High-Fidelity Bioelectrodes with Bidirectional Ion-Electron Transduction Capability by Integrating Multiple Charge-Transfer Processes.

Bioelectronics is an exciting field that bridges the gap between physiological activities and external electronic devices, striving for high resolution, high conformability, scalability, and ease of integration. One crucial component in bioelectronics is bioelectrodes, designed to convert neural activity into electronic signals or vice versa. Previously reported bioelectrodes have struggled to meet several essential requirements simultaneously: high-fidelity signal transduction, high charge injection capability, strain resistance, and multifunctionality. This work introduces a novel strategy for fabricating superior bioelectrodes by merging multiple charge-transfer processes. The resulting bioelectrodes offer accurate ion-to-electron transduction for capturing electrophysiological signals, dependable charge injection capability for neuromodulation, consistent electrode potential for artifact rejection and biomolecule sensing, and high transparency for seamless integration with optoelectronics. Furthermore, the bioelectrode can be designed to be strain-insensitive by isolating signal transduction from electron transportation. The innovative concept presented in this work holds great promise for extending to other electrode materials and paves the way for the advancement of multimodal bioelectronics.

Ultra-Highly Stiff and Tough Shape Memory Polyurea with Unprecedented Energy Density by Precise Slight Cross-Linking.

Shape memory polymers (SMPs) have attracted significant attention and hold vast potential for diverse applications. Nevertheless, conventional SMPs suffer from notable shortcomings in terms of mechanical properties, environmental stability, and energy density, significantly constraining their practical utility. Here, inspired by the structure of muscle fibers, an innovative approach that involves the precise incorporation of subtle, permanent cross-linking within a hierarchical hydrogen bonding supramolecular network is reported. This novel strategy has culminated in the development of covalent and supramolecular shape memory polyurea, which exhibits exceptional mechanical properties, including high stiffness (1347 MPa), strength (82.4 MPa), and toughness (312.7 MJ m-3), ensuring its suitability for a wide range of applications. Furthermore, it boasts remarkable recyclability and repairability, along with excellent resistance to moisture, heat, and solvents. Moreover, the polymer demonstrates outstanding shape memory effects characterized by a high energy density (24.5 MJ m-3), facilitated by the formation of strain-induced oriented nanostructures that can store substantial amounts of entropic energy. Simultaneously, it maintains a remarkable 96% shape fixity and 99% shape recovery. This delicate interplay of covalent and supramolecular bonds opens up a promising pathway to the creation of high-performance SMPs, expanding their applicability across various domains.

Multispecies transcriptomics identifies SIKE as a MAPK repressor that prevents NASH progression.

Nonalcoholic fatty liver (NAFL) remains relatively benign, but high-risk to end-stage liver diseases become highly prevalent when it progresses into nonalcoholic steatohepatitis (NASH). Our current understanding of the development of NAFL to NASH remains insufficient. In this study, we revealed MAP kinase (MAPK) activation as the most notable molecular signature associated with NASH progression across multiple species. Furthermore, we identified suppressor of IKKε (SIKE) as a conserved and potent negative controller of MAPK activation. Hepatocyte-specific overexpression of Sike prevented NASH progression in diet- and toxin-induced mouse NASH models. Mechanistically, SIKE directly interacted with TGF-ß-activated kinase 1 (TAK1) and TAK1-binding protein 2 (TAB2) to interrupt their binding and subsequent TAK1-MAPK signaling activation. We found that indobufen markedly up-regulated SIKE expression and effectively improved NASH features in mice and macaques. These findings identify SIKE as a MAPK suppressor that prevents NASH progression and provide proof-of-concept evidence for targeting the SIKE-TAK1 axis as a potential NASH therapy.

TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.

Binding Affinity and Mechanism of Six PFAS with Human Serum Albumin: Insights from Multi-Spectroscopy, DFT and Molecular Dynamics Approaches.

