Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning.

BACKGROUND: Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. METHODS: Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. RESULTS: Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P < 0.05) and diagnostic efficacy in the validation set. As indicated by the immune cell infiltration analysis, multiple immune cells may be involved in the development of pediatric sepsis. Additionally, all diagnostic characteristics may correlate with immune cells to varying degrees. CONCLUSIONS: The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

A signature of immune-related genes correlating with clinical prognosis and immune microenvironment in sepsis.

BACKGROUND: Immune-related genes (IRGs) remain poorly understood in their function in the onset and progression of sepsis. METHODS: GSE65682 was obtained from the Gene Expression Omnibus database. The IRGs associated with survival were screened for subsequent modeling using univariate Cox regression analysis and least absolute shrinkage and selection operator in the training cohort. Then, we assessed the reliability of the 7 IRGs signature's independent predictive value in the training and validation cohorts following the creation of a signature applying multivariable Cox regression analysis. After that, we utilized the E-MTAB-4451 external dataset in order to do an independent validation of the prognostic signature. Finally, the CIBERSORT algorithm and single-sample gene set enrichment analysis was utilized to investigate and characterize the properties of the immune microenvironment. RESULTS: Based on 7 IRGs signature, patients could be separated into low-risk and high-risk groups. Patients in the low-risk group had a remarkably increased 28-day survival compared to those in the high-risk group (P < 0.001). In multivariable Cox regression analyses, the risk score calculated by this signature was an independent predictor of 28-day survival (P < 0.001). The signature's predictive ability was confirmed by receiver operating characteristic curve analysis with the area under the curve reaching 0.876 (95% confidence interval 0.793-0.946). Moreover, both the validation set and the external dataset demonstrated that the signature had strong clinical prediction performance. In addition, patients in the high-risk group were characterized by a decreased neutrophil count and by reduced inflammation-promoting function. CONCLUSION: We developed a 7 IRGs signature as a novel prognostic marker for predicting sepsis patients' 28-day survival, indicating possibilities for individualized reasonable resource distribution of intensive care unit.

Inadvertent perioperative hypothermia and surgical site infections after liver resection.

BACKGROUND: In the overall surgical population, inadvertent perioperative hypothermia has been associated with an increased incidence of surgical site infection (SSI). However, recent clinical trials did not validate this notion. This study aimed to investigate the potential correlation between inadvertent perioperative hypothermia and SSIs following liver resection. METHODS: This retrospective cohort study included all consecutive patients who underwent liver resection between January 2019 and December 2021 at the First Affiliated Hospital, Zhejiang University School of Medicine. Perioperative temperature managements were implemented for all patients included in the analysis. Estimated propensity score matching (PSM) was performed to reduce the baseline imbalances between the normothermia and hypothermia groups. Before and after PSM, univariate analyses were performed to evaluate the correlation between hypothermia and SSI. Multivariate regression analysis was performed to determine whether hypothermia was an independent risk factor for postoperative transfusion and major complications. Subgroup analyses were performed for diabetes mellitus, age > 65 years, and major liver resection. RESULTS: Among 4000 patients, 2206 had hypothermia (55.2%), of which 150 developed SSI (6.8%). PSM yielded 1434 individuals in each group. After PSM, the hypothermia and normothermia groups demonstrated similar incidence rates of SSI (6.3% vs. 7.0%, P = 0.453), postoperative transfusion (13.3% vs. 13.7%, P = 0.743), and major complications (9.0% vs. 10.1%, P = 0.309). Univariate regression analysis revealed no significant effects of hypothermia on the incidence of SSI in the group with the highest hypothermia exposure [odds ratio (OR) = 1.25, 95% confidence interval (CI): 0.84-1.87, P = 0.266], the group with moderate exposure (OR = 1.00, 95% CI: 0.65-1.53, P = 0.999), or the group with the lowest exposure (OR = 1.11, 95% CI: 0.73-1.65, P = 0.628). The subgroup analysis revealed similar results. Regarding liver function, patients in the hypothermia group demonstrated lower γ-glutamyl transpeptidase (37 vs. 43 U/L, P = 0.001) and alkaline phosphatase (69 vs. 72 U/L, P = 0.016). However, patients in the hypothermia group exhibited prolonged activated partial thromboplastin time (29.2 vs. 28.6 s, P < 0.01). CONCLUSIONS: In our study of patients undergoing liver resection, we found no significant association between mild perioperative hypothermia and SSI. It might be due to the perioperative temperature managements, especially active warming measures, which limited the impact of perioperative hypothermia on the occurrence of SSI.

TNAP inhibition attenuates cardiac fibrosis induced by myocardial infarction through deactivating TGF-ß1/Smads and activating P53 signaling pathways.

Tissue nonspecific alkaline phosphatase (TNAP) is expressed widely in different tissues, modulating functions of metabolism and inflammation. However, the effect of TNAP on cardiac fibrosis remains controversial and needs to be further studied. The present study aims to investigate the role of TNAP on myocardial infarction (MI)-induced fibrosis and its mechanism. TNAP was upregulated in patients with MI, both in serum and injured hearts, and predicted in-hospital mortality. TNAP was also significantly upregulated after MI in rats, mostly in the border zone of the infarcted hearts combined with collagen synthesis. Administration of TNAP inhibitor, tetramisole, markedly improved cardiac function and fibrosis after MI. In the primary cultures of neonatal rat cardiac fibroblasts (CFs), TNAP inhibition significantly attenuated migration, differentiation, and expression of collagen-related genes. The TGF-ß1/Smads signaling suppression, and p-AMPK and p53 upregulation were involved in the process. When p53 inhibitor was administered, the antifibrotic effect of TNAP inhibition can be blocked. This study provides a direct evidence that inhibition of TNAP might be a novel regulator in cardiac fibrosis and exert an antifibrotic effect mainly through AMPK-TGF-ß1/Smads and p53 signals.