Plateau environment represents a common terrestrial characterized by multistress conditions including hypobaric hypoxia, low temperature, and intense radiation, yet sustain over 100 million permanent or transient inhabitants. While this extreme environment exerts profound impacts on cerebral architecture and gut microbiota homeostasis, precipitating cognitive deficits and microbiome-derived intestinal pathologies, the mechanistic interplay between plateau environment adaptation and microbial dynamics remains contentious. Here, we employ a microbiota-gut-brain axis framework to investigate whether probiotic intervention can ameliorate hippocampal impairments induced by simulated plateau environment exposure (3500–4000 m) in mice. Through simulated plateau environment exposure experiments, we revealed that extreme high-altitude conditions induced hippocampal memory dysfunction in mice, exacerbated oxidative stress damage in hippocampal tissues, and altered synaptic plasticity-related biomarkers including CREB transcription factor, BDNF protein levels, and electrophysiological power spectra. Administration of HL79 alleviated these burdens, including memory dysfunction and tissue damage, though complete reversal was not achieved. Combined hippocampal transcriptomic analyses suggested that HL79’s beneficial effects primarily involved modulation of lipid-related gene expression in the hippocampus, consistent with prior reports of plateau environmental impacts on gene expression. Serum metabolomic results further reinforced this inference that differential metabolites regulated by HL79 are mainly enriched in bile secretion, taurine and hypotaurine metabolism, linoleic acid metabolism, and PPAR signaling pathways, though the precise regulatory mechanisms require further elucidation. This research provides a novel microbiota-gut-brain axis-based regulatory strategy for adaptation to extreme plateau environments and offers new evidence for understanding the relationship between gut microbiota and plateau environment adaptation at high elevations.

Trimethylamine (TMA), produced by gut microbes, is a precursor to a risk factor for cardiovascular diseases. Currently, TMA-degrading bacteria in the human gut have rarely been studied. This study combined TMA-enriched cultures (from 104 young male stool samples) with metagenomic profiling to identify key microbial players of TMA degradation. The results showed that the contribution of Enterococcus to methane metabolism was significantly higher in TMA-enriched culture samples. The 68.58% up-regulation of dmd-tmd (dimethylamine/trimethylamine dehydrogenase) in the TMA-enriched group indicated that the anaerobic dehydrogenase pathway participated in TMA metabolism. Notably, we first identified that taxa containing dmd-tmd belonged to Christensenella timonensis. The up-regulation of genes involved in methanogenesis (M00563) as well as the significant enrichment of M00563 (Reporter Score = 2.223) indicated that the methanogenesis pathway may play a role. We constructed gene databases for genes involved in the anaerobic dehydrogenase pathway (1526 sequences for dmd-tmd, 1319 sequences for mauA, and 326 sequences for mauB, respectively) and the aerobic oxidation pathway (2146 sequences for tmm, 1445 sequences for tdm, and 1519 sequences for dmm, respectively) based on genomes from the Integrated Microbial Genome (IMG) database, most of which belong to Pseudomonadota. Screening gut metagenomes with these databases revealed low sequence identity (< 70%), possibly because of the underrepresentation of gut-specific genomes from IMG. This study links Christensenella timonensis to TMA degradation, providing potential targets for microbiota modulation and a gene-centric framework to advance the characterization of gut microbial TMA metabolism.

