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Hand, foot, and mouth disease (HFMD) is a common childhood infection caused by enteroviruses, which exhibit distinct regional and seasonal epidemiological patterns. Wastewater-based epidemiology is a crucial tool for monitoring population infection dynamics and viral subtype distribution. However, the lack of effective on-site viral detection methods limits timely early warning and effective surveillance of infectious disease outbreaks. This study developed a one-pot RT-RPA/CRISPR-Cas12a assay-based, string-powered flywheel microfluidic chip for the multiplex detection of HFMD viruses in wastewater. First, by leveraging the regulatory effect of heparin sodium on CRISPR/Cas12a activity, a one-pot RT-RPA/CRISPR-Cas12a system was constructed to detect four major subtypes of HFMD virus (EV-A71, CV-A16, CV-A6, and CV-A10). Subsequently, this method was integrated into a pull-wire, flywheel-type, dual-axis centrifugal microfluidic chip, named the Heparin-Inhibited CRISPR-Associated System Chip (HICAS-Chip), enabling integrated enrichment, purification, elution, and multiplexed detection. The HICAS-Chip allowed visual detection of nucleic acids at 10 aM sensitivity within 1 h, corresponding to the sensitivity of the one-pot RT-RPA/CRISPR-Cas12a assay. During a year-long wastewater monitoring program in Guiyang City, China, the HICAS-Chip identified EV-A71 and CV-A10 as the predominant circulating subtypes, with incidence peaks observed in June, November, and December. The wastewater detection results obtained using HICAS-Chip showed high concordance (95.83%) with RT-qPCR assays. This platform provides an efficient portable device for the early detection and continuous monitoring of HFMD epidemic trends by wastewater-based epidemiology.

The integration of semiconductor nanomaterials with electroactive bacteria offers a promising strategy for enhancing light-driven biohybrid systems. However, the generation of reactive oxygen species (ROS) during photocatalysis poses a significant challenge, impairing microbial viability and reducing process efficiency. In this study, we developed a novel biohybrid system by sequentially biosynthesizing cadmium sulphide (CdS) nanoparticles and manganese oxide (Mn3O4) nanozyme on the surface of Shewanella oneidensis MR-1, creating an S. oneidensis-CdS@Mn3O4 composite. The CdS nanoparticles facilitated efficient light absorption and electron transfer, significantly enhancing hydrogen production under visible light irradiation. However, ROS accumulation (·OH, O2⁻·, and H2O2) induced oxidative stress, reducing bacterial viability and metabolic activity. To address this, Mn3O4 nanozyme were introduced, demonstrating robust ROS-scavenging capabilities, reducing hydrogen peroxide (H2O2) levels by 66.7%, superoxide radical (O2⁻·) by 60.7%, and hydroxyl radical (·OH) by a significant margin. As a consequence, hydrogen production by S. oneidensis-CdS@Mn3O4 reached 1203.60 µmol g-dcw⁻¹ after 70 h of visible-light irradiation, which was 2.6-fold higher than that of S. oneidensis-CdS. Furthermore, Mn3O4 preserved cell viability, maintained higher NADH/NAD⁺ ratios, and enhanced ATP levels, indicating improved metabolic efficiency. Structural characterization via scanning electron microscopy (SEM) energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) confirmed the successful synthesis of CdS and Mn3O4 on bacterial surfaces, while photoelectrochemical analysis verified retained photosensitivity. This study presents a simple yet effective strategy for mitigating ROS-induced damage in bio-semiconductor systems, offering insights into the design of more stable and efficient biohybrid platforms for sustainable energy production.Key pointsA biohybrid system (S. oneidensis-CdS@Mn3O4) was constructed by sequential biosynthesis of CdS and Mn3O4 nanozyme.Mn3O4 efficiently scavenged ROS, increasing hydrogen production by 2.6-fold compared to S. oneidensis-CdS.

