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Abstract Background Marine microbes are a large and diverse group, which are exposed to a wide variety of pressure, temperature, salinity, nutrient availability and other environmental conditions. They provide a huge potential source of novel enzymes with unique properties that may be useful in industry and biotechnology. To explore the lipolytic genetic resources in the South China Sea, 23 sediment samples were collected in the depth < 100 m marine areas. Results A metagenomic library of South China Sea sediments assemblage in plasmid vector containing about 194 Mb of community DNA was prepared. Screening of a part of the unamplified library resulted in isolation of 15 unique lipolytic clones with the ability to hydrolyze tributyrin. A positive recombinant clone (pNLE1), containing a novel esterase (Est_p1), was successfully expressed in E. coli and purified. In a series of assays, Est_p1 displayed maximal activity at pH 8.57, 40°C, with ρ-Nitrophenyl butyrate (C4) as substrate. Compared to other metagenomic esterases, Est_p1 played a notable role in specificity for substrate C4 (kcat/Km value 11,500 S-1m M-1) and showed no inhibited by phenylmethylsulfonyl fluoride, suggested that the substrate binding pocket was suitable for substrate C4 and the serine active-site residue was buried at the bottom of substrate binding pocket which sheltered by a lid structure. Conclusions Esterase, which specificity towards short chain fatty acids, especially butanoic acid, is commercially available as potent flavoring tools. According the outstanding activity and specificity for substrate C4, Est_p1 has potential application in flavor industries requiring hydrolysis of short chain esters.

Although extensively studied, themechanismsbywhich estrogenpromotes breast cancer growth remain to be fully elucidated. Tamoxifen, an antiestrogen agent to treat ERα+ breast cancer, is also a high-affinity blocker of the chloride channels. In this study, weexplored the involvement of the chloride channels in the action of estrogen in breast cancer. We found that 17β-estradiol (17β-E2) concentration-dependently activated the chloride currents in ERα+ breast cancerMCF-7 cells. Extracellular hypertonic challenge and chloride channel blockers, NPPB and DIDS inhibited the 17β-E2-activated chloride currents. Decreased the ClC-3 protein expression caused the depletion of the 17β-E2-activated chloride currents. 17β-E2-activated chloride currents which relied on the ERα expression were demonstrated by the following evidences. Firstly, 17β- E2-activated chloride currents could not be observed in ERα- breast cancerMDA-MB-231 cells. Secondly, ER antagonists, tamoxifen and ICI 182,780, and downregulation of ERα expression inhibited or abolished the 17β-E2-activated chloride currents. Thirdly, ERα expression was induced in MDA-MB-231 cells by ESR1 gene transfection, and then 17β-E2-activated chloride currents could be observed. In MCF-7 cells, ERα and ClC-3 mainly located in nucleus and translocated to cell plasma and membrane with respect to co-localization following treatment of 17β-E2. Downregulation of ERα expression could decrease the expression of ClC-3 protein. Conversely, downregulation of ClC-3 expression did not influence the ERα expression. Taken together, our findings demonstrated that ClC-3 is a potential target of 17β-E2 and is modulated by the ERα in breast cancer cell. Pharmacological modulation of ClC-3 may provide a deep understanding in antiestrogen treatment of breast cancer patients. [ABSTRACT FROM AUTHOR]

Strata thermal conductivity (λ e) influences efficiency of medium-depth ground heat exchangers. However, a systematic approach to the acquisition of λ e is still lacking. Hence, stratigraphic heat conduction was analyzed using geophysical test in Shenyang, combined with composite modeling. Cenozoic strata (0–730m) exhibited an average λ e of 1.32 W·m−1·K−1 due to higher porosity and mud content; Archaean (730–2500m) strata displayed a higher λ e of 2.80 W·m−1·K−1, due to dense quartz sandstone with lower porosity and mud content. The CBHE in Shenyang can achieve excellent heat extraction relying on good thermal conduction. Spearman correlation revealed strong negative correlations between λ e and acoustic time difference, permeability, and porosity, while positive correlations were observed with depth, resistivity, wave speed, and rock skeleton. Higher rock skeleton thermal conductivity intensified the decrement effect of mud content on λ e , while higher mud content diminished the enhancement effect of rock skeleton thermal conductivity. As porosity increased, the decline in λ e slowed, particularly pronounced at higher saturation levels. λ e exhibited a gradual decrease with temperature, with a more notable change rate observed at lower porosity levels. Principles for enhancing thermal conduction were elucidated through a three-phase analysis. These findings provide foundation for the study and design of medium-depth boreholes. [Display omitted] • Conducted geological tests at a depth of 2500m in Shenyang, southern Songliao basin. • Created a combined thermal conductivity model considering temperature correction. • Analyzed the correlation and influence mechanism of geological factors. • Dense and hard rock formations (low porosity and mud content) favor thermal conduction. [ABSTRACT FROM AUTHOR]

