Genome analysis of the mpox (formerly monkeypox) virus and characterization of core/variable regions.

Since smallpox was eradicated in 1980, the monkeypox virus (MPXV) has emerged as the most threatening orthopoxvirus in the world. In this study, we conducted a comprehensive analysis of the currently published complete genome sequences of the monkeypox virus. The core/variable regions were identified through core-pan analysis of MPXV. Besides single-nucleotide polymorphisms, our study also revealed that specific genes, multi-copy genes, repeat sequences, and recombination fragments are primarily distributed in the variable region. This result suggests that variable regions are not only more susceptible to single-base mutations, but also to events such as gene loss or gain, as well as recombination. Taken together, our results demonstrate the genomic characteristics of the core/variable regions of MPXV, and contribute to our understanding of the evolution of MPXV.

Evaluation of immunoregulation and immunoprotective efficacy of Glaesserella parasuis histidine kinase QseC.

QseC is a membrane sensor kinase that enables bacteria to perceive autoinducers -3, adrenaline, and norepinephrine to initiate downstream gene transcription. In this study, we found that the QseC protein of Glaesserella parasuis can serve as an effective antigen to activate the host's immune response. Therefore, we investigated the immunogenicity and host protective effect of this protein. ELISA and indirect immunofluorescence results showed that QseC protein can induce high titer levels of humoral immunity in mice and regularly generate specific serum antibodies. We used MTS reagents to detect lymphocyte proliferation levels and found that QseC protein can cause splenic lymphocyte proliferation with memory and specificity. Further immunological analysis of the spleen cell supernatant revealed significant upregulation of levels of IL-1ß, IL-4 and IFN-γ in the QseC + adjuvant group. In the mouse challenge experiment, it was found that QseC + adjuvant can provide effective protection. The results of this study demonstrate that QseC protein provides effective protection in a mouse model and has the potential to serve as a candidate antigen for a novel subunit vaccine for further research.

Unraveling extracellular protein signatures to enhance live attenuated vaccine development through type II secretion system disruption in Vibriomimicus.

Type II secretion systems (T2SS) are important molecular machines used by bacteria to transport a wide range of proteins across the outer membrane from the periplasm. Vibrio mimicus is an epidemic pathogen threats to both aquatic animals and human health. Our previous study demonstrates that T2SS deletion reduced virulence by 307.26 times in yellow catfish. However, the specific effects of T2SS-mediated extracellular protein secretion in V. mimicus, including its potential role in exotoxin secretion or other mechanisms, require further investigation. Through proteomics and phenotypic analyses, this study observed that the ΔT2SS strain exhibited significant self-aggregation and dynamic deficiency, with a notable negative correlation with subsequent biofilm formation. The proteomics analysis revealed 239 different abundances of extracellular proteins after T2SS deletion, including 19 proteins with higher abundance and 220 proteins with lower and even absent in the ΔT2SS strain. These extracellular proteins are involved in various pathways, such as metabolism, virulence factors expression, and enzymes. Among them, purine, pyruvate, and pyrimidine metabolism, and the Citrate cycle, were the primary pathways affected by T2SS. Our phenotypic analysis is consistent with these findings, suggesting that the decreased virulence of ΔT2SS strains is due to the effect of T2SS on these proteins, which negatively impacts growth, biofilm formation, auto-aggregation, and motility of V. mimicus. These results provide valuable insights for designing deletion targets for attenuated vaccines development against V. mimicus and expand our understanding of the biological functions of T2SS.

Pentagalloyl Glucose: A Review of Anticancer Properties, Molecular Targets, Mechanisms of Action, Pharmacokinetics, and Safety Profile.

