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24 pages, 1771 KB  
Article
Carbendazim Transport and Interactions with Regenerated Cellulose Membranes Probed by Analytical Diafiltration
by Hernán Valle, Verónica Izquierdo and Manuel Palencia
Sci 2026, 8(9), 254; https://doi.org/10.3390/sci8090254 - 11 Sep 2026
Abstract
Carbendazim (CBDZ) is widely used for the prevention and control of fungal diseases in agricultural crops. Its extensive and recurrent application may lead to the occurrence of residues in agricultural environments and increase the potential for contamination of aquatic systems. In this study, [...] Read more.
Carbendazim (CBDZ) is widely used for the prevention and control of fungal diseases in agricultural crops. Its extensive and recurrent application may lead to the occurrence of residues in agricultural environments and increase the potential for contamination of aquatic systems. In this study, analytical diafiltration was used to investigate the transport and interfacial association of CBDZ with regenerated cellulose membranes (CELms) rather than to evaluate size-exclusion-based pesticide removal. Continuous diafiltration experiments using the washing mode were performed with an 8.0 ppm CBDZ solution and 10 kDa of CELm at different pH values (3.0–9.0), while permeate flow rate and CBDZ concentration in successive permeate fractions were monitored throughout the process. CBDZ membrane retention (Rm) ranged from (7.4 ± 3.3%) at pH 9.0 to (23.2 ± 2.0%) at pH 3.0, with a maximum membrane-associated amount (\(R_m^{max}\) ) of 478 μg CBDZ per g of CELm. The pH dependence of Rm was accurately described by Rm = 24.9740 + 0.1814 ph − 0.2375 ph2 for 3.0 ≤ pH ≤ 9.0 (r2 = 0.999). The results are consistent with adsorption-mediated interfacial association, mainly involving physicochemical interactions with hydroxyl- and carboxyl-containing functionalities of CELms, while electrostatic interactions contributed less than 3.0% within the pH range of 6.0–7.0. The diafiltration profiles were successfully described by the ExDM–IDZ model. The parameters governing the shape of the retention profile were Rm, associated with the horizontal asymptote, and (j), which describes the decay rate and was related to the evolution of CBDZ concentration and its apparent residence behavior during diafiltration. Overall, these results demonstrate that analytical diafiltration provides a useful framework for investigating the transport, partitioning, and adsorption-mediated interactions of low-molecular-weight, water-soluble pesticides with membrane materials. Full article
(This article belongs to the Section Environmental and Earth Science)
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39 pages, 1872 KB  
Review
Green-Synthesized Nanomaterials for Kidney Cancer: Current Progress and Future Perspectives
by Mariam R. Khalifa, Doaa S. R. Khafaga, Marwa T. Abo Gabal, Marwa Mohamed Abd El-Monem, Sara S. Zeidan, Shimaa S. Attia and Safaa Mahmoud Mohamed Abdelkhalek
Int. J. Mol. Sci. 2026, 27(18), 8113; https://doi.org/10.3390/ijms27188113 - 11 Sep 2026
Abstract
The kidney is an essential organ that has a crucial role in preserving homeostasis within the human body. Kidney cancer is considered a major clinical challenge owing to its resistance to traditional treatments such as chemotherapy, radiotherapy, and immunotherapy. Nanoparticles (NPs) gain great [...] Read more.
