Search Results (76,107)

Early intervention is pivotal for mitigating the progression of Alzheimer’s disease (AD). This study presents an electrochemical immunosensor targeting synaptic vesicle glycoprotein 2A (SV2A) to facilitate early AD diagnosis. A sensing interface was engineered using a nanocomposite of graphene oxide (GO) and 3-carboxyl polypyrrole (3-COOH-PPy). Leveraging the synergistic effects between the large specific surface area of GO and the superior conductivity of 3-COOH-PPy, the composite established an efficient electron transport network. This architecture provided abundant active sites for capture antibody immobilization while significantly enhancing interfacial electron transfer kinetics. Coupling this interface with an enzyme-mediated signal amplification strategy based on the horseradish peroxidase (HRP)-catalyzed TMB/H₂O₂ system, the immunosensor achieved high sensitivity. It exhibited a wide linear range of 2 ng/mL to 16 μg/mL with a low limit of detection (LOD) of 0.15 ng/mL. Furthermore, successful detection in C57 mouse serum samples validated the method’s reliability and potential for clinical application. In conclusion, this immunosensor offers a sensitive and robust platform for the early diagnosis of AD. Full article

Charge transport underpins essential biological processes, including cellular respiration, photosynthesis, and enzymatic catalysis. Advances in molecular electronics have enabled single-molecule measurements that unequivocally establish redox-active proteins as efficient electron conductors, with their metal cofactors serving as intrinsic redox relays. By contrast, ubiquitous non-redox proteins lacking such redox centers have long been considered poor conductors. However, recent research has challenged this view, demonstrating that efficient charge transport in non-redox proteins can be mediated through polypeptide backbones, aromatic side-chain arrays, and hydrogen bond networks. This review surveys progress in understanding the single-molecule conductance of non-redox proteins. Firstly, we elucidate the fundamental transport mechanisms, highlighting the interplay between coherent tunneling and thermally activated hopping. We then provide an overview of state-of-the-art experimental techniques for single-molecule characterization. Through analysis of diverse systems spanning short peptides to large enzymes, we illustrate how aromatic amino acid networks and dynamic conformational fluctuations govern conductance, enabling emerging applications in label-free biosensing and single-molecule protein/DNA sequencing. Finally, we discuss persistent challenges and outline future opportunities for integrating protein-based conductors into bioelectronic devices. This review aims to stimulate further research and pave the way for novel applications harnessing protein conductance. Full article

Fluid mechanics in disordered structures gives rise to rich multiscale dynamics through the interplay of topology, symmetry breaking, and fluid–structure interactions. Heterogeneous networks encode mechanical responses, regulate flow organization, and shape energy dissipation, enabling memory effects and emergent collective behaviors across both natural and engineered systems. These principles operate across vast scales: from seamounts with characteristic scales of $L\approx {10}^3\mathrm{m}$ and Froude numbers $Fr\approx {10}^{-2}--{10}^{-1}$ generating deep-ocean turbulent mixing, to marine tidal turbines operating at Reynolds numbers $Re\approx {10}^7--{10}^8$ and Euler numbers $Eu\approx {10}^{-1}--{10}^0$, where inertial forces dominate flow dynamics. Although the dominant physical forces may vary across scales—for example, planetary rotation and stratification in large-scale oceanic flows versus viscous or interfacial effects in microscale systems—the comparison of dimensionless parameters provides a useful framework for discussing similarities in flow organization and scaling behavior. Empirical observations, network-based descriptions, and multiscale simulations collectively demonstrate how topological features constrain symmetry, organize transport pathways, and support predictive reconstruction and inverse design. These principles underpin applications ranging from engineered systems that exploit broken symmetries to rectify chaotic transport, to biological architectures where flows mediate information transfer, locomotion, and structural self-organization. In this Review, we synthesize recent advances to propose a unifying physical paradigm: fluid flows actively interact with disorder, reorganize dissipation, and convert structural asymmetry into functional mechanical performance across scales. Full article

