Search Results (5,924)

Climate change and rapid urbanization are intensifying urban pluvial flooding and threatening sustainable urban development. This study proposes a three-stage, four-dimensional framework (TSFD-UPFR) to assess urban pluvial flood resilience across resistance, response, and recovery phases that integrate natural, infrastructural, social, and economic dimensions. Using a representative urban catchment affected by a typical extreme rainfall event, we couple hydrological–hydrodynamic simulations with multi-source remote sensing and socio-economic indicators at a 100 m grid resolution to enable spatially explicit assessment. The results indicate moderate overall resilience with pronounced spatial heterogeneity. Resistance is primarily constrained by drainage capacity and impervious surfaces, response is shaped by road connectivity and public service accessibility, and recovery is determined by essential facility restoration and economic support. Low-resilience clusters are concentrated in dense built-up areas and transport hubs, revealing structural weaknesses in adaptive capacity. By linking flood processes with socio-economic recovery dynamics, the framework captures cross-stage interactions within urban systems. The findings support climate-adaptive planning, targeted infrastructure investment, and resilience-oriented governance, contributing to sustainable and equitable urban transformation in megacities facing intensifying extreme rainfall. Full article

Reconciling hydropower development with aquatic biodiversity conservation is a central challenge for sustainable river management worldwide. Cascade dam configurations, in which multiple impoundments are arranged in series along a single channel, impose longitudinal environmental gradients that restructure biological communities across trophic levels. Whether the resulting multi-trophic responses are independently driven by shared abiotic gradients (environmental filtering) or mechanistically coupled through direct food-web interactions (trophic cascading) remains unresolved. We surveyed phytoplankton, zooplankton, and benthic macroinvertebrates simultaneously at seven stations along a 430 km gradient downstream of Danjiangkou Dam in the Hanjiang River, the largest tributary of the Yangtze River and the source of China’s South-to-North Water Diversion Middle Route, over eight seasonal campaigns (2015–2017). Variance partitioning, piecewise structural equation modeling, Mantel tests, and co-occurrence network analysis were applied to partition environmental and trophic pathways. Environmental filtering dominated community restructuring at all three trophic levels, while the biotic proxy for direct trophic interactions explained less than 0.4% of community variation, consistent with weak detectable trophic coupling at seasonal resolution. Distance from Danjiangkou Dam shaped downstream transparency and turbidity gradients that mediated trophic-level-specific responses along distinct environmental axes (pH and water temperature for phytoplankton, conductivity for zooplankton, and transparency for benthic macroinvertebrates). Benthic macroinvertebrates were systematically decoupled from the pelagic analytical framework, absent from the cross-trophic co-occurrence network and structured more by spatial configuration than by water-column variables. Hub species in the network were associated with downstream mineralized conditions, confirming that network architecture reflects shared environmental preferences rather than biotic interactions. These findings support a management shift from single-dam mitigation toward cascade-scale coordination of environmental flow regimes, sediment connectivity, and substrate restoration as integrated strategies for sustaining multi-trophic biodiversity in regulated rivers. Full article

The pathogenesis of inflammatory bowel disease (IBD) is driven by an interplay among intestinal dysbiosis and aberrant mucosal immune responses. This review centers on the microbiota as a pivotal pathogenic hub, systematically dissecting how three hallmark features of dysbiosis—reduced microbial alpha diversity, depletion of immunomodulatory commensals, and expansion of pro-inflammatory pathobionts—collectively compromise epithelial barrier function, promote bacterial translocation, and sustain chronic mucosal inflammation. We further integrate emerging evidence implicating bidirectional gut-brain axis communication in amplifying both peripheral inflammation and central nervous system (CNS)-mediated behavioral comorbidities. Building on this mechanistic framework, we critically evaluate next-generation microbiota-targeted interventions: standardized fecal microbiota transplantation (FMT), rationally designed live biotherapeutic products (LBPs), precision phage cocktails targeting defined pathobionts, and microbiome-informed dietary strategies. Collectively, these approaches represent a paradigm shift—from broad-spectrum immunosuppression toward mechanism-guided, ecosystem-level modulation—thereby advancing the goal of precision medicine in IBD. Full article