The kidney is an essential organ that has a crucial role in preserving homeostasis within the human body. Kidney cancer is considered a major clinical challenge owing to its resistance to traditional treatments such as chemotherapy, radiotherapy, and immunotherapy. Nanoparticles (NPs) gain great attention in cancer therapy due to their low toxicity, biocompatibility, and targeted drug delivery capability. This review focuses on the current role of green-synthesized NPs in renal cell carcinoma management and their applications in targeted drug delivery and cancer-specific targeting mechanisms with the demonstration of the environmentally friendly green synthesis approaches utilizing biological resources such as plant extracts and microorganisms, highlighting their advantages over conventional synthesis methods in terms of biocompatibility, sustainability, and reduced toxicity. Moreover, the therapeutic potential of nanomaterials is discussed, including magnetic NP-mediated thermal therapy, photothermal therapy, gene delivery systems, and RNA interference-based strategies. We underscore the challenges and limitations of NPs, including in vivo toxicity, biodistribution, clinical translation, large-scale production, batch-to-batch variability, long-term safety, scalability, repeatability, regulation, and reproducibility. There is growing potential to improve the treatment of kidney cancer. Hence, the promising prospects of nanotechnology in kidney cancer treatment provide a foundation for future research and clinical application. This comprehensive article highlights the significant contributions of nanomedicine to oncology and shows an optimistic perspective for more effective and precise treatment strategies for kidney cancer. Full article
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19 pages, 962 KB  
Article
High Glucose Alters Extracellular Vesicle Protein Composition and Promotes EV-Mediated Monocyte Adhesion to Endothelial Cells
by Verônica Vitória Vedam, Gisele Tatiane Soares da Veiga, Líndice Mitie Nisimura and Letusa Albrecht
Int. J. Mol. Sci. 2026, 27(18), 8107; https://doi.org/10.3390/ijms27188107 - 11 Sep 2026
Abstract
Diabetes mellitus prevalence is rising globally, linked to persistent hyperglycemia and endothelial dysfunction. Extracellular vesicles (EVs) play a role in diabetes pathology, involving complex intercellular communication that influences endothelial response. However, the mechanisms by which EVs contribute to endothelial dysfunction under hyperglycemia remain [...] Read more.
Diabetes mellitus prevalence is rising globally, linked to persistent hyperglycemia and endothelial dysfunction. Extracellular vesicles (EVs) play a role in diabetes pathology, involving complex intercellular communication that influences endothelial response. However, the mechanisms by which EVs contribute to endothelial dysfunction under hyperglycemia remain unknown. To investigate the effect of glucose-altered EVs on endothelial cells, we isolated EVs from HBMECs and THP-1 cells under normal- and high-glucose conditions (5.5 and 33 mM). We used NTA, electron microscopy, and LC-MS/MS for EV characterization. HBMECs in RPMI’s default glucose (11 mM) were exposed to 100 ng/mL of each EV condition, and adherent THP-1 CFSE+ cells were quantified. Long-term high glucose activated HBMECs without altering cell viability. Glucose level altered EV secretion, content, and function. For HBMECs, high glucose decreased EV release but shifted their cargo toward metabolism, barrier disruption, and neuronal protein content. For THP-1 cells, high glucose kept the EV release rate and shifted the cargo toward an inflammatory activation profile. Functionally, high-glucose EVs (mainly THP-1-derived) showed a pro-adhesive effect on endothelial cells. Here, we describe the impact of glucose on EV biology and how glucose-altered EVs can influence inflammation and endothelial responses, highlighting the importance of glycemic control in diabetic patients. Full article
20 pages, 7642 KB  
Review
Multi-Omics Insights into Climate-Driven Abiotic Stress Responses and Tolerance Mechanisms in Fruit Crops
by Kripa Shankar, Deepak Singh, Prashant Sharma, Nisha Singh, Rituraj Shukla, Pradeep Goel, Ram Kishor Patel, Dinesh Kumar and Mukesh Meena
Stresses 2026, 6(3), 66; https://doi.org/10.3390/stresses6030066 - 11 Sep 2026
Abstract
Climate change is intensifying drought, salinity, heat, chilling, flooding, and heavy-metal stresses across major fruit-producing regions, threatening yield stability and fruit quality in economically vital, perennial crops such as apple, grapevine, citrus, banana, strawberry, and peach. Because these species are long-lived, highly heterozygous, [...] Read more.
