Search Results (2,891)

To further investigate altitude-associated variations in gut microbiota and serum metabolites of plateau zokors (Eospalax baileyi) and elucidate their adaptive mechanisms to high-altitude environments, we performed fecal metagenomic sequencing and serum metabolomic profiling (Q200 platform) on individuals from high (3700 m, n = 6) and low (2700 m, n = 6) elevations, followed by integrated analysis of microbial and metabolomic datasets. Results indicated that in high-altitude plateau zokors, the relative abundance of Firmicutes decreased, while that of Bacteroidota increased. The dominant genera within this group were identified as Bacteroides and unclassified members of the Lachnospiraceae family. Moreover, the abundances of Bacteroides and unclassified members of the Muribaculaceae family increased with elevation. At the species level, seven fully annotated differentially abundant taxa were identified: Candidatus Amulumruptor caecigallinarius, Schaedlerella arabinosiphila, Muribaculum gordoncarteri, Heminiphilus faecis, Prevotellamassilia timonensis, Staphylococcus aureus, and Bacteroides graminisolvens. KEGG enrichment analysis indicated significant upregulation (p < 0.05) of energy supply pathways, such as oxidative phosphorylation, and antioxidant-related pathways, including β-alanine and lysine metabolism, in the high-altitude group. Conversely, cysteine and methionine metabolism pathways were markedly downregulated (p < 0.05). Serum levels of ursodeoxycholic acid and tauroursodeoxycholic acid (TUDCA) were significantly elevated (p < 0.05), while deoxycholic acid (DCA) levels decreased (p < 0.05). In conclusion, the composition and function of gut microbiota, along with serum metabolite profiles, differ significantly (p < 0.05) between plateau zokors from different altitudes. Through synergistic interactions between gut microbiota and host metabolites, plateau zokors develop adaptive mechanisms that integrate energy metabolism, oxidative stress response, intestinal barrier integrity, and mucosal immunity. This ultimately facilitates their acclimatization to high-altitude extreme environments characterized by hypoxia and low temperatures. Full article

Background: Low-flow, low-gradient aortic stenosis with reduced left ventricular ejection fraction is a heterogeneous condition with challenging severity assessment. Aortic valve calcification reflects fibro-calcific remodeling, while oxidative stress plays a key role in its pathogenesis. Serum uric acid, a marker of oxidative stress, may be associated with valvular calcification. This study investigated the relationship between serum uric acid levels and aortic valve calcification in this population. Methods: This retrospective study included 85 patients. Aortic valve calcification was quantified using computed tomography with the Agatston method, and patients were categorized as true severe or pseudo-severe according to sex-specific calcium thresholds. Of the patients, 57 were classified as true severe and 28 as pseudo-severe aortic stenosis. Results: Patients with higher calcification burden had significantly elevated serum uric acid levels (6.77 ± 1.57 vs. 5.08 ± 1.10 mg/dL, p < 0.001). Serum uric acid showed a modest correlation with aortic valve calcium score (ρ = 0.339, p = 0.002) and remained independently associated with CT-defined true severe low-flow, low-gradient aortic stenosis in multivariable analysis. ROC analysis yielded an area under the curve of 0.823 and identified a serum uric acid threshold of 5.45 mg/dL associated with a greater likelihood of CT-defined true severe low-flow, low-gradient aortic stenosis. Conclusions: Serum uric acid is associated with CT-derived aortic valve calcification and may provide insight into underlying fibro-calcific remodeling in this population. Full article

Dense granular materials under low confining stress and low shear velocity—conditions relevant to low-pressure powder handling, near-surface transport, and the upper layers of stored bulk solids—remain insufficiently characterized at the microstructural level. We perform three-dimensional discrete element method (DEM) simulations of annular shear of monodisperse glass spheres at σ = 1 kPa and v = 0.01 m/s, corresponding to an inertial number I ≈ 1.06 × 10⁻³ at the quasi-static limit of the dense flow regime. The steady-state friction coefficient stabilizes at μ_ss ≈ 0.78, consistent with the quasi-static limit of the μ(I) framework. The solid volume fraction decreases monotonically from φ ≈ 0.50 at the base to φ ≈ 0.35 near the top, while the tangential velocity decays exponentially with depth (decay length δ_s ≈ 10 mm). Particle trajectory tracking reveals a sharp kinematic transition near z ≈ 5–6 mm separating a quasi-rigid basal layer (z ≲ 5 mm) from an upper shear-active zone (z ≳ 6 mm). The contact force distribution follows an exponential decay P($f$/$⟨f⟩$) ∝ exp(−β·$f$/$⟨f⟩$) with β ≈ 0.45, with strong force chains selectively concentrated in the upper zone. Together, these four microstructural descriptors co-locate within a single transition band, providing quantitative benchmarks for material characterization and constitutive modelling at the lower boundary of dense flow. Full article