Pentagalloyl glucose (PGG) is a natural hydrolyzable gallotannin abundant in various plants and herbs. It has a broad range of biological activities, specifically anticancer activities, and numerous molecular targets. Despite multiple studies available on the pharmacological action of PGG, the molecular mechanisms underlying the anticancer effects of PGG are unclear. Here, we have critically reviewed the natural sources of PGG, its anticancer properties, and underlying mechanisms of action. We found that multiple natural sources of PGG are available, and the existing production technology is sufficient to produce large quantities of the required product. Three plants (or their parts) with maximum PGG content were Rhus chinensis Mill, Bouea macrophylla seed, and Mangifera indica kernel. PGG acts on multiple molecular targets and signaling pathways associated with the hallmarks of cancer to inhibit growth, angiogenesis, and metastasis of several cancers. Moreover, PGG can enhance the efficacy of chemotherapy and radiotherapy by modulating various cancer-associated pathways. Therefore, PGG can be used for treating different human cancers; nevertheless, the data on the pharmacokinetics and safety profile of PGG are limited, and further studies are essential to define the clinical use of PGG in cancer therapies.

Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway.

CONTEXT: Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo, suggesting its potential for cancer chemotherapy. OBJECTIVE: To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma. MATERIALS AND METHODS: CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. In vitro migration/invasion/western blot assay with 1, 1.5, 2 µM SAG and in vivo effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice. RESULTS: The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were -6.33, -6.31, and -6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells (p < 0.05) with IC50 values of 2.378 µM and 2.719 µM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth. CONCLUSIONS: Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.

Dual-Color Fluorescence Switch-On Probe for Imaging G-Quadruplex and Double-Stranded DNA in Living Cells.

A tripodal quinone-cyanine dye having one donor and three acceptors, that is, one quinone and three N-methylbenzothiazolium moieties, QCy(MeBT)3, was synthesized by simple Knoevenagel condensation between 2-hydroxybenzene-1,3,5-tricarbaldehyde and N-methyl-2-methylbenzothiazolium iodide. The 700 nm (λex, 570 nm) and 600 nm (λex, 470 nm) fluorescence emission of QCy(MeBT)3 was significantly and individually enhanced with the addition of G-quadruplex (G4) DNA and double-stranded DNA (dsDNA), respectively. The results of docking simulations and the response against the viscosity change revealed that the dual-fluorescence response was caused by the difference in the binding mode of QCy(MeBT)3 depending on the DNA structure. The results of fluorescence microscopy imaging experiments using QCy(MeBT)3 suggested that G4 DNAs and dsDNAs in the cell nucleus can be imaged with near-infrared (NIR, 700 nm) and red (600 nm) fluorescence emissions. Furthermore, pyridostatin-induced G4 formation in the living cells can be imaged with NIR fluorescence. The results indicated that QCy(MeBT)3 has huge potential to be a NIR-fluorescent molecular probe for analyzing the structural dynamics of nucleic acids in living cells with a normal fluorescence microscope.

Landscape of keratinocytes transcriptome alterations in response to Trichophyton mentagrophytes infection.

Dermatophytosis is an intractable superficial fungal infection of keratinized structures, with approximately 20% incidence in humans. Alterations of keratinocytes in the pathogenesis of dermatophytosis at the transcriptome level remain unclear. To understand and characterize such responses, keratinocytes were infected with Trichophyton mentagrophytes. After infection with 1 × 105 conidia/mL T. mentagrophytes for 24 h, the adherence of fungal hyphae to keratinocytes and the damage caused to cell morphology and structure were observed by light microscopy and transmission electron microscopy, respectively. Levels of pro-inflammatory cytokines IL-1α, IL-1ß, TNFα, and IL-8 significantly increased after infection. RNA-seq and bioinformatic analyses revealed that 766 genes were significantly whereas 2207 genes were repressed in the T. mentagrophyte-infected cells. Some of the differentially expressed genes (DEGs) were related to inflammation, immune responses, wound healing, metabolism, and oxidative stress. GO and KEGG pathway enrichment analyses revealed that DEGs and pathways involved in inflammatory response, immune response, and pathogen-induced dysfunction were significantly enriched in the infected cells. Furthermore, gene set enrichment analysis revealed that higher expression gene sets were mainly involved in immune responses, whereas lower expression gene sets were related to cell component organization or biogenesis and transporter activity. Furthermore, protein-protein interaction network and function analyses revealed that JUN, TP53, FOS, MYC, and HSP90AA1 play a key role in immune responses. Overall, our study systematically uncovered the transcriptome-level response of keratinocytes to T. mentagrophyte and provided insights into dermatophytosis treatment.

