Search Results (5,273)

Rural black-odorous waterbodies (RBOWBs) represent a critical environmental challenge in China, yet the vertical stratification of sedimentary bacterial communities and its underlying drivers remain poorly understood. This study combined 16S rRNA gene amplicon sequencing across five sediment depths (0–125 cm) with shotgun metagenomic analysis of surface sediments to investigate bacterial diversity, composition, and functional potential in typical rural black-odorous systems of Dongming County, Shandong Province. Results showed a clear decline in bacterial richness with increasing sediment depth, with the surface layer (0–25 cm) exhibiting 1.2–1.9 times higher diversity than deeper strata. Community composition displayed distinct vertical zonation: Chloroflexi and Thiobacillus dominated surface layers and were linked to carbon hydrolysis and desulfurization, whereas Bacillus and nitrifying bacteria prevailed in deeper anoxic layers. Metagenomic analysis revealed high genetic potential for carbohydrate metabolism, amino acid biosynthesis, and sulfur-nitrogen cycling, with glycoside hydrolases (GHs) and glycosyl transferases (GTs) being particularly abundant. Statistical correlations identified total phosphorus (TP₁), dissolved oxygen (DO), and pH of the overlying water—rather than sediment intrinsic nutrients—as the primary environmental factors associated with microbial functional stratification. These findings provide a mechanistic understanding of vertical microbial zonation in rural black-odorous sediment and offer a microbiological basis for developing depth-resolved sustainable remediation strategies. Full article

This study evaluated the effects of dietary supplementation with N-Carbamylglutamate (NCG) on growth performance, immune function, intestinal metabolites, and microbiota in Danzhou chickens. In a 35-day feeding trial, a total of 480 one-day-old female chicks were randomly assigned to a control group (basal diet) and three experimental groups supplemented with 400, 800, or 1200 mg/kg NCG, with 120 chicks in each group (n = 120). The results demonstrated that NCG, particularly at 400 mg/kg, significantly improved growth parameters, including average daily gain and feed conversion ratio, while enhancing immune function by increasing serum levels of immunoglobulins (IgA, IgY) and malate dehydrogenase (p < 0.05). Metabolomic analysis revealed that NCG modulated key pathways such as sphingolipid metabolism and mTOR signaling pathway, leading to significant changes in metabolites including L-arginine, ceramide, and docosahexaenoic acid (p < 0.05). 16S rDNA sequencing indicated that NCG induced structural shifts in the gut microbiota, primarily affecting Bacteroidota and Firmicutes, with several bacterial genera showing strong correlations with the observed metabolic changes (p < 0.05). Mechanistically, NCG promotes growth by facilitating arginine synthesis via the urea cycle and activating the mTOR signaling pathway, while its regulation of sphingolipid metabolism enhances immunomodulatory capacity. In conclusion, NCG enhances feed efficiency and immune competence by orchestrating the gut microbiota-metabolite network, demonstrating its potential for poultry production. Full article

Background/Objectives: Primary metabolic diseases including mitochondrial encephalomyopathies (ME), glycolytic enzymopathies, and disorders of lipid and amino acid metabolism can manifest with severe neurological and neuromuscular symptoms. Conversely, it is increasingly appreciated that primary neurodegenerative diseases can have metabolic etiology and pathophysiology. Pharmacological treatments have limited benefit for these classes of diseases, but dietary therapy is increasingly recognized as a tool for bolstering metabolic processes that can ameliorate neurological symptoms. The ketogenic diet is the best-established example, having long been used as a therapy for epilepsy. Replenishing metabolic intermediates (anaplerosis) especially substrates of the citric acid cycle (CAC) is currently being explored, with ongoing clinical trials of simple metabolic intermediates such as oxaloacetate or NAD+ to treat neurodegenerative diseases. We have shown ketogenic and anaplerotic therapies to be effective in a Drosophila model of ME; however, the full therapeutic potential and role of the CAC in neuronal health is still not well understood. Methods: Here, we have used genetic, behavioral, and dietary approaches to elucidate critical links between the CAC and neurological function. Results: We have found that stimulating the CAC can improve and sustain neurological health in the face of severe metabolic disease, and that its functions include a previously unrecognized role in maintaining normal circadian rhythms, whose disruption is often an early indicator or complicating factor in neurological and neurodegenerative disease. We investigated the hypothesis that the production of GTP by the CAC may be an important mechanistic contributor to the role of the CAC in neurological health and disease, and may underlie its therapeutic potential. Conclusions: Overall, our findings expand our understanding of the role of the CAC in neurological health and disease, support its development as a therapeutic target, and provide a foundation for further studies investigating the intersection between neurological disease and metabolic function. Full article