Per- and Polyfluoroalkyl Substances (PFAS) bioaccumulate in the human body, presenting potential health risks and cellular toxicity. Their transport mechanisms and interactions with tissues and the circulatory system require further investigation. This study investigates the interaction mechanisms of six PFAS with Human Serum Albumin (HSA) using multi-spectroscopy, DFT and a molecular dynamics approach. Multi-spectral analysis shows that perfluorononanoic acid (PFNA) has the best binding capabilities with HSA. The order of binding constants (298 K) is as follows: "Perfluorononanoic Acid (PFNA, 7.81 × 106 L·mol-1) > Perfluoro-2,5-dimethyl-3,6-dioxanonanoic Acid (HFPO-TA, 3.70 × 106 L·mol-1) > Perfluorooctanoic Acid (PFOA, 2.27 × 105 L·mol-1) > Perfluoro-3,6,9-trioxadecanoic Acid (PFO3DA, 1.59 × 105 L·mol-1) > Perfluoroheptanoic Acid (PFHpA, 4.53 × 103 L·mol-1) > Dodecafluorosuberic Acid (DFSA, 1.52 × 103 L·mol-1)". Thermodynamic analysis suggests that PFNA and PFO3DA's interactions with HSA are exothermic, driven primarily by hydrogen bonds or van der Waals interactions. PFHpA, DFSA, PFOA, and HFPO-TA's interactions with HSA, on the other hand, are endothermic processes primarily driven by hydrophobic interactions. Competitive probe results show that the main HSA-PFAS binding site is in the HSA structure's subdomain IIA. These findings are also consistent with the findings of molecular docking. Molecular dynamics simulation (MD) analysis further shows that the lowest binding energy (-38.83 kcal/mol) is fund in the HSA-PFNA complex, indicating that PFNA binds more readily with HSA. Energy decomposition analysis also indicates that van der Waals and electrostatic interactions are the main forces for the HSA-PFAS complexes. Correlation analysis reveals that DFT quantum chemical descriptors related to electrostatic distribution and characteristics like ESP and ALIE are more representative in characterizing HSA-PFAS binding. This study sheds light on the interactions between HSA and PFAS. It guides health risk assessments and control strategies against PFAS, serving as a critical starting point for further public health research.

Investigating sulfonamides - Human serum albumin interactions: A comprehensive approach using multi-spectroscopy, DFT calculations, and molecular docking.

The environmental and health risks associated with sulfonamide antibiotics (SAs) are receiving increasing attention. Through multi-spectroscopy, density functional theory (DFT), and molecular docking, this study investigated the interaction features and mechanisms between six representative SAs and human serum albumin (HSA). Multi-spectroscopy analysis showed that the six SAs had significant binding capabilities with HSA. The order of binding constants at 298 K was as follows: sulfadoxine (SDX): 7.18 × 105 L mol-1 > sulfamethizole (SMT): 6.28 × 105 L mol-1 > sulfamerazine (SMR): 2.70 × 104 L mol-1 > sulfamonomethoxine (SMM): 2.54 × 104 L mol-1 > sulfamethazine (SMZ): 3.06 × 104 L mol-1 > sulfadimethoxine (SDM): 2.50 × 104 L mol-1. During the molecular docking process of the six SAs with HSA, the binding affinity range is from -7.4 kcal mol-1 to -8.6 kcal mol-1. Notably, the docking result of HSA-SDX reached the maximum of -8.6 kcal mol-1, indicating that SDX may possess the highest binding capacity to HSA. HSA-SDX binding, identified as a static quenching and exothermic process, is primarily driven by hydrogen bonds (H bonds) or van der Waals (vdW) interactions. The quenching processes of SMR/SMZ/SMM/SDX/SMT to HSA are a combination of dynamic and static quenching, indicating an endothermic reaction. Hydrophobic interactions are primarily accountable for SMR/SMZ/SMM/SDX/SMT and HSA binding. Competition binding results revealed that the primary HSA-SAs binding sites are in the subdomain IB of the HAS structure, consistent with the results of molecule docking. The correlation analysis based on DFT calculations revealed an inherent relationship between the structural chemical features of SAs and the binding performance of HSA-SAs. The dual descriptor (DD) and the electrophilic Fukui function were found to have a significant relationship (0.71 and -0.71, respectively) with the binding constants of HSA-SAs, predicting the binding performance of SAs and HSA. These insights have substantial scientific value for evaluating the environmental risks of SAs as well as understanding their impact on biological life activities.

