Comparing efficacy and safety of first-line treatment of metastatic renal cell carcinoma: A Bayesian network meta-regression analysis.

Background: This Bayesian network meta-regression analysis provides a head-to-head comparison of first-line therapeutic immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) combinations for metastatic renal cell carcinoma (mRCC) using median follow-up time as covariate. Methods: We searched Six databases for a comprehensive analysis of randomised clinical trials (RCTs). Comparing progression free survival (PFS) and overall survival (OS) of different interventions at the same time node by Bayesian network meta-analysis. Bayesian network meta-regression analysis was performed on objective response rate (ORR), adverse events (AEs) (grade ≥ 3) and the hazard ratios (HR) associated with PFS and OS, with the median follow-up time as the covariate. Results: Eventually a total of 22 RCTs reporting 11,090 patients with 19 interventions. Lenvatinib plus Pembrolizumab (LenPem) shows dominance of PFS, and Pembrolizumab plus Axitinib (PemAxi) shows superiority in OS at each time point. After meta-regression analysis, for HRs of PFS, LenPem shows advantages; for HRs of OS, PemAxi shows superiority; For ORR, LenPem provides better results. For AEs (grade ≥ 3), Atezolizumab plus Bevacizumab (AtezoBev) is better. Conclusion: Considering the lower toxicity and the higher quality of life, PemAxi should be recommended as the optimal therapy in treating mRCC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD4202236775.

Strong Anchoring of Hydrogels through Superwetting-Assisted High-Density Interfacial Grafting.

Strong adhesion of hydrogels on solids plays an important role in stable working for various practical applications. However, current hydrogel adhesion suffers from poor interfacial bonding with solid surfaces. Here, we propose a general superwetting-assisted interfacial polymerization (SAIP) strategy to robustly anchor hydrogels onto solids by forming high-density interfacial covalent bonds. The key of our strategy is to make the initiator fully contact solid surfaces via a superwetting way for enhancing the interfacial grafting efficiency. The designed anchored hydrogels show strong bulk failure with a high breaking strength of ≈1.37 MPa, different from weak interfacial failure that occurs in traditional strategies. The strong interfacial adhesion greatly enhances the stability of hydrogels against swelling destruction. This work opens up new inspirations for designing strongly anchored hydrogels from an interfacial chemistry perspective.

One-pot method for preparation of capsaicin-containing double-network hydrogels for marine antifouling.

Marine biofouling which interferes with normal marine operation and also causes huge economic loss has become a worldwide problem. With the development of society, there is an urgent need to develop non-toxic and efficient anti-fouling strategies. Capsaicin is an environmentally friendly antifouling agent, but controlling the stable release of capsaicin from the coating is still a challenge to be solved. To achieve long-lasting antifouling property, in this work, we incorporate a derivative of capsaicin N-(4-hydroxy-3-methoxybenzyl)acrylamide (HMBA) to prepare double network (DN) hydrogels and make HMBA a part of the polymer network. Polyvinyl alcohol (PVA) has good hydrophilicity, and as a soft and ductile network, acrylamide (AM) and HMBA can polymerize to generate a rigid and brittle network. By adjusting the content of HMBA in the DN hydrogels, we can obtain a PVA-PAHX hydrogel with high mechanical strength, low swelling rate, and excellent antifouling effect, which provides a feasible way for the practical application of a hydrogel coating in long-term marine antifouling.

Investigation of organic impurity and its occurrence in industrial waste salt produced by physicochemical process.

Industrial waste salt is classified as hazardous waste to the environment. The organic impurity and its occurrence in industrial waste salt affect the salt resource utilization. In this paper, composition quantitative analysis, XRD, TG-DSC, SEM/FIB-SEM coupled with EDS, FTIR, XPS and GC-Ms were chosen to investigate the organic impurity and its occurrence in industrial waste salt. The organic impurities owe small proportion (1.77%) in the specimen and exhibit weak thermal stability within the temperature of 600°C. A clear definition of organic impurity, including 11 kinds of organic compounds, including aldehyde, benzene and its derivatives etc., were detected in the industrial waste salt. These organic impurities, owing (C-O/C-O-C, C-OH/C = O, C-C/CHx/C = C etc.)-containing function group substance, are mainly distributed both on the surface and inside of the salt particles. Meanwhile, the organic substance may combine with metal cations (Ni2+, Mg2+, Cu2+ etc.) through functional groups, such as hydroxide, carbonyl etc., which increases its stability in the industrial waste salt. These findings provide comprehensive information for the resource utilization of industrial waste salt from chemical industry etc.

