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Closed-loop chemical recycling provides a solution to the end-of-use problem of synthetic polymers. However, it remains a major challenge to design dynamic bonds, capable of effective bonding and reversible cleaving, for preparing chemically recyclable cross-linked polymers. Herein, we report a dynamic maleic acid tertiary amide bond based upon reversible amidation reaction between maleic anhydrides and secondary amines. This dynamic bond allows for the construction of polymer networks with tailorable and robust mechanical properties, covering strong elastomers with a tensile strength of 22.3 MPa and rigid plastics with a yield strength of 38.3 MPa. Impressively, these robust polymeric materials can be completely depolymerized in an acidic aqueous solution at ambient temperature, leading to efficient monomer recovery with >94% separation yields. Meanwhile, the recovered monomers can be used to remanufacture cross-linked polymeric materials without losing their original mechanical performance. This work unveils a general approach to design polymer networks with tunable mechanical performance and closed-loop recyclability, which will open a new avenue for sustainable polymeric materials. Closed-loop chemical recycling provides a solution to the end-of-use problem of synthetic polymers but the design of dynamic bonds for preparing chemically recyclable cross-linked polymers remains challenging. Here, the authors report a dynamic reversible amidation reaction between maleic anhydrides and secondary amines.

Background/Aims: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. Methods: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan’s National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. Results: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. Conclusion: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.

We report on the successful application of carboxyl-rich plasma polymerized (PP) films as a matrix layer for bioreceptor immobilization in surface plasmon resonance (SPR) immunosensing. Composition and chemical properties of the carboxyl-rich PP films deposited from a mixture of maleic anhydride and acetylene were investigated. Changes in the films stored in air, water, and buffer were studied and the involved chemical changes were described. Performance in SPR immunosensing was evaluated on interactions of human serum albumin (HSA) with a specific monoclonal antibody. The comparison with the mixed self-assembled monolayer of mercaptoundecanoic acid and mercaptohexanol (MUA/MCH) and one of the most widely used surfaces for SPR, the 2D and 3D carboxymethylated dextran (CMD), was presented to show the efficacy of plasma polymerized matrix layers for biosensing. The PP film-based SPR immunosensor provided a similar detection limit of HSA (100 ng/mL) as MUA/MCH- (100 ng/mL) and 3D CMD (50 ng/mL)-based sensors. However, the response levels were about twice higher in case of the PP film-based immunosensor than in case of MUA/MCH-based alternative. The PP film surfaces had similar binding capacity towards antibody as the 3D CMD layers. The response of PP film-based sensor towards HSA was comparable to 3D CMD-based sensor up to 2.5 μg/mL. For the higher concentrations (> 10 μg/mL), the response of PP film-based immunosensor was lower due to inaccessibility of active sites of the immobilized antibody inside the flat PP film surface. We have demonstrated that due to its high stability and cost-effective straightforward preparation, the carboxyl-rich PP films represent an efficient alternative to self-assembled monolayers (SAM) and dextran-based layers in label-free immunosensing.

In this work, the addition of 5%SiO.sub.2 to 7.5%WO.sub.3-ZrO.sub.2 catalyst increased the content of tetragonal ZrO.sub.2 and BET, which could promote the formation of W-O-Zr(Si) bonds between WO.sub.x species and 5%SiO.sub.2-ZrO.sub.2 material, thus reducing the degree of aggregation of WO.sub.x species. The oligomerized WO.sub.x species on the 7.5%WO.sub.3-5%SiO.sub.2-ZrO.sub.2 catalyst could not only remain stable, but also provided stable Lewis acid for the activation of hydrogen peroxide and maleic anhydride for epoxidation. In addition, the Si-O-Zr bond on SiO.sub.2-modified 7.5%WO.sub.3-ZrO.sub.2 catalyst could provide an additional Brønsted acid site for activating the hydrolysis of epoxysuccinic acid to DL-tartaric acid. Therefore, the DL-tartaric acid yield of SiO.sub.2-modified 7.5%WO.sub.3-ZrO.sub.2 catalyst was higher than that of 7.5%WO.sub.3-ZrO.sub.2 catalyst, and also higher than that of Na.sub.2WO.sub.4 catalyst.

