Search Results (2,770)

Background/Objectives: The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand crosslinks and maintenance of genomic stability. Germline loss of FA pathway function in the inherited Fanconi anemia syndrome leads to increased DNA damage and a range of clinical phenotypes, including a heightened risk of head and neck squamous cell carcinoma (HNSCC). Non-synonymous FA gene mutations are also observed in up to 20% of sporadic HNSCCs. The mechanistic target of rapamycin (mTOR) is known to stimulate cell growth, anabolic metabolism including protein synthesis, and survival following genotoxic stress. Methods/Results: Here, we demonstrate that FA− deficient (FA−) HNSCC cells exhibit elevated intracellular amino acid levels, increased total protein content, and an increase in protein synthesis indicative of enhanced translation. These changes are accompanied by hyperactivation of the mTOR effectors translation initiation factor 4E Binding Protein 1 (4E-BP1) and ribosomal protein S6. Treatment with the mTOR inhibitor rapamycin reduced the phosphorylation of these targets and blocked translation specifically in FA− cells but not in their isogenic FA− proficient (FA+) counterparts. Rapamycin-mediated mTOR inhibition sensitized FA− but not FA+ cells to rapamycin under nutrient stress, supporting a therapeutic metabolism-based vulnerability in FA− cancer cells. Conclusions: These findings uncover a novel role for the FA pathway in suppressing mTOR signaling and identify mTOR inhibition as a potential strategy for targeting FA− HNSCCs. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Effective management of fecal pollutants in rural sanitation is crucial for environmental health and public safety, especially in developing regions. In this study, temporal and regional variations in nutrient elements, heavy metals, pathogenic microorganisms (PMs), and antibiotic resistance genes (ARGs) of fecal samples from rural toilets in China were investigated. The moisture contents of the fecal samples average 92.7%, decreasing seasonally from 97.4% in summer to 90.6% in winter. The samples’ pH values range from 6.5 to 7.5, with a slight decrease in winter (6.8), while their electrical conductivity varies from 128.1 to 2150 μs/cm, influenced by regional diets. Chromium (9.0–49.7 mg/kg) and copper (31.9–784.4 mg/kg) levels vary regionally, with higher concentrations in Anhui and Guangxi Provinces due to dietary and industrial factors. Zinc contents range from 108.5 to 1648.9 mg/kg, with higher levels in autumn and winter, resulting from agricultural practices and Zn-containing fungicides, posing potential health and phytotoxicity risks. Seasonal and regional variations in PMs and ARGs were observed. Guangxi Province shows the high PM diversity in summer samples, while Jiangsu Province exhibits the high ARGs types in autumn samples. These findings highlight the need for improved waste management and sanitation solutions in rural areas to mitigate environmental risks and protect public health. Continued research in these regions is essential to inform effective sanitation strategies. Full article

Ericoid mycorrhizal fungi (EMF) enhance plant fitness and metabolic regulations in nutrient-poor soils, though the mechanisms diving these interactions require further elucidation. This study investigated the physiological and metabolic responses of blueberry seedlings following 2- and 3-weeks inoculation with Oidiodendron maius H14. The results indicated that EMF could significantly increases plant biomass, improve the accumulation of osmoregulatory substances in leaves. Additionally, the colonization rate of EMF are 26.18% and 30.22% after 2- and 3-weeks, respectively. The Metabolomics analysis identified 758 (593 up- and 165 down-regulated) and 805 (577 up- and 228 down-regulated) differential metabolites in roots at 2- and 3-weeks inoculation with O. maius H14, respectively. KEGG pathway annotation revealed that O. maius H14 triggered various amino acid metabolism pathways, including tryptophan metabolism and arginine and proline metabolism. These findings suggested that O. maius H14 stimulated root-specific biosynthesis of growth-promoting compounds and antimicrobial compounds. Concomitant downregulation of stress-associated genes and upregulation of glutamine synthetase suggest EMF modulates host defense responses to facilitate symbiosis. Thus, our results demonstrated that O. maius H14 orchestrates a metabolic reprogramming in blueberry roots, enhancing growth and stress tolerance through coordinated changes in primary and specialized metabolism, which could inform strategies for improving symbiosis and metabolic engineering in horticultural practices. Full article