Climate change is intensifying drought, salinity, heat, chilling, flooding, and heavy-metal stresses across major fruit-producing regions, threatening yield stability and fruit quality in economically vital, perennial crops such as apple, grapevine, citrus, banana, strawberry, and peach. Because these species are long-lived, highly heterozygous, and polyploid, conventional breeding for climate resilience remains slow and often inadequate, necessitating molecular strategies informed by systems-level understanding. This review synthesizes recent advances in multi-omics research spanning genomics, transcriptomics, proteomics, metabolomics, epigenomics, ionomics, and phenomics that have collectively decoded the regulatory architecture underlying abiotic stress perception, signaling, and tolerance in fruit crops. Hormonal networks, particularly abscisic acid (ABA) crosstalk with jasmonate, salicylic acid, ethylene, and brassinosteroids, emerge as central integrators of stress responses, coordinating stomatal regulation, osmolyte accumulation, antioxidant defense, and secondary metabolite biosynthesis. Genomic and pangenomic approaches have identified stress-associated loci and cultivar-specific structural variants, while transcriptomic and proteomic studies reveal transcription factor networks (MdERF38–MdMYB1, MaMYB4–MaHDA2, VvDREB1, CsNAC29) and post-translational regulatory switches governing tolerance mechanisms across drought, cold, salinity, and flooding stress. Metabolomic and ionomic profiling link biochemical reprogramming to fruit quality traits, whereas epigenomic mechanisms including DNA methylation, histone modifications, and small RNA regulation provide a chromatin-level layer mediating stress memory across growing seasons. Integration of these omics layers through systems biology, machine learning, and high-throughput phenomics is enabling functional validation via CRISPR-Cas9 and marker-assisted selection, translating correlative associations into causally validated breeding targets. Despite this progress, challenges including batch effects, tissue heterogeneity, and methodological inconsistencies in data integration continue to constrain translational applications. This highlights convergent regulatory hubs across stress types and species, underscoring multi-omics-guided precision breeding as the most promising pathway toward developing climate-resilient, high-quality fruit crop cultivars for sustainable global production. Full article
(This article belongs to the Section Plant and Photoautotrophic Stresses)
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22 pages, 3343 KB  
Article
Cultivation Age Drives Soil Organic Nitrogen Transformation in Vineyards via Reshaping chiA-Harboring Microbial Communities and Hy-Drolase Activities
by Zhubing Shao, Lei Yan, Shuo Fang, Xue Wang, Chunyan Yu, Guohui Wu and Hanwen Liu
Agriculture 2026, 16(18), 1955; https://doi.org/10.3390/agriculture16181955 - 11 Sep 2026
Abstract
Long-term grape cultivation alters soil acid–base properties and nitrogen transformation processes, yet the mechanisms underlying the changes in soil physical and chemical properties as well as nitrogen components remain unclear. In this study, four grape vineyards with cultivation ages of 0.5 (newly established, [...] Read more.
Long-term grape cultivation alters soil acid–base properties and nitrogen transformation processes, yet the mechanisms underlying the changes in soil physical and chemical properties as well as nitrogen components remain unclear. In this study, four grape vineyards with cultivation ages of 0.5 (newly established, Y0.5), 4 (Y4), 16 (Y16), and 22 years (Y22) in Penglai, Yantai, China, were selected as research subjects. Soil nitrogen pools, key nitrogen hydrolase activities, and chiA gene community assembly, as well as their internal regulatory relationships were investigated. The results revealed that cultivation age significantly reshaped soil nitrogen speciation: Y16 vineyards exhibited the highest concentrations of total nitrogen, mineral nitrogen, microbial biomass nitrogen, and labile hydrolyzable ammonium nitrogen (HAN), representing a critical inflection point of soil nitrogen supply capacity. With prolonged cultivation to 22 years, soil nitrogen pools shifted toward recalcitrant stable organic nitrogen (stable-SON), accompanied by significant accumulation of amino sugar nitrogen (ASN). Activities of N-acetyl-β-D-glucosaminidase (NAG), urease, amidase and leucine aminopeptidase were markedly suppressed in Y16 soils. Both Chao1 richness and Shannon diversity indices of chiA gene communities reached the minimum values at 16 years, and PCoA confirmed distinct community separation of Y16 from other age groups. Soil pH, ammonium nitrogen and nitrate nitrogen were the dominant environmental filters governing chiA community composition. Actinomycetota and Pseudomonadota dominated the chiA-harboring microbiota, with acid-tolerant Streptomyces significantly enriched in Y16, while keystone genera Nonomuraea and Pseudoxanthomonas mediated the conversion between labile and stable organic nitrogen pools. Redundancy analysis demonstrated that chiA community composition (25.5% explanation), chiA α-diversity (19.3% explanation), and NAG activity (14.6% explanation) were the primary drivers of soil organic nitrogen fraction variation. Results support a four-level cascading framework wherein stand-age-induced soil acidification and altered N inputs drive shifts in chiA-harboring microbial diversity and community structure, which in turn modulate nitrogen hydrolase activities and ultimately govern the reciprocal transformation between labile and stable organic nitrogen pools, resulting in stage-specific nitrogen supply capacity. This study clarifies the microbial gene–enzyme–nitrogen pool coupling mechanism in chronosequence vineyards and provides theoretical guidance for targeted nitrogen management of aged vineyards. Full article
(This article belongs to the Section Agricultural Soils)
24 pages, 886 KB  
Article
Can Low-Carbon Policy Enhance Green Total Factor Productivity of Manufacturing Enterprises? Evidence from China’s Low-Carbon City Pilot Policy
by Chunli Du, Kalbinur Kahar, Tao Wang and Xu Sun
Sustainability 2026, 18(18), 9367; https://doi.org/10.3390/su18189367 - 11 Sep 2026
Abstract
China’s Low-Carbon City Pilot (LCCP) policy aims to drive green economic transformation, but its firm-level effects on manufacturing are underexplored. This study takes the LCCP policy as a quasi-natural experiment and employs a staggered difference-in-differences (DID) model to examine its impact on manufacturing [...] Read more.