Building Ion-Conductive Supramolecular Elastomeric Protective Layer via Dynamic Hard Domain Design for Stable Zinc Metal Anodes.

The instability of zinc metal anode caused by zinc dendrite growth and severe parasitic reactions has significantly restricted the extensive application of rechargeable aqueous zinc-ion batteries (RAZBs). Herein, based on the strategy of dynamic hard domains, we develop an ion-conductive supramolecular elastomer consisting of Zn salts and the polyurethane-urea-polypropylene glycol polymer skeleton. This elastomer combines high mechanical strength, high ionic conductivity, decent hydrophobicity, and high adhesion to stabilize the electrode-electrolyte interface. In the elastomer system, this elastomer can dynamically adapt to the volume changes of Zn anodes during repeated zinc plating/stripping processes through the reversible dissociation/reassociation of hierarchical hydrogen bonds (H-bonds) formed by the polar groups of urea and urethane moieties. Meanwhile, the coordination of Zn2+ with soft polypropylene glycol (PPG) segments contributes to fast ion transport. This hydrophobic elastomer can also effectively inhibit water-induced corrosion by shielding the active Zn metal from the aqueous electrolyte. Based on the above synergies, the surface-modified anode shows excellent cycling stability above 550 h at a high current density of 5 mA cm-2 and a capacity of 2.5 mAh cm-2. Moreover, the assembled Zn//MnO2 full cell also displayed an enhanced electrochemical performance. This work provides inspiration for the design of solid electrolyte interphase (SEI) layers in aqueous battery chemistry to accelerate the application of RAZBs.

Fatigue-Free and Skin-like Supramolecular Ion-Conductive Elastomeric Interphases for Stable Lithium Metal Batteries.

The heterogeneity and continuous cracking of the static solid electrolyte interphase (SEI) are one of the most critical barriers that largely limit the cycle life of lithium (Li) metal batteries. Herein, we report a fatigue-free dynamic supramolecular ion-conductive elastomeric interphase (DSIEI) for a highly efficient and dendrite-free lithium metal anode. The soft phase poly(propylene glycol) backbone with loosely Li+-O coordinating interaction was responsible for fast ion transport. Simultaneously, the supramolecular quadruple hydrogen bonds (H-bonds) in the hard phases endow the elastomeric interphase with mechanical enhancement, while gradient H-bonds can dissipate strain energy via the sequential bonding cleavage. Such a design affords superior mechanical robustness, high ionic conductivity, gradient energy dissipation, and high Li+ transference number. Besides, anion enrichment in DSIEI assists in situ construction of a lithium fluoride-rich inner layer upon cycling. The resultant biomimetic bilayer structure enables the symmetric cells with superior cyclability of over 600 h at a high current density of 10 mA cm-2. Moreover, the DSIEI allows stable operation of the full cells under constrained conditions of limited lithium excess, a high-loading LiNi0.8Co0.1Mn0.1O2 cathode, and a low negative/positive capacity (N/P) ratio. This work presents a powerful strategy for deigning artificial SEI and achieving high-energy-density Li metal batteries.

Encapsulation of tea polyphenols into high amylose corn starch composite nanofibrous film for active antimicrobial packaging.

Starch-based composite nanofibrous films loaded with tea polyphenols (TP) were successfully fabricated through electrospinning high amylose corn starch (HACS) with aid of polyvinyl alcohol (PVA), referred as HACS/PVA@TP. With the addition of 15 % TP, HACS/PVA@TP nanofibrous films exhibited enhanced mechanical properties and water vapor barrier capability, and their hydrogen bonding interactions were further evidenced. TP was slowly released from the nanofibrous film and followed Fickian diffusion mechanism, which achieved the controlled sustained release of TP. Interesting, HACS/PVA@TP nanofibrous films effectively improved antimicrobial activities against Staphylococcus aureus (S. aureus) and prolonged the shelf life of strawberry. HACS/PVA@TP nanofibrous films showed superior antibacterial function by by destroying cell wall and cytomembrane, and degrading existing DNA fragments, stimulating excessive intracellular reactive oxygen species (ROS) generation. Our study demonstrated that the functional electrospun Starch-based nanofibrous films with enhanced mechanical properties and superior antimicrobial activities were potential for the application in active food packaging and relative areas.