Maternal undernutrition (MUN) causes severe metabolic disruption in the offspring of mammals. Here we determined the role of histone modification in hepatic gene expression in late-gestation fetuses of nutritionally restricted cows, an established model using low-nutrition (LN) and high-nutrition (HN) conditions. The chromatin immunoprecipitation sequencing results show that genes with an altered trimethylation of histone 3 lysine 4 (H3K4me3) are associated with cortisol synthesis and secretion, the PPAR signaling pathway, and aldosterone synthesis and secretion. Genes with the H3K27me3 alteration were associated with glutamatergic synapse and gastric acid secretion. Compared to HN fetuses, promoter H3K4me3 levels in LN fetuses were higher in GDF15, IRF2BP2, PPP1R3B, and QRFPR but lower in ANGPTL4 and APOA5. Intriguingly, genes with the greatest expression changes (>1.5-fold) exhibited the anticipated up-/downregulation from elevated or reduced H3K4me3 levels; however, a significant relationship was not observed between promoter CpG methylation or H3K27me3 and the gene set with the greatest expression changes. Furthermore, the stress response genes EIF2A, ATF4, DDIT3, and TRIB3 were upregulated in the MUN fetal liver, suggesting activation by upregulated GDF15. Thus, H3K4me3 likely plays a crucial role in MUN-induced physiological adaptation, altering the hepatic gene expression responsible for the integrated stress response and systemic energy metabolism, especially circulating lipoprotein lipase regulation. Full article

In this study, an artificially simulated enhanced UV-B radiation treatment of 96 kJ/m²·d⁻¹ was applied with natural sunlight as the control. By observing changes in biological tissue damage, peroxidase (POD) enzyme activity, and hormone content, combined with transcriptome analysis and quantitative fluorescence PCR validation, this study preliminarily elucidated the physiological mechanisms of plant-specific peroxidase (POD) in responding to enhanced UV-B radiation stress. Enhanced UV-B treatment significantly inhibited biological tissue growth, particularly during the rapid growth stage. At this stage, the treatment exhibited higher malondialdehyde (MDA) content, indicating increased oxidative stress due to the accumulation of reactive oxygen species (ROS). Despite the inhibition in growth, the treatment showed improvements in the accumulation of organic nutrients as well as the contents of abscisic acid (ABA), salicylic acid (SA), and methyl jasmonate (MeJA). Additionally, an increase in POD activity and lignin content was observed in the treatment, especially during the middle period of the rapid growth period. Transcriptome analysis revealed that two POD multigene family members, LOC123198833 and LOC123225298, were significantly upregulated under enhanced UV-B radiation, which was further validated through qPCR. In general, enhanced UV-B radiation triggered a defence response in biological tissue by upregulating POD genes, which can effectively help to scavenge excess ROS. Full article

Heavy metal pollution represents a pervasive environmental challenge that significantly exacerbates the ever-increasing crisis of antimicrobial resistance and the capacity of microorganisms to endure and proliferate despite antibiotic interventions. This review examines the intricate relationship between heavy metals and AMR, with an emphasis on the underlying molecular mechanisms and ecological ramifications. Common environmental metals, including arsenic, mercury, cadmium, and lead, exert substantial selective pressures on microbial communities. These induce oxidative stress and DNA damage, potentially leading to mutations that enhance antibiotic resistance. Key microbial responses include the overexpression of efflux pumps that expel both metals and antibiotics, production of detoxifying enzymes, and formation of protective biofilms, all of which contribute to the emergence of multidrug-resistant strains. In the soil environment, particularly the rhizosphere, heavy metals disrupt plant–microbe interactions by inhibiting beneficial organisms, such as rhizobacteria, mycorrhizal fungi, and actinomycetes, thereby impairing nutrient cycling and plant health. Nonetheless, certain microbial consortia can tolerate and detoxify heavy metals through sequestration and biotransformation, rendering them valuable for bioremediation. Advances in biotechnology, including gene editing and the development of engineered metal-resistant microbes, offer promising solutions for mitigating the spread of metal-driven AMR and restoring ecological balance. By understanding the interplay between metal pollution and microbial resistance, we can more effectively devise strategies for environmental protection and public health. Full article