Sepsis is a life-threatening syndrome defined by organ dysfunction arising from a dysregulated host response to infection. In its more severe forms, it may progress to multiple organ failure and is associated with a substantial increase in mortality risk. Nitric oxide (NO), a gaseous signaling mediator, has attracted attention because of its context-dependent roles in both physiological regulation and pathological processes. NO participates in intracellular signaling pathways and modulates protein function through post-translational mechanisms. In patients with sepsis, altered NO production has been closely linked to circulatory shock, vascular hyporeactivity, and multiple organ dysfunction, with particularly significant effects on cardiovascular and renal systems. Despite extensive investigation, the precise role of NO at different stages of sepsis remains incompletely defined. Clarifying the temporal and mechanistic aspects of NO dysregulation may help determine its utility as a biomarker and as a potential therapeutic target. Future clinical strategies should focus on modulating excessive NO activity without compromising its essential physiological functions, thereby improving the translational feasibility and clinical applicability of NO-directed interventions.

Chronic obstructive pulmonary disease (COPD) is now a major contributor to illness and death on a global scale. Traditional classifications based on pulmonary-function variables like the FEV1 (% predicted), lack sensitivity to early inflammatory changes and disease heterogeneity. In contrast, MiRNAs have emerged as promising biomarkers for respiratory conditions including COPD. The aim of this study was to examine the association between selected MiRNAs and COPD. A total of 200 COPD patients (GOLD I-IV, n=50 each) and 50 healthy controls were enrolled. Differentially expressed miRNAs were identified from the GEO database and validated by RT-qPCR. Univariate analysis and LASSO regression were used for feature selection. A logistic regression model incorporating selected variables was established for the forecast COPD severity. KEGG pathway enrichment of miR-518b target genes was performed using DAVID. Five miRNAs (miR-216a, miR-518b, miR-106a, miR-1233, and miR-184) were substantially increased in COPD and correlated with disease severity (P<0.001). LASSO regression identified FEV1 (% predicted), DLCO (% predicted), CAT score, miR-518b, and age as key predictors. The combined model showed excellent classification performance (AUC=0.953; sensitivity=92.9%; specificity=81.3%). MiR-518b emerged as a strong independent risk factor (OR=18.91, P=0.003). Gene set enrichment of miR-518b targets pointed to involvement in both the Toll-like receptor and Hippo pathways, implicating its critical roles in inflammation and airway remodeling. MiR-518b is closely associated with COPD severity and may be useful in clinical practice. A model integrating miRNA expression and clinical parameters provides high predictive value for COPD classification and supports precision diagnosis.

R-loops that contain a DNA:RNA hybrid and unpaired single-stranded DNA are important determinants of normal cell physiology and of the pathogenesis of numerous diseases. Although several different approaches to R-loop mapping in the genome have been developed, these techniques can produce conflicting results. In order to assess their robustness, a recent study by Chedin et al. compared the R-loop genomic distribution assessed using different methods in normal and cancer cell lines. Importantly, that study assumed a high degree of similarity between R-loop genomic distributions across different cellular types. Here, we compared DRIP datasets produced using the same protocol in different cell lines to show that only 26% of R-loop peaks are shared between chronic myeloid leukemia-derived HAP1 cells and human pluripotent stem cells. Meanwhile, HAP1-derived double knockout cell lines are characterized by much higher fractions of R-loop peaks that are identical both to each other (most of them) and to the R-loop peaks of their parental line (71 and 55%). We conclude that cellular type represents a major determinant of R-loop genomic distribution and, therefore, that only a systematic comparison of a large array of various cell/tissue type-derived R-loop datasets may address the inconsistencies between different R-loop mapping techniques.