Drug-induced kidney injury remains a major clinical challenge associated with diverse therapeutic agents and is an important cause of acute kidney injury, chronic renal dysfunction, and treatment-related morbidity. Growing evidence indicates that nephrotoxicity caused by anticancer, immunosuppressive, and anti-infective drugs is strongly driven by oxidative stress and redox homeostasis disruption. Excessive production of reactive oxygen species (ROS) in renal tubular cells overwhelms endogenous antioxidant defenses and triggers mitochondrial dysfunction, inflammatory signaling, and activation of stress-responsive pathways that culminate in tubular injury and renal functional decline. These processes promote apoptosis, necrosis, microvascular injury, and a reduction in the glomerular filtration rate, while dysregulation of redox-sensitive pathways involved in cell survival and repair further heightens renal vulnerability. This review summarizes current mechanistic insights into oxidative stress-mediated pathways of drug-induced nephrotoxicity, with emphasis on their translational relevance. In addition, it discusses emerging biomarkers for early detection and highlights recent advances in antioxidant-based and redox-modulating strategies that may help prevent renal injury and preserve kidney function. Full article

This study aimed to assess the species diversity and genetic structure of Meretrix clams around Hainan Island using mitochondrial cytochrome c oxidase subunit I (COI) DNA barcoding. The genus Meretrix is a common and economically important group of bivalves in the intertidal zones of Hainan Island, widely distributed in estuarine and nearshore sandy habitats and playing a significant role in local fisheries and aquaculture. In recent years, studies on Meretrix in Hainan have mainly focused on morphological identification and species records from limited coastal areas; however, due to the high phenotypic plasticity of shell morphology and the relatively subtle differences among species, traditional morphology-based identification remains challenging. Meanwhile, molecular systematic investigations of Meretrix in Hainan are still limited, particularly systematic studies using DNA barcoding to assess species diversity and geographic distribution patterns. A total of 141 individuals were collected from ten intertidal sites. Four species were identified—M. lyrata, M. lamarckii, M. meretrix and M. petechialis—with interspecific genetic distances (17.6–22.7%) far exceeding intraspecific variation (0.3–0.9%). Phylogenetic analysis based on COI sequences clearly distinguished four Meretrix species from the waters around Hainan Island, with each species forming a well-supported monophyletic clade, supporting their status as independent evolutionary lineages. In addition, two markedly divergent genetic lineages were detected within M. petechialis, suggesting that this species may possess a relatively complex population structure, one of which is typically found in northern Chinese waters, suggesting possible human-mediated introduction. Species richness was higher on the eastern coast, potentially influenced by regional hydrodynamic conditions. This study provides baseline DNA barcode data for Meretrix species in Hainan and supports the need for integrative management of this economically important resource. Full article

Volatile anesthetics have steadily become more popular in intensive care units for sedation for reasons related to their beneficial pharmacokinetic and pharmacodynamic properties. Common anesthetics such as isoflurane and sevoflurane rapidly reach sedative levels in the body, but they are also rapidly eliminated, allowing for quick recovery. These agents have minimal impact on the liver and kidneys, which makes them attractive options when compared to other agents including opioids, benzodiazepines, ketamine, and propofol. Use of delivery systems like AnaConDa^® (Anaesthetic Conserving Device; Sedana Medical AB, Danderyd, Sweden) has enabled providers to easily use these agents in the Intensive Care Unit (ICU). In this regard, they have recently provided additional beneficial consideration during intravenous drug shortages seen during the COVID-19 pandemic and at other times. These agents have shown organ-protective effects in the kidneys and lungs, which may even reduce the total time spent in the ICU. Pharmacodynamically, these anesthetics mediate their effects through central nervous system ion channels to exert analgesic and anxiolytic actions, thereby minimizing effects in the kidneys and lungs. These agents are primarily eliminated via exhalation, which makes them potential options for those with liver or kidney failure. This narrative review examines current efficacy and risks of using volatile anesthetics for sedation in the ICU setting and clinical roles for the future. Full article