Colloid Electrolyte with Weakly Solvated Structure and Optimized Electrode/Electrolyte Interface for Zinc Metal Batteries.

Aqueous zinc batteries are considered as a viable candidate for cost-effective and environmentally sustainable energy storage technology but are severely hampered by the notorious dendrite growth and parasitic reactions at the zinc anode side. Herein, we propose a bifunctional colloidal electrolyte design that utilizes upconversion nanocrystals, i.e., NaErF4@NaYF4, as a solid additive to provide the sustained release of functional metal and fluoride ions, which can effectively improve the reversibility of the Zn anode to inhibit dendrite growth and hydrogen evolution through forming an electrostatic shielding layer and in situ constructing a ZnF2-enriched protective interface. Experimental characterization and molecular dynamics simulation jointly confirm that the NaErF4@NaYF4 additive could modify the Zn2+ solvation environment in the vicinity of the NaErF4@NaYF4 surface via the strong electrostatic coupling with Zn2+ ions. As a consequence, the modified electrolyte enables stable zinc plating/stripping over 2100 h at a current density of 3 mA cm-2 and a capacity of 1 mAh cm-2 in symmetric cells. The assembled Zn||MnO2 full cells with a modified electrolyte can operate stably for 1600 cycles at 2 A g-1. This work thereby has great potential for the exploration of multifunctional electrolyte additives toward long-lasting aqueous Zn metal batteries.

Spatiotemporally Responsive Hydrogel Dressing with Self-Adaptive Antibacterial Activity and Cell Compatibility for Wound Sealing and Healing.

Adhesive hydrogels containing quaternary ammonium salt (QAS) moieties have shown attractive advantages in treatment for acute wounds, attributed to their high performances in wound sealing and sterilization. However, the introduction of QAS commonly leads to high cytotoxicity and adhesive deterioration. Herein, aimed to solve these two issues, a self-adaptive dressing with delicate spatiotemporal responsiveness is developed by employing cellulose sulfate (CS) as dynamic layers to coat QAS-based hydrogel. In detail, due to the acid environment of wound in the early stages of healing, the CS coating will quickly detach to expose the active QAS groups for maximum disinfectant efficacy; meanwhile, as the wound gradually heals and recovers to a neutral pH, the CS will remain stable to keep QAS screened, realizing a high cell growth-promoting activity for epithelium regeneration. Additionally, attributed to the synergy of temporary hydrophobicity by CS and slow water absorption kinetics of the hydrogel, the resultant dressing possesses outstanding wound sealing and hemostasis performance. At last, this work anticipates this approach to intelligent wound dressings based on dynamic and responsive intermolecular interaction can also be applied to a wide range of self-adaptive biomedical materials employing different chemistries for applications in medical therapy and health monitoring.

Learning Constrained Dynamic Correlations in Spatiotemporal Graphs for Motion Prediction.