Comprehensive analysis of transcriptome and metabolome analysis reveal new targets of Glaesserella parasuis glucose-specific enzyme IIBC (PtsG).

The ptsG (hpIIBCGlc) gene, belonging to the glucose-specific phosphotransferase system, encodes the bacterial glucose-specific enzyme IIBC. In this study, the effects of a deletion of the ptsG gene were investigated by metabolome and transcriptome analyses. At the transcriptional level, we identified 970 differentially expressed genes between ΔptsG and sc1401 (Padj<0.05) and 2072 co-expressed genes. Among these genes, those involved in methane metabolism, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, pyruvate metabolism, phosphotransferase system (PTS), biotin metabolism, Two-component system and Terpenoid backbone biosynthesis showed significant changes in the ΔptsG mutant strain. Metabolome analysis revealed that a total of 310 metabolites were identified, including 20 different metabolites (p < 0.05). Among them, 15 metabolites were upregulated and 5 were downregulated in ΔptsG mutant strain. Statistical analysis revealed there were 115 individual metabolites having correlation, of which 89 were positive and 26 negative. These metabolites include amino acids, phosphates, amines, esters, nucleotides, benzoic acid and adenosine, among which amino acids and phosphate metabolites dominate. However, not all of these changes were attributable to changes in mRNA levels and must also be caused by post-transcriptional regulatory processes. The knowledge gained from this lays the foundation for further study on the role of ptsG in the pathogenic process of Glaesserella parasuis (G.parasuis).

Association of recurrent APOBEC3B alterations with the prognosis of gastric-type cervical adenocarcinoma.

OBJECTIVE: Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive type of endocervical adenocarcinoma (ECA) with distinct histopathologic features and unfavorable treatment outcomes, but no genomic prognostic factor has been revealed. We aimed to systematically investigate the somatic alterations of GCA at genome-wide level and evaluate their prognostic value. METHODS: We performed whole-exome sequencing (WES) on 25 pairs of tumor and matched normal samples to characterize the genomic features of Chinese patients with GCA and investigated their relations to histopathological characterizations and prognosis. The prognostic value of the genomic alterations was evaluated in a total of 58 GCA patients. RESULTS: Mutations were commonly observed in reported GCA-related driver genes, including TP53 (32%), CDKN2A (20%), SKT11 (20%), BRCA2 (12%), SMAD4 (12%), and ERBB2 (12%). Recurrent novel trunk mutations were also observed in PBRM1 (12%), FRMPD4 (12%), and NOP2 (8%) with high variant allele frequency. Moreover, enrichment of the APOBEC signature was attributed to frequent gain of somatic copy number alteration (SCNA) of APOBEC3B (20%), which perfectly matched the nuclear-positive staining of APOBEC3B through immunohistochemistry. In contrast, APOBEC3B alteration was absent in patients with conventional type of ECA (N = 52). Notably, positive APOBEC3B was consistently enriched in patients with favorable prognosis in both the discovery cohort and an additional 33 GCA patients, thus indicating a significant association with lower relapse risk of GCA independent of cancer stage (P = 0.02). CONCLUSION: Our results can aid understanding of the molecular basis of GCA in the Chinese population by providing genomic profiles and highlighting the potential prognostic value of APOBEC3B for GCA through routine clinical IHC.

Effect of TiO2 Calcination Pretreatment on the Performance of Pt/TiO2 Catalyst for CO Oxidation.