Metabolic profiling enables comprehensive characterisation of the small molecules that are part of the biochemical composition of biological fluids. The most widely profiled biofluids include serum and plasma. Additionally synovial fluid provides a direct reflection of the metabolomic environment of joints and holds promise for biomarker discovery in arthropathies. However, the reproducibility of metabolomics data is highly sensitive to pre-analytical variation, and at the present time, standardised protocols for synovial fluid remain underdeveloped. This review aims to identify and evaluate the existing literature on effects of biofluid pre-analytical handling treatments on metabolic profiles. This review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A search was carried out to identify studies employing LC-MS, GC-MS, and NMR spectroscopy for the investigation of factors including sample collection variables, pre-centrifugation conditions, centrifugation parameters, post-centrifugations conditions, sample storage conditions, and freeze/thaw cycling. Best practice recommendations emerging from this review include the use of additive free serum and heparin plasma tubes, the centrifugation of samples within two hours of collection, immediate storage of samples at −80 °C, and avoidance of repeated freeze/thaw cycling. However, while pre-analytical influences have been extensively characterised for plasma and serum, evidence for synovial fluid remains limited. Overall, the findings highlight the existing recommendations for plasma and serum and demonstrate the need for standardised pre-analytical protocols and validation of quality control markers to advance synovial fluid metabolomics. Full article

Wetlands occupy a mere 6% of Earth’s land surface, yet they contribute 25–45% of global natural methane (CH₄) emissions. A key contradiction emerges here: it is the soil of these wetlands that serves as the host for methane-trophic microorganisms, which can oxidize the vast majority of the methane they produce under specific conditions (for example, the aerobic interface). A wetland’s role as either a net source or sink for atmospheric CH₄ is therefore a primary driver of hydrological variability. This research synthesis current understandings of how wet–dry cycles regulate methanotrophic communities and their CH₄ consumption capacity. Shifts in the water table directly modulate methanotroph physiology, community structure, and metabolic activity. These hydrological effects are further amplified or attenuated by nitrogen availability, plant-derived exudates, and edaphic properties. Herein, key knowledge gaps concerning the adaptive responses of methanotrophs to hydrological change are identified, and targeted research priorities improving predictions of wetland CH₄ fluxes under contrasting moisture regimes are accordingly outlined. This review synthesizes recent advances to highlight the mechanistic understanding essential for guiding wetland management strategies. Full article