Soil acidification is a widespread consequence of intensive agriculture and represents a major abiotic stress affecting plant performance, nutrient availability, and ecosystem functioning. Long-term tea (Camellia sinensis) plantations provide model systems of chronic acidification, where sustained low pH imposes strong environmental filtering on soil microbial communities. Although microbial responses to acidification have been extensively studied, research has focused predominantly on bacteria and fungi, leaving other key functional groups, particularly protists, largely overlooked. Here, we synthesize current knowledge on microbial communities in acidified soils and highlight trophic interactions, especially protist-mediated regulation, as a potentially critical but underexplored dimension linking abiotic stress to plant–soil processes. We propose that soil acidification may not only filter microbial community composition but also reshape trophic interactions. Based on evidence from other soil systems, protist-mediated trophic interactions could influence nutrient cycling, pathogen suppression, and ultimately plant responses under stress conditions. Integrating environmental filtering with trophic perspectives provides a conceptual framework for understanding microbiome dynamics in acidified soils. However, direct evidence linking protist-mediated trophic regulation to ecosystem functioning and plant performance in tea plantation soils remains limited and requires experimental validation. We further suggest that these systems provide unique opportunities to investigate how abiotic constraints and biotic interactions jointly shape plant performance. Addressing this gap is essential for advancing predictive understanding of plant–microbiome interactions under ongoing environmental change. Full article

The utilization of sugarcane molasses as a low-cost carbon source for riboflavin production is hindered by the reactive oxygen species (ROS) stress induced by its complex components, which suppresses microbial metabolism. To address this, we employed adaptive laboratory evolution (ALE) under progressively increasing stress to develop a sugarcane molasses-tolerant and high-yielding Ashbya gossypii. The adapted strain achieved a riboflavin titer of 298.39 ± 2.01 mg/L, representing a 99.4% increase over the parental strain (149.66 ± 4.97 mg/L), accompanied by a 96% increase in biomass (dry cell weight). Notably, the specific riboflavin production per unit biomass showed no significant difference between the two strains, indicating that the improved total yield was primarily driven by enhanced biomass accumulation. Transcriptomic analysis revealed the molecular basis for this enhanced biomass accumulation—the elevated expression of antioxidant enzymes (SOD1, PRDX5) mitigated ROS levels to support cellular growth, while the coordinated upregulation of the pentose phosphate pathway (E2.2.1.1) and purine metabolism genes (PPAT, ADE5, PFAS, ADSL) enhanced the supply of biosynthetic precursors, ribulose-5-phosphate (Ru5P) and GTP, for nucleotide biosynthesis and cell proliferation. These metabolic adjustments collectively enabled the adapted strain to achieve robust growth under sugarcane molasses stress, thereby driving the overall increase in riboflavin production. This study elucidates the molecular mechanism underlying ALE-improved riboflavin production and provides a promising strategy for its industrial fermentation using sugarcane molasses. Full article

This study targets biochar utilization in seasonally frozen Northeast China and addresses the insufficient research on aging characteristics and mechanisms of low-temperature wheat straw biochar under long-term freeze–thaw stress. A 60-day simulated freeze–thaw test with 12 h −20 °C freezing and 12 h 0 °C thawing per daily cycle was carried out on 300 °C wheat straw biochar (B300). We tracked dynamic shifts in pH and water absorption during aging, and comprehensively characterized particle size, micromorphology, pore structure, elemental composition and surface functional groups for fresh (CK-B300) and fully aged (FC-B300) biochar. Freeze–thaw cycling caused drastic aging: the average particle size dropped by 33.09%, specific surface area increased by 13.86%, while total pore volume and average pore size fell by 31.47% and 54.9%, respectively. Freeze–thaw oxidation raised the O/C ratio and enriched -OH, C=O functional groups; biochar pH declined by 12.94% alongside improved water absorption. This study confirms that biochar aging is jointly controlled by ice-crystal physical fragmentation and water-temperature oxidation, providing basic data and theoretical support for evaluating and applying biochar in cold freeze–thaw zones. Full article