The current knowledge of Staphylococcus warneri phages is limited, with few genomes sequenced and characterized. In this study, a prophage, vB_G30_01, isolated from Staphylococcus warneri G30 was characterized and evaluated for its lysogenic host range. The phage was studied using transmission electron microscopy and a host range. The phage genome was sequenced and characterized in depth, including phylogenetic and taxonomic analyses. The linear dsDNA genome of vB_G30_01 contains 67 predicted open reading frames (ORFs), classifying it within Bronfenbrennervirinae. With a total of 10 ORFs involved in DNA replication-related and transcriptional regulator functions, vB_G30_01 may play a role in the genetics and transcription of a host. Additionally, vB_G30_01 possesses a complete set of genes related to host lysogeny and lysis, implying that vB_G30_01 may influence the survival and adaptation of its host. Furthermore, a comparative genomic analysis reveals that vB_G30_01 shares high genomic similarity with other Staphylococcus phages and is relatively closely related to those of Exiguobacterium and Bacillus, which, in combination with the cross-infection assay, suggests possible cross-species infection capabilities. This study enhances the understanding of Staphylococcus warneri prophages, providing insights into phage–host interactions and potential horizontal gene transfer. [ABSTRACT FROM AUTHOR]

Microbial lipids are a group of promising renewable sources that are highly demanded by the food, feed, pharmaceutical, and biofuel industries. Sporobolomyces pararoseus is a well-studied oleaginous yeast that is usually considered superior for the industrial production of microbial lipids over other conventional microorganisms. The objective of this study was to investigate the specific effect of hydrogen peroxide treatment on the biosynthesis of microbial lipids in S. pararoseus via lipidomics and transcriptomics technologies. These results showed that hydrogen peroxide treatment significantly enhanced lipid production in S. pararoseus CJR, especially the triacylglycerols. The up-regulation of several key lipogenic genes might be one of the main reasons for this enhancement. Integrative analysis of the lipidome and transcriptome revealed that some key protein-encoding genes and transcription factors might play a crucial regulatory role in lipid biosynthesis under hydrogen peroxide stress. Together, the results presented herein not only provided a feasible fermentation process for boosting the yield of certain lipids but also deepened our understanding of the lipid biosynthesis in S. pararoseus CJR. This could serve as a molecular cornerstone for enhancing their yield through genetic engineering and then further facilitate commercial applications of microbial lipids synthesized by S. pararoseus in more industrial sectors. [Display omitted] • Sporobolomyces pararoseus is a promising platform organism for bio-refinery of microbial lipids. • H 2 O 2 treatment enhanced lipid synthesis in S. pararoseus , especially the triacylglycerols. • Multi-omics insights into the mechanism of H 2 O 2 resulted in this enhancement of lipid production. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a global infectious threat, and the emergence of multidrug-resistant TB has become a major challenge in eradicating the disease that requires the discovery of new treatment strategies. This study aimed to elucidate the immune infiltration and molecular regulatory network of T cell-interacting activating receptors on myeloid cell 1 (TARM1)-related genes based on a bioinformatics analysis. The GSE114911 dataset was obtained from the Gene Expression Omnibus (GEO) and screened to identify 17 TARM1-related differentially expressed genes (TRDEGs). Genes interacting with the TRDEGs were analyzed using a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A gene set enrichment analysis (GSEA) was used to identify the biological pathways significantly associated with a Mycobacterium tuberculosis (Mtb) infection. The key genes were obtained based on Cytoscape's cytoHubba plug-in. Furthermore, protein–protein interaction (PPI) networks were analyzed through STRING, while mRNA–RNA-binding protein (RBP) and mRNA–transcription factor (TF) interaction networks were developed utilizing the StarBase v3.0 and ChIPBase databases. In addition, the diagnostic significance of key genes was evaluated via receiver operating characteristic (ROC) curves, and the immune infiltration was analyzed using an ssGSEA and MCPCounter. The key genes identified in the GSE114911 dataset were confirmed in an independent GSE139825 dataset. A total of seventeen TRDEGs and eight key genes were obtained in a differential expression analysis using the cytoHubba plug-in. Through the GO and KEGG analysis, it was found that these were involved in the NF-κB, PI3K/Akt, MAPK, and other pathways related to inflammation and energy metabolism. Furthermore, the ssGSEA and MCPCounter analysis revealed a significant rise in activated T cells and T helper cells within the Mtb infection group, which were markedly associated with these key genes. This implies their potential significance in the anti-Mtb response. In summary, our results show that TRDEGs are linked to inflammation, energy metabolism, and immune cells, offering fresh insights into the mechanisms underlying TB pathogenesis and supporting further investigation into the possible molecular roles of TARM1 in TB, as well as assisting in the identification of prospective diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4+ Effective Memory T Cell (CD4+ TEM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4+ TEM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10−15) and LAG3 (rs67706382, p = 6.16× 10−16). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4+ TEM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4+ TEM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find. [ABSTRACT FROM AUTHOR]