There has been a growing interest in functional foods in recent years to improve health and boost immunity, particularly since the COVID-19 pandemic, which reflects their significant role in promoting health and preventing various diseases, especially metabolic disorders. This study investigated the antimicrobial, antioxidant, anticoagulant, and prebiotic activities of six different oils: Calotropis procera oil (CPO), Chia seed oil (CSO), Moringa oil (MO), Neem oil (NO), Black seed oil (BSO), and Wheat germ oil (WGO) and their potential applications in health and nutrition. The DPPH and ABTS assays were used to evaluate the antioxidant activity of these oils. A good diffusion assay and minimum inhibitory concentrations (MIC) method were used to investigate the antimicrobial activity against pathogenic bacteria and fungi of human interest. Also, the prebiotic activities of oils were tested on three probiotic strains of Lactobacillus to evaluate their role in promoting the growth of beneficial bacteria against the pathogenic E. coli. Furthermore, the haematological effect of these oils was investigated in vitro through measuring their anticoagulant, and Fibrinolytic activity. The results demonstrated that DPPH assay revealed that CPO and WGO exhibited the highest antioxidant activity with IC50 values of 15.2 µg/mL and 18.7 µg/mL, respectively, while BSO showed the least activity with an IC50 of 45.3 µg/mL. Antimicrobial activity, assessed using inhibition zone diameters, showed that CPO had the strongest effect against Staphylococcus aureus with a zone of 22 mm, followed by CSO at 19 mm. In terms of anticoagulant activity, CSO demonstrated the most potent fibrinolytic effect with a clot lysis percentage of 78%, while MO exhibited weaker activity at 35%. Prebiotic testing revealed that individual oils had limited effects on Lactobacillus growth, but a synergistic blend enhanced growth by 25% compared to controls. Overall, this study highlights the diverse health benefits of these oils and their potential as functional food ingredients that could contribute to improved health.

Cutaneous leishmaniasis (CL), classified as a neglected tropical disease (NTD), is a significant public health concern caused by Leishmania protozoa. It is transmitted through the bites of infected female sandflies and manifests in various forms, ranging from localized skin ulcers to social stigma due to scarring. Numerous reports highlight the life-threatening side effects of glucantim, the first-line treatment for this disease, indicating a pressing need foralternative drugs. This experimental study aims to assess the anti-leishmanial effects of chitosan and chitosan- amphotericin B against Leishmania major (L. major) in vitro and in vivo. Chitosan and amphotricine B were purchased, and different concentrations were prepared. L. major promastigotes were cultured in RPMI-1640 medium. In vitro anti-leishmanial activity was assessed against the promastigotes of L. major using vital staining. For the in vivo assessment, lesion sizes were measured before and after ointment treatments in Bagg Albino mice (BALB/c). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) assay was utilized to evaluate the cytotoxic effects of chitosan and chitosan–amphotericin B at varying concentrations on the L929 cell line. Additionally, the in vitro hemolytic activity was measured using a spectrophotometric method. The in vitro and in vivo experiments demonstrated that chitosan–amphotericin B exhibited superior inhibitory effects against L. major compared to either chitosan or amphotericin B alone, and even against the positive control, particularly at higher concentrations (P < 0.05). Furthermore, cytotoxicity tests indicated that both chitosan and amphotericin, whether used separately or in combination, had no cytotoxic effects on the L929 cell line or human blood samples in vitro and did not impact liver enzymes in vivo (P < 0.05). The findings from this in vitro and in vivo study highlighted the impressive anti-leishmanial effects of chitosan, which were further enhanced with the addition of amphotericin B.

Triterpenoids exhibit considerable potential and are extensively utilized in both food and pharmaceutical industries. However, Athelia termitophila (TMB) naturally harbors only trace amounts of these compounds. Consequently, this study sought to optimize the composition of the culture medium and its cultivation parameters to augment both triterpenoids biosynthesis and TMB biomass. To this end, a series of systematic experiments were carried out. At the outset, a One Factor at a Time (OFAT) approach was employed to identify key culture components and conditions. Based on the OFAT findings, six factors were selected for further investigation using the Plackett–Burman design (PBD) to assess their influence on triterpenoids production and biomass yield. The PBD outcomes pinpointed three critical factors—cultural duration, yeast extract powder, and KH2PO4—each of which was subjected to further optimization through the Box-Behnken design (BBD). The BBD analysis determined the optimal culture medium and conditions: 30 g/L corn starch, 13.44 g/L yeast extract powder, 4.74 g/L KH2PO4, a liquid-to-volume ratio of 130/250 mL, 6% inoculum volumes, and a cultivation period of 7.8 days. Upon optimization, both triterpenoids yield (1.9-fold increase) and mycelial biomass (1.66-fold increase) were significantly enhanced compared to the unoptimized medium. This study not only provides a robust methodology for enhancing triterpenoids content and mycelial biomass in TMB, but also contributes novel insights into the biosynthesis of triterpenoids.