China’s Low-Carbon City Pilot (LCCP) policy aims to drive green economic transformation, but its firm-level effects on manufacturing are underexplored. This study takes the LCCP policy as a quasi-natural experiment and employs a staggered difference-in-differences (DID) model to examine its impact on manufacturing enterprises’ green total factor productivity (GTFP). The findings are fourfold. (1) The LCCP policy significantly enhances manufacturing enterprises’ GTFP, a conclusion that has been validated through multiple robustness tests. (2) Green technological innovation and financing constraint mitigation serve as two key mediating channels. (3) Enterprise market power exerts a negative moderating effect. (4) The promotional effect of the LCCP policy on GTFP is more pronounced among manufacturing enterprises with a high degree of equity balance, state-owned enterprises, and heavily polluting enterprises. This paper offers empirical evidence and policy implications for how governments can effectively exert their guiding roles and how manufacturing enterprises can achieve a win-win outcome for both economic and environmental performance. Full article
6 pages, 1648 KB  
Communication
Low-Angle Twist Phase Boundary Mediated Plasticity in a High-Strength Ti78Fe22 Alloy
by Zhen-Di Zhang, Xiao-Gang Wang, Hui-Chao Wang, Zhao-Zhi Xu, Lu Lu, Shao-Bo Mi, Jian-Bing Qiang and Ying-Min Wang
Metals 2026, 16(9), 1012; https://doi.org/10.3390/met16091012 - 11 Sep 2026
Abstract
Ti-Fe alloys with improved strength-plasticity trade-off are promising low-cost engineering materials. In this work, we report the attainment of an A2 + B2-type superalloy microstructure featuring a low-angle twist boundary in an aged Ti78Fe22 alloy. The alloy delivered a high [...] Read more.
Ti-Fe alloys with improved strength-plasticity trade-off are promising low-cost engineering materials. In this work, we report the attainment of an A2 + B2-type superalloy microstructure featuring a low-angle twist boundary in an aged Ti78Fe22 alloy. The alloy delivered a high yield strength of 1590 ± 5 MPa and an exceedingly large plastic strain of 40 ± 2% at room temperature. Upon deformation, the low-angle twist boundary acted as the dislocation source for continued dislocation emission and regulated cross-slip. The massive production of dense parallel slips accommodates the large plastic strain under a high external stress. Full article
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23 pages, 1972 KB  
Article
Social Media Gratifications and Gastronomy Destination Choice: The Mediating Role of Pre-Visit Destination Impression
by Seung Ho Youn and Chenyu Fang
Tour. Hosp. 2026, 7(9), 296; https://doi.org/10.3390/tourhosp7090296 - 11 Sep 2026
Abstract
In this study, we use gratifications (U&G) theory to explore how social media shapes Millennials’ gastronomic destination choices. Rather than treating social media influence as uniform, we identify three key gratifications obtained from gastronomy-related content: experiential–inspirational, utilitarian decision-making, and information search and assurance. [...] Read more.
