dihydrogen citrate  from Sigma-Aldrich. Dipotassium hydrogen phosphate trihydrate  was purchased from Scharlau.Polypropylene glycol with a molecular weight of 400 g molTrametes versicolor (10 U mg−1) was acquired from Sigma-Aldrich. Sodium acetate (CH3COONa) pure from AnalaR Normapur and acetic acid  from Fisher Chemical was used to prepare sodium acetate buffer; disodium phosphate  and citric acid , both acquired from Panreac were used to prepare citrate-phosphate buffer; Tris-HCl buffer was prepared by using tris (hydroxymethyl) aminomethane  from PRONALAB and a hydrochloric acid solution .Commercial laccase from i using laccase, several reactional parameters were studied, namely pH, temperature, and initial dopamine concentrations.Enzymatic polymerization of dopamine was performed according to the adapted procedure by −1) was prepared in the multiple buffers and laccase (1.00 mg ml−1) was added to perform the enzymatic reaction. The reactions were kept at a controlled temperature (30°C) and continuously magnetic stirred (350 rpm) at atmospheric air for 1 h.The pH effect on enzymatic polymerization was studied using sodium acetate buffer for pHs 4.5 and 5.5; phosphate buffer for pH 6.5 and Tris-HCl buffer for pH 7.5 and 8.5 (0.05 M). Dopamine solution (2.00 mg ml−1) prepared in sodium acetate buffer at pH 5.5 (0.05 M) and laccase (1.00 mg ml−1). The reactions were performed at a controlled temperature in a range from 20 to 40°C and continuously magnetic stirred (350 rpm) at atmospheric air for 1 h.The influence of temperature was investigated. The assay was performed by adding a dopamine solution (2.00 mg ml−1 prepared in sodium acetate buffer at pH 5.5 (0.05 M) and laccase (1.00 mg ml−1). The reactions were kept at a controlled temperature (30°C) and continuously magnetic stirred (350 rpm) at atmospheric air for 1 h. Each assay was performed in triplicate. Reactions without laccase under the same conditions were carried out and considered as control.The effect of dopamine concentration was evaluated by adding a dopamine solution with different concentrations ranging from 0.25 to 3.00 mg mli. For this purpose, spectra were acquired in wavelength range from 250 to 500 nm.UV−vis spectroscopy was employed to monitor the oxidation of dopamine. The degree of dopamine polymerization was indirectly monitored at 305 and 480 nm using a UV-Vis spectrophotometer (Shimadzu UV-1800 Spectrometer). Both wavelengths correspond to PDA−1) and was used as a reference value in the calculation of the relative enzymatic polymerization.The relative enzymatic polymerization of dopamine in relation to the non-enzymatic was determined according to −1. Each measurement was analysed in triplicate. 1 Unit (U) of laccase activity corresponds to the amount of enzyme necessary for the oxidation of 1 μmol of the substrate (ABTS) per min (ε = 36.000 M−1 cm−1).The laccase activity was measured by adding 50 μl of sample to 250 μl of ABTS aqueous solution and 700 μl of citrate phosphate buffer . The increase in absorbance per min was spectrophotometrically measured at 420 nm and expressed in U·L−1 [prepared in Tris-HCl buffer at pH 8.5 (0.05 M)] and 200 μl of laccase (0.60 mg ml−1) + 600 μl Tris-HCl buffer. Then, laccase activity was measured as previously described. The laccase activity measured in Tris-HCl buffer pH 8.5 was considered as the control (100%).The enzymatic activity of laccase was evaluated in the presence of dopamine by adding 200 μl of dopamine solution with different concentrations ranging from 0.10 to 1.00 mg mli in the laccase activity method, the polymerization of dopamine was carried out by the traditional method using Tris-HCl buffer at pH 8.5 (0.05 M). 200 μl of PDAi solution was added to 200 μl of laccase solution (0.60 mg ml−1) + 600 μl Tris-HCl. Then, laccase activity was measured as previously described. The laccase activity in the Tris-HCL buffer pH 8.5, used in the production of PDAi, was considered as the control (100%).To evaluate the influence of PDAEELaccase%), dopamine (EEdopamine%) and PDAi (EEPDA%) was evaluated in five different ABS. The ABS ternary mixture compositions used were based on the previous binodal curves reported in the literature  to the ABS mixture compositions described above, replacing the water content, to attain a total ABS weight of 2 g. After the homogenization of the ABS, the phase separation was carried out by centrifugation at 3,500 rpm for 20 min at 25°C. The EELaccase % was considered as the percentage ratio between the laccase activity in the bottom phase (bot) to that in the opposite top phase (top), according to EEdopamine% for each ABS mentioned, 20 wt% of an aqueous dopamine solution (2.00 mg ml−1) was added to the ABS mixture compositions described above, replacing the water content, attaining a total ABS weight of 2 g. After the homogenization of the ABS, the phase separation was carried out by centrifugation at 3,500 rpm for 20 min at 25°C. The absorbance of each phase was measured at 280 nm using a Shimadzu UV-Vis spectrometer. EEdopamine% was determined according to To evaluate EEPDA %, produced by the enzymatic catalysis, the polymerization of dopamine was carried out using the previously mentioned five ABS at the same compositions. For each ABS, 20 wt% of dopamine solution (2.0 mg ml−1) and 10 wt% laccase aqueous solution (1.0 mg ml−1) were added to the ABS mixture compositions, replacing water content, for total ABS weight of 2 g. The reaction was incubated at 25°C and stirred for 1 h. Afterwards, both phases of the ABS were separated after centrifugation at 3,500 rpm for 30 min at 25°C. PDAi partition was assessed by recording the UV-Vis absorbance spectra ranging between 250 and 500 nm, through the analysis of absorbance at 480 nm. EEPDA% was determined according to i partition) of the top and bottom phases, respectively. DF corresponds to the dilution factor of each phase, W (top) to the weight of the top phase and W (bot) the weight of the bottom phase.To evaluate −1) + 40.6 wt% laccase solution at 2.56 mg ml−1. The reactions were performed for 1 h, incubated at 30°C and continuously under magnetic stirring (350 rpm). After 1 h, the phase separation was carried out by centrifugation at 3,500 rpm for 30 min at 25°C. Relative polymerization (fold) was determined according to −1 were evaluated. The conventional method of polymerization (without laccase) was also carried out in the same ABS and was considered as the reference: 33 wt% PPG 400 + 6.4 wt% K₂HPO₄ + 20 wt% dopamine solution (0.50–3.50 mg ml−1) + 40.6 wt% H2O at 30°C.Laccase-catalysed dopamine polymerization was carried out in the selected ABS composed of 33 wt% PPG 400 + 6.4 wt% K₂HPO₄ + 20 wt% dopamine solutions (0.50–3.50 mg ml−1 and after 1 h of incubation time at 25°C) was considered as the control (100%).To evaluate the effect of the ABS bottom phase in the laccase activity, the selected ABS composed of 33 wt% PPG 400 + 6.4 wt% K₂HPO₄ was prepared and the phase separation was carried out by centrifugation at 3,500 rpm for 30 min at 25°C. The laccase activity was determined in the bottom phase of the ABS that was used as a medium for laccase incubation. The laccase activity measured in water at the same conditions  + 40.6 wt% laccase solution (1.00 mg ml−1). After the first reaction cycle, the PDAi-enriched top phase was removed, and the same volume of a solution containing the respective top polymer-rich phase constituents (determined by the tie-line)   was adde(n cycle) and abs(1st cycle) correspond to the absorbance values at 480 nm obtained in the ABS top phase each cycle and the first cycle of reaction, respectively.Relative polymerization (%) was defined as the ratio between the obtained absorbance at the end of each cycle with respect to that obtained in the first cycle and was calculated according to To explore the potential of laccase in the polymerization of