Cellulose, a linear glucan linked by β-1,4 glycosidic bonds, is the most abundant renewable polysaccharide on earth. Complete enzymatic hydrolysis of cellulose liberates the readily metabolizable glucose that could be further converted to valuable biocommodities, and essential to this process are cellulases that hydrolyze the β-1,4 glycosidic bonds. Cellulases are among the most intensively studied and best understood enzymes, and many key residues have been uncovered and interrogated with respect to their functions in catalysis and/or substrate binding. However, it remains to be explored whether additional residues, especially in many poorly characterized cellulases such as processive endoglucanases, might also be functionally important. Here, we investigated a processive endoglucanase from an alkaliphilic bacterium Acetivibrio alkalicellulosi AaCel5A that consists of a glycohydrolase family 5 (GH5) domain and two tandem carbohydrate-binding module family 6 (CBM6) domains. Via structure-guided engineering, we uncovered the functional importance of a previously underexplored but relatively conserved histidine (histidine70 or His70). His70 itself appears to be largely dispensable for hydrolyzing β-1,4 glycosidic bonds, but it is important for efficient hydrolysis of short cellodextrins such as cellotriose, cellotetraose, and cellopentaose, likely through its ability to coordinate substrate binding. Our work thus provides important mechanistic insights into how processive endoglucanases may act on short cellodextrins.

Marbled eels are migratory between freshwater, brackish, and saltwater environments. Eel mucus contains biological components that are essential in protecting against environmental pathogens. The biological activity of mucus depends on endogenous and exogenous factors. This study aimed to determine the influence of solvents in extracting bioactive compounds from marbled eel mucus for aquaculture and human healthcare applications. The results show that different solvents affect the composition and biological activity of the extract from marbled eel mucus. The extracts have 19–23 other peaks of compounds, with retention times ranging from 0.8 to 60.0 min on high-performance liquid chromatography (HPLC). The selective extraction rate of components (% area) has significant differences between extracts with different solvents. The eel mucus extracted with acetone solvent exhibited the highest biological activity in all tests: IC50 = 36.603 mg/mL and SC% = 98.424% at 100 mg/mL for antioxidant activity; Antibacterial activity was demonstrated against S. aureus (IC50 = 65.00 ± 3.01 µg/mL) and B. subtilis (IC50 = 112.00 ± 7.89 µg/mL); The ability to inhibit human skin cancer cells (IC50 = 465.96 ± 8.54 µg/mL) and normal cells (IC50 = 453.36 ± 17.88 µg/mL). Extracts extracted with n-Hexane solvent showed higher safety for cells than extracts from other solvents (IC50 = 632.43 ± 18.80 µg/mL, higher than the value IC50 = 545.25 ± 26.36 µg/mL for skin cancer cells). These results provide important data for selecting and applying products derived from extracts of marbled eel mucus in the future, sparking excitement and optimism about this research’s potential impact on aquaculture and human health care.

This investigation aimed to examine the synergistic effects of fresh royal jelly and local wild Artemisia monosperma leaf extract as antibacterial, antioxidant, antibiofilm, and anti-Alzheimer activity. Gas chromatography-mass spectrometry (GC–MS) identified 16 compounds in Artemisia monosperma, including tricosadiynoic acid, hexadecenoic acid, octadecenoic acid. In contrast, fresh royal jelly contained 13 compounds, including dodecanoic acid, octadecynoic acid, hexadecenoic acid, heptatriacotanol, and their derivatives. The Artemisia monosperma extract exhibited significant antioxidant activity in the DPPH assay, with IC50 value of 5.48 ± 0.002 µg/mL. Fresh royal jelly exhibited an IC50 value of 14.56 ± 0.004 µg/mL. Both substances exhibited significant antibacterial activity in comparison to gentamycin. The Synergistic combination (1:1) effectively suppressed the growth of multidrug-resistant bacterial species, including Bacillus subtilis (ATCC 6633), Enterococcus faecalis (ATCC 10541), Staphylococcus aureus (ATCC 6538), Klebsiella pneumoniae (ATCC 13883), Salmonella typhi (ATCC 6539), and Pseudomonas aeruginosa (ATCC 90274), and decreased biofilm activity. Additionally, in vitro the of inhibition activity (IC50) of the Butyrylcholinesterase enzyme (BChE) for the plant extract, royal jelly and the Synergistic combination were 4.35 ± 0.002 µg/mL, 4.9 ± 0.002 µg/mL, and 3.55 ± 0.002 µg/mL, respectively while the IC50 of rivastigmine (positive control) was 3.9 ± 0.002 µg/mL. in silico analysis reported that the bioactive compounds demonstrated high binding affinities, between − 6.6 and − 10.3 kcal/mol, against the human acetylcholinesterase protein, beside ADMET analysis exhibited high gastrointestinal absorption and potential inhibitory effects on CYP1A2 and CYP2C9 enzymes. Our study indicated that the synergistic effect of Artemisia monosperma and royal jelly bioactive compounds exhibited a promising antibacterial, antioxidant, antibiofilm, and acetylcholinesterase inhibitory activities.