In plateau wetlands, the interactions of herbaceous roots with ectorhizosphere soil microorganisms represent an important way to realize their ecological functions. Global change-induced aridification of plateau wetlands has altered long-established functional synergistic relationships between plant roots and ectorhizosphere soil microbes, but we still know little about this phenomenon. In this context, nine typical wetlands with three different moisture statuses were selected from the eastern Tibetan Plateau in this study to analyze the relationships among herbaceous plant root traits and microbial communities and functions. The results revealed that drought significantly inhibited the accumulation of root biomass and surface area as well as the development of root volumes and diameters. Similarly, drought significantly reduced the diversity of ectorhizosphere soil microbial communities and the relative abundances of key phyla of archaea and bacteria. Redundancy analysis revealed that plant root traits and ectorhizosphere soil microbes were equally regulated by soil physicochemical properties. Functional genes related to carbohydrate metabolism were significantly associated with functional traits related to plant root elongation and nutrient uptake. Functional genes related to carbon and energy metabolism were significantly associated with traits related to plant root support and storage. Key genes such as CS,gltA, and G6PD,zwf help to improve the drought resistance and barrenness resistance of plant roots. This study helps to elucidate the synergistic mechanism of plant and soil microbial functions in plateau wetlands under drought stress, and provides a basis for evolutionary research and conservation of wetland ecosystems in the context of global change. Full article

Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats—the only mammals capable of powered flight—these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular and molecular mechanisms underlying bat muscle physiology remain largely unknown. To enable mechanistic investigation of these traits, we established the first myoblast cell lines from the pectoralis muscle of Pteronotus mesoamericanus, a highly maneuverable aerial insectivore. Using both spontaneous immortalization and exogenous hTERT/CDK4 gene overexpression, we generated two stable cell lines that retain proliferative capacity and differentiate into contractile myotubes. These cells exhibit frequent spontaneous contractions, suggesting robust functional integrity at the neuromuscular junction. In parallel, we performed transcriptomic and metabolic profiling of native pectoralis tissue in the closely related Pteronotus parnellii to define molecular programs supporting muscle specialization. Gene expression analyses revealed enriched pathways for muscle metabolism, development, and regeneration, highlighting supporting roles in tissue maintenance and repair. Consistent with this profile, the flight muscle is triglyceride-rich, which serves as an important fuel source for energetically demanding processes, including muscle contraction and cellular recovery. Integration of transcriptomic and metabolic data identified three key metabolic modules—glucose utilization, lipid handling, and nutrient signaling—that likely coordinate ATP production and support metabolic flexibility. Together, these complementary tools and datasets provide the first in vitro platform for investigating bat muscle research, enabling direct exploration of muscle regeneration, metabolic resilience, and evolutionary physiology. Full article