Background: Plant growth-promoting rhizobacteria (PGPR), as a group of environmentally friendly bacteria growing in the rhizosphere of plants, play an important role in plant growth and development and resistance to environmental stresses. However, their limited understanding has led to the fact that their large-scale use in agriculture is still scarce, and the mechanisms by which beneficial bacteria are selected by plants and how they interact with them are still unclear. Method: In this study, we investigated the interaction between the auxin-producing strain Bacillus aryabhattai LAD and maize roots, and performed transcriptomic and metabolomic analyses of Bacillus aryabhattai LAD after treatment with maize root secretions(RS). Results: Our results show that there is a feedback effect between the plant immune system and bacterial auxin. Bacteria activate the immune response of plant roots to produce reactive oxygen species(ROS), which in turn stimulates bacteria to synthesize IAA, and the synthesized IAA further promotes plant growth. Under the condition of co-culture with LAD, the main root length, seedling length, root surface area and root volume of maize increased by 197%, 107%, 89% and 75%, respectively. In addition, the results of transcriptome metabolome analysis showed that LAD was significantly enriched in amino acid metabolism, carbohydrate metabolism and lipid metabolism pathways after RS treatment, including 93 differentially expressed genes and 45 differentially accumulated metabolites. Conclusion: Our findings not only provide a relevant model for exploring the effects of plant-soil microbial interactions on plant defense functions and thereby promoting plant growth, but also lay a solid foundation for the future large-scale use of PGPR in agriculture for sustainable agricultural development. [ABSTRACT FROM AUTHOR]

Medium-depth ground source heat pumps with borehole heat exchanger are pivotal in energy-saving and decarbonization. The heat transfer performance of borehole is important for design, with stratum thermal conductivity significantly influencing heat exchange, and economic considerations also act as a vital constraint on technological advancements. However, there is limited on-site testing in severe cold regions, especially in the Songliao Basin. Stratum thermal conductivity usually relies on empirical values, and its diverse impacts are not integrated into borehole heat transfer model. Additionally, previous studies optimized borehole design only from the thermal perspective. To address these gaps, we conducted an inaugural test in Shenyang. Geologic-based heat transfer model explores the geological influences, heat transfer performance, and heat extraction cost. At a depth of 2500 m, the formation's thermal conductivity is 2.45 W⋅m⁻1 K⁻1. The heat extraction, at a flow rate of 26.0 m3 h−1, achieves 352.3 kW with an inlet-outlet temperature differential of 11.7 °C. The effects of saturation, porosity, and lithology on stratum thermal conductivity were also explored. Furthermore, considering heat extraction cost, optimal depths for borehole utilizing PE-RT II and stainless-steel vacuum pipe are 2790 m (10.3 CNY·W−1) and 3140 m (10.2 CNY·W−1), with critical depths, 2910 m, governing the selection of economic inner pipe. This research establishes medium-depth ground source heat pumps as the preferred choice for low-carbon transformation in building heating, domestic hot water, and industrial and agricultural heat applications. [Display omitted] • Songliao basin's CBHE field test in severe cold region at a depth of 2500 m. • Achieved heat extraction capacity of 353.2 kW at a flow rate of 26.0 m³·h⁻1. • Utilized a geologic-based CBHE model to elucidate stratum properties influence on heat transfer. • Identified 2910 m as the critical depth for inner pipe selection and optimal depth is determined. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. Methods: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. Results: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, − 1.88; 95% CI = − 2.60 to − 1.15), azithromycin (MD, − 1.74; 95% CI = − 2.52 to − 0.95), doxycycline (MD, − 1.53; 95% CI = − 2.05 to − 1.00), ceftriaxone (MD, − 1.22; 95% CI = − 1.89 to − 0.55), penicillin (MD, − 1.22; 95% CI = − 1.80 to − 0.64), and penicillin or ampicillin (MD, − 0.08; 95% CI = − 1.01 to − 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch–Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). Conclusions: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. Systematic review registration: PROSPERO CRD42022354938. [ABSTRACT FROM AUTHOR]