Marine antifouling coatings with surface topographies triggered by phase segregation.

Marine biofouling is a ubiquitous and longstanding challenge that causes both economic and environmental problems. To address this, several antifouling strategies have been proposed, such as the release of biocidal compounds or surface chemical/physical design. Here we report a coating with surface structures (chemical heterogeneity) triggered by phase segregation, which endues the good antifouling properties, alongside robust mechanical properties, low underwater oil adhesion, and excellent optical transparency. This is achieved by arranging the hydrophobic and hydrophilic components to control the assembly and phase separation under the cross-linking and localized swelling process. The structure designs are based on the poly(ethylene glycols) (PEG), zwitterions, and hydrophobic components, which may lower the entropic and enthalpic driving forces for the adsorption of the marine organisms. Our approach could provide an effective way of manufacturing novel coating with amphiphilic micro/nanodomains structure, particularly for the marine industry. And we also showed that the coatings were stable under different temperatures and shear environments. To illustrate the applicability of such a robust coating in marine biofouling, we demonstrated significantly reduced algal adhesion and barnacle attachment in the sea (p < 0.01). We envision that this work will provide great potential for the application in antifouling marine coatings.

Bioinspired Hydrogel-Polymer Hybrids with a Tough and Antifatigue Interface via One-Step Polymerization.

Hydrogel hybrids are one of the key factors in life activities and biomimetic science; however, their development and utilization are critically impeded by their inadequate adhesive strength and intricate process. In nature, barnacles can stick to a variety of solid surfaces firmly (adhesive strength above 300 kPa) using a hydrophobic interface, which inspires us to firmly combine hydrogels and polymers through introducing an adhesive layer. By spreading a hydrophobic liquid membrane directly, tough combination of a hydrogel and a polymer substrate could be achieved after one-step polymerization. The fracture energy of the hydrogel attached to the surface of polyvinyl chloride was up to 1200 J m-2 and the tensile strength reached 1.21 MPa. Furthermore, the adhesion samples with this method exhibit an antifatigue performance, having withstood large bends and twists. It should be pointed out that this approach can also be applied to a variety of complicated surfaces. This work may expand the application range of hydrogels and provides an inspiration for hydrogel adhesion.

Hydrophilic/Hydrophobic Heterogeneity Anti-Biofouling Hydrogels with Well-Regulated Rehydration.

Hydrogels, as a representative of soft and biocompatible materials, have been widely used in biosensors, biomedical devices, soft robotics, and the marine industry. However, the ir-recoverability of hydrogels after dehydration, which causes the loss of original mechanical, optical, and wetting properties, has severely restricted their practical applications. At present, this critical challenge of maintaining hydrogels' accurate character has attracted less attention. To address this, here we report a hydrogel based on synergistic effects to achieve both well-regulated rehydration and deswelling properties. The hydrogel after dehydration can quickly restore its original state both on the macro- and microscale. In addition, the hydrogel has excellent mechanical stability after several dehydration-rehydration cycles. All of these properties offer a possibility of water condition endurance and increase the service life. The robust property is attributed to the hydrophilic-hydrophobic and ionic interactions induced by the synergy of hydrophilic/oleophilic heteronetworks. Moreover, zwitterionic segments as hydrophilic network play a vital role in fabricating anti-biofouling hydrogels. The durable and reusable hydrogel may have promising applications for biomedical materials, flexible devices, and the marine industry.

Design of hierarchical comb hydrophilic polymer brush (HCHPB) surfaces inspired by fish mucus for anti-biofouling.