The purpose of this work was to obtain specialized enrichment cultures from an original extreme acidophilic consortium of extremely acidophilic microorganisms and to study their microbial community composition and biotechnological potential. At temperatures of 25, 35, 40 and 50 °C, distinct enrichments of extremely acidophilic microorganisms used in the processes of bioleaching sulfide ores were obtained using nutrient media containing ferrous sulfate, elemental sulfur and a copper sulfide concentrate as nutrient inorganic substrates, with and without the addition of 0.02% yeast extract. The microbial community composition was studied using the sequencing of the V3–V4 hypervariable region of the 16S rRNA genes. The different growth conditions led to changes in the microbial composition and relative abundance of mesophilic and moderately thermophilic, strict autotrophic and mixotrophic microorganisms in members of the genera Acidithiobacillus, Sulfobacillus, Leptospirillum, Acidibacillus, Ferroplasma and Cuniculiplasma. The dynamics of the oxidation of ferrous iron, sulfur, and sulfide minerals (pyrite and chalcopyrite) by the enrichments was also studied in the temperature range of 25 to 50 °C. The study of enrichment cultures using the molecular biological method using the metabarcoding method of variable V3–24 V4 fragments of 16S rRNA genes showed that enrichment cultures obtained under different conditions differed in composition, which can be explained by differences in the physiological properties of the identified microorganisms. Regarding the dynamics of the oxidation of ferrous ions, sulfur, and sulfide minerals (pyrite and chalcopyrite), each enrichment culture was studied at a temperature range of 25 to 50 °C and indicated that all obtained enrichments were capable of oxidizing ferrous iron, sulfur and minerals at different rates. The obtained enrichment cultures may be used in further work to increase bioleaching by using the suitable inoculum for the temperature and process conditions. Full article

The soil-borne fungal pathogen Verticillium dahliae causes devastating vascular wilt disease in numerous crops, including cotton. In this study, we reveal that VdSOX1, a highly conserved sarcosine oxidase gene, is significantly upregulated during host infection and plays a multifaceted role in fungal physiology and pathogenicity. Functional deletion of VdSOX1 leads to increased fungal virulence, accompanied by enhanced microsclerotia formation, elevated carbon source utilization, and pronounced upregulation of effector genes, including over 50 predicted secreted proteins genes. Moreover, the VdSOX1 knockout strains suppress the expression of key defense-related transcription factors in cotton, such as WRKY, MYB, AP2/ERF, and GRAS families, thereby impairing host immune responses. Transcriptomic analyses confirm that VdSOX1 orchestrates a broad metabolic reprogramming that links nutrient acquisition to immune evasion. Our findings identify VdSOX1 as a central regulator that promotes V. dahliae virulence by upregulating effector gene expression and suppressing host immune responses, offering novel insights into the molecular basis of host–pathogen interactions and highlighting potential targets for disease management. Full article

Cardiorenal syndrome (CRS) is a multifactorial clinical condition characterized by the bidirectional deterioration of cardiac and renal function, driven by mechanisms such as renin–angiotensin–aldosterone system (RAAS) overactivation, systemic inflammation, oxidative stress, endothelial dysfunction, and fibrosis. The aim of this narrative review is to explore the key molecular pathways involved in CRS and to highlight emerging therapeutic approaches, with a special emphasis on nutritional interventions. We examined recent evidence on the contribution of mitochondrial dysfunction, uremic toxins, and immune activation to CRS progression and assessed the role of dietary and micronutrient factors. Results indicate that a high dietary intake of sodium, phosphorus additives, and processed foods is associated with volume overload, vascular damage, and inflammation, whereas deficiencies in potassium, magnesium, and vitamin D correlate with worse clinical outcomes. Anti-inflammatory and antioxidant bioactives, such as omega-3 PUFAs, curcumin, and anthocyanins from maqui, demonstrate potential to modulate key CRS mechanisms, including the nuclear factor kappa B (NF-κB) pathway and the NLRP3 inflammasome. Gene therapy approaches targeting endothelial nitric oxide synthase (eNOS) and transforming growth factor-beta (TGF-β) signaling are also discussed. An integrative approach combining pharmacological RAAS modulation with personalized medical nutrition therapy and anti-inflammatory nutrients may offer a promising strategy to prevent or delay CRS progression and improve patient outcomes. Full article

