Research最新文献

Bioplastics derived from renewable food crops or agricultural feedstocks are alternatives to petrochemical materials, but it is challenging to balance their mechanical properties, thermal stability, and shapeability. Here, we report a thermally stimulated supramolecular bioplastic that employs polyethylene glycol to optimize the assembly of cellulose and polyvinyl alcohol molecules. The resulting bioplastic showed a reinforced supramolecular architecture, with a mechanical elastic modulus of 3.23 GPa and an impact resistance higher than 8.15 kJ·m^-1. It also showed thermal stability from -40 to 135 °C while maintaining its structural integrity and toughness, giving it potential applications for various shaping processes, including weaving, pouring, and molding. The bioplastic could also undergo natural soil biodegradation within 55 d and exhibited promising recyclability and economic feasibility. This study provides a strategy for configuring supramolecular structures and enhancing the design and manufacture of bioplastics with optimal comprehensive properties.

Autoimmune diseases (AIDs) are a group of immune-related disorders primarily affecting joints and surrounding tissues, often marked by chronic inflammation and autoimmune activation. Common types include systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune cardiovascular diseases, and skin conditions. While their pathogenesis is unclear, recent studies suggest that abnormal gut microbiota may contribute. Previous research has shown that various patients with rheumatic disease exhibit altered gut microbiota, characterized by decreased microbial diversity, overall compositional changes, and microbiota-mediated functional alterations. Bacterial species closely associated with AIDs include Prevotella copri, Ruminococcus gnavus, and Ligilactobacillus salivarius. Dysregulated gut microbiota activates host immune responses through multiple mechanisms, including compromised intestinal barrier, systemic translocation, molecular mimicry of self-antigen epitopes, and changes in microbiota-derived metabolites, thereby substantially contributing to the development and progression of AIDs. Microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acid metabolites, are actively involved in driving disease progression. In addition, the therapeutic outcomes and adverse effects of immunotherapeutic agents can be modulated by gut microbiota through their impact on drug biotransformation processes. Clinically, analyzing gut microbiota characteristics can aid in disease diagnosis and prognosis prediction. Therapeutic strategies such as fecal microbiota transplantation, probiotics, prebiotics, and the Mediterranean diet may become effective measures for managing AIDs. This article reviews recent research progress, future directions, and the potential of microbiota-based interventions in treating AIDs.

Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ) represent major neurodevelopmental disorders with distinct typical ages of onset. These disorders exhibit substantial genetic and phenotypic overlap, yet their shared and disorder-specific neurobiological mechanisms remain unclear. We analyzed resting-state functional magnetic resonance imaging data from 2,176 participants (ASD, ADHD, SCZ, and healthy controls). Using heterogeneous matrix factorization, we extracted meta-blood-oxygen-level-dependent signals to reduce individual heterogeneity and constructed functional connectivity networks. Partial least squares identified a shared transdiagnostic abnormal connectivity pattern (STACP) and disorder-specific connectivity deviations (DSCDs). We annotated edges with transcriptomic, neurotransmitter, and mitochondrial maps for biological interpretation. The STACP involved connections linking deep regulatory systems (cerebellum, brain stem, and subcortical network) and cortical perceptual-executive networks (default mode, visual, frontoparietal, and somatomotor). The DSCDs of ASD and ADHD implicated overlapping networks with opposite functional connectivity directions (decreased in ASD and increased in ADHD), while SCZ showed more widespread desynchronization. STACP-related genes were enriched for synaptic development, cytoskeletal remodeling, and lipid metabolism, expressed in midbrain and deep-layer cortical neurons, and associated with serotonin transporter and cytochrome c oxidase. DSCDs were linked to glutamatergic plasticity and immune activation in ASD, dopaminergic regulation and glia-neuron interactions in ADHD, and broad synaptic plus immune-metabolic dysregulation in SCZ. Together, these findings provide a systems-level characterization of shared and disorder-specific neurobiological features across major neurodevelopmental disorders observed at different life stages.