Terpenoids constitute the largest class of plant-specialized metabolites, playing essential roles throughout the plants’ life cycle and having diverse applications for humans in nutrition, medicine, and flavor. 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is a rate-limiting enzyme of the mevalonate (MVA) pathway, producing sesquiterpenes, saponins, and other terpenoids. HMGR is post-translationally regulated by downstream MVA products through its N-terminal regulatory domain, limiting terpenoid production. To overcome this bottleneck, we employed a virus-based CRISPR/Cas9 system to genetically modify the N-terminal regulatory domain of HMGR in petunia (Petunia × hybrida) and lettuce (Lactuca sativa L.). In petunia, HMGR1-edited lines exhibited vigorous growth, larger flowers, and increased production of sesquiterpenes. Interestingly, they also showed enhanced production of phenylpropanoid volatiles, revealing a connection between these pathways. Transcript analysis revealed altered expression of genes involved in terpenoid biosynthesis, pyruvate metabolism, phenylpropanoid biosynthesis, and gibberellin- and auxin-related pathways, indicating enhanced carbon flux through these metabolic networks. In lettuce, HMGR7-edited plants displayed elevated emission of sesquiterpenes, apocarotenoids, and the phenylpropanoid benzaldehyde. Together, these results establish a transgene-free strategy to enhance the production of terpenoid and phenylpropanoid volatiles, and provide a framework for developing resilient, nutrient-enriched crops. Full article

Obesity is a major risk factor for heart failure and atrial fibrillation. This study investigated the effects of diet-induced obesity on the molecular and cellular mechanisms of cardiomyocyte contractility in the left and right atria (LA and RA). Female Wistar rats were fed a Western diet (WD) for 18 weeks. Sarcomere dynamics and calcium transients were measured in unloaded cardiomyocytes. Actin–myosin interactions and contractile protein phosphorylation were assessed via an in vitro motility assay and phosphoprotein-specific gel electrophoresis. WD-fed rats developed obesity, hypertension, and metabolic alterations in the absence of echocardiographic or histological evidence of cardiac remodeling or systolic dysfunction. In LA cardiomyocytes, contractile dysfunction was indicated by increased calcium transient amplitude coupled with reduced shortening amplitude and relengthening velocity. This functional impairment correlated with a slowed myosin cross-bridge cycle and dephosphorylation of cMyBP-C. In contrast, RA cardiomyocytes displayed only molecular changes in response to obesity, including altered phosphorylation of most sarcomeric proteins and a decelerated cross-bridge cycle, but showed no evident contractile dysfunction. Thus, an 18-week WD reflects the early stages of contractile impairment, where functional deficits are specific to the LA, while RA alterations are confined to the molecular level. Full article

Background/Objectives. Ultraviolet B (UVB) radiation is a key etiological factor for skin cancer, inducing oxidative stress, DNA damage and apoptosis. Nicotinamide (NAM), a NAD⁺ precursor, has shown photoprotective properties, although the mechanisms underlying this effect have not been fully elucidated. This study sought to elucidate the role of NAM in counteracting UVB-induced oxidative damage in HaCaT cells and to assess the contribution of NAD⁺ metabolism to these effects. Methods. HaCaT were exposed to low-dose UVB irradiation (40 mJ/cm²) and treated with NAM (25 μM), alone or in combination with the NAMPT inhibitor FK866 (1 nM) for 4 and 24 h. Oxidative stress, lipid peroxidation and DNA damage were evaluated by DCFDA assay, TBARS assay and comet assay, respectively. Cell proliferation, cell cycle progression and apoptosis were assessed using Ki67 immunofluorescence, flow cytometry analysis and Annexin V/PI staining. Transcriptional activity for oxidative stress- and apoptosis-related markers was analyzed by RT-qPCR. Results. NAM significantly reduced UVB-induced ROS production at both 4 and 24 h post-irradiation in an NAD⁺-dependent manner, as demonstrated by the reversal of its effects following NAMPT inhibition. NAM also decreased oxidative DNA damage accompanied by reduced OGG1 expression, a marker of oxidative stress. Moreover, NAM restored HaCaT proliferation and reduced early apoptosis, particularly at 24 h post-UVB exposure. These protective effects were mediated by NAD⁺. Conclusions. Our results show that NAM confers robust protection to HaCaT cells from UVB-induced oxidative stress and cellular damage, largely mediated by NAD⁺-dependent pathways, supporting its potential role as a systemic photoprotective agent in skin cancer prevention. Full article