dopamine, the enzymatic polymerization was investigated at pH 5.5 and compared to the alkaline conventional method at pH 8.5. Both reactions were carried out at 30°C for 1 h. In the presence of laccase, the colourless of the initial dopamine solution rapidly (∼1 min) changed to a reddish solution, indicating the fast polymerization of dopamine. After 1 h of reaction, the red colour became more intense (dark red) . Comparai was assessed by UV-Vis absorption intensities at 305 and 480 nm, which correspond to the formation of dopamine semiquinone and dopaminechrome intermediate species, respectively. The subsequent oxidation of these species leads to the formation of PDA . It should be noted that the conventional dopamine polymerization was also evaluated at a pH range between 4.5 and 7.5 and, as expected, no polymerization was observed. The respective detailed data are reported in the To improve the performance of the enzymatic polymerization of dopamine, the following reaction parameters were optimised: pH, temperature, and initial dopamine concentrations. −1 at 30°C. According to the results, it is evident that the optimal pH for the enzymatic polymerization of dopamine was pH 5.5. The efficiency of the enzymatic reaction at pH 5.5 was improved by approximately 7.2-fold. In addition, all pHs ranging from 4.5 to 7.5 present better relative dopamine polymerization than the conventional polymerization. As expected, the lowest polymerization value corresponds to pH 8.5 which is similar to the conventional approach. This can be explained by the higher pH since the laccase performance decreases due to the inhibitory effect of OH− on the active site of the enzyme  a relative polymerization increase of ∼3-fold was obtained in relation to the maximum value observed for the conventional non-enzymatic method at 2.00 mg ml−1.At the optimum pH and temperature (pH 5.5 and 30°C), the initial dopamine concentration was optimised in the range of 0.25–3.00 mg ml−1). Under these conditions, the relative enzymatic dopamine polymerization achieves 7.4-fold in comparison to the conventional dopamine polymerization. These results confirm that the use of laccase has many advantageous for the PDAi production. In addition, the laccase reuse is important to achieve a more sustainable and economic process. Therefore, the reuse of laccase in ABS is further investigated to improve the process.The parameters for the enzymatic dopamine polymerization were optimised  of all ABS, with an EELaccase of 100%. These results are in accordance with previous works demonstrating that proteins and enzymes have a high affinity for the more hydrophilic phase , whereas for PPG 400 + [Ch][DHP], PPG 400 + [Ch][DHC], and PPG 400 + PEG 400, PDAi and laccase preferentially migrate to the bottom-phase, with an EEPDA to the top-phase ranging from 17.2 to 32.2%. Thus, these ABS were excluded for further studies since the PDAi was in the same phase of laccase. On the other hand, the ABS composed of PPG 400 + K2HPO4 led to the best EEPDA of 77.8%. PDAi preferentially migrated to the PPG-rich top phase while laccase complete migrated to the salt-rich bottom phase. Thus, this ABS was the most promising system for the separation of PDAi while allowing the recovery and reuse of laccase. In addition, the colour obtained in the top phase after 1 h of reaction confirmed that the dopamine polymerization was successfully catalysed by laccase, Regarding the EEdopamine % was determined and the results are depicted in EEdopamine for the bottom phase from 59.8 to 74.4%. Since dopamine is more hydrophilic than PDAi, this behaviour is expected due to the hydrophilic character of the bottom phase .The polymerization of dopamine in the selected ABS was evaluated. Using the conditions previously selected, the reaction was carried out in a system composed of PPG 400 + Kobserved , which d2HPO4 by determining the ideal initial dopamine concentration in the ABS. The optimisation was evaluated based on the relative polymerization increase using different concentrations of dopamine, from 0.10 to 0.70 mg ml−1 after 1 h of reaction. The optimisation of the laccase-catalysed dopamine polymerization was carried out in the selected ABS composed of PPG 400 + K−1 up to 0.60 mg ml−1, respectively. Above this value, the relative dopamine polymerization remains constant, following a similar trend to that previously observed in −1 lead to an outstanding polymerization increase in comparison with the conventional polymerization method performed without laccase, again demonstrating the high efficiency of the laccase-catalysed reaction.The results depicted in 2HPO4. Compared to the control (laccase in water at the same conditions), the laccase maintains 80% of the enzymatic activity in the K2HPO4 rich-phase. The decrease in laccase activity in the bottom phase can explain the difference in the relative polymerization between the results in the ABS and in aqueous solution. However, despite some loss in enzymatic activity in the ABS, this technique allows the recovery and reuse of the enzyme with good performance.Comparing to the performance of laccase in aqueous solution, a decrease in optimum dopamine concentration is observed. To explain this behaviour, the enzymatic activity of laccase was evaluated in the bottom phase of the ABS composed of PPG 400 + K−1 the polymerization remains constant, this concentration was chosen for further assays. The choice of the initial concentration of dopamine is important to make the process profitable, making it more sustainable and economical, and avoiding the unnecessary use of the substrate.Since above 0.60 mg ml−1), an integrated platform for laccase reuse and PDAi recovery was developed using the ABS composed of PPG 400 + K2HPO4. The polymerization reaction was carried out in the ABS for four consecutive cycles. A scheme of the integrated reaction—extraction platform developed, including the recycling of the laccase and dopamine and the K2HPO4-rich phase is illustrated in After selecting the optimum dopamine concentration (0.60 mg mli (relative polymerization), i. Similar behaviour is reported in the literature, where intermediates of certain laccase reactions  act as laccase inhibitors decreasing the enzyme activity  in the laccase activity tests with ABTS was evaluated and compared to the control . The results presented in i are also laccase substrates for the formation of solid PDA, more than one substrate is competing for the active site of laccase during the measurement with ABTS and consequently contributing for the decrease in the values of enzyme activity during the cycles. In addition, the influence of dopamine in the ABTS method was also evaluated and as expected once dopamine is also laccase substrate, the enzyme activity relative to the control was 6% . The EE of oligorutin was 67% and it was similar to that obtained in this study for PDAi in the first cycle (∼75%).According to the literature, only one work can be found on polymerization studies using laccase and ABS. This work studied the oligomerization of rutin in ABS composed of PEG 600 and [Ch][DHP] . A totalThe outcomes from successive cycles, considering good relative dopamine polymerization values, demonstrate the robustness of the reaction-extraction process proposed with ABS for integrated biocatalytic processes.2HPO4 ABS enable enzymatic processes while simultaneously extracting the products to the opposite phase. This selectivity demonstrates that it is possible to reuse the enzyme in a liquid support matching the ABS phase by allowing the extraction of the products from the enzyme. Therefore, ABS was here demonstrated as an efficient, and integrated reaction—separation platform to carry out the biocatalytic polymerization reactions, further allowing the reuse of the enzyme without compromising high polymerization rates and performance. For four consecutive reaction cycles, the phase containing the confined laccase was reused, with the final cycle having a relative polymerization of 68.9%. To sum up, it was found that the PPG 400 + K2HPO4 ABS is an efficient system since it allows the separation of PDAi and laccase to opposite phases and the confinement and further reuse of laccase, thus, being an adequate liquid support for biocatalytic reactions and processes integration.Laccase improves the dopamine polymerization reaction, achieving high polymerization rates when compared with the conventional polymerization method. The results show that PPG 400 + K