In this study, we use gratifications (U&G) theory to explore how social media shapes Millennials’ gastronomic destination choices. Rather than treating social media influence as uniform, we identify three key gratifications obtained from gastronomy-related content: experiential–inspirational, utilitarian decision-making, and information search and assurance. The study investigates how these gratifications directly and indirectly affect destination choice through pre-visit destination impressions. Data were collected from 418 Chinese Millennials. Validity of measurements was confirmed through exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and reliability tests, with hypotheses tested using Hayes’ PROCESS Model 4. Findings indicate that pre-visit destination impression significantly predicts destination choice and mediates the influence of all three gratifications. Experiential–inspirational gratification has the greatest overall impact; experiential–inspirational and information search and assurance gratifications operate through both directly and indirectly, while utilitarian decision-making gratification operates primarily through pre-visit impressions. By integrating U&G theory with pre-visit impressions, this study offers a novel pathway-specific explanation of social media’s role in gastronomic destination choice, suggesting that different gratifications activate distinct psychological mechanisms rather than a uniform process. It also advances destination-choice research by highlighting pre-visit impression as a rapid evaluative mechanism linking digital gratification and behavioral decision. Full article
15 pages, 753 KB  
Article
Bullying, Cyberbullying, and Recent Poor Mental Health Among U.S. High School Students: A Cross-Sectional Indirect-Association Analysis
by Sangmi Kim, Seon-Kyeong Ahn, Jeoung Min Lee, Courtney Cronley, Julie Cerel and Ick-Joong Chung
Adolescents 2026, 6(5), 72; https://doi.org/10.3390/adolescents6050072 - 11 Sep 2026
Abstract
Background: Cyberbullying victimization is associated with recent poor mental health among adolescents, but the roles of digital and offline contextual indicators require careful interpretation. Objective: Guided primarily by Stress Process Theory and secondarily by bounded routine activity concepts, this study examined cross-sectional associations [...] Read more.
Background: Cyberbullying victimization is associated with recent poor mental health among adolescents, but the roles of digital and offline contextual indicators require careful interpretation. Objective: Guided primarily by Stress Process Theory and secondarily by bounded routine activity concepts, this study examined cross-sectional associations among traditional school bullying, cyberbullying, social media use, physical activity frequency, and recent poor mental health among U.S. high school students. Methods: Complete-case 2023 Youth Risk Behavior Survey data for U.S. high school students (N = 10,295; 49.5% female; 42.7% White, 21.9% Hispanic/Latino, 11.2% Black or African American, and 24.2% all other races) were analyzed in two non-survey-weighted, model-based indirect-association specifications using PROCESS Model 6. Both models adjusted for sex, grade, sexual identity, race/ethnicity, and the alternate bullying indicator. Results: Traditional bullying and cyberbullying were each positively associated with more frequent recent poor mental health after mutual adjustment (β = 0.113 and β = 0.111, respectively). No indirect associations were statistically supported in the traditional bullying model. In the cyberbullying model, the indirect association through social media use was statistically supported but small, and the sequential indirect association through social media use and physical activity frequency was statistically supported but extremely small. Conclusions: Findings support a cautious, cross-sectional interpretation in which bullying victimization is treated as peer-related strain and social media use and physical activity frequency are contextual indicators rather than causal mediators. Full article
(This article belongs to the Collection Featured Research in Adolescent Health)
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23 pages, 951 KB  
Review
Mechanisms of Piezo1-Mediated Mechanotransduction in Thrombotic Diseases
by Hanrong Dong, Yunlun Li and Wenqing Yang
Int. J. Mol. Sci. 2026, 27(18), 8102; https://doi.org/10.3390/ijms27188102 - 11 Sep 2026
Abstract
The mechanical cation channel Piezo1 has been confirmed as a key membrane mechanical protein that can convert physical forces into biological signals, serving as a molecular hub linking hemodynamic stimulation with thrombotic diseases. Studying mechanical sensitive channels in the cardiovascular system is helpful [...] Read more.