Primary Sjögren’s disease (SjD) is characterized by lymphocyte infiltration into exocrine glands. Mitochondrial dysfunction is a critical pathological mechanism underlying SjD, and mitophagy plays a vital role in clearing damaged mitochondria. This study used bioinformatic analysis to explore the potential roles of mitophagy-related genes in SjD pathogenesis and immune infiltration. Bioinformatic analysis was performed on the SjD microarray datasets to identify differentially expressed genes (DEGs). Mitophagy-related DEGs were selected and analyzed using functional enrichment, protein–protein interaction (PPI) networks, and machine learning (Least Absolute Shrinkage and Selection Operator [LASSO] and Random Forest) to identify hub genes. Their diagnostic value was assessed by receiver operating characteristic (ROC) curves. Immune infiltration and its correlation with hub genes were also evaluated. Hub gene expression in the salivary glands of patients was validated using qRT-PCR. Regulatory networks were also predicted. Three hub genes (GABARAPL1, PINK1, and SQSTM1) were identified. They showed high diagnostic specificity and were downregulated in SjD salivary glands. Immune infiltration analysis revealed increased levels of activated natural killer (NK) cells, memory B cells, plasma cells, CD8+ T cells, Tfh cells, and M1 macrophages, but decreased levels of Tregs and M2 macrophages. Hub gene expression was correlated with specific immune cell subsets. Regulatory network predictions highlighted potential upstream regulators and therapeutic compounds. This study identified three mitophagy-related hub genes linked to immune dysregulation in SjD, providing novel insights into disease mechanisms and potential therapeutic targets. Full article

Cunninghamia lanceolata (C. lanceolata), a pivotal economic timber species in southern China, faces increasing threats from global warming and heat stress. Due to limited knowledge regarding its stress response mechanisms, uncovering the molecular basis of heat tolerance is crucial for breeding resilient varieties. Therefore, the objective of this study was to elucidate the physiological and molecular mechanisms of C. lanceolata in response to heat stress. In this study, we performed a time-series transcriptomic analysis on leaves of C. lanceolata ‘6421’ seedlings exposed to heat stress (39 °C) for 0, 1, 4, 8, 12, and 16 h. A total of 1130 differentially expressed genes (DEGs) were identified, with functions primarily enriched in signal transduction, protein folding, and the MAPK and NF-kappa B signaling pathways. Weighted gene co-expression network analysis (WGCNA) revealed a complex regulatory network, identifying ClHsf8 as a central hub transcription factor. To validate its function, ClHsf8 was cloned and overexpressed in tobacco (Nicotiana benthamiana). Under heat stress conditions, transgenic plants exhibited enhanced thermotolerance compared to wild-type controls, characterized by significantly higher activities of antioxidant enzymes (SOD, POD, and CAT) and reduced accumulation of MDA and H₂O₂. Our findings elucidate the molecular regulatory mechanisms of C. lanceolata in response to high temperatures and demonstrate the functional role of ClHsf8 in conferring heat tolerance, providing a theoretical foundation for the genetic improvement of heat-resilient cultivars. Full article

Regenerative medicine is becoming more widely integrated with longevity-oriented and preventive care as populations age and chronic degenerative diseases burden healthcare systems. Mesenchymal stem cell (MSC) therapies have progressed from experimental interventions to approved products, yet scalability, safety, cost, and regulatory complexity constrain widespread implementation in medical wellness contexts. The predominant therapeutic effects of MSCs are mediated via paracrine mechanisms, leading to cell-free approaches based on the MSC secretome—a complex mixture of bioactive factors including all types of biomolecules and assemblies thereof, such as exosomes. These acellular products offer compelling advantages: multiple batches from single-donor sources, standardized dosing, reduced allogeneic cell risks, and shorter outpatient-compatible administration. Preclinical and clinical data indicate that secretome-based products exert potent regenerative effects in osteoarthritis, chronic wounds, stroke, traumatic brain injury, and neurodegenerative diseases. This review examines the evolution from cell-based to cell-free regenerative strategies, focusing on human umbilical cord Wharton’s jelly MSC secretome for precision longevity medicine. It compares MSC therapies with secretome- and exosome-based formulations across mechanistic, manufacturing, safety, practical and regulatory dimensions. Regional perspectives highlight Southeast Asia, and especially Thailand, as an emerging regenerative-longevity hub. Finally, it outlines the preventive patient journey integrating cell-free interventions within multi-modal programs aimed at extending healthspan. Full article