To further advance the performance and safety of autonomous mobile robots (AMRs), an integrated chassis control framework is proposed. In the longitudinal motion control module, a velocity-tracking controller was designed with the integrated feedforward and feedback control algorithm. Besides, the nonlinear model predictive control (NMPC) method was applied to the four-wheel steering (4WS) path-tracking controller design. To deal with the failure of key actuators, an active fault-tolerant control (AFTC) algorithm was designed by reallocating the driving or braking torques of the remaining normal actuators, and the weighted least squares (WLS) method was used for torque reallocation. The simulation results show that AMRs can advance driving stability and braking safety in the braking failure condition with the utilization of AFTC and recapture the braking energy during decelerations. Compared with the traditional automated guided vehicles (AGVs), autonomous mobile robots (AMRs) have higher flexibility and intelligence, representing a more sophisticated, flexible, and cost-effective technology, in favor of smart manufacturing, smart factory, and intelligent logistics . AMRs arIn recent years, different kinds of advance control methods have been applied to the motion control of robots, including optimal control , model pTo deal with the failure of actuators, a fault-tolerant control has been widely studied ,26,27. IMost studies only consider the failure of one actuator, which cannot cover all failure conditions. In this research, all kinds of failure conditions of IWMs were studied. Besides, few studies consider the regenerative braking and actuator failure in the motion control process of AMR at the same time. The contributions of this research are summarized as follow: (1) To deal with the system nonlinearity and external disturbances, an integrated feedforward and feedback control algorithm was designed for longitudinal motion control of AMR; (2) To realize the collaborative steering of 4WS, the nonlinear model predictive control (NMPC) method was applied to the path-tracking controller design; (3) To address the braking failure of actuators, an active fault-tolerant control (AFTC) algorithm was designed for AMR by redistributing the braking torques of the rest normal actuators.The rest of this paper is organized as follows. To realize autonomous driving, the motion control for AMR mainly consists of longitudinal motion control and lateral motion control. Lateral motion control is reflected by the path-tracking issue. Longitudinal motion control is related to the drive and brake control, which is a critical issue in this study.IWMs are the key components for AMR. On one hand, in-wheel motors can be used to drive the AMR. On the other hand, regenerative braking can be realized with in-wheel motors, recovering the braking energy. AMR is usually equipped with four in-wheel motors for independent drive, and four EMB systems for independent braking. Due to so many actuators, the reliability of the system is decreased. Therefore, safety is a critical issue for AMR. In the braking process, if braking failure of actuators occurs, this reduces safety. To maximize regenerative braking energy, IWMs have higher braking priority than EMBs. EMBs are usually used to compensate the rest braking force. Therefore, we mainly discuss the braking failure of IWMs in this paper.The chassis control framework for AMR is illustrated in Some assumptions are made in this paper. First, only seven degrees of freedom are considered for the vehicle dynamic model, i.e., longitudinal motion, lateral motion, yaw motion of the vehicle and the four wheels’ motion. Pitch motion, roll motion, and vertical motion of AMR are ignored. Drive anti-skid control is not considered in the longitudinal motion control strategy. This paper mainly focuses on the velocity-tracking control and braking control. Additionally, the longitudinal acceleration of the wheel center is considered equal to the longitudinal acceleration of the AMR at CG.r denotes the yaw rate at the center of gravity (CG), i = fl, fr, rl, rr) denotes the steering angle of each wheel . i = fl, fr, rl, rr) denotes the longitudinal force of each tire, The longitudinal dynamic model is derived as follows .(1)m denotes the lateral force of each tire, which is expressed with the Dugoff tire model [The lateral dynamic model is expressed by (5)m(v˙yre model .The yaw dynamic model is written according to (7)Izr˙=Additionally, the dynamic model of each wheel is derived byAs The yaw angel A combination of (5), (7), (11) and (12) yields the following path-tracking model for AMR.For velocity-tracking controller design, (1) is rewritten as follows.After Taylor expansion of (2) regarding Then, the simplified longitudinal dynamic model can be expressed asBased on the wheel dynamic model (10), it can be derived thatSubstitution of (19) into (18) yieldsThe total torque of four wheels According to the model (20), the feedforward controller is derived as follows.Substitution of (22) into (20) yieldsThe feedback controller is designed by PID. Furthermore, defining the state vector To solve the feedback PID controller, the following performance index function is constructed:Furthermore, the solution problem of the feedback PID controller can be transformed into the minimization of the performance index function, i.e.,Finally, the linear-quadratic optimization approach is used to solve the feedback PID controller ,42.For the path-tracking controller design, the path-tracking model (13) is expressed in the discreate state-space form as follows.Based on the discreate model (27), NMPC is applied to the path-tracking controller design. The prediction horizon and the control horizon are defined by Based on (28), this yields the output sequence as follows.Besides, the reference output sequence is expressed byMoreover, the control sequence is expressed as follows.The proposed path tracking controller aims to minimize the tracking error Finally, the NMPC path-tracking controller can be solved with the following optimization.In this section, we only discuss the braking failure of IWMs. If IWMs have failure in the driving process, the AFTC mechanism is triggered immediately. After that, the AMR starts braking to guarantee safety. Therefore, we do not discuss the driving failure of IWMs independently.Since the total torque of four wheels Besides, the external yaw moment is generated by IWMs and EMBs, i.e.,To guarantee yaw stability, i in To maximize the regenerative braking energy, IWMs has higher braking priority than EMBs. Therefore, the first step is to determine if Since Once For IWMs, the following torque distribution model is derived.Based on (36), the weighted least squares (WLS) method is used to distribute the torques of IWMs. The cost function for IWM torque distribution is constructed as follows.Furthermore, (40) is rewritten asThen, the WLS method for IWMs torque distribution is described as follows.Based on (42), the torques for four IWMs, i.e., For EMBs, the following torque distribution model is derived.Based on (43), the cost function for EMBs torque distribution is derived as follows.Furthermore, (45) is rewritten asThen, the WLS method for EMB torque distribution is