The mechanical cation channel Piezo1 has been confirmed as a key membrane mechanical protein that can convert physical forces into biological signals, serving as a molecular hub linking hemodynamic stimulation with thrombotic diseases. Studying mechanical sensitive channels in the cardiovascular system is helpful for understanding the working mechanism of these channels and providing new therapeutic targets for thrombotic diseases. This article systematically summarizes the expression and functional roles of the Piezo1 channel in cell types involved in thrombosis, including platelets, endothelial cells, red blood cells, immune cells, etc. This article also discusses the mechanical gating structural basis of Piezo1 and its activation mechanism and downstream signaling pathways in the thrombosis-related mechanical microenvironment. Based on the existing evidence, Piezo1 has significant pathological significance in the occurrence and development of thrombotic diseases, and targeting Piezo1 may provide new strategies for anti-thrombotic treatment. Future research needs to further clarify the differential regulatory mechanisms of the Piezo1 channel in different hemodynamic environments and evaluate its safety and efficacy as a drug target. Full article
(This article belongs to the Section Molecular Biology)
23 pages, 807 KB  
Article
Associations Between FTO (Fat Mass- and Obesity-Associated) Gene Allelic Load and Heart Rate Responses to Submaximal Exercise in Humans: A Cross-Sectional Study
by Habib Al Ashkar, Nora Kovacs, Karoly Nagy, Roza Adany and Peter Piko
Biology 2026, 15(18), 1607; https://doi.org/10.3390/biology15181607 - 11 Sep 2026
Abstract
Obesity is a widespread condition strongly linked to increased cardiovascular risk, and heart rate (HR) responses to physical activity are widely used physiological indicators of this relationship. Although the role of fat mass- and obesity-associated (FTO) gene variants in obesity risk [...] Read more.
Obesity is a widespread condition strongly linked to increased cardiovascular risk, and heart rate (HR) responses to physical activity are widely used physiological indicators of this relationship. Although the role of fat mass- and obesity-associated (FTO) gene variants in obesity risk is well established, their potential associations with HR changes during and after physical activity (independent of adiposity) have not yet been fully elucidated. This study examined whether common FTO polymorphisms (rs9939609, rs1121980, rs1558902, and rs9941349) and an exploratory FTO multi-variant score (MVSFTO), representing regional variation across the high-LD FTO locus, are associated with HR responses to a brief submaximal exercise stimulus. A population-based cohort of Hungarian adults (n = 660) completed the YMCA 3-min step test, with HR measured at rest, at first-minute post-exercise (HRaft), and at 5- (HR5min) and 10-min recovery (HR10min). Acute HR response (ΔHR) and percent of predicted maximal HR (HRmax%) were calculated. Linear regression analyses showed no association between any FTO variant and resting HR (all p > 0.05). In contrast, all four candidate SNPs demonstrated significant negative associations with HRaft (β ≈ −3.6 to −4.2, all p ≤ 0.005), ΔHR (β ≈ −3.7 to −3.9, p ≤ 0.005), and HRmax% (β ≈ −2.5, p = 0.001). The MVSFTO revealed even more pronounced and consistent associations: higher MVSFTO burden was associated with lower HRaft (β = −4.19, p = 0.001), HR5min (β = −2.06, p = 0.004), HR10min (β = −1.15, p = 0.009), ΔHR (β = −4.04, p = 0.001), and HRmax% (β = −2.47, p = 0.001). Exploratory four-way mediation decompositions and saturated structural equation models indicated that these inverse associations remained statistically robust after multivariable adjustment for measured BMI and leisure-time physical activity (all direct paths p ≤ 0.001). Furthermore, multi-trait latent cluster analysis identified distinct phenotypic profiles consistent with these findings, showing that individuals with high MVSFTO burden and moderate physical activity exhibit blunted exercise HR reactivity across recovery phases. Rather than establishing biological causality or clinical cardiovascular benefit, these observational findings demonstrate that regional FTO locus variation captured by the multi-variant score is statistically associated with inter-individual variability in short-term post-exercise HR reactivity, providing hypothesis-generating insights that warrant validation in prospective cohorts and interventional exercise trials. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
17 pages, 1864 KB  
Article
Genetic Evidence for Metabolites Mediated Causal Inference Between Gut Microbiota and Venous Thromboembolism
by Pin Huang, Wenxiao Wei, Ying Xiao and Qian Zhu
Genes 2026, 17(9), 1098; https://doi.org/10.3390/genes17091098 - 11 Sep 2026
Abstract
Background: More efficient and safe preventive treatments for venous thromboembolism (VTE) are warranted to decrease the incidence of hemorrhage. Emerging evidence has highlighted the pivotal role of the intestinal microbiota alterations and their metabolites in the pathophysiology of VTE process. However, the [...] Read more.