Background/Objectives: Dihydroartemisinin (DHA), a bioactive metabolite of Artemisia annua, displays potent antitumor activity in multiple cancers. However, its dose-dependent transcriptional regulatory networks in colorectal cancer (CRC) remain insufficiently understood. This study aimed to clarify the molecular mechanisms of low- and high-dose DHA in human CRC cells and reveal the dose-dependent crosstalk among related biological processes. Methods: We integrated RNA-seq transcriptomic profiling and functional validation in HCT116 cells treated with 20 μM (low-dose) or 50 μM (high-dose) DHA. Differentially expressed genes (DEGs) were screened at FDR ≤ 0.05 and |log₂(fold change)| ≥ 1, followed by GO and KEGG enrichment analyses. Results: DHA inhibited cell viability dose-dependently, with an IC₅₀ of 50 μM. We identified 280 and 678 DEGs in low-and high-dose groups, respectively. Low-dose DHA induced apoptosis via GADD45α/β and ATF4/DDIT3-mediated endoplasmic reticulum stress and triggered senescence through G2/M phase arrest. High-dose DHA mainly modulated gene expression signatures associated with ferroptosis by regulating iron homeostasis and lipid peroxidation at the transcriptional level. Both doses suppressed glycolysis, lipid, and folate metabolism; high-dose DHA also inhibited MGAT5B-mediated glycosylation. DHA regulated five core signaling pathways dose-dependently, with high-dose DHA further repressing Wnt3a/16 and BMP4/6. Conclusions: This study first identifies ferroptosis-related gene networks as key transcriptional targets. It reveals dose-dependent crosstalk among cell death, senescence, metabolic reprogramming, and signaling, providing a transcriptomic framework and gene targets for optimizing DHA-based colorectal cancer therapy. Full article

Background: Antimicrobial-resistant Escherichia coli and Klebsiella pneumoniae represent an increasing challenge in community-acquired pediatric diarrheal infections. Understanding the genomic basis and dissemination of resistance in outpatient settings is essential for guiding antimicrobial use. Methods: Eighteen Gram-negative isolates obtained from pediatric outpatients with acute diarrhea were analyzed using selective culture methods, antimicrobial susceptibility testing, and whole-genome sequencing. Multilocus sequence typing, serotyping, virulence profiling, antimicrobial resistance gene detection, plasmid replicon typing, mobile genetic element analysis, and core genome-based phylogenetic analysis were performed. Phenotypic resistance profiles were correlated with genomic resistance determinants. Results: Klebsiella pneumoniae (55.56%) and Escherichia coli (44.44%) were identified, with all isolates exhibiting putative multidrug resistance-associated genomic profiles. Extended-spectrum β-lactamase genes, particularly blaCTX-M variants, were strongly associated with resistance to third-generation cephalosporins. In contrast, fluoroquinolone resistance correlated with gyrA and parC mutations and plasmid-mediated qnr genes. Phylogenetic analysis revealed diverse lineages harboring resistance determinants. In silico plasmid analysis revealed that key resistance genes co-occurred with IncF-type plasmids and mobile genetic elements, including ISEcp1, IS26, and class 1 integrons, suggesting putative plasmid association rather than confirmed localization. Conclusions: These findings highlight the small scale of plasmid-mediated antimicrobial resistance among E. coli and K. pneumoniae causing pediatric community-acquired diarrhea. The integration of phenotypic and genomic analyses underscores the need for continuous resistance surveillance to support rational antibiotic use in outpatient settings. Full article

NASA intends to return humans to the Moon, where partial gravity will put them at risk of musculoskeletal deconditioning. Resveratrol (RSV) is a promising nutritional countermeasure that may protect muscle health during disuse; however, its efficacy and mechanism in simulated lunar gravity are unknown. Forty adult male Wistar rats underwent 14 days of normal loading or partial weight-bearing at 20% of normal loading (PWB20). Unloaded animals received daily RSV supplementation with or without an ERα antagonist to test whether ERα was required to mediate RSV benefits. Muscle function was longitudinally assessed, and a Western blot was used to quantify key signaling proteins in the soleus muscle. PWB20 led to a significant reduction in grip strength (−14.2%) associated with marked changes in electrophysiological muscle properties. RSV-supplemented animals performed better throughout the study, but not when Erα was inhibited. RSV supplementation resulted in a greater ERα phosphorylation ratio compared to PWB20 alone (3.5 vs. 1.91). These results suggest that RSV can mitigate muscle deconditioning in a lunar gravity analog and that ERα signaling is required. Full article