Background: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. Objective: We aimed to structure XN’s mechanistic hierarchy with emerging translational relevance across disease areas. Methods: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. Results: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-oncogenic and pro-inflammatory pathways, such as NF-κB, PI3K/Akt/mTOR, STAT3, HIF-1α, and selective MAPK cascades, while activating cytoprotective signaling, such as the Nrf2/ARE and AMPK pathways. Through these coordinated actions, XN modulates redox homeostasis, mitochondrial integrity, apoptosis, autophagy, ferroptosis, and inflammatory responses. In oncology, XN demonstrates broad-spectrum anticancer activity in preclinical models by inhibiting proliferation; inducing cell cycle arrest and apoptosis; suppressing epithelial–mesenchymal transition, angiogenesis, and metastasis; and restoring chemosensitivity in resistant cancers, including breast, lung, gastric, liver, and head-and-neck carcinomas. Beyond cancer, XN exhibits multi-organ protective bioactivities through antioxidative, antimicrobial, antiviral, and anti-inflammatory activities; inhibition of ferroptosis and excitotoxicity; and preservation of mitochondrial integrity. It shows beneficial effects in preclinical models of Parkinson’s disease, Alzheimer’s disease, hepatic steatosis and fibrosis, renal ischemia–reperfusion injury, cardiovascular dysfunction, skin photoaging, and atopic dermatitis. Human subject studies demonstrate that XN is safe and well tolerated, with observed reductions in oxidative DNA damage and inflammatory cytokine release. Recent advances in micellar formulations have improved XN’s systemic bioavailability and thus its translational feasibility. Conclusions: In summary, XN is a safe, multifunctional natural compound with strong potential for modulating disease-relevant biological pathways associated with cancer, neurodegenerative diseases, metabolic disorders, and inflammatory skin conditions. Continued efforts to enhance its bioavailability and conduct rigorous clinical trials are essential to fully establish its clinical relevance in patient populations. Full article

Background: Schizophrenia is strongly associated with severe oral health deterioration, driven by cognitive deficits, behavioral dysfunction, and medication-related biological changes. Objective: To examine how neurocognitive dysfunction in schizophrenia, particularly cognitive deficits, is associated with poorer oral hygiene control, motivation, and self-regulation, contributes to oral health decline by disrupting everyday oral hygiene behaviors and dental care engagement, and to discuss the implications of this framework for interdisciplinary prevention strategies. Methods: This manuscript follows a narrative review design aimed at conceptually integrating evidence on neurocognitive mechanisms underlying oral health decline in schizophrenia. To identify relevant literature, a targeted search of PubMed/MEDLINE, Scopus, and Web of Science was conducted, covering publications from 2000 to 2025. The search strategy was used to support thematic exploration and conceptual synthesis, rather than to perform a systematic study selection or quantitative evidence aggregation. This narrative review summarizes findings from 90 peer-reviewed studies selected from the available literature. Results: Executive dysfunction, attentional deficits, and low motivation impair routine oral hygiene and delay dental care-seeking. Antipsychotic-induced xerostomia, metabolic disturbances, oxidative stress, immune dysregulation, and oral microbiome dysbiosis accelerate periodontal breakdown and caries progression. These interacting processes generate a self-reinforcing cycle of inflammation, tissue destruction, and treatment avoidance. Epidemiological data show markedly elevated DMFT/DMFS indices and up to a three-fold higher risk of edentulism compared with the general population. Emerging evidence suggests that integrated psychiatric–dental care models may be associated with improvements in oral health and care engagement, although current findings are largely preliminary and based on small or heterogeneous study populations, including related neurocognitive disorders. Conclusions: Unlike existing epidemiological syntheses, this review highlights oral health deterioration in schizophrenia as a functionally mediated consequence of neurocognitive impairment, underscoring the need for preventive approaches aligned with patients’ cognitive and motivational capacities. Full article