Human motion prediction is challenging due to the complex spatiotemporal feature modeling. Among all methods, graph convolution networks (GCNs) are extensively utilized because of their superiority in explicit connection modeling. Within a GCN, the graph correlation adjacency matrix drives feature aggregation, and thus, is the key to extracting predictive motion features. State-of-the-art methods decompose the spatiotemporal correlation into spatial correlations for each frame and temporal correlations for each joint. Directly parameterizing these correlations introduces redundant parameters to represent common relations shared by all frames and all joints. Besides, the spatiotemporal graph adjacency matrix is the same for different motion samples, and thus, cannot reflect samplewise correspondence variances. To overcome these two bottlenecks, we propose dynamic spatiotemporal decompose GC (DSTD-GC), which only takes 28.6% parameters of the state-of-the-art GC. The key of DSTD-GC is constrained dynamic correlation modeling, which explicitly parameterizes the common static constraints as a spatial/temporal vanilla adjacency matrix shared by all frames/joints and dynamically extracts correspondence variances for each frame/joint with an adjustment modeling function. For each sample, the common constrained adjacency matrices are fixed to represent generic motion patterns, while the extracted variances complete the matrices with specific pattern adjustments. Meanwhile, we mathematically reformulate GCs on spatiotemporal graphs into a unified form and find that DSTD-GC relaxes certain constraints of other GC, which contributes to a better representation capability. Moreover, by combining DSTD-GC with prior knowledge like body connection and temporal context, we propose a powerful spatiotemporal GCN called DSTD-GCN. On the Human3.6M, Carnegie Mellon University (CMU) Mocap, and 3D Poses in the Wild (3DPW) datasets, DSTD-GCN outperforms state-of-the-art methods by 3.9%-8.7% in prediction accuracy with 55.0%-96.9% fewer parameters. Codes are available at https://github.com/Jaakk0F/DSTD-GCN.

Extremely strengthening fatigue resistance, elastic restorability and thermodynamic stability of a soft transparent self-healing network based on a dynamic molecular confinement-induced bioinspired nanostructure.

Soft self-healing materials are crucial for the development of next-generation wearable electronics that could function in dynamic environments and resist mechanical damage. However, several challenges remain, including fatigue fracture, poor elasticity, and thermodynamic lability, which significantly limit their practical applications. Here, with a model system of soft self-healing polyurea, we propose a molecular engineering strategy of transforming inherently fragile materials with an island-like structure into resilient ones with a bicontinuous nanophase separation structure using 2-ureido-4-pyrimidinone (UPy) supramolecular motifs as structural regulators. The dynamic and continuous hard domains modified by UPy formed a repairable bicontinuous network similar to those of the reticular layer in animal dermis. This design allows for a simultaneous and tremendous improvement in the fatigue threshold (34.8-fold increase), elastic restorability (the maximum elongation for full dimensional recovery increasing from 6 times to 13 times), and thermodynamic stability (4 orders of magnitude improvement in the characteristic flow transition relaxation time), without significantly compromising the compliance, autonomous self-healing, and optical transparency. These mechanical and thermodynamic improvements address current limitations in unfilled soft self-healing materials as reliable substrates for transparent strain-electronics.

Room-Temperature Self-Healing Soft Composite Network with Unprecedented Crack Propagation Resistance Enabled by a Supramolecular Assembled Lamellar Structure.

Soft self-healing materials are compelling candidates for stretchable devices because of their excellent compliance, extensibility, and self-restorability. However, most existing soft self-healing polymers suffer from crack propagation and irreversible fatigue failure due to easy breakage of their dynamic amorphous, low-energy polymer networks. Herein, inspired by distinct structure-property relationship of biological tissues, a supramolecular interfacial assembly strategy of preparing soft self-healing composites with unprecedented crack propagation resistance is proposed by structurally engineering preferentially aligned lamellar structures within a dynamic and superstretchable poly(urea-ureathane) matrix (which is elongated to 24 750× its original length). Such a design affords a world-record fracture energy (501.6 kJ m-2 ), ultrahigh fatigue threshold (4064.1 J m-2 ), and outstanding elastic restorability (dimensional recovery from 13 times elongation), and preserving low modulus (1.2 MPa), high stretchability (3200%), and high room-temperature self-healing efficiency (97%). Thereby, the resultant composite represents the best of its kind and even surpasses most biological tissues. The lamellar 2D transition-metal carbide/carbonitride (MXene) structure also leads to a relatively high in-plane thermal conductivity, enabling composites as stretchable thermoconductive skins applied in joints of robotics to thermal dissipation. The present work illustrates a viable approach how autonomous self-healing, crack tolerance, and fatigue resistance can be merged in future material design.

Vascular smooth muscle-inspired architecture enables soft yet tough self-healing materials for durable capacitive strain-sensor.