As the demand for portable, efficient, and precise diagnostic technologies continues to grow in modern healthcare, traditional ELISA systems are increasingly limited by expensive and proprietary equipment. Here, we developed CRiBDL-ELISA (Classification-Regression Integrated Deep Learning Microbubble-Based Enzyme-Linked Immunosorbent Assay), a smartphone-based platform for precise biomarker detection across 5 orders of magnitude. The biomarkers captured on the well plates are labeled with platinum nanoprobes, which generate distinctive bubble patterns in the presence of hydrogen peroxide. A user-friendly smartphone application integrates imaging, YOLO-based object detection, image preprocessing, deep learning inference, and result visualization to enable one-click analysis with real-time feedback. Concentration-dependent bubble patterns captured by the smartphone camera allow precise biomarker quantification without the need for additional optical hardware. The platform achieved a detection limit of 0.001 ng/mL for CRP and PCT, which was enhanced to &#x223c;0.0001 ng/mL for NT-proBNP and cTnI via postprocessing. Quantification demonstrated high accuracy with R2 = 0.9983 and 0.9979 for CRP and PCT, and R2 = 0.9948 and 0.9942 for NT-proBNP and cTnI. Clinical validation showed 100.00% and 97.22% accuracy for CRP and NT-proBNP samples, respectively. Notably, NT-proBNP measurements showed strong concordance with commercial electrochemiluminescence platforms (R2 = 0.97), validating the clinical reliability. This CRiBDL-ELISA platform enables high-throughput biomarker quantification directly from microplates without specialized instrumentation, providing a cost-effective, robust, and portable solution for clinical diagnostics.

Multidrug-resistant bacteria (MDRB) have become a global health crisis that challenges the effectiveness of conventional antibiotics. Bacterial extracellular vesicles (BEVs) are nanoscale bilayered membrane vesicles secreted by both Gram-positive and Gram-negative bacteria. They can encapsulate proteins, lipids, and nucleic acids, and transfer these molecules between bacteria and host cells without direct contact. Owing to their natural ability to transport bioactive molecules, BEVs have recently gained attention as potential anti-infective platforms. They can deliver antimicrobial agents directly to resistant pathogens and act as vaccine carriers by triggering innate and adaptive immunity. Advances in BEV isolation, drug loading, and bioengineering have expanded their therapeutic potential. However, challenges such as large-scale manufacturing, immunogenicity control, and regulatory standardization still hinder clinical translation. This review summarizes the mechanisms, engineering strategies, and biomedical applications of BEVs against MDRB and discusses future perspectives for their safe and effective clinical use as antimicrobial nanoplatforms.

Although the core pathophysiological pathways of chronic urticaria (CU) are increasingly understood, the upstream triggers and factors contributing to disease chronicity remain poorly understood. Emerging evidence suggests that gut microbiota dysbiosis represents a potentially modifiable upstream factor, which has been predominantly investigated in patients with chronic spontaneous urticaria (CSU). Multi-omics and Mendelian randomization studies have provided convergent evidence linking gut dysbiosis to systemic inflammation and mast cell instability. This is characterized primarily by the depletion of short-chain fatty acid (SCFA)-producing taxa (e.g., Faecalibacterium, Roseburia and Bifidobacterium) and the relative enrichment of pro-inflammatory Proteobacteria (particularly Enterobacteriaceae). Mechanistically, these alterations may lower the mast cell activation threshold and promote systemic immune dysregulation through specific metabolic shifts, such as the depletion of SCFAs and unsaturated fatty acids, and the translocation of endotoxins (e.g., lipopolysaccharide) due to compromised intestinal barrier function. In this review, we discuss how the use of Mendelian randomization (MR) and germ-free mouse models can advance the gut-urticaria axis (with a primary focus on CSU) from mere correlation to causation, while highlighting the crucial need to account for clinical confounders. Finally, we evaluate the clinical translational potential and associated challenges of microbiome-targeted interventions (e.g., probiotics, faecal microbiota transplantation) as novel adjuvant therapies.

The controlled synthesis of large-area, high-quality two-dimensional (2D) MoS2 single crystals from a single nucleus is essential for applying this ultrathin semiconductor to next-generation integrated circuits to extend Moore's law. However, the complexity of traditional synthesis reactions hinders the reproducibility and controllability required for practical implementation. Here, we simplify the synthesis reactions by employing a distinctive all-in-one K2MoS4 precursor. Through thermal decomposition, this precursor simultaneously provides Mo and S sources, a growth promoter, and a protector, a mechanism confirmed by comprehensive theoretical calculations, in situ X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The single-crystal domain size of the obtained monolayer MoS2 derived from a single nucleus reaches up to 6 mm, exceeding that of other gas-phase synthesized samples. Furthermore, these large monolayer samples exhibit high crystallinity and uniformity, with room-temperature carrier mobilities as high as &#x223c;105 cm2 V-1 s-1. Our study underscores the critical role of chemical reaction design in synthesizing large-scale 2D semiconductors, paving the way for their application in scalable next-generation electronics.