Pullulan is a polymer produced by Aureobasidium spp. The yield of pullulan production can be impacted by the cellular differentiation of Aureobasidium spp., which changes with alterations in the growth environment. To improve pullulan yield, identifying key factors that regulate cellular differentiation is crucial. In this study, the main form of pullulan synthesis in Aureobasidium pullulans NG was through swollen cells (SC). The results showed that citric acid (CA) can regulate the cellular differentiation of Aureobasidium pullulans NG by accumulating higher levels of CA in the cells to maintain growth in SC form and increase pullulan production. The addition of 1.0% CA to Aureobasidium pullulans NG for 96 h resulted in a significant increase in pullulan production, producing 18.32 g/l compared to the control group which produced 10.23 g/l. Our findings suggest that controlling cellular differentiation using CA is a promising approach for enhancing pullulan production in Aureobasidium pullulans. Key points: • The regulation of cell differentiation in Aureobasidium pullulans NG is demonstrated to be influenced by citric acid. • Intracellular citric acid levels in Aureobasidium pullulans NG have been shown to support the growth of swollen cells. • Citric acid has been found to increase pullulan production in Aureobasidium pullulans NG. [ABSTRACT FROM AUTHOR]

Background: Phages play a pivotal role in the evolution of microbial populations. The interactions between phages and their hosts are complex and may vary in response to host physiology and environmental conditions. Here, we have selected the genomes of some representative Bacillus prophages and lysosomes from the NCBI database for evolutionary analysis. We explored their evolutionary relationships and analyzed the protein information encoded by hundreds of Bacillus phages. Results: We obtained the following conclusions: First, Bacillus phages carried some known functional gene fragments and a large number of unknown functional gene fragments, which might have an important impact on Bacillus populations, such as the formation of spores and biofilms and the transmission of virulence factors. Secondly, the Bacillus phage genome showed diversity, with a clear genome boundary between Bacillus prophages and Bacillus lytic phages. Furthermore, genetic mutations, sequence losses, duplications, and host-switching have occurred during the evolution of the Bacillus phage, resulting in low genome similarity between the Bacillus phages. Finally, the lysis module played an important influence on the process of Bacillus phage cross-species infestation. Conclusions: This study systematically described their protein function, diversity, and genome evolution, and the results of this study provide a basis for evolutionary diversity, horizontal gene transfer and co-evolution with the host in Bacillus phages. [ABSTRACT FROM AUTHOR]

The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases. [ABSTRACT FROM AUTHOR]

Viral infection has a central role in regulating microbial community structure and function. However, assessment of soil viruses controlling microbial community succession and biogeochemical cycling remains rare. Here, we show that viral infections substantially shifted soil bacterial community structure, and the induced prophages (VT) and extracted extracellular viruses (V and V2) decreased the bacterial community diversity at the early stage of the experiment. However, the taxonomic composition of soil bacterial communities was influenced differently under different treatments. The relative abundance of Pseudomonas , Flavobacterium , Janthinobacterium , and Pedobacter was decreased in VT, while the relative abundance of Janthinobacterium and Pedobacter was decreased in V and V2. Soil viruses decreased CO 2 production and increased N 2 O production, while enhancing microbial necromass formation and accumulation. Our findings can contribute to our understanding of microbial death pathways and the functionality of microbial carbon pump in soil ecosystem, providing new insights into the ecological role of soil viruses in biogeochemical cycling. [ABSTRACT FROM AUTHOR]