Despite effective antiretroviral therapy, HIV persists in diverse tissue reservoirs that pose major barriers to a cure. This review examines the heterogeneous maintenance mechanisms of HIV reservoirs in lymph nodes, intestinal mucosa, and the central nervous system (CNS). It analyzes how distinct tissue microenvironments—including immune-privileged niches, specialized cellular subsets, and local signaling networks—govern viral persistence and latency. Lymph nodes function as a dynamic hub interconnected with systemic reservoirs; the intestinal mucosa represents a site shaped by barrier integrity, microbial translocation, and mucosal immunity; the CNS constitutes a compartmentalized sanctuary protected by the blood–brain barrier. The review further discusses tissue-specific antiretroviral drug penetration and targeted clearance strategies, providing a foundation for developing multi-site intervention approaches toward HIV cure. Full article

This study seeks to examine the attractiveness of higher education institutions as community spaces for students and the significance of the services they provide. It aims to explore students’ perspectives on planning their long-term futures, particularly in assessing whether the university environment serves as a stronger influence than their place of origin or family background. The role of the university is particularly significant if it is located outside the student’s town of origin, so the student’s decision to attend a particular institution is not necessarily based on the specific undergraduate program or the prestige of the university. The study combines a review of the national and international literature with an empirical investigation, utilizing a questionnaire survey to analyze students’ decision-making processes. Many students perceived the university as a transitional “island”, offering a temporary space to inhabit before embarking on their future careers. The degree obtained serves as a “passport” to professional opportunities, while the university experience provides a unique community environment and represents a significant step toward independence and separation from familial influence. These findings hold particular relevance for universities, which are continually redefining their roles in response to changing student expectations. Many students view the university not merely as a site of learning but as a precursor to adulthood and a foundational space for personal growth. This study addresses a gap in the existing literature by focusing on the appeal of universities as local hubs and comparing their influence to the retaining power of family ties, offering insights for student development. Full article

Alcohol-induced liver damage (AILD), characterized by oxidative stress and inflammation, is a major health concern. While black ginseng extract (BGE) exhibits diverse pharmacological activities, its protective effects against AILD and underlying molecular mechanisms remain unclear. This study evaluated the protective effects of BGE against AILD using in vivo, in vitro, and in silico models. In mice, daily oral administration of 25% ethanol (5 g/kg) for 2 weeks induced liver injury. BGE (100–500 mg/kg) significantly reduced serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT)levels while increasing catalase (CAT) and superoxide dismutase (SOD) activities. In ethanol-treated HepG2 cells, BGE inhibited nitric oxide (NO) production and suppressed cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) expression while increasing heme oxygenase-1 (HO-1)expression. Ginsenoside Rh1, quantified at 4.7 mg/g via quadrupole linear ion trap tandem mass spectrometry coupled with UPLC (UPLC-Q-TRAP-MS/MS), was identified as a key bioactive compound. Network pharmacology and molecular docking analyses revealed key inflammatory signaling pathways and core hub genes associated with ginsenoside Rh1. Integrated analyses suggest that ginsenoside Rh1 contributes to the multi-target effects of BGE by modulating inflammatory signaling pathways. Collectively, BGE is a potential therapeutic candidate for the prevention and treatment of AILD, with ginsenoside Rh1 serving as a key bioactive constituent and quality control marker. Full article

(1) Background: As security breaches rise, the “Security by Design” approach is imperative for software organizations. (2) Problem: A significant gap remains between declared security priorities and actual developer behavior. This gap widens in hybrid environments, where social mechanisms that reinforce security norms weaken. (3) Objective: This research investigates the organizational mechanisms translating security priorities into secure coding behavior and proposes a framework to maintain them in distributed teams. (4) Methods: We surveyed 244 software developers across international sites of a large IT enterprise. Using validated measures, we tested a mediation model linking priorities, climate, and behavior, with remote work as a moderator. (5) Results: Organizational Security Climate mediates the relationship between priorities and behavior. Crucially, remote work significantly weakens this mediation, showing that “hybrid friction” disrupts the transmission of security norms. (6) Conclusions: We created a framework for building a security climate in hybrid teams by introducing explicit mechanisms, such as traceable leadership signals and structured network hubs. This ensures clear DevSecOps integration and consistent security implementation across all locations. Full article