derived as follows.Based on (47), the torques for four IWMs, i.e., Three simulation cases were designed and carried out via the co-simulation platform based on Carsim and Simulink as shown in In this case, a straight-line braking condition was carried out. The AMR accelerated to 15 m/s and then started to brake after the 10th second. Three kinds of braking modes were compared in this case, i.e., regenerative braking (IWM), mechanical braking (EMB) and hybrid braking (IWM + EMB). The three kinds of braking modes were realized based on the same AMR with the parameters in The path lengths of AMR with different kinds of braking modes are illustrated in Regenerative braking powers with different kinds of braking modes are depicted in The wheel torques of AMR for three kinds of braking modes are displayed in From the above simulation results, it can be seen that the regenerative braking mode was beneficial to braking energy recovery. However, it led to longer braking distance, which reduces braking safety. The mechanical braking mode could shorten the braking distance but not recover the braking energy. In general, the hybrid braking mode had the advantages of the above two kinds of braking modes, i.e., maximizing the regenerative braking efficiency and advancing the braking safety.This case aimed to validate the AFTC algorithm for the AMR on a curved road; the hybrid braking mode was used. The AMR accelerated to 20 m/s and then started to brake after the 12th second. However, failure of the FL IWM occurred at the 10th second and failure of the RL IWM at the 12th second.The velocities of AMR under three kinds of conditions are depicted in The regenerative braking results are shown in The wheel torques of AMR with failure and with AFTC are illustrated in In this case, the braking failure condition of three IWMs was studied, further validating the effectiveness of the AFTC algorithm. The AMR accelerated to 20 m/s and then started to brake after the 12th second. However, the FL IWM had a failure at the 10th second, and the RL and RR IWMs had a braking failure at the 12th second.The path-tracking results of the AMR in this case are illustrated in The regenerative braking results of AMR are shown in The wheel torques of AMR under the failure condition and the AFTC condition are displayed in A chassis control framework was designed for an AMR. To address the braking failure of IWMs, an AFTC algorithm was studied by redistributing the braking torques of normal IWMs and four EMBs. Torque redistribution was carried out based on the WLS method. Three simulation cases were conducted to evaluate the feasibility and effectiveness of the proposed control algorithms. The simulation results indicate that the hybrid braking mode can help AMR recover the braking energy and advance braking safety. Moreover, the AFTC algorithm can deal with the braking failure of IWMs and realize braking energy recovery at the same time.The hybrid conditions of IWM braking failure and EMB braking failure will be studied in future work.


This EH/sodium carbonate/sodium bicarbonate (CBS) solution system can break down large aggregates of PVA molecules into small ones and promote the uniform distribution of EH in the solution, resulting in the improved stability of crosslinked PVA nanofibers. We firstly report that the uniform dispersion of crosslinking agents in the electrospinning solution plays a vital role in improving the stability of spinning solutions and the water resistance of crosslinked PVA nanofibers by comparing crosslinking performances between water-based epoxy and conventional water-based blocked isocyanate (BI). This work could open up a novel strategy and green approach for the stabilization of water-based nanofibers.With the ever-growing concern about environmental conservation, green production and water-based nanofibers have attracted more and more interest from both academic and industrial fields; nevertheless, the stabilization process of water-based nanofibers is primarily relying on the application of organic solvent-based crosslinking agents. In this work, we develop a green approach to fabricate water-resistant polyvinyl alcohol (PVA) nanofibers by using a water-based epoxy compound, N In the past few decades, electrospinning has become a prevalent method for preparing nanofibrous materials because of its ease of manufacturing, high efficiency and multiple functions. Attributed to their high volume-to-length ratio, large specific surface area, small pore size and high porosity, electrospun nanofibers have found applications in a wide range of fields, such as air filtration , water tPVA has many outstanding properties, e.g., good adhesion, oil resistance, degradability and biocompatibility, and as a result, it has been used for various applications such as electronic product packaging film , clothin1, N6-bis(oxiran-2-ylmethyl) hexane-1,6-diamine (EH) was employed to crosslink PVA nanofibers, which was uniformly distributed in the spinning solution and nanofibers, and the produced nanofibers obtained stable crosslinked structure after heat treatment. The influences of processing conditions, e.g., solution homogeneity, heating temperature and time and addition of sodium carbonate/sodium bicarbonate (denoted as CBS) on the crosslinking efficiency have been studied. The crosslinking agent EH distributed uniformly within the nanofibers and produced highly stabilized PVA nanofibers. For comparison, water-based blocked isocyanate (BI) was unevenly distributed in the PVA nanofibers resulting in the relatively low water resistance of PVA nanofibers.In this research, we developed an environmentally friendly approach to crosslink PVA nanofibers with excellent water resistance, revealing the importance of homogeneous dispersion of crosslinking agents in PVA nanofibers on improving the fiber stability. The water-soluble epoxy compound N1, N6-bis(oxiran-2-ylmethyl) hexane-1,6-diamine) (35% solid content) was purchased from Shaoxing Oucheng Chemical  Co., Ltd. Water-based blocked isocyanate (35% solid content) was purchased from Guangzhou Yele New Material  Co., Ltd. Sodium carbonate and sodium bicarbonate (CBS) were obtained from Sinopharm Chemical Reagent  Co., Ltd. All these reagents were of analytical grade. Ultrapure water was used throughout the experiments.PVA  was obtained from Aladdin Reagent  Co., Ltd. Epoxy crosslinking agent EH  with a heating/cooling rate of 20 °C/min in the nitrogen atmosphere with temperature range between 30 °C and 800 °C. The stability of the spinning solution was measured by a stability analyzer  at 25 °C with a scan frequency of 1 time/hour. The hydrodynamic diameter distribution was determined by a Litesizer 500  at 25 °C.The morphology of nanofibers was observed by field emission scanning electron microscopy . The elements in the fibers were analyzed by energy disperse spectroscopy (EDS) connected to FE-SEM (FEI Scios 2 HiVac). XPS analysis was carried out on Smartlab SE , and wide spectra in the range of 0–1100 eV and narrow spectra at high resolution for all elements were recorded. FTIR spectra of nanofiber membranes were recorded by a FTIR spectrometer  at room temperature. The crystallization of nanofibers was investigated via an X-ray diffractometer  with Cu K2 and dried in a vacuum oven at 60 °C for 24 h to ensure complete drying. The dried nanofiber membranes (~0.03 g in weight) were immersed in 20 mL water at 25 °C for 120 min. After incubation, these samples were taken out and dried in an oven at 60 °C for 6 h. The weight loss of samples  was calculated using Equation (1)i and wf are the initial and final weights of samples, respectively. All the experiments were carried out in triplicate and their average weight loss was recorded.The nanofiber membranes were cut into a square of 4 cmPVA nanofibers without heat treatment dissolved in water immediately. After heating