The fashion industry’s business is becoming increasingly complicated and active. This industry is expected to be highly competitive, particularly in the retail sector. Therefore, this research aims to examine the impact of supply chain information sharing and quality management on firm performance, with supply chain agility as a mediating variable, in the Asian fashion industry. A total of 169 participants from the fashion sector in a developing country were surveyed. The proposed hypotheses were examined using a quantitative approach, employing Partial Least Squares Structural Equation Modeling (PLS-SEM) via SmartPLS to assess and validate the measurement model. The results indicate that supply chain information sharing and quality management have a significant impact on a firm’s performance. Similarly, the sharing of supply chain information and quality management has a significant impact on firm performance by mediating supply chain agility. The study offers actionable insights for managers in volatile fashion supply chains. Firms can enhance performance by sharing real-time demand and inventory information, strengthening key quality practices, and adopting flexible, data-driven production processes. Integrating information sharing, quality management, and agility enables faster responses to shifting consumer trends, thereby improving overall competitiveness in fast-fashion environments. This study offers valuable guidance for supply chain professionals seeking to enhance practices within their networks. The results underscore the strategic importance of information sharing and quality management in promoting agility, an essential capability for achieving a competitive advantage. Additionally, the insights generated are relevant to practitioners, policymakers, and industry leaders aiming to strengthen supply chain responsiveness and resilience. Full article

Cardiovascular-kidney-metabolic (CKM) syndrome integrates excess adiposity, metabolic dysfunction, kidney impairment, subclinical cardiovascular diseases, and clinical events along a staged continuum that invites unified prevention and treatment. Ultra-processed foods (UPFs) are a complex, high-prevalence exposure that may influence risk across CKM stages through nutrient profiles, additives, processing-induced compounds, and packaging-related contaminants. This review synthesizes epidemiologic, mechanistic, and translational evidence with attention to exposure definition and analytic rigor. We summarize NOVA-based UPF operationalization across dietary assessment tools, highlighting misclassification of mixed dishes, brand heterogeneity, and energy under-reporting, and we propose further examination of energy-adjusted models, calibration, and harmonized metrics. Observational studies consistently associate higher UPF intake with adiposity, diabetes, chronic kidney disease, cardiovascular events, and mortality, with modest to moderate effect sizes that are heterogeneous across populations. Mechanistic data from metabolomics, lipidomics, proteomics, and the gut microbiome converge on pathways of inflammation, lipid metabolism, oxidative and metabolic stress, and intestinal barrier dysfunction; in selected cohorts, multi-omics modules account for a substantial minority of UPF-outcome associations. We outline quality-control pipelines, batch-effect prevention/correction, and multiple-testing control necessary for reproducible diet-omics. Translationally, targeted lipidomic and proteomic panels show promise for CKM risk stratification and monitoring but require validation, clinical thresholds, and guideline endorsement. Equity and global context, including differences in product mix, food systems, and care capacity, modify population impact. We conclude with a research agenda prioritizing harmonized exposure metrics, error-aware modeling, standardized multi-omics workflows, and adequately powered, stage-specific interventions capable of testing mediation and prognostic utility. Full article

This study investigates the psychological mechanisms through which coaching leadership influences employees’ bootlegging innovation behavior. Drawing on leadership and organizational behavior theories, we propose a serial mediation model in which work meaning and organizational psychological ownership jointly transmit the effects of coaching leadership on employees’ informal innovative behavior. Using survey data collected from 427 employees, the results demonstrate that coaching leadership positively predicts bootlegging innovation behavior. Moreover, both work meaning and organizational psychological ownership independently mediate this relationship. Importantly, the findings further support a sequential mediation pathway, indicating that coaching leadership enhances employees’ perceptions of work meaning, which subsequently fosters stronger organizational psychological ownership and, in turn, stimulates bootlegging innovation behavior. By elucidating the intertwined motivational and ownership-based psychological processes underlying informal innovation, this study advances the literature on coaching leadership and employee-driven innovation. The findings also offer practical insights for managers seeking to cultivate grassroots innovation by fostering meaningful work experiences and a sense of psychological ownership among employees. Full article