Growth differentiation factor-15 (GDF-15) is an established marker of oxidative stress and a general stress-response mitokines. In this study, we aim to investigate the association of GDF-15 with the metabolic signature of gut and mitochondrial activity in HF and ageing population. A total of 25 HF (67.9 ± 10.0 years) and 29 age-matched healthy participants (HPs) (67.8 ± 11.1 years) were recruited and underwent detailed body composition assessment via dual X-ray absorptiometry; total fat mass and appendicular lean soft tissue index (ALSTI/body mass index (BMI)) were calculated. Utilizing semi-targeted Gas Chromatography–Mass Spectrometry on fasting plasma, a panel of gut microbial-derived (e.g., hippuric acid, indole derivatives, and sarcosine) and tricarboxylic acid cycle metabolites was identified. Results showed higher GDF-15 tertiles were associated with greater HF prevalence, fat mass, NT-proBNP, and TNF-α (p < 0.05). Gut-derived metabolites exhibited phenotype-specific patterns; 3-hydroxyindole predicted higher fat mass in HP; hippuric acid was inversely related in HF; and sarcosine correlated with GDF-15 only in HP. In HF, GDF-15 was strongly driven by pyruvic and fumaric acid, indicating disease-specific mitochondrial stress. In conclusion, these observed associations could be evaluated in future mechanistic studies as sensitive biomarkers of systemic oxidative stress markers, informing potential microbiome-targeted therapeutic avenues. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily driven by chronic inflammation from viral hepatitis, metabolic dysfunction, alcohol-induced liver disease, and cirrhosis. Conventional therapies often fail in advanced stages, highlighting the need for mechanism-based, precision-guided interventions. Plant-derived secondary metabolites represent a promising class of bioactive compounds with structural diversity, multitarget activity, anti-inflammatory effects, and favorable toxicity profiles. This review follows a semi-systematic narrative that synthesizes preclinical and experimental evidence on the anti-inflammatory and anticancer properties of key phytochemicals, including epigallocatechin-3-gallate, galangin, resveratrol, quercetin, curcumin, berberine, genistein, and thymoquinone. These compounds consistently modulate critical inflammation-driven signaling pathways, PI3K/AKT/mTOR, NF-κB, JAK/STAT, Wnt/β-catenin, and MAPK, resulting in apoptosis induction, cell cycle arrest, inhibition of angiogenesis, and reduced invasion and metastasis in multiple HCC models. Despite strong preclinical evidence, clinical translation remains limited by variable bioavailability, incomplete safety data, and insufficient human studies. A staged development strategy is recommended: standardized formulations, Good Laboratory Practice-compliant pharmacokinetic/toxicology studies, validation in patient-derived models, and early-phase, biomarker-guided clinical trials with combination therapy arms. Addressing regulatory, manufacturing, and quality control considerations will be essential for advancing these compounds as adjuvant or complementary agents in precision HCC therapy. Full article