Transient receptor potential (TRP) channels are a large, eukaryotic ion channel superfamily that control diverse physiological functions, and therefore are attractive drug targets 1 – 5 . More than 210 structures from more than 20 different TRP channels have been determined, and all are tetramers 4 . Despite this wealth of structures, many aspects concerning TRPV channels remain poorly understood, including the pore-dilation phenomenon, whereby prolonged activation leads to increased conductance, permeability to large ions and loss of rectification 6 , 7 . Here, we used high-speed atomic force microscopy (HS-AFM) to analyse membrane-embedded TRPV3 at the single-molecule level and discovered a pentameric state. HS-AFM dynamic imaging revealed transience and reversibility of the pentamer in dynamic equilibrium with the canonical tetramer through membrane diffusive protomer exchange. The pentamer population increased upon diphenylboronic anhydride (DPBA) addition, an agonist that has been shown to induce TRPV3 pore dilation. On the basis of these findings, we designed a protein production and data analysis pipeline that resulted in a cryogenic-electron microscopy structure of the TRPV3 pentamer, showing an enlarged pore compared to the tetramer. The slow kinetics to enter and exit the pentameric state, the increased pentamer formation upon DPBA addition and the enlarged pore indicate that the pentamer represents the structural correlate of pore dilation. We thus show membrane diffusive protomer exchange as an additional mechanism for structural changes and conformational variability. Overall, we provide structural evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research. High-speed atomic force microscopy single-molecule imaging and cryo-EM analysis discover and reveal the structure of a TRPV3 pentamer, providing evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research.

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that may advance to fibrosis and lead to mortality; however, no pharmacotherapy is currently available. We tested the hypothesis that inhibition of both the sodium–glucose cotransporters 1 and 2 with licogliflozin would lead to improvement in NASH. A total of 107 patients with phenotypic or histologic NASH were randomized (1:2:2) to receive oral administration of either placebo ( n  = 21), licogliflozin 30 mg ( n  = 43) or 150 mg ( n  = 43) once daily for 12 weeks. Licogliflozin 150 mg showed a significant 32% (80% confidence interval (CI): 21–43%; P  = 0.002) placebo-adjusted reduction in serum alanine aminotransferase after 12 weeks of treatment, the primary endpoint of the study. However, the 30 mg dose of licogliflozin did not meet the primary endpoint (placebo-adjusted reduction 21% (80% CI: 7–32%; P  = 0.061)). Diarrhea occurred in 77% (33 of 43), 49% (21 of 43) and 43% (9 of 21) of patients treated with licogliflozin 150 mg, 30 mg and placebo, respectively, which was mostly mild in severity. No other major safety concerns were identified. Treatment with 150 mg licogliflozin led to reductions in serum alanine aminotransferase in patients with NASH. Studies of longer duration and in combination with drugs that have different mechanisms of action are needed to validate these findings and to define a role of licogliflozin as a therapeutic option for NASH. ClinicalTrials.gov identifier: NCT03205150. In a phase 2a clinical trial in patients with nonalcoholic steatohepatitis, dual inhibition of sodium–glucose cotransporters 1 and 2 with 150 mg of licogliflozin led to reductions in serum alanine aminotranferase levels.

This works aims at the development thermosetting resins derived from epoxidized linseed oil (ELO) of high biobased content, by using a mixture of crosslinking agents, i.e. methyl nadic anhydride (MNA) and maleinized linseed oil (MLO). By using only MNA as crosslinking agent, the obtained resins are characterized by high stiffness and, consequently, high fragility. When MLO content increasing in the crosslinking mixture, up to 25 wt%, a decrease in mechanical resistant and thermomechanical is detected, thus indicating that MLO can provide flexibility to ELO-based thermosetting resins which is an interesting issue to obtain tailored properties by selecting the appropriate mixture composition. In general, the thermosetting resin crosslinked with 10 wt% MLO and 40 wt% MNA gives balanced properties together with noticeable biobased content, thus broadening the potential of these materials for uses in green composites and coatings.