at 160 °C for 10 min, the morphology of PVA nanofibers did not change significantly, as shown in Both the PVA aqueous solution and EH solution had acidic pH; however, it was reported that epoxy groups had high reaction rates with the hydroxyl group at alkaline conditions . Therefo−1 was assigned to the stretching vibration of carbonyl from the acetate groups present in the partially hydrolyzed PVA. There was a strong absorption peak at 1400–1480 cm−1 corresponding to C–N in the spectra of PVA/EH and PVA/EH/CBS nanofibers, and corresponding to C–N belonging to epoxy crosslinker EH, which proved crosslinker EH had been introduced into PVA nanofibers. In the PVA/EH/CBS nanofiber spectrum, there was a strong absorption peak at 1110–1190 cm−1 corresponding to C–O–C, which indicated that the etherification reaction between the epoxy group and the hydroxyl group occurred in PVA/EH/CBS nanofiber [The FTIR spectra of PVA, PVA/EH and PVA/EH/CBS nanofibers are shown in anofiber .3, respectively, and three new crystallization peaks at 56.21°, 65.97° and 75.05°, corresponding to the diffraction planes of (004), (301) and (222) of Na2CO3, respectively, which came from the precipitated Na2CO3 and NaHCO3 crystals in PVA nanofibers. The crystal structure of nanofibers was studied by XRD as shown in The TGA results in It was found that the temperature and time of heat treatment had obvious influences on the crosslinking reaction between epoxy and hydroxyl groups. The rising temperature and prolonged treatment both decreased the weight loss of PVA/EH/CBS nanofibers after being immersed in water, revealing an improved crosslinking degree of PVA nanofibers as shown in 2CO3/NaHCO3 molecular ratio was set as 3:2. The prepared nanofibers with different EH contents were treated at 160 °C for 10 min, and they had smaller weight loss in water with the growing EH content, as expected  is the average value of backscattering light intensities at a height of h, Si−1(h) is the backscattering light intensity of the previous scan and H is the height of sample in the glass cylinder sample bottle. In general, the TSI value of a stable solution is not affected by the rest time. The stability of solutions is also investigated by monitoring the changes in transmission (T) and backscatter (BS) signals of the solutions as shown in 12H24O2N2 and the molecular formula of BI was C22H34O6N4. The EDS mapping results in The distribution of PVA and crosslinking agents in the nanofibers was investigated by EDS and XPS. The molecular formula of EH was CXPS spectra of C1s and O1s of PVA/EH/CBS nanofibers are provided in Combing the particle size results and XPS results of nanofibers, it seems reasonable to postulate that the homogeneous distribution of EH in the solution breaks down PVA coil aggregates, and as a result, EH distributed uniformly within the nanofibers which enabled hydroxyl and epoxy groups to have a large chance to contact for esterification reaction as shown in Water-soluble epoxy crosslinking agent EH was applied to stabilize electrospun PVA nanofibers. The addition of CBS significantly improved the crosslinking reaction. When the heating temperature was 160 °C, the water resistance of the crosslinked PVA nanofibers reached the best result after heat treatment for 10 min. FTIR spectroscopy confirmed that the hydroxyl groups of PVA and epoxy groups of EH formed chemical crosslinks. The particle size results showed that the particle size of the PVA molecule chains could be effectively reduced from 8335.2 nm to 467.2 nm and contribute to the formation of stable electrospinning solutions. The use of an epoxy EH/CBS system that uniformly disperses in PVA solutions can significantly improve the crosslinking degree and the water resistance of PVA nanofibers. For comparison, water-based blocked isocyanate was applied to crosslink PVA nanofibers, with lower water stability due to the phase separation of PVA/BI dispersion. This work provides a new strategy to develop high efficiency water-based crosslinking agents for stabilizing electrospun nanofibers.


Nanostructured materials and systems find various applications in biomedical fields. Hybrid organo–inorganic nanomaterials are intensively studied in a wide range of areas, from visualization to drug delivery or tissue engineering. One of the recent trends in material science is biomimetic approaches toward the synthesis or modification of functional nanosystems. Here, we describe an approach toward multifunctional nanomaterials through the biomimetic polymerization of dopamine derivatives. Magnetite nanoparticles were modified with a combination of dopamine conjugates to give multifunctional magneto-fluorescent nanocomposites in one synthetic step. The obtained material showed excellent biocompatibility at concentrations up to 200  Nanomaterials and nanostructured systems emerged in the biomedical field of study in the middle of the last century and still attract a lot of attention due to their unique properties ,2,3,4. SFifteen years ago, analysis of a mussel’s surface attachment mechanisms revealed that it is mediated through the adhesive foot protein, Mefp-5 (Mytilus edulis foot protein-5) rich with 3,4-dihydroxy-L-phenylalanine (DOPA) and lysine residues that bear catechol and amino groups, respectively . This diFurther development of the concept shifted the attention from commercially available dopamine to dopamine derivatives and other polyphenols for surface modification. In this approach, firstly, functional monomers are synthesized by conventional organic synthesis, and then the coating is applied on the substrate’s surface. Such a two-step procedure allows separation of the `’organic” and the `’colloidal” stages to simplify the characterization and purification of the products and increase the ratio between the applied and successfully immobilized motifs. One of the benefits of such an approach is also in its versatility and opportunity to immobilize several functional groups simultaneously by deposition of a mixture of several dopamine derivatives, but this possibility has only limited representation in the scientific literature ,24,25.Here, we present a biomimetic approach to the creation of multifunctional hybrid systems with magneto-optical properties based on the application of dopamine derivatives. Composites were synthesized by biomimetic polydopamine formation using biocompatible magnetite nanoparticles and two organic precursors with carboxylic and fluorescent residues. Application of two different dopamine derivatives in one process allowed us to introduce a carboxyl group and fluorophore in one synthetic step in a controlled manner and to create an organo–inorganic composite material for biomedical applications. Physicochemical properties, cytotoxicity and in vivo behavior were described.Magnetite nanoparticles (MNPs) that were chosen as a magnetic component of the system were obtained by the coprecipitation of a non-stochiometric mixture of Fe(II) and Fe(III) chlorides with ammonium hydroxide, brought to pH 7 and ultrasonically threatened as was described in our earlier works ,27,28. Td +29 mV d. As wasd +29 mV e 26,29],29∘ corrd +29 mV f.Modification of the MNPs was performed via biomimetic polymerization of dopamine derivatives (DDs). Two dopamine derivatives were used in this study, namely, 4-[[2-ethyl]amino]-4-oxobutanoic acid (DopSuc) and N-Cyanine-7-3,4-dihydroxyphenethylamine (DopCy7) which were synthesized by acylation of dopamine via conventional organic synthetic protocols see a. The efInvestigation of the DopSucCy7@Ferria by Fourier-transform infrared spectroscopy (FTIR) was carried out to characterize the organo–inorganic composites and confirm the modification of MNPs. The results are presented in de group . A weak material .Biocompatibility of the synthesized material was accessed for in vitro and in vivo applications. Due to