Catastrophically mechanical failure of soft self-healing materials is unavoidable due to their inherently poor resistance to crack propagation. Here, with a model system, i.e., soft self-healing polyurea, we present a biomimetic strategy of surpassing trade-off between soft self-healing and high fracture toughness, enabling the conversion of soft and weak into soft yet tough self-healing material. Such an achievement is inspired by vascular smooth muscles, where core-shell structured Galinstan micro-droplets are introduced through molecularly interfacial metal-coordinated assembly, resulting in an increased crack-resistant strain and fracture toughness of 12.2 and 34.9 times without sacrificing softness. The obtained fracture toughness is up to 111.16 ± 8.76 kJ/m2, even higher than that of Al and Zn alloys. Moreover, the resultant composite delivers fast self-healing kinetics (1 min) upon local near-infrared irradiation, and possesses ultra-high dielectric constants (~14.57), thus being able to be fabricated into sensitive and self-healing capacitive strain-sensors tolerant towards cracks potentially evolved in service.

In-depth insight into the Yb3+ effect in NaErF4-based host sensitization upconversion: a double-edged sword.

NaErF4 is the most extensively studied host for self-sensitized upconversion (UC), and Yb3+ is the most commonly used energy absorber. It has been reported that the red luminescence of Er3+ can be enhanced by introducing Yb3+ into the NaErF4 host lattice, where Yb3+ ions serve as trapping centers to confine the excitation energy. Also, it has been pointed out that the Yb3+ doping in the shell of NaErF4-hosted core-shell nanocrystals can further improve the red emission intensity. Conversely, it can be argued that the Yb3+ doping in the shell always results in the luminescence quenching of the NaErF4 core. These imply that the impact of Yb3+ on NaErF4-based host-sensitized UC is rather complicated and must be probed deeply. In this study, we thoroughly discussed the effect of Yb3+ located in the core/shell on the NaErF4-based host sensitization UC and afforded the related mechanism interpretations. In the NaErF4 core nanocrystals, the green-dominated UCL presented an enhancement on increasing the concentration of the Yb3+ dopant owing to the promoted energy harvesting for luminescence. Furthermore, the emission properties of NaErF4:10%Yb shelled with diverse inert layers were also investigated, and the intensity difference of these core-inert shell nanoparticles could be explained by the lattice mismatch and shell thickness. In NaErF4:10%Yb@NaYF4:Yb with variable Yb3+ doping in the shell, the red-dominated UCL was generally weakened with more Yb3+ localized in the shell, which was ascribed to the competition of energy pooling and energy dissipation of Yb3+ in the outer layer. Therefore, Yb3+ ions wield a two-sided influence (termed a "double-edged sword") on the UC emissions of the Er3+ host. Additionally, we demonstrated the application potential of such UCNPs in water sensing and high-level anti-counterfeiting. This work offers an in-depth insight into the UC mechanism of Yb3+-doped NaErF4 nanocrystals and inspires the engineering of novel luminescent materials with distinguished properties.

Prognostic Value of Immunotyping Combined with Targeted Therapy in Patients with Non-Small-Cell Lung Cancer and Establishment of Nomogram Model.

Objective: Bioinformatics methods were used to analyze non-small-cell lung cancer gene chip data, screen differentially expressed genes (DEGs), explore biomarkers related to NSCLC prognosis, provide new targets for the treatment of NSCLC, and build immunotyping and line-map model. Methods: NSCLC-related gene chip data were downloaded from the GEO database, and the common DEGs of the two datasets were screened by using the GEO2R tool and FunRich 3.1.3 software. DAVID database was used for GO analysis and KEGG analysis of DEGs, and protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape 3.8.0 software, and the top 20 hub genes were analyzed and screened out. The expression of pivot genes and their relationship with prognosis were verified by multiple external databases. Results: 159 common DEGs were screened from the two datasets. PPI network was constructed and analyzed, and the genes with the top 20 connectivity were selected as the pivotal genes of this study. The results of survival analysis and the patients' survival curve was reflected in the line graph model of NSCLC. Conclusion: Through the screening and identification of the VIM-AS1 gene, as well as the analysis of immune infiltration and immune typing, the successful establishment of the rosette model has a certain guiding value for the molecular targeted therapy of patients with non-small-cell lung cancer.

