A highly sensitive and robust electrochemical biosensor for microRNA detection based on PNA-DNA hetero-three-way junction formation and target-recycling catalytic hairpin assembly amplification.

Robust and sensitive methods for the detection of microRNAs (miRNAs) are crucial in the clinical diagnosis of cancers. In this study, a novel electrochemical biosensor with high sensitivity for miRNA-21 detection is developed, which relies on the formation of a peptide nucleic acid (PNA)-DNA hetero-three-way junction (H3WJ) and target-recycling catalytic hairpin assembly (CHA) amplification. The electroneutral PNA probes are initially immobilized onto a gold electrode to construct the sensor. Upon introduction of miRNA-21, target-recycling CHA is initiated, resulting in abundant double-stranded CHA products. Subsequently, association between the PNA probes and these products leads to the formation of PNA-DNA H3WJs. Consequently, the electrode surface is densely populated with numerous electroactive Ferrocene (Fc) groups, resulting in a significantly amplified current response for highly sensitive detection of miRNA-21 at concentrations as low as 0.15 fM. This approach demonstrates remarkable specificity towards target miRNAs and can be utilized for quantitative monitoring of miRNA-21 expression in human cancer cells. More importantly, the sensor exhibits exceptional stability and shows a significant reduction in background noise during miRNA detection, making this method a highly promising sensing platform for monitoring various miRNA biomarkers to facilitate the diagnosis of diverse cancers.

Thymosin beta-4 participate in antibacterial immunity and wound healing in black tiger shrimp, Penaeus monodon.

Thymosin beta-4 (Tß4) is a ubiquitous protein with multiple and diverse intracellular and extracellular functions in vertebrates, which play fundamental roles in innate immune against pathogens and wound healing. In this study, the full-length cDNA of Tß4 was cloned from Penaeus monodon (designated as PmTß4), using the technology of rapid amplification of cDNA ends (RACE). The cDNA of PmTß4 was 1361 bp with an open reading frame (ORF) of 501 bp, which encoding a polypeptide of 166 amino acid. The Quantitative Real-time PCR (qRT-PCR) analysis results showed that PmTß4 was ubiquitously expressed in all the tested shrimp tissues, with the highest expression level was detected in the hemolymph, while the lowest expression level in the muscle. The expression level of PmTß4 was significantly up-regulated in hepatopancreas after challenged by Vibrio parahaemolyticus, Vibrio harveyi and Staphylococcus aureus. In vitro antimicrobial test showed that the recombinant protein of PmTß4 (rPmTß4) had broad-spectrum of antimicrobial activity, which could inhibit both the growth of gram-negative bacteria and gram-positive bacteria, including Vibrio vulnificus, V. parahaemolyticus, Streptococcus agalactiae, S. aureus and Aeromonas hydrophila. Moreover, rPmTß4 had a certain binding ability to different bacteria, and this binding ability exhibits a strong dose-dependent effect. In vivo, PmTß4 could facilitate external bacterial clearance in shrimp, and have beneficial to shrimp survival post V. parahaemolyticus infection. Furthermore, wound-healing assay was carried out to study the role of PmTß4 in the process of wound healing. The results showed that the PmTß4 expression was significantly up-regulated by injury treatment, and exerted positive effects to promote wound healing. In addition, PmTß4 can significantly increase the expression level of superoxide dismutase (SOD) and Catalase (CAT) after injury treatment in shrimp, which would involve in scavenging reactive oxygen species (ROS) caused by the wound. In conclusion, these results indicated that PmTß4 may play important roles in antibacterial immunity and wound healing in Penaeus monodon.

Structure of a fungal 1,3-ß-glucan synthase.

1,3-ß-Glucan serves as the primary component of the fungal cell wall and is produced by 1,3-ß-glucan synthase located in the plasma membrane. This synthase is a molecular target for antifungal drugs such as echinocandins and the triterpenoid ibrexafungerp. In this study, we present the cryo-electron microscopy structure of Saccharomyces cerevisiae 1,3-ß-glucan synthase (Fks1) at 2.47-Å resolution. The structure reveals a central catalytic region adopting a cellulose synthase fold with a cytosolic conserved GT-A-type glycosyltransferase domain and a closed transmembrane channel responsible for glucan transportation. Two extracellular disulfide bonds are found to be crucial for Fks1 enzymatic activity. Through structural comparative analysis with cellulose synthases and structure-guided mutagenesis studies, we gain previously unknown insights into the molecular mechanisms of fungal 1,3-ß-glucan synthase.