the presence of carboxylic groups on the surface of the composite, it could be modified via conventional biochemical approaches, for example by carbodiimide chemistry. To evaluate this possibility, the particles were modified with trastuzumab, a well-known antibody against human epidermal growth factor receptor 2 (HER2) which is a specific cancer marker   technique which is described in detail elsewhere . Brieflyintegers a. At theintegers b.For evaluation of the composite biodistribution profile, mice were injected with 300 ectively c,d. The Here, we described the potency of the biomimetic surface modification strategy with dopamine derivatives for the production of bio-applicable multifunctional systems. This strategy is based on oxidative polymerization of dopamine and dopamine derivatives under mild conditions that result in in situ formation of organic coatings on a substrate. While the exact mechanism of the occurring process remains unknown and under intense investigation, this approach can be widely used for the creation of various nanostructured materials and systems. It is accepted that the mechanism of dopamine polymerization involves its oxidation by dissolved oxygen into quinone intermediates that undergo intramolecular cyclization resulting in 5,6-dihydroxyindole ,36. ThesIn our study, we selected two compounds, DopSuc and DopCy7, with different roles. The first one was selected as a synthetically available compound to introduce usable carboxyl groups to the surface of inorganic material. DopCy7 derivative was taken as a model compound due to its spectral characteristic. Its excitation and emission peaks lie in the near-infrared region in the so-called near-infrared window of tissue transparency. This molecule was designed for in vivo imaging in biological experiments, and its conjugation to magnetic nanoparticles potentially led to the production of bifunctional magneto-optical diagnostic agents by biomimetic modification process.It was shown earlier that the effectiveness of the whole process of PDA formation is dependent on the rates of eumelanin- and melanin-like polymers formation, their nucleation, and deposition of the substrate’s surface ,19. A hi surface . In addiBiomimetic polymerization of DopSuc and DopCy7 from their mixture led to the formation of a hybrid bifunctional layer with carboxylic groups and fluorescent motifs at the same time. This strategy could potentially be used for the introduction of more than two functional groups simultaneously and will be investigated in detail in our further works.The initial purpose of the study was to evaluate the potency of the biomimetic surface modification strategy for the creation of bio-applicable systems. One of the main criteria for the bioapplicability of materials is their bioactivity and toxicity. The synthesized composite material was based on an iron oxide core, namely magnetite. Magnetite is known for its good biocompatibility and can be easily metabolized in the body. Moreover, it is the only magnetic material approved for parenteral administration . The MNP degrees ,41.Selectivity of the antibody-conjugated nanoparticles toward a corresponding antigen was evaluated on HER2-expressing and nonexpressing cell lines BT-474 and EMT6/P respectively. It was found that at concentrations up to 50 hed data .In vivo behavior of nanomaterials and nanosystems was mainly determined by their circulation time in the bloodstream and biodistribution profile after retro-orbital injection. Injection into the retroorbital sinus  is actively used in various areas of in vivo research for intravenous injection in mice along with injection into the lateral tail vein ,44. In oThe biodistribution profile from both optical visualization and MPQ studies showed that particles are mainly located in the liver and spleen—organs that play a major role in nanoparticle clearance. It was described earlier that Kupffer cells in the liver and splenic macrophages react rapidly to the protein corona that is formed on injected nanoparticles unless the surface of the letter is protected from protein adsorption. Thus, the observed biodistribution correlates with the literature data ,50.Chemicals: All reagents and solvents were obtained or distilled according to standard procedures. Sodium phosphate dibasic dihydrate, Tris base, sulfo-N-hydroxysuccinimide (sulfo-NHS), N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC), sodium phosphate monobasic monohydrate, dimethyl sulfoxide (DMSO), pyridine, dopamine hydrochloride, triethylamine and succinic anhydride were obtained from Sigma Aldrich . Cyanine7-NHS activated ester was obtained from Lumiprobe . HER2 antibodies (Trastuzumab) were obtained from Genentech .Cell culture: Mouse mammary cell line EMT6/P and a human mammary cell line with a stable expression of HER2 receptor BT-474 were cultured in DMEM medium  supplemented with 10% fetal bovine serum , penicillin/streptomycin , and 2 mM L-glutamine . Cells were incubated under a humidified atmosphere with 5% COFerria):Synthesis of magnetite nanoparticles ethyl]amino]-4-oxobutanoic acid (DopSuc): To a solution of 1.89 g, (10 mmol) dopamine hydrochloride in 20 mL of pyridine 1.05 g (10.5 mmol) of succinic anhydride was added under nitrogen atmosphere. The solution was stirred at room temperature overnight. After that, the mixture was evaporated to 5 mL, mixed with 0.1 M HCl, and extracted with ethylacetate (4 × 20 mL). The organic phase was washed with 0.1 M HCl, water, and brine, dried over sodium sulfate, and evaporated. The residue was crystallized from isopropanol to give a white solid. , mp 128–129 For N-Cyanine-7-3,4-dihydroxyphenethylamine (DopCy7): 19 mg (0.1 mmol) of dopamine hydrochloride and 14 Biomimetic modification of MNPs: For PDA layer formation experiments, 100 Conjugation with HER2 antibodies: HER2 antibodies were conjugated with the composite by carbodiimide strategy; 1 mg of the material in 100 Efficiency of antibodies conjugation: The number of antibodies conjugated to the hybrid material was measured by the BCA protein assay kit . A total of 50 R is the radius of nanoparticles (20 or 72 nm), and The approximate density of antibody conjugation (D) was calculated by Equation :(2)D=NAbCytotoxicity: The cytotoxicity of NPs was investigated using the MTT test. EMT6/P and BT-474 cells were plated onto a 96-well plate at 2.5 × 102 atmosphere at 37 Flow cytometry: For flow cytometry, Cyanine5-labeled nanoparticle conjugates were prepared by mixing 100 g, resuspended in 100 To determine Cy5-Ab-DopSucCy7@Ferria cell-binding efficiency, the harvested EMT6/P and BT-474 cells were washed with PBS, resuspended in 300 Circulation half-life studies: Female BALB/c mice of 24–26 g weight were used for in vivo studies. Some 300 Biodistribution studies: In vivo and ex vivo fluorescent analysis of biodistribution was performed on a LumoTrace FLUO bioimaging system  using For the MPQ analysis of magnetic-particle biodistribution, the organs and tissues were extracted 1 h after nanoparticle injection and placed in the measuring coil of the MPQ detector. The integral magnetic signal from each organ was normalized to the total signal from all measured organs. Such data were then averaged between three different animals.Here, we described the application of the biomimetic dopamine polymerization approach for the creation of a multifunctional magnetic fluorescent composite in a single step from a mixture of dopamine derivatives. Magnetic nanoparticles were modified with dopamine conjugates under mild conditions, leading to multifunctional organo–inorganic composites. The synthesized material showed excellent biocompatibility and a typical biodistribution profile. The contingency of the modification process and bioactivity of the synthesized materials proved the potency of the proposed strategy, which will be further evaluated in upcoming works.