In order to improve the CO catalytic oxidation performance of a Pt/TiO2 catalyst, a series of Pt/TiO2 catalysts were prepared via an impregnation method in this study, and various characterization methods were used to explore the effect of TiO2 calcination pretreatment on the CO catalytic oxidation performance of the catalysts. The results revealed that Pt/TiO2 (700 °C) prepared by TiO2 after calcination pretreatment at 700 °C exhibits a superior CO oxidation activity at low temperatures. After calcination pretreatment, the catalyst exhibited a suitable specific surface area and pore structure, which is beneficial to the diffusion of reactants and reaction products. At the same time, the proportion of adsorbed oxygen on the catalyst surface was increased, which promoted the oxidation of CO. After calcination pretreatment, the adsorption capacity of the catalyst for CO and CO2 decreased, which was beneficial for the simultaneous inhibition of the CO self-poisoning of Pt sites. In addition, the Pt species exhibited a higher degree of dispersion and a smaller particle size, thereby increasing the CO oxidation activity of the Pt/TiO2 (700 °C) catalyst.

Effect of a Cocatalyst on a Photoanode in Water Splitting: A Study of Scanning Electrochemical Microscopy.

With a proper band gap of ∼2.4 eV for solar light absorption and suitable valence band edge position for oxygen evolution, scheelite-monoclinic bismuth vanadate (BiVO4) has become one of the most attractive photocatalysts for efficient visible-light-driven photoelectrochemical (PEC) water splitting. Several studies have indicated that surface modification of BiVO4 with a cocatalyst such as NiFe layered double hydroxide (LDH) can significantly increase the PEC water splitting performance of the catalyst. Herein, we experimentally investigated the charge transfer dynamics and charge carrier recombination processes by scanning electrochemical microscopy (SECM) with the feedback mode on the surface of BiVO4 and BiVO4/NiFe-LDH as model samples. The ratio of rate constants for photogenerated hole (kh+0) to electron (ke-0) via the photocatalyst of BiVO4/NiFe-LDH reacting with the redox couple is found to be five times larger than that of BiVO4 under illumination. In this case, the ratio of the rate constants kh+0/ke-0 stands for the interfacial charge recombination process. This implies the cocatalyst NiFe-LDH suppresses the electron back transfer greatly and finally reduces the surface recombination. Control experiments with cocatalysts CoPi and RuOx onto BiVO4 further verify this conclusion. Therefore, the SECM characterization allows us to make an overall analysis on the function of cocatalysts in the PEC water splitting system.

An AI-Application-Oriented In-Class Teaching Evaluation Model by Using Statistical Modeling and Ensemble Learning.

In-class teaching evaluation, which is utilized to assess the process and effect of both teachers' teaching and students' learning in a classroom environment, plays an increasingly crucial role in supervising and promoting education quality. With the rapid development of artificial intelligence (AI) technology, the concept of smart education has been constantly improved and gradually penetrated into all aspects of education application. Considering the dominant position of classroom teaching in elementary and undergraduate education, the introduction of AI technology into in-class teaching evaluation has become a research hotspot. In this paper, we propose a statistical modeling and ensemble learning-based comprehensive model, which is oriented towards in-class teaching evaluation by using AI technologies such as computer vision (CV) and intelligent speech recognition (ISR). Firstly, we present an index system including a set of teaching evaluation indicators combining traditional assessment scales with new values derived from CV and ISR-based AI analysis. Next, we design a comprehensive in-class teaching evaluation model by using both the analytic hierarchy process-entropy weight (AHP-EW) and AdaBoost-based ensemble learning (AdaBoost-EL) methods. Experiments not only demonstrate that the two modules in the model are respectively applicable to the calculation of indicators with different characteristics, but also verify the performance of the proposed model for AI-based in-class teaching evaluation. In this comprehensive in-class evaluation model, for students' concentration and participation, ensemble learning module is chosen with less root mean square error (RMSE) of 8.318 and 9.375. In addition, teachers' media usage and teachers' type evaluated by statistical modeling module approach higher accuracy with 0.905 and 0.815. Instead, the ensemble learning approaches the accuracy of 0.73 in evaluating teachers' style, which performs better than the statistical modeling module with the accuracy of 0.69.