Background: More efficient and safe preventive treatments for venous thromboembolism (VTE) are warranted to decrease the incidence of hemorrhage. Emerging evidence has highlighted the pivotal role of the intestinal microbiota alterations and their metabolites in the pathophysiology of VTE process. However, the specific species involved the VTE process and the potential underlying mechanisms remain unclear. Methods: The causal relationships between 82 species and VTE were assessed using two-sample Mendelian Randomization (MR) analyses. Instrumental variables (F > 10) without horizontal pleiotropy were selected using the PhenoScanner and MR PRESSO global test. Subsequently, causal estimates were primarily derived using the inverse variance weighted method. The reliability of the results was further examined utilizing various sensitivity analyses, reverse MR analysis and multivariate MR analysis. Additionally, the potential mediated effects of gut microbiota-related metabolites were explored and replicated using the mediation MR analysis. Moreover, genome annotation and pathway enrichment analysis were conducted to investigate the role of CAG-81 sp000435795 in the related metabolites metabolism. Results: We identified independent and positive causal effects of CAG-81 sp000435795 and CAG-877 sp000433455 on VTE, which remained robust across multiple sensitivity analyses. Mediation analysis further revealed that the causal effect of CAG-81 sp000435795 on VTE risk was partially mediated by albumin, Omega-3 fatty acids and polyunsaturated fatty acids (PUFA), which were all validated in the replicated cohorts. Furthermore, CAG-81 sp000435795 might participate in the metabolism of albumin and fatty acids. Conclusions: Our findings provide evidence supporting a causal role of CAG-81 sp000435795 in the VTE pathogenesis and implicate microbes associated metabolites, albumin and Omega-3, as potential mediators. Full article
(This article belongs to the Special Issue Genetic Mechanisms and Functional Insights in Microbiome Research)
26 pages, 6974 KB  
Review
Targeting Viral Precursor Proteases for Innovative Therapeutic Development
by Chaoping Chen
Drugs Drug Candidates 2026, 5(3), 50; https://doi.org/10.3390/ddc5030050 - 11 Sep 2026
Abstract
Proteolytic processing of viral polyproteins by virally encoded proteases is essential for the replication of many RNA viruses, including retroviruses and coronaviruses, which are two of the best characterized model systems discussed in this review. These proteases are initially synthesized as polyprotein precursors [...] Read more.
Proteolytic processing of viral polyproteins by virally encoded proteases is essential for the replication of many RNA viruses, including retroviruses and coronaviruses, which are two of the best characterized model systems discussed in this review. These proteases are initially synthesized as polyprotein precursors that possess intrinsic, albeit comparatively low, catalytic activity and undergo tightly regulated autoprocessing to generate the mature enzymes required for viral replication. Accumulating evidence indicates that protease precursors are catalytically and mechanistically distinct from their mature counterparts, exhibiting unique biochemical properties and regulatory features that govern their activation. Therefore, precursor autoprocessing represents a critical checkpoint in viral maturation and an attractive, yet largely unexplored, target for antiviral intervention. This review examines the current understanding of the molecular mechanisms underlying precursor autoprocessing of HIV-1 protease and coronavirus main protease, with particular emphasis on the structural, biochemical, and regulatory features that distinguish precursor enzymes from their mature forms. It also highlights the experimental challenges associated with studying these highly dynamic and conformationally heterogeneous precursors, as well as recent advances in functional screening platforms that have enabled the discovery of proof-of-concept small molecules targeting precursor autoprocessing. Notably, several hit compounds retain activity against HIV-1 variants resistant to clinically approved protease inhibitors (PIs), while also inhibiting the wild-type strain. Together, these findings suggest that protease precursor autoprocessing may serve as a promising antiviral target and provide a conceptual framework for the development of next-generation therapeutics that complement existing mature-protease inhibitors. Full article
(This article belongs to the Special Issue Therapeutic Protease and Peptidase Inhibitors)
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57 pages, 1168 KB  
Review
Antioxidants in Oxidative Stress and Obesity-Associated Diseases: Molecular Mechanisms and Potential Health Implications
by Bee Ling Tan
Biomedicines 2026, 14(9), 2049; https://doi.org/10.3390/biomedicines14092049 - 11 Sep 2026
Abstract
Obesity has become a major global public health concern, with prevalence rates rising dramatically over the past several decades and affecting more than one billion people worldwide. The increasing burden of obesity has been largely driven by sedentary lifestyles and the consumption of [...] Read more.