Vermicomposting is a sustainable biotechnological process that transforms organic waste through the synergistic activity of earthworms, such as Eisenia fetida, and their associated microbiota. This study evaluated bacterial and physicochemical dynamics during the vermicomposting of bovine manure by analyzing the microbial composition of the substrate and the gut of E. fetida at three time points (weeks 0, 6, and 12). The V3–V4 region of the 16S rRNA gene was sequenced, and microbial diversity was characterized using QIIME2. Significant differences in alpha diversity (observed features, Shannon index, and phylogenetic diversity) and beta diversity indicated active microbial succession. Proteobacteria, Bacteroidota, and Actinobacteriota were the dominant phyla, with abundances varying across habitats and over time. A significant enrichment of Proteobacteria, Bacteroidota, and the genera Chryseolinea, Flavobacterium, and Sphingomonas was observed in the manure treatments. In contrast, Actinobacteriota, Firmicutes, and the genera Methylobacter, Brevibacillus, Enhygromyxa, and Bacillus, among others, were distinctive of the gut samples and contributed to their dissimilarity from the manure treatments. Simultaneously, the physicochemical parameters indicated progressive substrate stabilization and nutrient enrichment. Notably, the organic matter and total organic carbon contents decreased (from 79.47% to 47.80% and from 46.10% to 27.73%, respectively), whereas the total nitrogen content increased (from 1.70% to 2.23%); these effects reduced the C/N ratio, which is a recognized indicator of maturity, from 27.13 to 12.40. The macronutrient contents also increased, with final values of 1.41% for phosphorus, 1.50% for potassium, 0.89% for magnesium, and 2.81% for calcium. These results demonstrate that vermicomposting modifies microbial communities and enhances substrate quality, supporting its use as a biofertilizer for sustainable agriculture, soil restoration, and agrochemical reduction. Full article

Soil degradation resulting from intensive agricultural practices, the excessive use of agrochemicals, and climate-induced stresses has significantly impaired soil fertility, disrupted microbial diversity, and reduced crop productivity. Plant growth-promoting bacteria (PGPB) represent a sustainable biological approach to restoring degraded soils by modulating plant physiology and soil function through diverse molecular mechanisms. PGPB synthesizes indole-3-acetic acid (IAA) to stimulate root development and nutrient uptake and produce ACC deaminase, which lowers ethylene accumulation under stress, mitigating growth inhibition. They also enhance nutrient availability by releasing phosphate-solubilizing enzymes and siderophores that improve iron acquisition. In parallel, PGPB activates jasmonate and salicylate pathways, priming a systemic resistance to biotic and abiotic stress. Through quorum sensing, biofilm formation, and biosynthetic gene clusters encoding antibiotics, lipopeptides, and VOCs, PGPB strengthen rhizosphere colonization and suppress pathogens. These interactions contribute to microbial community recovery, an improved soil structure, and enhanced nutrient cycling. This review synthesizes current evidence on the molecular and physiological mechanisms by which PGPB enhance soil restoration in degraded agroecosystems, highlighting their role beyond biofertilization as key agents in ecological rehabilitation. It examines advances in nutrient mobilization, stress mitigation, and signaling pathways, based on the literature retrieved from major scientific databases, focusing on studies published in the last decade. Full article

Candidozyma auris is a multidrug-resistant, thermo- and osmotolerant yeast capable of persisting on biotic and abiotic surfaces, attributes likely linked to its cell wall composition. Here, seven putative genes encoding yapsins, aspartyl proteases GPI-anchored to the membrane or cell wall, were identified in the genomes of C. auris CJ97 and 20-1498, from clades III and IV, respectively. The C. auris YPS1 gene is orthologous to the SAP9 of C. albicans. The YPS7 gene is orthologous to YPS7 in C. glabrata and S. cerevisiae, so that they may share similar roles. An in silico analysis suggested an interaction between pepstatin and the catalytic domain of Yps1 and Yps7. Although this inhibitor, when combined with caffeine, had a subtle effect on the growth of C. auris, it induced alterations in the cell wall. CauYPS1 and CauYPS7 expression increased under nutrient starvation and NaCl, and at 42 °C. The transcriptome of the 20-1498 strain suggests that autophagy may play a role in thermal stress, probably degrading deleterious proteins or maintaining cell wall and vacuolar homeostasis. Therefore, CauYps1 and CauYps7 may play a role in the cell wall integrity of C. auris in stress conditions, and they could be a target of new antifungal or antivirulence agents. Full article