Multiplex genome editing by natural transformation in Vibrio mimicus with potential application in attenuated vaccine development.

Vibrio mimicus (V. mimicus) is a significant pathogen in freshwater catfish, though knowledge of virulence determinants and effective vaccine is lacking. Multiplex genome editing by natural transformation (MuGENT) is an easy knockout method, which has successfully used in various bacteria except for V. mimicus. Here, we found V. mimicus strain SCCF01 can uptake exogenous DNA and insert it into genome by natural transformation assay. Subsequently, we exploited this property to make five mutants (△Hem, △TS1, △TS2, △TS1△TS2, and △II), and removed the antibiotic resistance marker by Flp-recombination. Finally, all of the mutants were identified by PCR and RT-PCR. The results showed that combination of natural transformation and FLP-recombination can be applied successfully to generate targeted gene disruptions without the antibiotic resistance marker in V. mimicus. In addition, the five mutants showed mutant could be inherited after several subcultures and a 668-fold decrease in the virulence to yellow catfish (Pelteobagrus fulvidraco). This study provides a convenient method for the genetic manipulation of V. mimicus. It will facilitate the identification and characterization of V. mimicus virulence factors and eventually contribute to a better understanding of V. mimicus pathogenicity and development of attenuated vaccine.

Molecular characterization of a p38 mitogen-activated protein kinase gene from Scylla paramamosain and its expression profiles during pathogenic challenge.

A novel p38 MAPK gene from S. paramamosain was cloned and characterized by rapid amplification of cDNA ends (RACE) technology. S. paramamosain p38 (Sp-p38) MAPK gene consists of an open reading frame of 1095bp encoding a 365-amino-acid protein, which showed close phylogenetic relationship to Litopenaeus vannamei p38 MAPK. The tissue distribution patterns showed that Sp-p38 MAPK was widely expressed in all examined tissues, with the highest expression in hemocytes and intestines. The expression levels of Sp-p38 MAPK in hemocytes was up-regulated post-stimulation, which reached the peak at 6h and 12h after bacteria (S. aureus and V. harveyi) and WSSV infection, respectively. In conclusion, our data contributed to define the biological characteristics of Sp-p38 MAPK and further demonstrated the critical role of Sp-p38 MAPK in vivo during the viral and bacterial infection.

Strong metal support interaction (SMSI) and MoO3 synergistic effect of Pt-based catalysts on the promotion of CO activity and sulfur resistance.

In industrial applications, Pt-based catalysts for CO oxidation have the dual challenges of CO self-poisoning and SO2 toxicity. This study used synthetic Keggin-type H3PMo12O40 (PMA) as the site of Pt, and the Pt-MoO3 produced by decomposition of PMA was anchored to TiO2 to construct the dual-interface structure of Pt-MoO3 and Pt-TiO2, abbreviated as Pt-P&M/TiO2. Pt-0.125P&M/TiO2 with a molar ratio of Pt to PMA of 8:1 showed both good CO oxidation activity and SO2 tolerance. In the CO activity test, the CO complete conversion temperature T100 of Pt-0.125P&M/TiO2 was 113 ℃ (compared with 135 ℃ for Pt/TiO2). In the SO2 resistance test, the conversion efficiency of Pt-0.125P&M/TiO2 at 170 ℃ remained at 60% after 72 h, while that of Pt/TiO2 was only 13%. H2-TPR and XPS tests revealed that lattice oxygen provided by TiO2 and hydroxyl produced by MoO3 increased the CO reaction rate on Pt. According to the DFT theoretical calculation, the electronegative MoO3 attracted the d-orbital electrons of Pt, which reduced the adsorption energy of CO and SO2 from - 4.15 eV and - 2.54 eV to - 3.56 eV and - 1.52 eV, respectively, and further weakened the influence of strong CO adsorption and SO2 poisoning on the catalyst. This work explored the relationship between catalyst structure and catalyst performance and provided a feasible technical idea for the design of high-performance CO catalysts in industrial applications.