[Determination of 10 carbamate pesticide residues in liquid milk by ultra performance liquid chromatography-tandem mass spectrometry with pass-through solid-phase extraction purification].

Carbamates are used in broad-spectrum insecticides and herbicides, and have highly efficient, low-residue, and long-lasting characteristics. However, this type of pesticide exerts mutagenic, teratogenic, carcinogenic, and other adverse effects, and its frequent use can exceed the recommended scope and limits. Research on the determination of carbamate pesticides mainly focuses on foods of plant origin and pays less attention to foods of animal origin. The methods for carbamate determination described in the current national standards have complicated operating procedures and low efficiency. Therefore, highly efficient and accurate methods for carbamate detection in milk must be established. In this work, a rapid method based on pass-through solid-phase extraction (SPE) purification coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of 10 carbamate pesticides in liquid milk. The pretreatment and instrument methods were systematically optimized. The milk sample was extracted with acetonitrile, and then purified using a Captiva EMR-Lipid filtration kit. The purified extract was separated on an ACQUITY UPLC BEH C18 column with mobile phase of methanol and 0.1% formic acid aqueous solution in gradient elution. The flow rate was 0.3 mL/min. Column temperature was 35 ℃. Quantitative analysis was performed using the external standard method with matrix matching curves. The 10 carbamate pesticides showed good linear relationships in the mass concentration range of 2-200 µg/L, with correlation coefficients greater than 0.999. The limits of detection (LODs) and quantification (LOQs) for the 10 carbamate pesticides were 0.045-0.23 and 0.15-0.77 µg/kg, respectively. Recovery tests were conducted using the blank-matrix method at three spiked levels of 15, 50, and 100 µg/kg, and good recoveries for the 10 carbamate pesticides were obtained. In particular, the recoveries for the three spiked levels of 15, 50, and 100 µg/kg were 68.7%-93.3% with relative standard deviations (RSDs) of 1.8%-8.0%. The proposed method is efficient, convenient, accurate, and suitable for the rapid detection of the 10 carbamate pesticides in liquid milk. Compared with the conventional NH2 and ENVITM-18 SPE columns used in the national standard determination method, the proposed method demonstrated better purification effects. The recoveries for aldicarb sulfoxide, aldicarb sulfone, methomyl, and carbaryl after purification using the Captiva EMR-Lipid kit increased from 60% to 80%. Thus, the proposed method is suitable for targets with strong polarity and gives measurement results with good repeatability and accuracy.

Intervention effect of Lycium barbarum polysaccharide on lead-induced kidney injury mice and its mechanism: A study based on the PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional medicinal application of Lycium barbarum is centered on the improvement of eyesight, as well as the nourishment of liver and kidney functions. Lycium barbarum polysaccharide (LBP), serving as the principal active constituent of Lycium barbarum, has been identified as the main contributor to these beneficial effects. Previous studies have indicated that Lycium barbarum polysaccharide exhibits a renoprotective effect against lead-induced injury, but its mechanism and efficacy remain unclear. AIM OF THE STUDY: The objective of this study was to examine the effectiveness of LBP in preventing lead-induced renal injury and investigate both the toxic mechanism of lead-induced renal injury and the efficacy mechanism of LBP against it, with a focus on the PI3K/AKT/mTOR signaling pathway. MATERIALS AND METHODS: The drug effect and mechanism of LBP on lead-induced kidney injury were investigated by administering positive drugs and LBP to mice with established lead-induced kidney injury. RESULTS: The renal function of mice with lead-induced renal injury was significantly restored, renal tissue lesions and renal mitochondrial damage were delayed, a disorder of hematological parameters induced by lead was improved, the increase of lead-induced renal index was reduced, and the body weight of mice with lead-induced renal injury was increased by the LBP intervention, as revealed by the results of pharmacodynamic experiments. Based on PI3K /AKT /mTOR signaling pathway, the toxic mechanism of lead-induced kidney injury and the pharmacodynamic mechanism of LBP against lead-induced kidney injury were studied. The results showed that lead could activate the TLR4 receptor, and then activate PI3K /AKT /mTOR signaling pathway, inhibit autophagy of kidney tissue cells, and enhance apoptosis of kidney tissue cells to induce kidney injury; LBP inhibits the activation of TLR4 receptor, which in turn inhibits the PI3K/AKT/mTOR signaling pathway, enhances the autophagy of kidney tissue cells, reduces the apoptosis of kidney tissues, and delays lead-induced kidney injury.