The tomato hind (Cephalopholis sonnerati) is a marine aquaculture fish species with high economic value. Elucidating the mechanisms underlying its growth regulation is crucial for the development of the aquaculture industry. To analyze the biological mechanisms underlying growth differences, individuals with extreme body sizes at 8 months of age from the same batch were selected in this study. A combined experiment of “body size × feeding status” was constructed, and transcriptome sequencing and weighted gene co-expression network analysis (WGCNA) were performed on brain and muscle tissues. The results showed that 2553 differentially expressed genes (DEGs) were identified between individuals with distinct body sizes, which were significantly enriched in growth regulation pathways such as PI3K–Akt, MAPK, and FoxO. Feeding differences affected 4480 genes, which were significantly enriched in signaling pathways including the insulin signaling pathway. WGCNA further identified co-expression modules (brown4, blue, coral1) significantly correlated with growth, as well as hub genes including pik3r1 and eif4ebp2. Comprehensive analysis demonstrated that the growth regulation of C. sonnerati operates as a cascade network. Brain tissues perceive signals through neuroactive ligand–receptor interactions and integrate and transduce these signals via core pathways including Ras–MAPK and PI3K–Akt. Finally, growth processes are executed in muscle tissues by regulating glycogen metabolism, protein synthesis, and other processes, which are precisely regulated by terminal processes such as cellular senescence. Among them, pik3r1 and eif4ebp2, as key molecular switches, play a central role in integrating upstream signals and precisely regulating downstream growth programs. This study preliminarily clarifies the molecular mechanism network of growth differences in C. sonnerati, providing a theoretical basis and candidate genes for the genetic improvement of its growth traits. Full article

Alpha-mangostin (AM), a xanthone from Garcinia mangostana, has shown promising nephroprotective properties, but its mechanisms in acute kidney injury (AKI) remain incompletely defined. In this study, we applied an integrative network pharmacology pipeline combined with molecular docking to clarify AM’s multi-target mechanisms in AKI. We identified 128 predicted AM targets and intersected them with AKI-related genes, yielding 122 shared targets. Protein–protein interaction analysis identified ten hub genes—TNF, AKT1, IL6, SRC, CTNNB1, HSP90AA1, NFKB1, HIF1A, PPARG, and PTGS2—implicating inflammatory, hypoxia, and cell-survival pathways. KEGG enrichment highlighted HIF-1 signaling, PI3K–Akt signaling, chemokine signaling, AGE–RAGE signaling, and pathways related to cellular senescence and oxidative stress, while GO terms emphasized responses to chemical/oxygen-containing compounds, kinase activity, signal transduction, and apoptosis. Molecular docking against the ten hub proteins showed favorable binding energies across multiple targets. The strongest predicted affinities were observed for PTGS2 (−11.13 kcal/mol), TNF (−9.74 kcal/mol), and AKT1 (−9.48 kcal/mol). Docking positioned AM within the COX-2 catalytic pocket, engaging key catalytic and hydrophobic residues similar to known inhibitors. MD simulation interaction analysis confirmed that AM maintained stable contacts with key human PTGS2 residues, characterized by dominant hydrogen bonds and water-bridge interactions with SER353, TYR355, ARG513, and SER530, along with consistent hydrophobic contacts, and persistent interactions sustained throughout the 200 ns trajectory. Collectively, these results suggest that AM modulates interconnected inflammatory, hypoxic, and survival pathways relevant to AKI, acting as a multi-target ligand with notable interaction involving COX-2, TNF, and AKT1. Further experimental validation and formulation strategies to improve bioavailability are recommended for the advancement of AM toward therapeutic evaluation in AKI. Full article