The rapid development of flexible electronic technology is driving profound changes in the material system. In this revolution, organic materials have gained unprecedented development space due to their structural tunability, biocompatibility, and mechanical flexibility. However, their practical applications have long been limited by core bottlenecks, including low carrier mobility, poor environmental stability, and performance degradation caused by disordered molecular arrangements. In this context, covalent organic frameworks (COFs) and metal-organic frameworks (MOFs) are high-dimensional organic materials that provide nanoscale frameworks for excitons and electronics, exhibiting inorganic-like optoelectronic behaviors and performances. Fluorene-based organic semiconductors are a key class of organic materials that have been widely explored and applied across flexible devices, including organic light-emitting diodes (OLEDs), organic photovoltaics (OPVs), and others. It is emerging to explore the organic high-dimensional materials for accelerating flexible electronics facing organic intelligence. Given the outstanding features of MOFs and COFs, incorporating fluorene-based molecular fragments into these materials may yield superior performance. In the review, we summarize fluorene-based topological designs, synthesis, and characterization of COFs and MOFs, along with their application in adsorption, sensing, photocatalysis, and electrocatalysis. Finally, we discuss future challenges, such as scalability and carrier mobility improvement, and opportunities, providing insights for high-performance flexible electronic applications.

The exponential growth of the electric vehicle (EV) market has triggered a massive accumulation of spent lithium-ion batteries (sLIBs), which urgently requires sustainable recycling strategies to reduce environmental risks and ensure the availability of key mineral resources. While traditional pyrometallurgical and hydrometallurgical processes are established for large-scale operations, they are limited by high energy consumption, high reagent consumption, and hazardous secondary emissions. This review systematically evaluates current recycling methods, ranging from traditional smelting and acid-leaching to emerging electrochemical paradigms. A primary focus is placed on the redox-mediated method, a transformative electrochemical strategy designed to overcome the high energy consumption of traditional strategies and the inherent kinetic limitations in direct electrochemical extraction. This method introduces a redox mediator that decouples the electrochemical reaction into the mediator regeneration reaction at the electrode interface and the delithiation reaction at the solid-liquid interface, thereby enabling efficient and targeted energy-supplying recycling. Furthermore, the redox mediator recovery method can be ingeniously combined with value-added processes such as hydrogen production and zinc deposition, significantly reducing energy consumption and carbon footprint compared to traditional methods. This article shows the value of the redox mediator method, which combines waste treatment and resource regeneration.

The treatment of infected skin wounds remains a significant clinical challenge due to bacterial infection, delayed healing, and the rise of antibiotic-resistant bacteria. This study aims to develop a dual-crosslinked hydrogel dressing with integrated antibacterial and pro-healing functions to promote the regeneration of infected wounds. A dual-network hydrogel (CC/Cu2+ gel) was fabricated through the self-assembly of porcine small intestinal submucosa (SIS) collagen and subsequent ionic crosslinking between chitosan and Cu2+. The material's microstructure, mechanical properties, cytocompatibility, hemocompatibility, and antibacterial activity against S.aureus and E.coli were systematically characterized. The efficacy in promoting infected wound healing was evaluated using a full-thickness skin defect model in Bama miniature pigs. The incorporation of Cu2+ formed a denser polymer network, significantly enhancing the compressive modulus and strength of the hydrogel. The CC/Cu2+-5 gel formulation demonstrated effective antibacterial activity while maintaining acceptable cytocompatibility and hemocompatibility. In vitro, it facilitated fibroblast proliferation, collagen expression, and angiogenesis. In vivo, it accelerated wound closure, achieving a 98.97% healing rate within 24 days, and promoted well-structured epidermal and dermal regeneration, as confirmed by histological and immunofluorescent analyses. The CC/Cu2+ dual-crosslinked hydrogel, leveraging the synergistic effect of SIS collagen and copper ions, represented a promising functional dressing for managing infected wounds.