Fagopyrum tataricum ethanol extract ameliorates symptoms of hyperglycemia by regulating gut microbiota in type 2 diabetes mellitus mice.

Type 2 diabetes mellitus (T2DM) is typically accompanied by sudden weight loss, dyslipidemia-related indicators, decreased insulin sensitivity, and altered gut microbial communities. Fagopyrum tataricum possesses many biological activities, such as antioxidant, hypolipidemic, and hypotensive activities. However, only a few studies have attempted to elucidate the regulatory effects of F. tataricum ethanol extract (FTE) on intestinal microbial communities and its potential relationships with T2DM. In this study, we established a T2DM mouse model and investigated the regulatory effects of FTE on hyperglycemia symptoms and intestinal microbial communities. FTE intervention significantly improved the levels of fasting blood glucose, the area under the curve of oral glucose tolerance test (OGTT), and glycosylated serum protein, as well as pancreas islet function correlation index. In addition, FTE effectively improved hepatic and cecum injuries and insulin secretion due to T2DM. It was also revealed that the potential hypoglycemic mechanism of FTE was involved in the regulation of protein kinase B (AKT-1) and glucose transporter 2 (GLUT-2). Furthermore, compared with the Model group, the FTE-H intervention exhibited a significantly decreased ratio of Firmicutes to Bacteroidetes at the phylum level, reduced relative abundance of pernicious bacteria at the genus level, such as Desulfovibrio, Oscillibacter, Blautia, Parabacteroides, and Erysipelatoclostridium, and ameliorated inflammatory response and insulin resistance. Moreover, the correlation between gut microbiota and hypoglycemic indicators was predicted. The results showed that Lachnoclostridium, Lactobacillus, Oscillibacter, Bilophila, and Roseburia have the potential to be used as bacterial markers for T2DM. In conclusion, our research showed that FTE alleviates hyperglycemia symptoms by regulating the expression of AKT-1 and GLUT-2, as well as intestinal microbial communities in T2DM mice.

Adaptive enhancement design of non-significant regions of a Wushu action 3D image based on the symmetric difference algorithm.

The recognition of martial arts movements with the aid of computers has become crucial because of the vigorous promotion of martial arts education in schools in China to support the national essence and the inclusion of martial arts as a physical education test item in the secondary school examination in Shanghai. In this paper, the fundamentals of background difference algorithms are examined and a systematic analysis of the benefits and drawbacks of various background difference algorithms is presented. Background difference algorithm solutions are proposed for a number of common, challenging problems. The empty background is then automatically extracted using a symmetric disparity approach that is proposed for the initialization of background disparity in three-dimensional (3D) photos of martial arts action. It is possible to swiftly remove and manipulate the background, even in intricate martial arts action recognition scenarios. According to the experimental findings, the algorithm's optimized model significantly enhances the foreground segmentation effect of the backdrop disparity in 3D photos of martial arts action. The use of features such as texture probability is coupled to considerably enhance the shadow elimination effect for the shadow problem of background differences.

Human iPSC-derived endothelial cells promote CNS remyelination via BDNF and mTORC1 pathway.

Damage of myelin is a component of many diseases in the central nervous system (CNS). The activation and maturation of the quiescent oligodendrocyte progenitor cells (OPCs) are the crucial cellular processes for CNS remyelination, which is influenced by neuroinflammation in the lesion microenvironment. Endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) have shown promise in restoring function in various preclinical animal models. Here we ask whether and whether transplantation of hiPSC-ECs could benefit remyelination in a mouse model of CNS demyelination. Our results show that in vitro, hiPSC-ECs increase OPC proliferation, migration and differentiation via secreted soluble factors including brain-derived neurotrophic factor (BDNF). hiPSC-ECs also promote the survival of oligodendrocyte lineage cells in vitro and in vivo. Transplantation of hiPSC-ECs into a toxin-induced demyelination lesion in mouse corpus callosum (CC) leads to increased density of oligodendrocyte lineage cells and level of myelin in demyelinated area, correlated with a decreased neuroinflammation and an increased proportion of pro-regenerative M2 phenotype in microglia/macrophages. The hiPSC-EC-exposed oligodendrocyte lineage cells showed significant increase in the level of phosphorylated S6 ribosomal protein (pS6) both in vitro and in vivo, indicating an involvement of mTORC1 pathway. These results suggest that hiPSC-ECs may benefit myelin protection and regeneration which providing a potential source of cell therapy for a wide range of diseases and injuries associated with myelin damage.