Protein secretion plays a crucial role in numerous biological processes, yet its underlying mechanisms remain incompletely understood. This study investigates the role of Sec72, a component of the Sec complex in Saccharomyces cerevisiae, in protein targeting and translocation to the endoplasmic reticulum. We discovered that deleting SEC72 significantly enhances the secretion of proteins with strongly hydrophobic signal peptides (SPs), accompanied by observable changes in cellular functions, such as iron homeostasis, cell wall assembly, and protein synthesis. Importantly, we identified specific gene modifications that, in combination with SEC72 deletion, enable a yeast strain to secrete α-amylase up to 6.5 g/l in fed-batch fermentation. These findings deepen our understanding of SP-mediated protein translocation and provide a basis for optimizing yeast hosts for more effective protein production.

Traditional gas sensing systems are facing efficiency challenges due to physically separated von Neumann architectures, making the construction of in-sensor computing neuromorphic olfactory systems urgently needed for low-power and low-latency scenarios. In this study, a reconfigurable neuromorphic heterostructure memristor based on MXene@SnS₂@PANI and an in-sensor computing olfactory system were proposed. Notably, the reconfigurable neuromorphic olfactory electronics differ fundamentally from conventional sensors. Specifically, the memristor's circuit architecture supports both synaptic and neuronal computational functions, enabling reconfigurable responses to both electrical and gas stimuli within a single device, which substantially minimizes circuit complexity. Through modulation of the energy band under both gas and electrical signals, the device achieves reconfigurable neuromorphic computing features supporting both volatile and nonvolatile conductance updates. Under electrical stimulation, it demonstrates integrate-and-fire neuronal dynamics for gas flow recognition via a spiking neural network. Under gas exposure, neuromorphic synaptic behaviors are realized, enabling gas concentration identification through reservoir computing. The system has been successfully implemented for real-time hazardous gas monitoring and automated ventilation control, paving the way for next-generation neuromorphic intelligent sensing systems.

Alkaline zinc-ferricyanide flow batteries (AZFFBs) emerge as promising candidates for long-duration energy storage. However, at cryogenic temperatures, these systems suffer from electrolyte solidification, anodic zinc dendrite formation, zinc-related side reactions, and cathodic Fe(CN)₆ ^4- precipitation-induced capacity decay. Herein, we propose a synergistic solvation strategy in which Li⁺ and Cl^- jointly inhibit the formation of tetrahedral hydrogen bond networks, thereby lowering the liquid-solid transition peak temperature of both the anolyte and catholyte. Meanwhile, Cl^- is utilized to construct a water-poor solvation structure around Zn(OH)₄ ^2- to optimize zinc deposition and inhibit the side reactions, while Li⁺ enhances the solubility of Fe(CN)₆ ^4- by incorporating additional water molecules into its solvation structure through strong ion-dipole interactions. The optimized AZFFB exhibits outstanding low-temperature performance, achieving stable cycling at -20 °C with an average coulombic efficiency of 99.54%. It also demonstrates excellent stability at room temperature, sustaining over 500 cycles at 28 °C with an average coulombic efficiency of 99.79%, representing more than a 22-fold extension in cycle life. Additionally, the AZFFB exhibits robust stability under fluctuating temperature conditions. These breakthroughs markedly enhance the potential of AZFFBs as viable solutions for extreme-environment energy storage, particularly in polar region microgrids, cold-climate off-grid power systems, and subsea power applications.