Extracellular vesicles (EVs) have emerged as promising biomarkers for liquid biopsy. However, their clinical detection is hampered by heterogeneity and low abundance. Herein, a dual-mode biosensor is constructed based on a biomimetic nanozyme for the highly sensitive and selective detection of tumor-derived EVs (tEVs). The biomimetic nanozyme is engineered through a dual-preservation effect involving coordination and confinement. In this design, the Fe2+-coordinated graphene quantum dots (Fe-GQDs, denoted as Fe-G) are spatially confined within DNA flower-like structures (Fe-G@DFs). This architecture effectively stabilizes the low-valence state of Fe2+ as the catalytically active center and enhances the peroxidase (POD)-like activity of the nanozyme. This system features an enzymology-inspired biomimetic activation, where the acidic condition triggers the disintegration of DFs, releasing the active Fe-G nanozymes with photothermally reinforced catalytic activity. Accordingly, colorimetric and photothermal dual-readout detection of tEVs is achieved with an ultrahigh sensitivity as low as 1.08 &#xd7; 103 particles mL-1. Moreover, by integrating multiple aptamer-MB probes (targeting HER2, MUC1, and GPC3) with machine learning, a sensor array is constructed to classify different cancer types and distinguish liver cancer patients from those with hepatitis and healthy individuals, demonstrating the clinical potential of this assay for noninvasive diagnosis.

Constipation, a prevalent gastrointestinal disorder, significantly impairs quality of life. Emodin, a bioactive anthraquinone found in traditional herbal remedies like Rheum palmatum, is empirically known for its laxative effects, yet its precise molecular mechanism remains incompletely understood. This study aimed to elucidate the laxative potential of emodin and delineate its underlying mechanism, with a specific focus on the activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. This therapeutic effect was abrogated in W1282X cystic fibrosis mice lacking functional CFTR, demonstrating CFTR-dependency. In HT-29 human colonic epithelial cells, emodin activated the CFTR chloride channel detected by a fluorescence-based membrane potential assay in a concentration-dependent manner with a half-maximal effective concentration (EC&#x2085;&#x2080;) of 10&#x207b;&#x2075;&#xb7;&#x2077; M and a maximal effect reaching 68.3% of that induced by the positive control, genistein. Mechanistic investigations revealed that emodin did not alter the total protein abundance of CFTR but significantly enhanced its phosphorylation. Pharmacological inhibition of the cAMP/protein kinase A (PKA) pathway attenuated emodin-induced CFTR activation and laxative effects. Consistently, emodin upregulated the mRNA expression of key cAMP/PKA pathway components, PRKACB and CREB1. In conclusion, our findings demonstrate that emodin alleviates constipation by activating the CFTR chloride channel. This effect is mediated through the cAMP/PKA signaling pathway, which enhances CFTR phosphorylation and channel activity, thereby promoting chloride-dependent fluid secretion into the colonic lumen. This study clarifies a pivotal molecular mechanism for emodin's laxative action and supports its therapeutic potential.

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High-power applications demand piezoceramics that combine large piezoelectric strain coefficients d33 and low mechanical loss (high Qm). In this study, [001]-textured Pb(Mg1/3Nb2/3)O3-PbZrO3-PbTiO3 (PMN-PZT) ceramics are fabricated using BaTiO3 seeds to induce grain orientation and manganese doping for hardening. Notably, by leveraging the rapid oxygen transport mechanism within the perovskite lattice, ceramics sintered in an oxygen atmosphere achieves a high relative density of 98%-99%, significantly exceeding the 95.6% achieved in air. The dense textured ceramics exhibit excellent combined soft and hard properties, showing high d33 of 1025 pC/N and high Qm of 810. Their performance under high drive is further evaluated via electrical transient response method. The results indicate that even at a high vibration velocity of 1.0 m/s, the dense ceramics maintained a high Qm of 560, higher than that of the less-dense textured counterparts (Qm = 140). Moreover, reduced strain hysteresis suggests that the dense microstructure enhances domain wall pinning, thereby mitigating mechanical losses due to inhomogeneous strain under high fields. In summary, this work demonstrates that oxygen-atmosphere sintering effectively improves both mechanical and electrical properties in textured ceramics, showing great promise for high-power piezoelectric applications.