Eliminating the Imbalanced Mobility Bottlenecks via Reshaping Internal Potential Distribution in Organic Photovoltaics.

The imbalanced carrier mobility remains a bottleneck for performance breakthrough in even those organic solar cells (OSCs) with recorded power conversion efficiencies (PCEs). Herein, a counter electrode doping strategy is proposed to reshape the internal potential distribution, which targets to extract the low mobility carriers at far end. Device simulations reveal that the key of this strategy is to partially dope the active layer with a certain depth, therefore it strengthens the electric field for low mobility carriers near counter electrode region while avoids zeroing the electric field near collection electrode region. Taking advantage of these, PCE enhancements are obtained from 15.4% to 16.2% and from 16.9% to 18.0%, respectively, via cathode p-doping and anode n-doping. Extending its application from opaque to semitransparent devices, the PCE of dilute cell rises from 10.5% to 12.1%, with a high light utilization efficiency (LUE) of 3.5%. The findings provide practical solutions to the core device physical problem in OSCs.

Drug Permeability: From the Blood-Brain Barrier to the Peripheral Nerve Barriers.

Drug delivery into the peripheral nerves and nerve roots has important implications for effective local anesthesia and treatment of peripheral neuropathies and chronic neuropathic pain. Similar to drugs that need to cross the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) to gain access to the central nervous system (CNS), drugs must cross the peripheral nerve barriers (PNB), formed by the perineurium and blood-nerve barrier (BNB) to modulate peripheral axons. Despite significant progress made to develop effective strategies to enhance BBB permeability in therapeutic drug design, efforts to enhance drug permeability and retention in peripheral nerves and nerve roots are relatively understudied. Guided by knowledge describing structural, molecular and functional similarities between restrictive neural barriers in the CNS and peripheral nervous system (PNS), we hypothesize that certain CNS drug delivery strategies are adaptable for peripheral nerve drug delivery. In this review, we describe the molecular, structural and functional similarities and differences between the BBB and PNB, summarize and compare existing CNS and peripheral nerve drug delivery strategies, and discuss the potential application of selected CNS delivery strategies to improve efficacious drug entry for peripheral nerve disorders.

The role of type II esophageal microbiota in achalasia: Activation of macrophages and degeneration of myenteric neurons.

OBJECTIVE: The gut microbiota plays a critical role in the appropriate development and maintenance of the enteric nervous system (ENS). Esophageal achalasia (EA) is a rare motility disorder characterized by the selective degeneration of inhibitory neurons in the esophageal myenteric plexus. This study aimed to evaluate the composition of the esophageal microbiota in achalasia and explore the potential microbial mechanisms involved in its pathogenesis. DESIGN: The lower esophageal mucosal microbiota was analyzed in patients with achalasia and control participants using 16 S rRNA sequencing. The association between the esophageal microbiota and achalasia was validated by inducing esophageal dysbiosis in C57BL/10 J and C57BL/10ScNJ (TLR4KO) mice via chronic exposure to ampicillin sodium in their drinking water. RESULTS: The esophageal microbiota in EA patients had lower diversity and a predominance of Gram-negative bacteria (Type II microbiota) compared to that in the healthy controls. Additionally, the relative abundance of Rhodobacter decreased significantly in patients with achalasia, which correlated with an enrichment of lipopolysaccharide (LPS) biosynthesis based on the COG database. Antibiotic-treated mice showed an esophageal microbiota characterized by increased abundance of Gram-negative bacteria (Type II microbiome), decreased abundance of Rhodobacter, and enriched LPS biosynthesis. Compared to the control and TLR4KO mice, the antibiotic-treated wild-type mice had higher LES resting pressure, increased LES contraction rate after carbachol stimulation, and decreased relaxation response to L-arginine. Moreover, the number of myenteric neurons decreased, while the number of lamina propria macrophages (LpMs) increased after antibiotic exposure. Furthermore, the TLR4-MYD88-NF-κB pathway was up-regulated, and the production of TNF-α, IL-1ß, and IL-6 increased in the antibiotic-treated mice. CONCLUSIONS: Patients with achalasia exhibit esophageal dysbiosis, which may induce aberrant esophageal motility.

Regulating the H2O2 Activation Pathway on a Well-Defined CeO2 Nanozyme Allows the Entire Steering of Its Specificity between Associated Enzymatic Reactions.