Anti-biofouling surfaces are of high importance owing to their crucial roles in biosensors and biomedical devices, especially in the marine industry. However, traditional anti-biofouling surfaces based on either the release of biocidal compounds or surface peeling will contaminate the environment. The outstanding performances of natural anti-biofouling surfaces motivate the development of new bioinspired antifouling surfaces. Herein, a universal strategy inspired by the special performance of fish skin mucus is proposed for rationally designing anti-biofouling surfaces using grafted hierarchical comb hydrophilic polymer brushes (HCHPBs) on plastics and elastomers. The results show that the plastic substrate surface grafted PAA (polyacrylic acid)-g-PEG (polyethylene glycol) (MW 2000, 6000, and 11 000 Da) exhibits excellent hydrophilic and underwater oleophobic properties, and also shows good performance in terms of lubricity and drag reduction in water, which can be attributed to the HCHPB and the nanostructure on plastic surfaces. In addition, the modified substrate shows superior and long-lasting anti-biofouling properties to resist the adhesion of algae compared to the initial substrate. This comprehensive investigation is of great importance to understand the physicochemical properties of hierarchical comb hydrophilic polymer brushes and the mechanism against the adhesion of marine microorganisms.

Thermodynamics and mechanics of stretch-induced crystallization in rubbers.

The aim of the present paper is to provide a quantitative prediction of the stretch-induced crystallization in natural rubber, the exclusive reason for its history-dependent thermomechanical features. A constitutive model based on a micromechanism inspired molecular chain approach is formulated within the context of the thermodynamic framework. The molecular configuration of the partially crystallized single chain is analyzed and calculated by means of some statistical mechanical methods. The random thermal oscillation of the crystal orientation, considered as a continuous random variable, is treated by means of a representative angle. The physical expression of the chain free energy is derived according to a two-step strategy by separating crystallization and stretching. This strategy ensures that the stretch-induced part of the thermodynamic crystallization force is null at the initial instant and allows, without any additional constraint, the formulation of a simple linear relationship for the crystallinity evolution law. The model contains very few physically interpretable material constants to simulate the complex mechanism: two chain-scale constants, one crystallinity kinetics constant, three thermodynamic constants related to the newly formed crystallites, and a function controlling the crystal orientation with respect to the chain. The model is used to discuss some important aspects of the micromechanism and the macroresponse under the equilibrium state and the nonequilibrium state involved during stretching and recovery, and continuous relaxation.

Hydrogel with Ultrafast Self-Healing Property Both in Air and Underwater.

Self-healing hydrogels have a great potential application in 3D printing, soft robotics, and tissue engineering. There have been a large number of successful strategies for developing hydrogels that exhibit rapid and autonomous recovery. However, developing a gel with an excellent self-healing performance within several seconds is still an enormous challenge. Here, an ultrafast self-healing hydrogel based on an agarose/PVA double network (DN) is presented. The gel utilizing a dynamic borate bond exhibits 100% cure in strength and elongation after healing for 10 s in air, and this hydrogel shows an excellent self-healing property underwater as well. In addition, the agarose/PVA DN hydrogel exhibits a smart self-healing property for an in situ priority recovery, ensuring that the shape and the function are the same as those of the original one. With the combination of self-healing properties, such a hydrogel could be applied to a board range of areas.

Designing Bioinspired Anti-Biofouling Surfaces based on a Superwettability Strategy.

Anti-biofouling surfaces are of high importance owing to their crucial roles in biosensors, biomedical devices, food processing, the marine industry, etc. However, traditional anti-biofouling surfaces based on either the release of biocidal compounds or surface chemical/physical design cannot satisfy the practical demands when meeting real-world complex conditions. The outstanding performances of natural anti-biofouling surfaces motivate the development of new bioinspired anti-biofouling surfaces. Herein, a novel strategy is proposed for rationally designing bioinspired anti-biofouling surfaces based on superwettability. By utilizing the trapped air cushions or liquid layers, Lotus leaf inspired superhydrophobic surfaces, fish scales inspired underwater superoleophobic surfaces, and Nepenthes pitcher plants inspired omniphobic slippery surfaces have been successfully designed as anti-biofouling surfaces to effectively resist proteins, bacteria, cells, and marine organisms. It is believed that these novel superwettability-based anti-biofouling surfaces will bring a new era to both biomedical technology and the marine industry, and will greatly benefit human health and daily life in the near future.

Interfacial Engineering of Hierarchically Porous NiTi/Hydrogels Nanocomposites with Exceptional Antibiofouling Surfaces.

Seamlessly bridging the hard and the soft, a strategy to fabricate hierarchically porous NiTi/hydrogels nanocomposites is reported. The nanocomposite surface can hold high-content water while keeping its hierarchical nanoscale topography, thus showing exceptional antibiofouling performance. This strategy will lead to antibiofouling alloy (e.g., NiTi)/hydrogel nanocomposites for improved stents and other blood-contacting implants and medical devices.