Obesity has become a major global public health concern, with prevalence rates rising dramatically over the past several decades and affecting more than one billion people worldwide. The increasing burden of obesity has been largely driven by sedentary lifestyles and the consumption of energy-dense, nutrient-poor diets, although its etiology is multifactorial, involving complex interactions among genetic, metabolic, endocrine, and environmental factors. Beyond excess adiposity, obesity is closely associated with numerous chronic diseases, including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), hypertension, cancer, and chronic inflammatory disorders. Emerging evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of obesity and its related metabolic complications. Reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are generated during normal cellular metabolism, serve important physiological functions in cell signaling and redox regulation. However, excessive production of these reactive species or impairment of endogenous antioxidant defense systems disrupts redox homeostasis, leading to oxidative damage to lipids, proteins, and nucleic acids. Such alterations contribute to cellular dysfunction, chronic inflammation, and disease progression. In this context, dietary antioxidants have attracted considerable attention due to their ability to neutralize free radicals, inhibit lipid peroxidation, and restore redox balance. Natural antioxidants derived from fruits, vegetables, and other plant-based foods may act individually or synergistically to enhance cellular defense mechanisms against oxidative stress. Furthermore, growing evidence suggests that antioxidant-rich dietary patterns may offer protective effects against obesity-associated metabolic disturbances and chronic diseases. However, clinical benefits of isolated antioxidant supplementation remain inconsistent and appear to depend on dose, bioavailability, baseline redox status, disease stage, and the preservation of physiological redox signaling. Understanding the molecular mechanisms underlying antioxidant-mediated regulation of redox homeostasis may facilitate the development of nutritional strategies for obesity prevention and management, while contributing to the reduction in oxidative stress and obesity-related disease burden and the promotion of long-term health. Full article
(This article belongs to the Special Issue Antioxidants in Treating Obesity and Metabolic Diseases)
20 pages, 660 KB  
Article
Unravel a Knot: Exploring Double Edged Effects of Gratitude Mindset on Social Behaviors
by Wenya Yang, Jianwei Zhang, Guangxia Guo, Xinchen Niu, Tingting Zhang and Meiting Xiong
Behav. Sci. 2026, 16(9), 1628; https://doi.org/10.3390/bs16091628 - 11 Sep 2026
Abstract
While abundant evidence supports gratitude’s positive functions, recent findings have also revealed its potential to trigger aggressive behaviors. However, existing theories struggle to fully explain this apparent paradox. To address this gap, we introduce the construct of the gratitude mindset and explore its [...] Read more.
While abundant evidence supports gratitude’s positive functions, recent findings have also revealed its potential to trigger aggressive behaviors. However, existing theories struggle to fully explain this apparent paradox. To address this gap, we introduce the construct of the gratitude mindset and explore its paradoxical impact on social behaviors. Study 1 (N = 221) employed an experiment to verify the distinct effect of the gratitude mindset on altruistic and aggressive behavior. Based on a three-wave survey, Study 2 (N = 462) revealed that a gratitude-is-enhancing mindset (GIEM) was positively associated with altruistic behavior and negatively associated with aggressive behavior, whereas a gratitude-is-inhibiting mindset (GIIM) was positively associated with aggressive behavior and negatively associated with altruistic behavior. Moreover, moral imagination partially mediated the effects of GIEM on altruistic behavior and aggressive behavior; moral disengagement partially mediated the effects of GIIM on altruistic behavior and aggressive behavior. These findings suggest that the gratitude mindset has both theoretical and practical relevance for understanding social behavior. Full article
(This article belongs to the Section Social Psychology)
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