Nanozymes are promising alternatives to natural enzymes, but their use remains limited owing to poor specificity. For example, CeO2 activates H2O2 and displays peroxidase (POD)-like, catalase (CAT)-like, and haloperoxidase (HPO)-like activities. Since they unavoidably compete for H2O2, affecting its utilization in the target application, the precise manipulation of reaction specificity is thus imperative. Herein, we showed that one can simply achieve this by manipulating the H2O2 activation pathway on pristine CeO2 in well-defined shapes. This is because the coordination and electronic structures of Ce sites vary with CeO2 surfaces, wherein the (100) and (111) surfaces display nearly 100% specificity toward POD-/CAT-like and HPO-like activities, respectively. The antibacterial results suggest that the latter surface can well-utilize H2O2 to kill bacteria (cf., the former), which is promising for anti-biofouling applications. This work provides atomic insights into the synthesis of nanozymes with improved activity, reaction specificity, and H2O2 utilization.

Cuproptosis-related gene SLC31A1 expression correlates with the prognosis and tumor immune microenvironment in glioma.

Cuproptosis is a newly discovered form of cell death. It is regulated by a string of genes. The genes are identified to influence the tumor progression, but in glioma, the cuproptosis-related genes are little studied. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) were used to screen for SLC31A1 gene expression in glioma and healthy tissue samples. The results were validated using the Gene Expression Omnibus (GEO) and quantitative real-time polymerase chain reaction (qPCR). The Human Protein Atlas (HPA) and the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to validate our results at the protein level. Multivariable analysis and Kaplan-Meier survival curves were used to examine the relationship among SLC31A1 gene expression, clinical parameters, and survival rates. The online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to find the genes and proteins that correlate to SLC31A1. The immune infiltration analysis was performed using the Tumor Immune Estimation Resource (TIMER) databases. Small interfering RNA was used to knock down the SLC31A1 expression, and the cell proliferation, apoptosis, and migration were analyzed using cell counting kit-8, flow cytometry, and transwell. The glioma patients have higher SLC31A1 expression levels, which increase as the World Health Organization (WHO) grade escalates. The survival analysis illustrates that the SLC31A1 gene expression negatively correlates with overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The immune infiltration analysis shows the SLC31A1 gene positively correlates with T helper 2 (Th2) cells, macrophages, and M2-type macrophages and negatively correlates with plasmacytoid dendritic cells (pDCs), natural killer (NK) CD56bright cells, and CD8 T cells. The in vitro KD experiment shows the SLC31A1 knockdown depressed the glioma cell proliferation and migration and promoted the apoptosis rate. The SLC31A1 gene expression can shorten the survival time of glioma patients. In vitro study shows that SLC31A1 can promote cell proliferation, and migration, and depress the cell apoptosis of glioma cells. It also can promote the formation of a tumor-suppressive microenvironment.

Honeybee as a food nutrition analysis model of neural development and gut microbiota.

Research on the relationships between the gut microbiota and the neurophysiology and behavior of animals has grown exponentially in just a few years. Insect behavior may be controlled by molecular mechanisms that are partially homologous to those in mammals, and swarming insects may be suitable as experiment models in these types of investigations. All core gut bacteria in honeybees can be cultivated in vitro. Certain gut microflora of bees can be genetically engineered or sterilized and colonized. The bee gut bacteria model is established more rapidly and has a higher flux than other sterile animal models. It may help elucidate the pathogenesis of intestinal diseases and identify effective molecular therapeutic targets against them. In the present review, we focused on the contributions of the honeybee model in learning cognition and microbiome research. We explored the relationship between honeybee behavior and neurodevelopment and the factors determining the mechanisms by which the gut microbiota affects the host. In particular, we concentrated on the correlation between gut microbiota and brain development. Finally, we examined strategies for the effective use of simple animal models in animal cognition and microbiome research.

Review of Marine Cyanobacteria and the Aspects Related to Their Roles: Chemical, Biological Properties, Nitrogen Fixation and Climate Change.