Background/Objectives: The G protein-coupled estrogen receptor (GPER) is known to interact with cellular stress responses and DNA damage pathways. Therefore, exposure to ionizing radiation may modulate the biological consequences of single-nucleotide polymorphisms in the GPR30 gene. This study aims to evaluate the association between GPER polymorphisms and radiation sensitivity. Methods: The study included 50 healthcare workers exposed to ionizing radiation and 36 healthy individuals with no known occupational exposure to radiation. Genomic DNA was isolated and PCR products were purified using GeneAll kits. Genomic regions encompassing three GPER single-nucleotide polymorphisms (rs3808350, rs3808351, and rs11544331) were amplified by polymerase chain reaction (PCR), followed by DNA sequencing analysis using the BigDye Cycle Sequencing Kit. In addition, an in silico functional and clinical annotation of rs11544331 was performed using Ensembl VEP, SIFT, PolyPhen-2, AlphaMissense, CADD, UniProt, and ClinVar. Results: Genotypic, dominant, and allelic analyses revealed no significant association between radiation exposure and the rs3808350 or rs3808351 polymorphisms. In contrast, a statistically significant association was observed for rs11544331. The frequency of individuals carrying the CT and TT genotypes (CT + TT) was significantly higher in the ionizing radiation-exposed group compared with the control group (OR = 2.981; 95% CI: 1.106–7.904; p = 0.0241). In allelic analysis, the T allele was more prevalent in the exposed group and was significantly associated with radiation exposure (OR = 2.959; 95% CI: 1.282–6.606; p = 0.0110). In silico analysis confirmed that rs11544331 corresponds to the p.Pro16Leu substitution in GPER1; however, SIFT, PolyPhen-2, AlphaMissense, CADD, and ClinVar consistently indicated a tolerated, benign, likely benign, or low-deleteriousness profile. Conclusions: GPER-mediated stress responses and genetic polymorphisms may play a potential role in determining genetic susceptibility following exposure to ionizing radiation. Full article

Zinc deficiency is increasingly recognized as a risk factor for neurodegenerative diseases, yet the underlying molecular mechanisms remain incompletely understood. In this study, we investigated the impact of intracellular zinc depletion on oxidative stress and inflammasome activation in microglial (SIM-A9) and neuronal (SH-SY5Y) cell models, and evaluated the protective effects of polyphenolic compounds. Intracellular zinc chelation with the membrane-permeable chelator TPEN markedly increased reactive oxygen species (ROS) production, reduced cell viability, and upregulated the mRNA expression of NLRP3 inflammasome-related genes and pro-inflammatory cytokines. In contrast, extracellular zinc chelation had no effect, highlighting the critical role of intracellular zinc homeostasis in maintaining redox balance. Zinc supplementation significantly attenuated these responses. Among 32 polyphenols screened by DPPH radical scavenging assay, caffeic acid derivatives—chicoric acid (ChA), rosmarinic acid (RA), and caffeic acid phenethyl ester (CAPE)—exhibited the most potent antioxidant activity, surpassing that of edaravone. These compounds suppressed ROS production and differentially protected against zinc deficiency-induced cellular damage. ChA showed the strongest ROS inhibitory activity (IC50: 1.9 µM in SIM-A9), RA provided robust cytoprotection even at low concentrations, and CAPE most effectively suppressed inflammasome-related gene expression and inhibited aggregation of both Aβ1–42 and the highly neurotoxic pyroglutamate-modified variant pEAβ3–42. These findings demonstrate that intracellular zinc deficiency drives ROS-dependent upregulation of NLRP3 inflammasome-related genes, and suggest that caffeic acid derivative polyphenols may serve as complementary agents for mitigating neuroinflammatory and amyloidogenic processes relevant to Alzheimer’s disease. Full article