A robust double-network hydrogel with under sea water superoleophobicity fabricated via one-pot, one-step reaction.

A robust double-network (DN) hydrogel fabricated by a one-pot, one-step reaction is reported. The DN hydrogels not only have high mechanical strength and extremely low underwater oil adhesion, but also exhibit excellent characteristics, such as short processing duration, moderate swelling and free shaping. The DN hydrogel is durable in artificial sea water, and its mechanical property can be easily adjusted by adjusting the crosslinking agent concentration. In addition, because a large number of free hydroxyl groups remain in their networks, the mechanical property of the hydrogel can be enhanced and repaired by presenting more glutaraldehyde in the system.

Controllable drug release and effective intracellular accumulation highlighted by anisotropic biodegradable PLGE nanoparticles.

Control of the stretching or compressing ratio of spherical nanoparticles (NPs) leads to a dramatic change in the shape and size of particles based on amphiphilic biodegradable poly(lactide-co-glycolide-b-ethylene glycol-b-lactide-co-glycolide) (PLGE) triblock copolymers. Drug release, endocytosis and intracellular accumulation tests on these anisotropic PLGE NPs show significantly enhanced properties in comparison with spherical NPs, indicating they are good candidates for drug delivery.

Crack Identification of Cantilever Plates Based on a Kriging Surrogate Model.

This work presents an effective method to identify the tip locations of an internal crack in cantilever plates based on a Kriging surrogate model. Samples of varying crack parameters (tip locations) and their corresponding root mean square (RMS) of random responses are used to construct the initial Kriging surrogate model. Moreover, the pseudo excitation method (PEM) is employed to speed up the spectral analysis. For identifying crack parameters based on the constructed Kriging model, a robust stochastic particle swarm optimization (SPSO) algorithm is adopted for enhancing the global searching ability. To improve the accuracy of the surrogate model without using extensive samples, a small number of samples are first used. Then an optimal point-adding process is carried out to reduce computational cost. Numerical studies of a cantilever plate with an internal crack are performed. The effectiveness and efficiency of this method are demonstrated by the identified results. The effect of initial sampling size on the precision of the identified results is also investigated.

Effect of initiator on photopolymerization of acidic, aqueous dental model adhesives.

This study evaluated different initiator systems in self-etching model adhesives, in which camphorquinone (CQ) or [3-(3,4-dimethyl-9-oxo-9H-thioxanthen-2-yloxy)-2-hydroxylpropy] trimethylammonium chloride (QTX) was employed as a photoinitiator (dye). N-phenylglycine (NPG), ethyl 4-dimethylaminobenzoate (4E) or 2-(dimethylamino) ethyl methacrylate (DMAEMA) was used as the coinitiator (CI). The role of diphenyliodonium hexafluorophosphate (DPIHP) in the polymerization process was also studied. The concentrations of dye, CI, and DPIHP in model adhesives were all maintained at 0.022 mmol per gram monomer. The model adhesive contained two monomers: (bis[2-(methacryloyloxy)ethyl] phosphate) (2MP) and 2-hydroxyethyl methacrylate (HEMA) whose mass ratio was 1:1, thus representing an acidic and hydrophilic formulation. The polymerization rate and the degree of conversion (DC) of the model adhesives with 5, 15, or 25% water content were determined using FTIR/ATR with a time-based spectrum analysis. The results indicated that with CQ as the photoinitiator, 4E appeared to be the most efficient CI, whereas the CQ-DMAEMA combination led to very low radical generation efficiency (DC < 5%). DPIHP exhibited little effect on the polymerization process. With QTX as the photoinitiator, however, DPIHP played an essential role. Without DPIHP, all three QTX-CI systems failed to initiate polymerization (DC < 5%). The QTX-DPIHP combination, on the other hand, was found to be a viable initiator system. The above results provide the critical information for the development of self-etching adhesive systems.

Effects of water content and initiator composition on photopolymerization of a model BisGMA/HEMA resin.