Tuberculosis, induced by Mycobacterium tuberculosis (Mtb), continues to pose a significant global public health challenge. Ferroptosis has emerged as a pivotal factor in tuberculosis pathogenesis, however, the mechanism has not yet been fully clarified. Therefore, the aim of this study was to hypothesize and validate potential ferroptosis-related genes in Mtb infection through bioinformatics analysis, thereby offering insights for further investigation. The mRNA microarray expression profile datasets were sourced from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were derived using GEO2R. Subsequently, the shared DEGs between the GSE174566 and GSE227851 datasets were intersected with the genes in the ferroptosis database. The ferroptosis-associated shared DEGs (Ferr-sDEGs) were validated in the GSE20050 dataset. They were subjected to PPI, Cytoscape and Friends analysis, the infiltration correlation of immune cells and qRT-PCR. A total of 11 Ferr-sDEGs were identified, and 9 genes were validated. These analyses revealed that the key Ferr-sDEGs contributed to ferroptosis during Mtb infection and these key Ferr-sDEGs were relatively independent, implying that ferroptosis may be triggered by various mechanisms. Concurrently, the infiltration and correlation analysis demonstrated that multiple types of immune cells could be activated by the key Ferr-sDEGs. Ultimately, qRT-PCR validated that the expression levels of key Ferr-sDEGs. In conclusion, ferroptosis serves a pivotal function in the pathogenesis of tuberculosis. IL1B, PTGS2, TNFAIP3, HMOX1, SOCS1, CD82, and NUPR1 may be vital genes associated with the ferroptosis induced by Mtb infection.

In this study, Allium sativum, garlic, was selected to isolate endophytic bacteria and to evaluate the antimicrobial, antiviral, antioxidant, and cytotoxic activities of their produced metabolites followed by identification of the biosynthetic gene cluster of the antimicrobial metabolites using Oxford Nanopore Technology (ONT). Two bacterial isolates, C6 and C11, were found to have a broad-spectrum antagonistic effect against four standard microbial strains and were molecularly identified using 16 S ribosomal RNA sequence analysis and deposited in a local culture collection as B. velezensis CCASU-C6, and B. subtilis CCASU-C11, respectively. Optimization for the maximum production of antimicrobial metabolites revealed that a four-day incubation period was optimal, with sucrose and tryptone serving as the best carbon and nitrogen sources for the fermentation media. Response surface methodology model using the central composite design was created resulting in a 1.2-fold and 1.8-fold improvement in antimicrobial metabolite(s) production of C6 and C11 isolates, respectively. The optimal production conditions were found to be a temperature of 33 °C, pH of 7, and an agitation rate of 200 rpm for C6 metabolite, and a temperature of 37 °C, pH of 7, and an agitation rate of 250 rpm for C11 metabolite. Both bacterial isolates displayed antioxidant and antiviral activity and mild cytotoxic action. Genomic sequence and antiSMASH analysis showed that the biosynthetic gene clusters of bacillomycin, mycosubtilin, fengycin, and macrolactin H in B. velezensis CCASU-C6 and bacillibactin and Macrolactin H in B. subtilis CCASU-C11 showed 100% conservation.