Marine cyanobacteria are an ancient group of photosynthetic microbes dating back to 3.5 million years ago. They are prolific producers of bioactive secondary metabolites. Over millions of years, natural selection has optimized their metabolites to possess activities impacting various biological targets. This paper discusses the historical and existential records of cyanobacteria, and their role in understanding the evolution of marine cyanobacteria through the ages. Recent advancements have focused on isolating and screening bioactive compounds and their respective medicinal properties, and we also discuss chemical property space and clinical trials, where compounds with potential pharmacological effects, such as cytotoxicity, anticancer, and antiparasitic properties, are highlighted. The data have shown that about 43% of the compounds investigated have cytotoxic effects, and around 8% have anti-trypanosome activity. We discussed the role of different marine cyanobacteria groups in fixing nitrogen percentages on Earth and their outcomes in fish productivity by entering food webs and enhancing productivity in different agricultural and ecological fields. The role of marine cyanobacteria in the carbon cycle and their outcomes in improving the efficiency of photosynthetic CO2 fixation in the chloroplasts of crop plants, thus enhancing the crop plant's yield, was highlighted. Ultimately, climate changes have a significant impact on marine cyanobacteria where the temperature rises, and CO2 improves the cyanobacterial nitrogen fixation.

The alleviating effect of ellagic acid on DSS-induced colitis via regulating gut microbiomes and gene expression of colonic epithelial cells.

The anti-inflammatory effect of ellagic acid (EA) and its possible underlying mechanism in dextran sulfate sodium (DSS)-induced mouse chronic colonic inflammation were studied. It was observed that EA administration significantly alleviated the colonic inflammation phenotypes, including decreasing the disease activity index (DAI), enhancing the body weight loss, and improving the shortened length of the colon and pathological damage of colon tissue. Additionally, EA reshaped the constitution of the gut microbiota by elevating the ratio of Bacteroidetes along with Bacteroides and Muribaculaceae, while decreasing the proportion of Firmicutes. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2) revealed that the metabolic function of the gut microbiota was also changed. Furthermore, mouse colon transcriptome analysis showed that the tight junction and peroxisome proliferator-activated receptor (PPAR) signaling pathways were activated and the expressions of related genes were upregulated after EA intervention. These results showed that EA could remodel the gut bacterial composition, change the intestinal epithelial cell gene expressions in mice, and consequently improve the colonic inflammatory symptoms.

Classification and characterisation of extracellular vesicles-related tuberculosis subgroups and immune cell profiles.

Around the world, tuberculosis (TB) remains one of the most common causes of morbidity and mortality. The molecular mechanism of Mycobacterium tuberculosis (Mtb) infection is still unclear. Extracellular vesicles (EVs) play a key role in the onset and progression of many disease states and can serve as effective biomarkers or therapeutic targets for the identification and treatment of TB patients. We analysed the expression profile to better clarify the EVs characteristics of TB and explored potential diagnostic markers to distinguish TB from healthy control (HC). Twenty EVs-related differentially expressed genes (DEGs) were identified, and 17 EVs-related DEGs were up-regulated and three DEGs were down-regulated in TB samples, which were related to immune cells. Using machine learning, a nine EVs-related gene signature was identified and two EVs-related subclusters were defined. The single-cell RNA sequence (scRNA-seq) analysis further confirmed that these hub genes might play important roles in TB pathogenesis. The nine EVs-related hub genes had excellent diagnostic values and accurately estimated TB progression. TB's high-risk group had significantly enriched immune-related pathways, and there were substantial variations in immunity across different groups. Furthermore, five potential drugs were predicted for TB using CMap database. Based on the EVs-related gene signature, the TB risk model was established through a comprehensive analysis of different EV patterns, which can accurately predict TB. These genes could be used as novel biomarkers to distinguish TB from HC. These findings lay the foundation for further research and design of new therapeutic interventions aimed at treating this deadly infectious disease.

Screening and Metabolomic Analysis of Lactic Acid Bacteria-Antagonizing Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a conditional Gram-negative pathogen that produces extracellular virulence factors that can lead to bloodstream invasion, severely harm tissues, and disseminate bacteria, ultimately leading to various diseases. In this study, lactic acid bacteria (LAB) with strong antagonistic ability against P. aeruginosa were screened, and the regulatory mechanism of LAB against P. aeruginosa was evaluated. The results showed that the three selected LAB strains had strong inhibition ability on the growth, biofilm formation, and pyocyanin expression of P. aeruginosa and a promoting effect on the expression of autoinducer-2. Among them, Lactipantibacillus plantarum (Lp. plantarum) LPyang is capable of affecting the metabolic processes of P. aeruginosa by influencing metabolic substances, such as LysoPC, oxidized glutathione, betaine, etc. These results indicate that LPyang reduces the infectivity of P. aeruginosa through inhibition of its growth, biofilm formation, pyocyanin expression, and regulation of its metabolome. This study provides new insights into the antagonistic activity of Lp. plantarum LPyang against P. aeruginosa.