The start-up process of water-lubricated bearings (WLBs) exhibits strong nonlinearity and is highly sensitive to the surface topography of both the bush and the journal. However, due to machining errors and operational wear in practical manufacturing and service, the bush inevitably develops surface waviness and wear, which significantly influence its start-up behavior. This issue is particularly critical in high-speed underwater unmanned vehicles, where lightweight design precludes the use of oil lubrication systems, making WLBs a more economically favorable and reliable alternative. To address this, the present study establishes a start-up tribo-dynamic model that comprehensively incorporates both bush surface waviness and wear to systematically investigate their coupled effects on the tribo-dynamic behavior during WLB start-up. The research findings indicate that axial surface waviness reduces the hydrodynamic effect during the start-up phase. Consequently, a higher rotational speed is needed to generate the necessary hydrodynamic pressure for the WLB to start up successfully. The significance of the influence exerted by circumferential surface waviness on start-up behavior is determined by its frequency number, m. A larger m leads to greater fluctuations in both hydrodynamic pressure and contact pressure. Furthermore, when wear occurs, the amplitude of bush surface waviness mediates the influence of wear depth on start-up performance, thereby modifying the optimal wear depth previously established for smooth bearings. These findings highlight the importance of controlling circumferential waviness frequency during machining and manufacturing processes to optimize WLB start-up reliability and service life. Full article

Background: Patients with diabetes mellitus exhibit increased susceptibility to peri-implant inflammation and implant failure due to systemic metabolic dysfunction, impaired immunity, and delayed tissue healing. The oral microbiome is increasingly recognized as a key intermediary in these pathogenic processes. Aims: This review aims to systematically evaluate the available literature examining the relationships among the oral microbiome, biomaterial biocompatibility, and inflammatory changes in peri-prosthetic tissues in insulin-dependent diabetic patients. Methods: A systematic search of PubMed and Scopus databases identified studies published between January 2000 and July 2025. Eligible studies (25 in total) included clinical, histological, microbiological, or immunohistochemical investigations involving diabetic patients rehabilitated with dental implants or prostheses. Study selection and reporting followed PRISMA 2020 guidelines. Results: Diabetic cohorts showed consistent microbial alterations, including a higher relative abundance of periopathogenic species (P. gingivalis, T. forsythia, and F. nucleatum), lower microbial diversity, and greater biofilm-forming potential. Histological analyses frequently described increased inflammatory infiltrates, higher cytokine expression, and reduced soft-tissue integration. Biomaterial surface characteristics were also associated with differences in microbial adhesion, while hyperglycemia was linked to microbial and host-response patterns suggestive of greater pathogenicity and inflammation. Collectively, these findings suggest that diabetes-associated dysbiosis may be associated with increased peri-implant inflammatory changes and altered peri-implant homeostasis. Conclusions: The oral microbiome may be involved in inflammatory activity and biocompatibility at the tissue–implant interface in diabetic patients. A better understanding of host–microbe–material interactions may support risk assessment and help inform future personalized management strategies, such as targeted antimicrobial approaches, probiotic modulation, and biomaterial surface optimization, although these implications should be interpreted cautiously given the predominantly observational and heterogeneous nature of the available evidence. Full article

Introduction: Remote ischaemic conditioning (RIC) is a promising treatment for neurological disorders. It involves cycles of temporary ischaemic stimulus, usually applied to a limb, and has shown significant improvement in neurological function in many trials. This review focuses on identifying and summarising the biomarkers of RIC that can enhance clinical practice and understanding of its mechanisms. Methods: A search was conducted in MEDLINE and EMBASE up to August 2025 using terms related to ischaemic conditioning. Studies were included if they were RCTs involving cerebrovascular disease, used RIC as treatment, and measured mechanistic biomarkers. We extracted and summarised data on study design, participant characteristics, RIC intervention protocols (including timing, frequency, duration, and pressure), biomarker types and measurement methods, timing of biomarker assessment, and main findings relating biomarker changes to clinical outcomes. Results: The review identified twenty-one RCTs examining biomarkers, including serum biomarkers, imaging markers, and other physiological indicators. Key biomarkers identified include systemic inflammatory cytokines and various imaging markers such as cerebral blood flow (CBF), white matter hyperintensities (WMH), and brachial artery flow-mediated dilation (BA-FMD). Conclusions: The evidence suggests that RIC modulates various biomarkers linked to neuroprotection and recovery. Reliable biomarkers of RIC would enhance the understanding of its mechanisms and improve targeted therapies. The clinical utility of these biomarkers requires further validation through large-scale trials. Standardised protocols and longitudinal studies are essential for optimising RIC therapy and improving patient outcomes in stroke and cerebral small vessel disease. Future research should focus on expanding our understanding of these biomarkers and their interactions with RIC, leading to more personalised and effective treatments. Full article