Research最新文献

The overuse and misuse of antibiotics have led to widespread resistance in bacteria, which makes infections difficult to treat. The insufficient prevention measures, limited treatment options, and delayed antibiotic developments call for immediate global actions to discover effective and safe treatments for bacterial infections. Over the past decades, more and more studies have found that bacterial extracellular vesicles (BEVs) secreted by bacteria with nanoscale size, lipid bilayer structure, pathogen-associated molecular patterns, and inherent bioactive substances are the ideal candidates for bacterial infection treatment. Meanwhile, advanced engineering approaches have further endowed these BEVs with more customizable properties to effectively fight against bacterial infections. Herein, the present review begins with an overview of the biogenesis and biocomponents of BEVs to better comprehend their bioactivities against bacterial infections. Their isolation and engineering approaches are then introduced, with an emphasis on the diverse genetic, physical, and chemical strategies to functionalize them with desirable capacities for the optimal treatment of bacterial infections. Recent advances in exploring the natural BEVs as antibacterial and antiadhesion agents, as well as the engineered BEVs as vaccine antigens, vaccine adjuvants, and delivery nanocarriers, are expounded successively. Discussions on the new trend of engineering BEVs as nanoweapons to combat bacterial infections, in terms of advantages and challenges, are provided at the end to expedite these BEV-based therapeutic modalities for bacterial infections from bench to bedside.

High-precision sensors are of fundamental importance in modern society and technology. Although there are various schemes for the construction of sensors relying on different physical mechanisms, obtaining sensors with higher levels of sensitivity and stronger robustness has always been expected. In particular, non-Hermitian quantum sensors have recently attracted substantial attention due to their unique properties. So far, 2 types of non-Hermitian sensors based on exceptional points and topological zero modes have been realized. Here, high-order exceptional bound states with robust properties are constructed for the first time. Based on these states, we propose theoretically and demonstrate experimentally another new type of non-Hermitian quantum sensors. Such sensors not only are robust against disorders but also have unprecedented sensitivity. Their sensing performance can display the improvement of many orders of magnitude over the previous non-Hermitian sensors. Furthermore, we design and fabricate such sensors based on circuit networks. Taking weak magnetic field detection as an example, we also experimentally demonstrate their sensing capabilities. Our work opens up new avenues for the development of highly sensitive sensors, which have a wide range of applications in various fields.

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.].