Research最新文献

The worldwide decline in male fertility represents a growing public health challenge, with fluoride exposure recognized as a key environmental factor exacerbating this decline. Fluoride hurts male reproduction, yet the specific mechanism remains unclear. Here, we demonstrate that fluoride reduced mouse sperm quality, destroyed the structure of testicular tissue, and caused severe damage to testicular somatic cells (Leydig and Sertoli cells). Meanwhile, the number of autophagosomes increased in Leydig cells and decreased in Sertoli cells. Network toxicology and functional analysis identified miR-34a-5p as the pivotal miRNA orchestrating fluoride-induced autophagic imbalance in testicular somatic cells. REST was identified as a novel miR-34a-5p target gene exhibiting pro-autophagic activity. Fluoride down-regulates miR-34a-5p and up-regulates REST in Leydig cells, whereas it exerts the opposite effects in Sertoli cells. The rescue experiment elucidated specific mechanisms: Fluoride down-regulates miR-34a-5p in Leydig cells, thereby derepressing REST to activate autophagy. Conversely, in Sertoli cells, fluoride up-regulates miR-34a-5p to suppress REST expression and inhibit autophagy. Collectively, the present study reveals an important mechanism underlying fluoride-induced male reproductive toxicity and provides a potential therapeutic target.

While sleep disorders are a known correlate of social memory deficits, the underlying neurocircuitry and molecular mechanisms remain poorly understood. Using an oxytocin (OXT)-specific sensor imaging approach, we discovered that chronic sleep deprivation (SD) reduced OXT neuropeptide release in the hippocampal CA2 and prelimbic cortex (PrL), thereby disrupting social memory encoding and retrieval processes, respectively. Using fiber photometry recordings and in vitro electrophysiology, we identified the activity of the predominantly OXT-expressing neurons in the paraventricular hypothalamic nucleus (PVN^OXT) were reduced following SD. Specific optogenetic activation of the PVN^OXT-CA2 pathway during encoding phase or PVN^OXT-PrL pathway during retrieval transiently restored SD-induced social memory deficits. Conversely, optogenetic high-frequency activation of PVN^OXT neurons enhanced the function of both PVN^OXT-CA2 and PVN^OXT-PrL pathways, promoting increased OXT release and providing sustained protection against SD-induced social memory deficits. These findings offer causal evidence that the PVN^OXT-CA2 and PVN^OXT-PrL pathways exert distinct modulatory roles in sleep-related social memory deficits and thereby nominate these pathways as precise targets for neuromodulation in sleep-related cognitive disorders.

Upon tumor metastasis, lymph nodes (LNs) undergo mechanical stiffening, yet how this change influences T cell activation within the microenvironment remains incompletely understood. In particular, the dynamic mechanical forces during activation are transduced by cell-extracellular matrix (ECM) interactions, while cell-cell interactions persist. Here, we established a novel T cell culture platform using hydrogels with tunable stiffness and decoupled presentation of RGD peptide and anti-CD3 monoclonal antibody, separately mimicking ECM-T cell and T cell-antigen-presenting cell interactions. This platform closely mimics the LN microenvironment during T cell activation. By integrating experiments with mathematical modeling, we revealed that T cells sensed mechanical changes in the microenvironment requiring RGD/integrin ligation, while stiff matrix up-regulated F-actin aggregation instead of myosin contraction, deforming the nucleus and promoting yes-associated protein nucleus translocation, resulting in interleukin-2 expression and T cell activation. Our findings shed light on the mechanobiological mechanism underlying the potential benefits of immunotherapy in patients with LN metastases and provide an optimized mechanical platform for studying T cell activation and expansion in vitro.

Lightweight multifunctional aerogels hold great promise in applications, e.g., electromagnetic microwave absorption, thermal insulation, and acoustic damping. However, conventional aerogels often suffer from limited functionalities, complicated manufacturing, and poor sustainability. Metal-organic frameworks (MOFs), with tunable porosity and abundant active sites, offer a compelling route to high-performance multifunctional aerogels, but it has remained a grand challenge to develop sustainable multifunctional MOF-based aerogels. Here, we report a sustainable multifunctional bio-aerogel (Ni-CCA) by integrating hierarchical scale-like topological Ni-MOF-NH₂ with cellulose through simple pretreatment using deep eutectic solvent followed by stepwise assembly-carbonization. The resulting aerogel features an ultralow density and a 3-dimensional layered porous structure. With 5 wt.% filler loading, Ni-CCA achieves a minimum reflection loss (RL_min) of -53.47 dB and an effective absorption bandwidth of 4.42 GHz, along with a radar cross-section suppression of 27.90 dB·m². Additionally, Ni-CCA shows enhanced flame retardancy (64.3% reduction in peak heat release), low thermal conductivity [33.3 mW/(m·K)] and improved acoustic damping (NRC of 0.31, 15 to 23 dB attenuation). The multifunctionalities of this bio-aerogel stem from its hierarchical architecture and synergistic loss mechanisms, offering a promising strategy for creating the next generation of lightweight multifunctional protective materials.

Stretchable conductive hydrogel composites with infrared stealth and electromagnetic interference (EMI) shielding are in high demand for aerospace, military, and soft robotics. However, realizing stable and efficient performance with low conductive filler content under harsh conditions remains a substantial challenge. Herein, a flexible multifunctional double network hydrogels with high performance and environmental stability was constructed via transition metal carbide/nitride (MXene)/(NH₄)₂SO₄-treated strategy-assisted ultrasonic dispersion and thermal polymerization method. The synergistic effect of MXene and (NH₄)₂SO₄ within the hydrogel system led to a 3-fold enhancement in mechanical properties, 20-dB improvement in EMI shielding effectiveness, and 40% enhancement in the gauge factor with only 0.12 wt % conductive filler. Benefiting from its high conductivity, efficient thermal insulation, and composite network structure, the double network hydrogels maintain stable EMI shielding and infrared stealth performance under various harsh conditions including repeated stretching, prolonged water evaporation, low-temperature freezing, high-temperature heating, alcohol lamp flame exposure, and high-strain stretching. These findings demonstrate that the hydrogels combine ultra-low filler efficiency, environmental robustness, and multifunctional adaptability, making it a promising candidate for next-generation aerospace, military, and wearable electronic applications.

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.