Behaviour of M. aeruginosa-Microplastic composite pollutants in coagulation and sludge storage.

Microcystis aeruginosa (M. aeruginosa) blooms and microplastics pollution have been major global water pollution concern in lakes and reservoirs. In this study, the behaviour of M. aeruginosa-microplastic composite pollutants in inorganic coagulant (PACl) and organic coagulant (HTCC) treatment was investigated. Results showed that, in coagulation stage, the dissolved extracellular polymers secreted by M. aeruginosa could promote the adhesion of microplastics to algae, so as to combine them into the algal flocs, thus improving the sedimentation and removal efficiency of microplastics. On the other hand, whilst microplastics increased the size of algal flocs in PACl coagulation and improved algal removal efficiency, they had the opposite effect on HTCC coagulation. And the removal of algal metabolites including microcystins were improved by the presence of microplastics. In sludge storage stage, the oxidative and mechanical damage effects of microplastics promoted the rupture of M. aeruginosa cells in PACl sludge but not in HTCC sludge, which mean more potential risks in recycling of PACl sludge water. Besides, microplastics promoted the proliferation of beneficial bacteria such as Poterioochromonas and Coccomyxa, which contributed to the control of sludge pollution.

Histidine Kinase QseC in Glaesserella parasuis Enhances the Secretion of Proinflammatory Cytokines by Macrophages via the p38 and NF-κB Signaling Pathways.

The qseC gene is a two-component system that encodes a histidine protein kinase and is highly conserved among different Glaesserella parasuis strains. In this study, we used qRT-PCR and enzyme-linked immunosorbent assay to confirm that Toll-like receptor 4 (TLR4) plays a role in the expression of proinflammatory cytokines interleukin (IL)-1ß and IL-6 by stimulating RAW 264.7 macrophages with QseC. Furthermore, we revealed that blocking the p38 and NF-κB pathways that regulate signaling can significantly reduce the production of proinflammatory cytokines induced by QseC. In summary, our data suggest that QseC is a novel proinflammatory mediator that induces TLR4-dependent proinflammatory activity in RAW 264.7 macrophages through the p38 and NF-κB pathways.

An interpretable machine learning model for predicting 28-day mortality in patients with sepsis-associated liver injury.

Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV_glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73-0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS_min), blood urea nitrogen (BUN) and admission_age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS_min, BUN and age at admission(admission_age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction.

Gut microbiota is involved in male reproductive function: a review.

Globally, ~8%-12% of couples confront infertility issues, male-related issues being accountable for 50%. This review focuses on the influence of gut microbiota and their metabolites on the male reproductive system from five perspectives: sperm quality, testicular structure, sex hormones, sexual behavior, and probiotic supplementation. To improve sperm quality, gut microbiota can secrete metabolites by themselves or regulate host metabolites. Endotoxemia is a key factor in testicular structure damage that causes orchitis and disrupts the blood-testis barrier (BTB). In addition, the gut microbiota can regulate sex hormone levels by participating in the synthesis of sex hormone-related enzymes directly and participating in the enterohepatic circulation of sex hormones, and affect the hypothalamic-pituitary-testis (HPT) axis. They can also activate areas of the brain that control sexual arousal and behavior through metabolites. Probiotic supplementation can improve male reproductive function. Therefore, the gut microbiota may affect male reproductive function and behavior; however, further research is needed to better understand the mechanisms underlying microbiota-mediated male infertility.