Dryland soils of the Caspian region of western Kazakhstan are exposed to environmental stress, including drought, alkalinity, low soil organic matter content, and anthropogenic pressure. In this preliminary study, bacterial communities were investigated in 18 soil samples collected from six sampling groups across Makat (M1, M2), Isatay (I1, I2), and Beyneu (B1, B2) districts. Soil physicochemical properties were measured, and bacterial diversity was analyzed using 16S rRNA gene sequencing of the V3–V4 region. Community composition analysis indicated spatial heterogeneity among the sampled groups. M1 and I1 showed the highest taxon richness, whereas B2 contained the highest number of unique taxa. Genus-level profiles showed that B1 and M2 were mainly associated with Rubrobacter and related actinobacterial taxa; B2 contained higher proportions of Marinobacter, Tychonema, Qipengyuania, and Halomonas; and I2 was enriched with Antarcticibacterium, Salinimicrobium, Rhodococcus, Gillisia, Marinobacter, Dietzia, and Pontibacter. Correlation analysis showed that several bacterial taxa were associated with soil organic matter content, total nitrogen, total phosphorus, exchangeable cations, and pH, although the overall Mantel relationship between soil properties and community structure was not significant. FAPROTAX-based prediction indicated differences in putative heterotrophic, nitrogen-related, sulfur-related, and hydrocarbon-associated functional categories among sites. Because FAPROTAX predictions are based on taxonomic composition, these results should be interpreted only as putative functional potential and not as evidence of actual microbial metabolic activity. These findings suggest that the sampled Caspian dryland soils contain distinct bacterial assemblages and taxa with potential ecological relevance; however, their role in dryland soil resilience or bioremediation should be verified through future culture-based, metagenomic, and functional validation studies. Full article

Glycine betaine transport systems are widely exploited by bacteria to survive osmotic stress and represent potential entry routes for antimicrobial delivery. Here, we investigate the bactericidal glycine betaine analog Tox-GB and its uptake, intracellular fate, and antimicrobial activity in Escherichia coli K-12 under osmotic stress. We show that the xenobiotic enters cells via a hierarchical uptake route involving the osmotically regulated compatible solute transporters ProU and ProP, ABC- and MFS-type transporters, respectively. ProU functions as the primary high-affinity transporter at low concentrations, whereas ProP provides a secondary uptake route at somewhat higher substrate levels. Loss of either transporter confers partial resistance, while simultaneous inactivation of both systems causes full resistance, underscoring their functional redundancy and the robustness of Tox-GB import. Intracellularly, Tox-GB undergoes oxygen-dependent degradation, yielding 4-nitrobenzaldehyde and dimethylglycine. While 4-nitrobenzaldehyde contributes to toxicity under aerobic conditions, Tox-GB remains bactericidal under anaerobic conditions, indicating additional oxygen-independent mechanisms involving either the parent compound or unidentified metabolites. These findings suggest a complex intracellular fate and multifactorial mode of action. Despite initial promise as a Trojan horse antimicrobial strategy, the use of Tox-GB for practical applications faces key limitations. Resistance readily emerges via transporter inactivation, and intrinsic resistance occurs in species lacking appropriate compatible solute uptake systems. Structural constraints in glycine betaine transporters further restrict design flexibility. Osmotic regulation limits activity to specific niches, and potential host toxicity stemming from reactive metabolites raises safety concerns. Collectively, these findings highlight the mechanistic complexity and translational challenges faced by glycine betaine–derived xenobiotics as antimicrobial agents. Full article

Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut–heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management. Full article

Polyethylene microplastics (PE-MPs) are ubiquitous constituents of waste activated sludge (WAS), acting as a major land-based source threatening coastal environmental integrity. However, how particle size and dose govern the methanogenic outcome during WAS digestion remains poorly defined. This study evaluated two particle sizes (50 vs. 300 µm) and doses (100 vs. 200 particles/gTS) to elucidate the differential effects of PE-MPs on methane yield and the underlying biological mechanisms. The results show that, while low-dose treatments either slightly inhibited methane yield (RS1) or had no significant effect (RL1), high-dose treatments (RS2 and RL2) achieved a net positive effect, with significant increases of 10.2% (p < 0.05) and 9.0% (p < 0.05) relative to the control, respectively. Nevertheless, RS2 and RL2 achieved methanogenic enhancement via distinctly different biological pathways. RS2 harnessed the stress of reactive oxygen species (ROS) (110.5% of the control) to drive community restructuring and biomass accrual (positive correlation between ROS intensity and total VS, Pearson’s r = 0.99). Key syntrophic and electrogenic taxa (e.g., Syntrophales, Bacteroidetes vadinHA17) exhibited a fully interconnected, decentralized network, thereby achieving tight coupling between hydrolysis and methanogenesis. RL2 leveraged the physical carrier effect to promote granulation and biomass growth, enriching Syntrophobacter to enhance propionate degradation. This culminated in a highly modular, sparse network characterized by localized competitive interactions. Together, dosage governs the net methanogenic effect of PE MPs, whereas particle size dictates the mechanistic routes of action. This work offers a mechanistic framework to optimize energy recovery from PE-MP-contaminated sludge while mitigating secondary environmental risks, providing a science-based strategy for the sustainable management of plastic-laden sludge that reconciles renewable energy recovery with pollution control. Full article