The escalating global demand for large-scale, cost-effective, and sustainable high-quality protein has positioned single-cell protein (SCP) production from one-carbon (C1) gases as a highly promising solution. In this study, eight chemolithoautotrophic hydrogen-oxidizing bacteria (HOB) were isolated from mangrove sediments. Based on the 16S rRNA gene sequence analysis, they belonged to genera Sulfurimonas, Sulfurovum, Thiomicrolovo, and Marinobacterium. Among these, Thiomicrolovo sp. ZZH C-3 was identified as the most promising candidate for SCP production based on the highest biomass and protein content, and was selected for further characterization. Strain ZZH C-3 is a Gram-negative, short rod-shaped bacterium with multiple flagella. It can grow chemolithoautotrophically by using molecular hydrogen as an energy source and molecular oxygen as an electron acceptor. Genomic analysis further confirmed that ZZH C-3 harbors a complete reverse tricarboxylic acid (rTCA) cycle gene set for carbon fixation, and diverse hydrogenases (Group I, II, IV) for hydrogen oxidation. Subsequently, its cultivation conditions and medium composition for SCP production were systematically optimized using single-factor experiments and response surface methodology (RSM). Results showed that the optimal growth conditions were 28 °C, pH 7.0, and with 1 g/L (NH₄)₂SO₄ as the nitrogen source, 5–10% oxygen concentration, 9.70 mg/L FeSO₄·7H₂O, 0.17 g/L CaCl₂·2H₂O, and 1.90 mg/L MnSO₄·H₂O. Under the optimized conditions, strain ZZH C-3 achieved a maximum specific growth rate of 0.46 h⁻¹. After 28 h of cultivation, the optical density at 600 nm (OD₆₀₀) reached 0.94, corresponding to a biomass concentration of 0.60 g/L, and the protein content ranked at 73.56%. The biomass yield on hydrogen (Y_H2) was approximately 3.01 g/g H₂, with an average H₂-to-CO₂ consumption molar ratio of about 3.78. Compared to the model HOB Cupriavidus necator, strain ZZH C-3 exhibited a lower H₂/CO₂ consumption ratio, superior substrate conversion efficiency, and high protein content. Overall, this study not only validated the potential of mangrove HOB for SCP production but also offers new insights for future metabolic engineering strategies designed to enhance CO₂-to-biomass conversion efficiency. Full article

Wildland firefighting involves prolonged, high-intensity physical work performed under hot, variable, and operationally demanding conditions, placing firefighters at substantial risk of heat-related illness. This paper synthesizes current evidence on the mechanisms, contributing factors, and management of heat stress in wildland firefighting, with a specific focus on physiologically and operationally relevant considerations aligned with NIOSH, NFPA, and USFS guidelines. Heat stress is conceptualized as a cumulative process resulting from the interaction of metabolic heat production, environmental heat load, protective clothing, and individual susceptibility. Key environmental contributors include high ambient temperatures, humidity, and solar and fire-related radiant heat, while occupational demands such as sustained heavy work, extended shift durations, limited recovery, and the thermal burden of personal protective equipment further exacerbate risk. Individual factors—including fitness, hydration status, acclimatization, fatigue, and underlying health conditions—modify heat tolerance and vulnerability. This review highlights evidence-based exposure management strategies tailored to wildland fire operations, including work–rest cycles, heat acclimatization protocols, and practical cooling interventions, and addresses the operational constraints that shape their implementation. This paper further emphasizes the role of standardized training programs in prevention, early symptom recognition, and rapid response. Together, these integrated approaches provide a focused framework for reducing heat-related morbidity and enhancing wildland firefighter safety. Full article

Human herpesviruses (HHVs) are notorious, ubiquitous intracellular pathogens that establish lifelong infections in the host. They tightly manipulate host signaling pathways that play central roles in key cellular processes such as cell survival, metabolism, immune responses, and oncogenic transformation. Among the many pathways explored, the phosphatidylinositol-3-kinase (PI3K)/Akt signaling axis has emerged as a central and conserved target exploited by all eight HHVs. Herpesviruses can induce PI3K/Akt signaling at multiple stages of their life cycle, beginning at viral entry and extending through lytic replication, latency maintenance, immune evasion, and virus-associated tumorigenesis. Mechanistically, herpesviruses engage both host cell receptors and viral effector proteins to activate PI3K, drive Akt phosphorylation, and thereby orchestrate downstream signaling pathways that favor viral replication, survival, and immune evasion. Transient activation of this pathway supports viral replication, whereas sustained signaling promotes latent infection and oncogenesis, particularly in Epstein–Barr virus and Kaposi’s sarcoma-associated herpesvirus. This review provides a comparative analysis of PI3K/Akt pathway manipulation across all HHVs, highlighting shared strategies and virus-specific adaptations. We further discuss ongoing clinical trials and therapeutic opportunities targeting the PI3K/Akt axis, emphasizing its potential as a host-directed antiviral and anticancer strategy. Full article