Irreversible electroporation (IRE) is a nonthermal ablation modality used clinically for treating unresectable tumors while preserving vital structures through controlled application of pulsed electric fields. Previous data suggest that patient outcomes are enhanced with the induction of an anti-tumor immune response, but current research focuses on using immune checkpoint inhibitors, which function through conventional immune pathways that may be down-regulated by cancer or dysregulated by chemo-induced lymphodepletion. Chimeric antigen receptor (CAR) T cells overcome this limitation, as they are engineered with synthetic receptors that redirect lymphocytes to recognize and target cells expressing tumor-specific structures. CARs are engineered to have an increased binding affinity compared to in situ T-cell binding, amplify internal stimulation cascades, and release pro-inflammatory cytokines that can modulate the endogenous immune system. However, there are still major limitations for adoptive cell therapies in solid tumors, including life-threatening on-target off-tumor cytotoxicity, antigen escape, and failure to infiltrate and persist in solid tumors. Given the substantial evidence that IRE overcomes many of the challenges associated with immune infiltration and persistence in solid tumors, there is a strong premise for using targeted cell therapies following IRE, which would then target residual cancer that could repopulate the lesion. Here, we present the first proof-of-concept combination of IRE with CAR T cells. We validated that the cell membrane CAR target is not affected in electroporated cells that survive IRE, allowing for subsequent binding and elimination of residual tumor. The research demonstrates the feasibility and synergy of a novel combination of 2 clinically used techniques.

[This corrects the article DOI: 10.34133/research.0704.].

Gastric cancer (GC) remains a leading cause of global cancer mortality. Analysis of clinical tissues and multiple cohorts (TCGA, ACRG, Singapore, KUGH) associated high RBM15 expression with favorable prognosis. Functional assays in vitro and in vivo demonstrated that RBM15 suppresses GC cell proliferation, migration, and invasion. Integrated RNA-seq and bioinformatics analyses identified the oncogene ECT2 and the epithelial-mesenchymal transition (EMT) pathway as key downstream effectors of RBM15. Mechanistically, RBM15 regulates the m6A methylation of ECT2 mRNA at the 2,909-base pair site, which modulates its binding to the reader protein IGF2BP3, as confirmed by MeRIP, RIP-qPCR, and RNA pull-down assays. A luciferase reporter assay further validated that this m6A modification regulates ECT2 expression. Furthermore, animal and patient-derived organoid models revealed that RBM15 enhances the sensitivity of GC to 5-fluorouracil (5-FU) chemotherapy in an ECT2-dependent manner. In conclusion, this study defines a novel RBM15/IGF2BP3-ECT2 signaling axis that regulates EMT and chemosensitivity in GC via m6A methylation, providing both mechanistic insights and a potential therapeutic strategy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease globally and constitutes an independent risk factor for cardiovascular disease and mortality. Paeoniflorin (PF), the primary active compound derived from the traditional Chinese herb Paeonia lactiflora Pall., demonstrates multiple pharmacological activities. However, its anti-MASLD mechanisms remain incompletely elucidated. This study revealed that PF markedly ameliorates MASLD pathology by reducing hepatic lipid accumulation, inflammation, and fibrosis; ameliorating insulin resistance and liver function parameters; modulating key lipid metabolism genes (acetyl-coA carboxylase [ACC], sterol regulatory element-binding protein 1 [SREBP1], peroxisome proliferator-activated receptor gamma [PPAR-γ], fatty acid synthase [FASN], carnitine palmitoyltransferase 1 [CPT1], peroxisome proliferator-activated receptor alpha [PPAR-α], adipose triglyceride lipase [ATGL], and cluster of differentiation 36 [CD36]); decreasing pro-inflammatory factors (interleukin-1β [IL-1β], IL-6, tumor growth factor-α [TGF-α], and monocyte chemoattractant protein-1 [MCP-1]); and suppressing hepatic fibrosis markers (alpha-smooth muscle actin [α-SMA], tissue inhibitor of metalloproteinases-1 [TIMP1], collagen type I alpha 1 chain [COL1α1], fibronectin 1 [FN1], platelet-derived growth factor receptor beta [PDGFRβ], and plasminogen activator inhibitor-1 [PAI-1]). Through integrated transcriptomics and pharmacological overexpression approaches, we identified the SYK/SH3BP2 signaling pathway as the crucial mechanism driving MASLD pathogenesis. PF effectively attenuated hepatic metabolic dysregulation, inflammation, and fibrotic activation through inhibition of this pathway. Our work provided the first evidence establishing the SYK/SH3BP2 signaling axis as a pivotal pathway in MASLD progression, unveiling novel therapeutic targets while furnishing a mechanistic foundation for PF's potential application in MASLD treatment.