Arteriovenous fistulas (AVFs) in the craniocervical junction (CCJ) region are a rare occurrence with special clinical manifestations. This study retrospectively reviewed patients with CCJ AVFs treated at our neurosurgical center, aiming to enhance the understanding of CCJ AVFs.n = 20) and patients with CCJ AVF without spinal arterial feeders (n = 93). Clinical presentation, angiographic characteristics, intraoperative findings, and treatment outcomes were analyzed.A total of 113 patients with CCJ AVFs treated at our neurosurgical center between January 2013 and December 2020 were enrolled. They were grouped as patients with CCJ AVFs with spinal arterial feeders (p = 0.001). Subarachnoid hemorrhage (SAH) was the most common clinical presentation, especially in the group with spinal arterial feeders (p < 0.001). There were significant differences in AVF type, fistula location, and direction of the venous drainage between the two groups (p < 0.001). Intervention embolization combined with microsurgery was more common in treating AVFs with spinal arterial feeders (p = 0.006). Spinal arterial feeders did not affect the outcome (p = 0.275).The patients’ median age was 55 years (IQR 47.5–62 years). The proportion of males in the group without spinal arterial feeders was significantly higher (SAH was the most common presentation of CCJ AVFs in this study. Microsurgery and interventional embolization were optional treatment strategies. The angioarchitecture of CCJ AVFs was essential for selecting treatment strategies. The craniocervical junction (CCJ), which includes the occipital bone and condyles, the atlas, and the axis, has unique and complex vascular and bone anatomy , 2. ArteThe study was approved by the medical ethics committee of our hospital. Informed consent was obtained from all patients. The data supporting the findings of this study were available from the corresponding author upon reasonable request.This retrospective study included 113 patients with CCJ AVFs who were treated at our institution between January 2013 and December 2020. We collected patients’ clinical and radiological data, including baseline patient characteristics , treatment strategies, outcomes . SAH was the most common clinical presentation, especially in the group with spinal arterial feeders (p < 0.001). For patients with SAH, 63 (96.9%) patients presented with mild neurological dysfunction (Hunt and Hess grade 1–3). There was no significant difference in mRS scores between the two groups before the operation (p = 0.313).The clinical characteristics data of two groups of patients are listed in p < 0.001). For CCJ AVFs with spinal arterial feeders, the most common CCJ AVF type was RAVF, with 15 (62.5%) fistulas. In contrast, there was no RAVF or PAVF in CCJ AVFs without spinal arterial feeders.As shown in p < 0.001).On the side of the lesion, CCJ AVFs with spinal arterial feeders were equally distributed on the left and right, while CCJ AVFs without spinal arterial feeders were more distributed on the left, and three (3.1%) fistulas were fed by both vertebral arteries. CCJ AVFs with spinal arterial feeders showed no tendency in fistula location, while most of the CCJ AVFs without spinal arterial feeders were located at the C-1 level, with 79 (80.6%) fistulas, and 6 (6.1%) fistulas were located at the level of the foramen magnum. There were differences in the location of the fistula between the two groups . Aneurysmal structures occurred at 32 (26.2%) fistulas, and CCJ AVFs with spinal arterial feeders seemed more likely to form aneurysmal structures (p < 0.001). Varices of draining veins occurred at 81 (66.4%) fistulas.There were 109 (89.3%) fistulas with intradural drainage and 15 (12.3%) fistulas with epidural drainage. The draining veins of CCJ AVFs without spinal arterial feeders were more inclined to drain to intradural, especially descending intradural (p = 0.009). Microsurgery was more common in the treatment of CCJ AVFs without spinal arterial feeders (p = 0.030) (p = 0.006). All patients were evaluated by angiography or intraoperative indocyanine green angiography for AVFs disconnected.Treatment and outcome information is listed in = 0.030) , and intThe incidence of postoperative complications was 18.0%, and there was no significant difference between the two groups. The most common complications were infection, and all infected patients recovered well. Cerebrospinal fluid (CSF) leak occurred in three (2.5%) patients. Spinal infarction occurred in one (0.8%) patient; during microsurgery, AVFs ruptured and bled again. After strict hemostasis, spinal cord infarction occurred, and the patient's lower limb muscle strength decreased. Cerebral infarction occurred in one (0.8%) patient; this patient developed cerebral vasospasm and cerebral infarction on the 8th day after microsurgery, later underwent decompressive craniectomy, and died after 1 month. In one (0.8%) patient, the VA was occluded on the side of the lesion due to treatment requirements, and the patient suffered from intermittent dizziness after occlusion. Cranial nerve paralysis occurred in one (0.8%) patient who presented with numbness of the tongue root.p < 0.001). After treatment, 92 (81.4%) patients had good outcomes (mRS scores 0–2). Spinal arterial feeders did not affect the outcome (p = 0.275).The median mRS scores of pretreatment and post-treatment were 2 and 1. The mRS scores improved after treatment , and descending intradural drainage  were significantly associated with SAH.As shown in In the previous study, we carefully explored the classification and treatment strategies of CCJ AVFs with spinal arterial feeders using our single-center data . In the In the previous systematic review, CCJ AVFs often occurred in middle age, and the male-to-female ratio was about 3:1 , 10. In Previous studies have shown that VHM and SAH are the most common clinical presentation of CCJ AVF patients , 11, 12.According to the experience of previous studies, microsurgery and interventional embolization were optional treatment strategies for CCJ AVFs. Nevertheless, like AVFs in other parts of the spinal cord, microsurgery was favored for CCJ AVFs, and it usually resulted in better outcomes , 16–19. Simple microsurgical treatment was more appropriate for lesions without spinal feeders and those mainly located in the dorsal or lateral position. According to the dorsal or lateral position of the lesion, the posterior median approach and the far lateral approach were selected. If the lesion only had a single draining vein, we preferred to electrocoagulate and disconnect the draining vein. In treating AVF with multiple arterial feeders and drainage varices, test occlusion and intraoperative ICG fluorescence angiography were necessary to determine the location of the shunt and abnormal blood vessels , 20, 21.I2: 0%, p < 0.001)  . Similar< 0.001) ; yet, isp = 0.016), which might be related to the long microsurgery time due to the complex angioarchitecture. Notably, in the group with spinal arterial feeders, no patients had infarction-related complications, which might be related to more patients in this group undergoing both interventional embolization and microsurgery. In a recent multicenter study, the complications’ overall incidence was 26% (25/97). Ischemic complications were the most common complications, and the associated risk factors were interventional embolization  and spinal arterial feeders  , and the most common complications were infections. The incidence of intracranial infection was higher in the group with spinal arterial feeders (= 0.045) , 22. In /122, andp = 0.043) and hemorrhagic presentation (p = 0.002) were significant predictors of better outcomes (p = 0.0389) in patients with DAVF (p = 0.001) and complications , while spinal arterial feeders was not a significant factor (p = 0.64)  . In the The present study also has several limitations. First, this was a retrospective single-center study. The experience of our center may not necessarily apply to other centers. Second, this study mainly used mRS scores for outcome ranks, which may not be sufficient to reflect subtle changes. Third, incorrect mRS scores also may occur, especially during telephone interviews. Thus, prospective multicenter studies should be conducted to further confirm these findings and guide clinical treatment.This study divided CCJ AVFs into two groups according to whether they were with or without spinal arterial feeders. SAH was the most common presentation of CCJ AVFs. Microsurgery and interventional embolization were optional treatment strategies. The angioarchitecture of CCJ AVF was essential to our choice of treatment strategies. As microsurgery was often safer and more reliable, it could be the first treatment choice.