Switch-associated protein 70 protects against nonalcoholic fatty liver disease through suppression of TAK1.

BACKGROUND AND AIMS: NAFLD is a progressive disease without known effective drug treatments. Switch-associated protein 70 (SWAP70) is a guanine nucleotide exchange factor that participates in the regulation of many cellular processes. However, the role of SWAP70 in NAFLD remains unclear. This study aimed to identify the function and mechanism of SWAP70 in NAFLD. APPROACH AND RESULTS: The results showed that the expression of SWAP70 was significantly increased in mice and hepatocytes after metabolic stimulation. Overexpression of SWAP70 in hepatocytes suppressed lipid deposition and inflammation, and SWAP70 knockdown created the inverse effect. Using hepatocyte-specific Swap70 knockout and overexpression mice fed a high-fat, high-cholesterol diet, we demonstrated that SWAP70 suppressed the progression of nonalcoholic steatohepatitis by inhibiting lipid accumulation, inflammatory response, and fibrosis. Mechanically, RNA sequencing analysis and immunoprecipitation assays revealed that SWAP70 inhibited the interaction between transforming growth factor ß-activated kinase 1 (TAK1) binding protein 1 and TAK1 and sequentially suppressed the phosphorylation of TAK1 and subsequent c-Jun N-terminal kinase/P38 signaling. Inhibition of TAK1 activation blocked hepatocyte lipid deposition and inflammation caused by SWAP70 knockdown. CONCLUSIONS: SWAP70 is a protective molecule that can suppress the progression of NAFLD by inhibiting hepatic steatosis and inflammation. SWAP70 may be important for mitigating the progression of NAFLD.

A conventional immune regulator mitochondrial antiviral signaling protein blocks hepatic steatosis by maintaining mitochondrial homeostasis.

BACKGROUND AND AIMS: Although the prevalence of NAFLD has risen dramatically to 25% of the adult population worldwide, there are as yet no approved pharmacological interventions for the disease because of uncertainty about the underlying molecular mechanisms. It is known that mitochondrial dysfunction is an important factor in the development of NAFLD. Mitochondrial antiviral signaling protein (MAVS) is a critical signaling adaptor for host defenses against viral infection. However, the role of MAVS in mitochondrial metabolism during NAFLD progression remains largely unknown. APPROACH AND RESULTS: Based on expression analysis, we identified a marked down-regulation of MAVS in hepatocytes during NAFLD progression. By using MAVS global knockout and hepatocyte-specific MAVS knockout mice, we found that MAVS is protective against diet-induced NAFLD. MAVS deficiency induces extensive mitochondrial dysfunction during NAFLD pathogenesis, which was confirmed as impaired mitochondrial respiratory capacity and membrane potential. Metabolomics data also showed the extensive metabolic disorders after MAVS deletion. Mechanistically, MAVS interacts with the N-terminal stretch of voltage-dependent anion channel 2 (VDAC2), which is required for the ability of MAVS to influence mitochondrial function and hepatic steatosis. CONCLUSIONS: In hepatocytes, MAVS plays an important role in protecting against NAFLD by helping to regulate healthy mitochondrial function. These findings provide insights regarding the metabolic importance of conventional immune regulators and support the possibility that targeting MAVS may represent an avenue for treating NAFLD.

Highly thermoconductive yet ultraflexible polymer composites with superior mechanical properties and autonomous self-healing functionality via a binary filler strategy.

It is still a formidable challenge to develop ideal thermal dissipation materials with simultaneous high thermal conductivity, excellent mechanical softness and toughness, and spontaneous self-healing. Herein, we report the introduction of sandwich-like boron nitride nanosheets-liquid metal binary fillers into an artificial poly(urea-urethane) elastomer to address the above issue, which confers the composite elastomer with a unique thermal-mechanical-healing combination, including a low modulus, high in-plane thermal conductivity and high mass loading of rigid fillers but self-recoverability and room-temperature self-healing.