Stanford type A aortic dissection (TAAD) is a life-threatening cardiovascular condition associated with high mortality. Ferroptosis has been implicated in TAAD pathogenesis, but comprehensive analyses and experimental validation of ferroptosis-related driver genes (FRDGs) remain limited. This study systematically investigated FRDGs in TAAD using bioinformatics and experimental approaches. Differentially expressed ferroptosis-related driver genes (DEFRDGs) were identified by integrating the GSE153434 dataset with the FerrDb database. Functional enrichment analysis was subsequently performed, followed by the construction of a protein–protein interaction (PPI) network, assessment of immune cell infiltration, and prediction of potential miRNA interactions. Candidate hub genes were then validated using an independent cohort (GSE52093) and clinical tissue samples, with their diagnostic value evaluated via receiver operating characteristic (ROC) curve analysis and their protein expression confirmed by immunohistochemistry. We identified 25 DEFRDGs (17 upregulated, 8 downregulated) enriched in oxidative stress, iron binding, and ferroptosis/HIF-1 signaling pathways. Six hub genes (HIF1A, IL6, TIMP1, SAT1, HMOX1, LPCAT3) were significantly upregulated in validation cohorts, five genes (HIF1A, TIMP1, SAT1, HMOX1, LPCAT3) achieved an area under the curve (AUC) of 1.000, while IL6 also exhibited high diagnostic accuracy (AUC = 0.914). Fibroblast infiltration was elevated in TAAD tissues. Further miRNA interaction prediction revealed the potential involvement of miRNAs, such as miR-138-5p, miR-18b-5p, miR-199a-5p, miR-185-5p, miR-506-3p and miR-4644. Immunohistochemistry confirmed increased protein expression of HIF1A, SAT1, and LPCAT3. These three genes emerge as key ferroptosis-related drivers in TAAD. Their consistent upregulation and strong diagnostic performance support ferroptosis as a potential therapeutic target and provide a basis for mechanism-focused interventions. Full article

Against the background of the acceleration of the integration of the “double carbon” target and transportation energy, the green transformation and business model innovation of highway service areas, as a high-energy-consumption traffic node, are becoming more and more urgent. However, the existing research focuses on a single technology path, and lacks a systematic quantitative evaluation of the “PV–charging–new format” coordination mechanism and its operating efficiency. Therefore, this paper proposes a collaborative framework that integrates photovoltaic power generation, new energy charging piles, and diversified new formats, and introduces a random forest regression algorithm. Based on the actual operation data of the Guangxi expressway service area, the synergistic effect and regional heterogeneity of multiple factors are systematically evaluated. The results show that a photovoltaic system can reduce the unit electricity price by 25–35%, and the investment recovery period is about 7 years. When the penetration rate of charging piles increases to 35%, the annual income can reach CNY 3.285 million, and the return on investment increases to 2.3 times when the utilization rate exceeds 80%. The new business combination can increase the average daily income by 13.3–26.7%. At the same time, the coordinated implementation of the three elements can achieve an annual net income increase of 27–32%, which is better than the linear superposition of the benefits of a single measure. In addition, the analysis of regional heterogeneity shows that the photovoltaic benefit in the western mountainous area is outstanding, the charging benefit in the coastal area is significant, and the comprehensive benefit in the central hub area is the best. This study provides a quantitative basis to support decisions on the differentiated development path of expressway service areas in the background of traffic–energy integration. Full article

Energy management of multi-carrier energy hubs (MCEHs) is a challenging task, particularly when fuel cell electric vehicle (FCEV) stations are included, due to the stochastic nature of FCEV demand, system loads, and integrated renewable energy resources (RERs) such as wind turbines (WTs) and photovoltaic (PV) systems. This paper aims to optimize the energy management of an MCEH-based microgrid to simultaneously minimize total operating costs and emissions. To this end, a novel enhanced quadratic interpolation optimization (EQIO) algorithm is proposed. The proposed EQIO algorithm incorporates two key improvements: a best-to-mean quasi-oppositional-based learning (BMQOBL) strategy and an evaluation mutation (EM) strategy. The performance of EQIO is evaluated using the CEC 2022 benchmark functions, and the obtained results are compared with those of other optimization techniques. Three case studies are investigated: (i) energy management of the MCEH microgrid without RERs, (ii) sustainable operation (with RERs), and (iii) sustainable operation with RERs combined with the application of demand-side response (DSR). Moreover, the proposed framework explicitly supports long-term sustainability goals by enhancing renewable energy utilization, reducing the carbon footprint, and promoting cleaner transportation through efficient integration of FCEV infrastructure. The results demonstrate that integrating RERs reduces operating costs and emissions by 51.47% and 59.69%, respectively, compared to the case without RERs. Furthermore, the combined application of RERs and DSR achieves cost and emission reductions of 55.26% and 53.93%, respectively, compared to the case without RERs. Full article