Objectives: This study investigated the effects of exercise selection and rest interval duration on post-exercise cardiac autonomic modulation following resistance exercise (RE). Methods: Eleven (4 females) resistance-trained individuals performed a single RE session consisting of either a multi-joint exercise (back squat) or a single-joint exercise (leg extension), using rest intervals of 1 or 2 min between sets. Heart rate variability (HRV) was assessed at baseline (pre-exercise) and 30 min following the RE session. RR intervals were recorded for 15 min with participants resting in the supine position on an examination bed in a quiet environment. For HRV analysis, a 5-min artifact-free segment of RR intervals was selected and processed using Kubios HRV software, version 4.3.0 (Kubios Oy, Kuopio, Finland). The HRV metrics analyzed included the root mean square of successive differences (RMSSD), low-frequency normalized (LF), the low-frequency/high-frequency (LF/HF) ratio, and the standard deviation of transverse dispersion (SD1). Results: A significant main effect of time was observed for RMSSD, LF, and the LF/HF ratio. The back squat exercise elicited a significant reduction (p < 0.05) in vagal-related indices (RMSSD and SD1) regardless of interval duration. Longer rest intervals were associated with increased (p < 0.05) sympathetic modulation, as reflected by higher LF and LF/HF values 30 min post-exercise. No significant time × group interactions were observed for most HRV variables. Conclusions: Exercise selection and rest interval duration differentially influence post-exercise cardiac autonomic responses following RE. Multi-joint exercises induce greater vagal withdrawal, whereas longer rest intervals favor sympathetic predominance during recovery. These findings highlight the importance of manipulating RE variables to manage autonomic stress and recovery. Full article

Background/Objectives: textbook outcome (TO) is an established surgical quality measure, but failure is recognized only after postoperative events. We evaluated whether intraoperative stress burden (blood loss, fluid administration, and transfusion) is associated with adapted TO attainment and overall survival (OS) after curative-intent gastrectomy. Methods: in 2352 patients with gastric adenocarcinoma (2010–2020), an intraoperative stress burden score summed three binary components (blood loss > 200 mL, fluid > 68 mL/kg, and any transfusion) and was categorized as low, intermediate, or high. Adapted TO required R0 resection, ≥15 retrieved nodes, no Clavien–Dindo ≥ III complication, no unplanned reoperation, no 30-day mortality, and length of stay ≤ 12 days. Multivariable logistic and Cox models, overlap weighting, and sensitivity analyses were applied. Results: the median age was 60 years; 66.9% were male, 67.7% had pT3–4 and 42.0% pN2–3 disease, and 30.1% underwent minimally invasive surgery. TO attainment declined with increasing burden (78.0%, 70.5%, and 65.2%; p < 0.001). Intermediate and high burden were associated with TO failure (adjusted odds ratios 1.50 and 1.68), though the high-burden association was attenuated after adjusting for operative time. High burden was associated with worse OS (adjusted hazard ratio 1.36; 95% CI 1.15–1.62; 1.44 after overlap weighting). Risk was time-varying—strongest in the first postoperative year (HR 2.03), persisting at 12–60 months (HR 1.54), and absent beyond 60 months. Conclusions: higher intraoperative stress burden identified patients with lower adapted TO attainment and increased early mortality after gastrectomy. External validation is needed. Full article

Gate definition is a major challenge in p-GaN gate AlGaN/GaN HEMT structures because of the high selectivity and low plasma damage required during the etching process. In this work, self-terminated etching, developed to limit surface damage and loss of the underlying AlGaN layer, is investigated. A comparison of two over-etch chemistries (Cl₂/O₂/N₂ and BCl₃/SF₆) revealed that the oxygen-based process yields superior results in terms of AlGaN surface morphology, producing a smoother surface and a more conformal p-GaN profile, while the fluorine-based process exhibited more anisotropic behavior, leading to p-GaN residues and surface pitting. To address across-wafer non-uniformity, a temperature gradient strategy using the tunable electrostatic chuck was developed. The optimized process was evaluated through automatic defect control and device robustness under drain bias-stress. A total reduction in defectivity and reliable HEMT devices across the wafer under high drain-source bias were achieved. These results demonstrate the effectiveness of the proposed solution, offering significant improvements in process efficiency and manufacturability. Full article