AIMS: The purpose of this study was to evaluate the effects of photoinitiator type and water content on the polymerization rate (Rp) and degree of conversion (DC) of a model BisGMA/HEMA-based resin. MATERIALS AND METHODS: The comonomer mixture consisted of BisGMA/HEMA (60/40 by weight). Different two- or three-component photoinitiator systems were incorporated. Two-component systems were 0.5% CQ (camphorquinone) and 0.5% DMAEMA (2-(dimethylamino) ethyl methacrylate) or 0.5% CQ and 0.5% 4E (ethyl 4-dimethylaminobenzoate). The three-component systems were added 1% DPIHP (diphenyliodonium hexafluorophosphate) to the above systems. Each system was tested as made, or after addition of 5, 10, 15wt% water. When cured under a conventional dental light, the Rp and DC of each formulation was determined using time-resolved attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy. RESULTS: For mixtures containing two-component initiator systems, when the hydrophobic initiator CQ was used in combination with hydrophilic DMAEMA, Rps and DCs were dramatically decreased as a function of water content. The Rps and DCs of the hydrophobic CQ/4E system were higher than those of the CQ/DMAEMA system in the presence of water. For three-component initiator systems, incorporation of DPIHP enhanced the polymerization of all mixtures in the presence of water compared to their counterpart two-component initiators. Interestingly, the CQ/DMAEMA caused greater DC and Rp when DPIHP was used. SIGNIFICANCE: The hydrophobicity/hydrophilicity of photoinitiator components significantly affects both the DC as well as Rp when in the presence of water. The results indicate that formulation of photoinitiator components should be based on the effectiveness of the bonding systems under both dry and wet conditions.

Long-range self-governing motion of polymer gel on a gradiently charged insulating substrate.

Herein, we report a special poly(vinyl alcohol)/dimethylsulfoxide (PVA/DMSO) gel electromechanical system with great self-governed capability. The system is operated in air by applying a noncontacted DC electric field. When the applied electric field exceeds a certain critical value, the gel exhibits fast and self-governing locomotion on the gradiently charged glass substrate. In contrast to field-controlled gel systems developed earlier, the crawling direction of the gel is independent of the direction of the applied electric field and can be actively controlled. The maximum crawling velocity can reach 3.22 mm s(-1), which is much larger than that of the actuators described earlier. Furthermore, some factors that influence the critical driving electric field and the average crawling speed of the gel were studied. The mechanism analysis indicates that, the self-governing linear motion of the gel is due to the spatially and temporally varying electrostatic interaction between the gel and the applied electric field in response to the gradient change of the charge density and the charge polarity on the substrate.

Effects of a solubility enhancer on penetration of hydrophobic component in model adhesives into wet demineralized dentin.

AIMS: The purpose of this study was to evaluate the effects of a polymerizable solubility enhancer, poly (ethylene glycol) dimethacrylate (PEGDMA) in BisGMA/HEMA model adhesives on adhesive phase separation, adhesive penetration and structural integrity of adhesive/dentin (a/d) interfaces. MATERIALS AND METHODS: The occlusal one-third of the crown was removed from 10 unerupted human third molars, each tooth was separated in half by cutting perpendicular to the acid conditioned dentin surface and treated with BisGMA/HEMA model adhesives with and without PEGDMA. Five-micron-thick sections of adhesive/dentin interface specimens were cut and stained with Goldner's trichrome for light microscopy. Companion slabs were analyzed with micro-Raman spectroscopy and scanning electron microscopy (SEM). The macrophase separation in the model adhesives with/without PEGDMA was also detected using cloud point measurements in the presence of water. RESULTS: The addition of PEGDMA enhanced the water solubility/compatibility of the BisGMA/HEMA model adhesives. Micro-Raman spectral analysis of the dentin/adhesive interface indicated that there was a gradual decrease in penetration of BisGMA component for model adhesive without PEGDMA, while homogeneous distribution of the hydrophobic BisGMA component was noted in the interface with adhesive containing PEGDMA. The addition of PEGDMA dramatically facilitated infiltration of the hydrophobic monomers into the wet demineralized dentin. The SEM and staining results showed that the addition of PEGDMA would also improve the integrity at the interface between pure adhesive and hybrid layers. SIGNIFICANCE: The addition of PEGDMA could reduce phase separation, enhance the infiltration of BisGMA-based adhesives into the wet, demineralized dentin substrates, and promote homogeneous distribution of the hydrophobic component throughout the interface.