Solar-thermal-electrical generators offer a promising route for the conversion of solar energy into electricity. Their reliability can be enhanced by integrating phase change materials (PCMs) to buffer thermal fluctuations and ensure stable operation, yet conventional PCMs often suffer from low thermal conductivity and poor solar capture. Herein, photosensitive Co/C-anchored reduced graphene oxide (rGO) conductive framework was fabricated via metal-organic framework (MOF) pyrolysis-assisted zinc volatilization strategy. This design enables the in situ formation of MOF-derived uniformly dispersed cobalt nanoparticles within rGO framework. After the encapsulation of paraffin wax (PW), the resultant rGO@Co/C-PW composite PCMs demonstrate a remarkable solar-thermal conversion efficiency of 92.5% under 100 mW&#xb7;cm-2 irradiation, attributed to the synergistic interplay between the broadband absorption and non-radiative relaxation of graphitic carbon and the localized surface plasmon resonance of Co nanoparticles. rGO@Co/C-PW also exhibits enhanced thermal conductivity, high phase change enthalpy, and excellent long-term cycling stability, supported by regulated non-isothermal phase transition kinetics via heterogeneous nucleation and spatial confinement. When integrated into a thermoelectric module, a sustained and stable power output of 8.82&#xa0;mW under 100&#xa0;mW&#xb7;cm-2 is generated, capable of powering small electronic devices. This study provides valuable insights into developing next-generation PCMs integrating solar-thermal conversion, thermal energy storage, and thermoelectric output.

Reflux esophagitis (RE) can progress to severe complications if not diagnosed and treated promptly. MIR99AHG is downregulated in the precursor disease of RE. This study aims to investigate the expression and regulatory mechanisms of MIR99AHG in RE. This study included 176 patients with RE. RT-qPCR was used to detect the expression of MIR99AHG, miR-200a-3p, Bax, Bcl-2, and caspase-3 For cellular experiments: cell proliferation, apoptosis, and the levels of inflammatory cytokines in cell culture supernatants were assessed using CCK-8 assay, Annexin V-FITC/PI double staining, and ELISA, respectively. DLR validated the binding between MIR99AHG and miR-200a-3p. ROC analysis evaluated their diagnostic value. Pearson correlation analysis assessed their relationship. In the RE and cell model groups, MIR99AHG expression was downregulated while miR-200a-3p expression was upregulated. MIR99AHG targeted and bound miR-200a-3p, negatively regulating its expression. Both demonstrated significant diagnostic value. Following modeling with acid salts and bile salts, cellular proliferation capacity decreased, apoptosis rates increased, and inflammatory factor levels rose. Upon overexpression of MIR99AHG, miR-200a-3p expression levels were downregulated, leading to enhanced cellular proliferation capacity, reduced apoptosis rates, and decreased inflammatory factor levels. MIR99AHG represents a promising clinical biomarker in RE. By downregulating miR-200a-3p levels, MIR99AHG may promote proliferation and repair of esophageal mucosal epithelial cells, inhibit excessive apoptosis, and mitigate local inflammatory responses, thereby exerting multifaceted protective effects during RE progression.

The exposome framework promises comprehensive characterization of chemical, physical, and biological exposures shaping human health, yet the measurement capacity now vastly outpaces interpretation and action. Here, we synthesize emerging frontiers that define the translation of exposome science into prevention: moving from "chemical dark matter" in high-resolution mass spectrometry toward functional exposomics; integrating the microbial exposome as both the target and modulator of exposures; deploying AI-enabled causal inference to bridge molecular precision with population-scale patterns; and embedding exposome evidence into proactive interventions, green chemistry, environmental redesign, and environmental justice frameworks. Progress over the next six decades will depend not only on measurement comprehensiveness but also on our capacity to shift from documenting environmental harm to designing healthier environments.