A series of polyester prepolymers was synthesized from itaconic acid, phthalic anhydride, propane-1,2-diol and diethylene glycol by condensation polymerization. The use of itaconic acid as a source of unsaturation (instead of more common maleic anhydride giving fumarate moieties) enabled to replace styrene reactive diluent by methyl methacrylate. Room temperature curing of a model polyester resin was initiated by butanone peroxide in combination with several cobalt-, iron- and vanadium-based accelerators. Measurements of gelation time and exothermic behavior in thermally isolated installation revealed very promising catalytic properties for oxidovanadium(IV) dibutylphosphate. In follow-up tests, mechanical properties of the model unsaturated polyester resin were tuned by variation in propane-1,2-diol/diethylene glycol ratio and composition of acrylate/methacrylate reactive diluent. Mixtures of methyl methacrylate with secondary crosslinking agents (e.g., ethylene dimethacrylate, triethyleneglycol dimethacrylate and trimethylolpropane triacrylate) enabled to improve ultimate tensile strength, Young’s modulus, tensile toughness and impact toughness. Reported experimental data indicate that the described styrene- and cobalt-free system is very promising for reduction in health and ecological issues of currently used unsaturated polyester resins curable at room temperature. Graphical Abstract

Enzymes provide optimal three-dimensional structures for substrate binding and the subsequent accelerated reaction. Such folding-dependent catalytic behaviors, however, are seldom mechanistically explored with reduced structural complexity. Here, we demonstrate that the α-helix, a much simpler structural motif of enzyme, can facilitate its own growth through the self-catalyzed polymerization of N -carboxyanhydride (NCA) in dichloromethane. The reversible binding between the N terminus of α-helical polypeptides and NCAs promotes rate acceleration of the subsequent ring-opening reaction. A two-stage, Michaelis–Menten-type kinetic model is proposed by considering the binding and reaction between the propagating helical chains and the monomers, and is successfully utilized to predict the molecular weights and molecular-weight distributions of the resulting polymers. This work elucidates the mechanism of helix-induced, enzyme-mimetic catalysis, emphasizes the importance of solvent choice in the discovery of new reaction type, and provides a route for rapid production of well-defined synthetic polypeptides by taking advantage of self-accelerated ring-opening polymerizations. The folding-dependent catalytic behavior of enzymes is of fundamental biological importance, yet mechanistically underexplored. Here, the authors show that an α-helix, commonly found in proteins, can facilitate its own growth through the self-catalyzed polymerization of N-carboxyanhydride in solvents with low polarity.

This study investigates the feasibility of producing filaments and 4D printed parts with shape memory properties using Polylactic Acid/Ethylene-Butyl Acrylate-Maleic Anhydride (PLA/EBA-MAH) blends. The blends were melt blended and characterized using various techniques, including Fourier Transform Infrared Spectroscopy (FTIR) to analyze chemical interactions, Scanning Electron Microscopy (SEM) to study morphology, and Rheological analysis for viscoelastic behavior assessment. Dynamic Mechanical Analysis (DMA) was conducted to evaluate mechanical properties and glass transition temperature. The PLA/EBA-MAH 50/50 blend exhibited a co-continuous morphology, and storage modulus and viscosity decreased with increasing EBA-MAH content, emphasizing the enhanced processability of these compositions. In 4D printing experiments, the filaments demonstrated successful extrusion and shape memory activation. The 4D printed parts exhibited shape recovery in a rheometer, showcasing remarkable memory retention upon deformation. This achievement is noteworthy, as the majority of the literature focuses on shape memory activation solely in water for hydrophilic polymers. The successful production of filaments and 4D printed parts with shape memory properties at a high filling density (100%) and an orientation of approximately 45° further extends their potential in diverse applications, particularly for flexible filaments with shape memory capabilities. Overall, this research not only demonstrates the successful production of filaments and 4D printed structures but also highlights the impressive shape memory behavior of PLA/EBA-MAH blends. The combination of favorable rheological properties and shape memory activation expands the potential of these blends for applications requiring flexible and shape-shifting materials.