Human herpesvirus 8 (HHV-8) or Kaposi sarcoma herpesvirus is the cause of Kaposi sarcoma (KS), the most prevalent cancer related to acquired immune deficiency syndrome. About 90% of the time, KS is accompanied by cutaneous lesions; however, systemic illness can develop without cutaneous involvement. Today’s highly active antiretroviral therapy (HAART) era has seen a decrease in the prevalence of KS. In immunocompromised individuals, it may be challenging to differentiate between pneumonia and the clinical characteristics of pulmonary KS, which might make diagnosis more challenging. HAART is the first-line therapy for KS, and its usage has reduced the incidence of KS. Depending on how severe the illness is, systemic chemotherapy could be helpful. We report the case of a young man who presented with pulmonary symptoms in the presence of a pharyngeal mass and was later found to have bilateral pulmonary metastasis. Interestingly, this diagnosis was made in the absence of classic cutaneous lesions. The patient was counseled for quality of life with medication and intervention compliance, and a consultation with an oncologist was set up. Moritz Kaposi, a Hungarian physician, originally characterized Kaposi sarcoma (KS) in its typical form in 1872 as an angio-proliferative disease . A vascuAccording to the WHO GLOBOCAN data for 2018, there were 19,902 KS fatalities  and 41,799 new KS diagnoses  [A 31-year-old African American male with a history of HIV diagnosed one month prior with a current CD4 count 28 and viral load 44 came to our medical institution complaining of escalating exhaustion, lethargy, diarrhea, nausea, vomiting, and dyspnea on exertion for four days. He also had a moderate cough and yellowish sputum, but he denied experiencing any orthopnea, paroxysmal nocturnal dyspnea, chest discomfort, fever, shortness of breath, dizziness, syncope, recent travel, or any ill contacts.Pneumocystis jirovecii pneumonia, oropharyngeal and esophageal Candida, and was advised to get tested for HIV and start definitive management. However, the patient refused despite counseling stating he had tested negative in the past and declined the consent for HIV testing; hence, he was discharged undiagnosed.He was hospitalized six months earlier due to fever, an ineffective cough, increasing dyspnea with exertion, and excessive perspiration but no concomitant hemoptysis or pleuritic discomfort. He had chronic complaints of throat irritation, a scratchy sensation on his tongue, and slight difficulty while swallowing food. However, he denied associated dysphagia or odynophagia. He was treated for He smoked 10 cigarettes per day but quit one year ago. He denied the use of alcohol or other illicit substances. He endorsed being heterosexual and engaging in regular unprotected intercourse, including anal intercourse.Candida infection. A mass projecting from the posterior pharynx was also visualized, associated with difficulty in swallowing and regurgitation along with submandibular adenopathy. A review of other systems revealed no abnormality.During this admission, he was noted to be emaciated and chronically ill-appearing with temporal wasting. He was lethargic, febrile, and tachycardic, with a heart rate of 124 beats/minute. He also tested positive for coronavirus disease 2019 (COVID-19) and was hypoxic with an oxygen saturation of 77% on room air. He had bilateral coarse crackles with bilateral pedal edema. His oral examination revealed white plaques in the throat and buccal cavity, indicative of a His labs were significant for hemoglobin of 8.3 g/dl and hematocrit of 25.2%, with features of malnutrition . The chest X-ray revealed bilateral extensive patchy airspace opacities involving all lung fields, primarily involving bilateral lung bases, and interval increase compared to a prior study that was suggestive of an atypical infectious process and further need for malignancy evaluation  ruled out pulmonary embolism but revealed several bilateral lung nodules with ground-glass opacities concerning for metastases. Hence, a chest CT was done that indicated innumerable, bilateral, randomly distributed lung nodules with multiple patchy and confluent areas of ground-glass opacities, indicating a possible disseminated fungal infection with septic emboli, lymphoma, or metastatic disease Figure . HoweverA CT of the abdomen further demonstrated upper abdominal and mesenteric adenopathy, with the largest measuring 3 cm, and extensive retroperitoneal adenopathy, with the largest measuring 2.2 cm in the left para-aortic region Figure .He was started empirically for possible community-acquired bacterial pneumonia with ceftriaxone 2 g daily and azithromycin 500 mg once a day, as well as empiric treatment for pneumocystis with trimethoprim-sulfamethoxazole 20 mg/kg/day divided every eight hours and caspofungin 50 mg every 24 hours. Due to oxygen saturation being less than 90%, 40 mg of daily oral prednisone was initiated for five days with a taper and intravenous (IV) fluconazole 400 mg once daily on day one and then transitioned to 200 mg IV once daily for 14 days for oral candidiasis. Bictegravir-emtricitabine-tenofovir 50-200-25 mg was also started after the patient consented to the treatment.The large epiglottic mass was causing increased respiratory distress secondary to airway obstruction leading to increased oxygen requirement. An elective tracheostomy was done to prevent respiratory decompensation and percutaneous gastrostomy for nutritional support.A biopsy was done of the retropharyngeal mass, which was positive for KS. Neoplastic spindle cells were positive for vascular markers CD31 and ERG, and HHV-8, findings consistent with KS. No evidence of lymphoma was found Figure .For further management, consultation with the oncology department was done for possible radiation therapy to shrink the tumor along with chemotherapy for metastasis to the lungs. In addition, per discussion with the oncology department, the patient was scheduled for a left retroperitoneal lymph node biopsy to aid the staging of the KS. He was counseled regarding the quality of life with the medication and the benefits of chemotherapy and radiotherapy. However, the patient refused any further intervention and refused to undergo chemotherapy and radiotherapy. Because he had decision-making capacities, his autonomy was respected, and he was discharged from the hospital with HAART (bictegravir-emtricitabine-tenofovir) medication only.Trends of KS and HIVDr. Moritz Kaposi originally described KS in 1872 .Based on the clinical circumstances in which it develops, KS is classified into four types, namely, classic, endemic, iatrogenic, and AIDS-related Table .PathologyThe course of KS lesions has been defined as occurring through three primary pathologic stages ,12. ThinTreatmentThe majority of the treatment to date has been palliative. The goal of therapy for AIDS-related KS includes symptom relief, KS progression prevention, cosmesis improvement, and reduction of related edema, organ compromise, and psychological stress . Liquid Our case highlights the atypical visceral presentation without any cutaneous manifestation of KS in a non-compliant patient diagnosed with HIV. Non-adherence to HAART in patients with HIV may lead to multiple opportunistic presentations, including KS, that may disseminate in different locations, particularly in the airway leading to respiratory failure due to airway occlusion. Therefore, clinicians should not fixate on incidental COVID-19 findings in patients who are non-adherent to HIV medications. In addition, high suspicion is required despite the absence of cutaneous manifestation of KS in HIV patients with low CD4 count in the presence of compromised immune response.