Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Preoperative N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T and Outcomes After Major Noncardiac Surgery: A Prospective Cohort Study.

BACKGROUND: Patients undergoing noncardiac surgery have varying risk of cardiovascular complications. This study evaluated preoperative N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T to enhance cardiovascular events prediction for major noncardiac surgery. METHODS: This prospective cohort study included adult patients with cardiovascular disease or risk factors undergoing elective major noncardiac surgery at four hospitals in China. Blood samples were collected within 30 days before surgery for N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T measurements. The primary outcome was a composite of any cardiovascular events within 30 days after surgery. Logistic regression models were used to assess associations, and the predictive performance was evaluated primarily using area under the receiver-operating-characteristic curve (AUC) and fraction of new predictive information. RESULTS: Between June 2019 and September 2021, 2833 patients were included, with 435 (15.4%) experiencing the primary outcome. In the logistic regression model that included clinical variables and both biomarkers, the odds ratio for the primary outcome was 1.68 (95% CI 1.37-2.07) when comparing the 75th percentile to the 25th percentile of N-terminal pro-B-type natriuretic peptide distribution, and 1.91 (95% CI 1.50-2.43) for high-sensitivity troponin T. Each biomarker enhanced model discrimination beyond clinical predictors, with a change in AUC of 0.028 for N-terminal pro-B-type natriuretic peptide and 0.029 for high-sensitivity cardiac troponin T, and a fraction of new information of 0.164 and 0.149, respectively. The model combining both biomarkers demonstrated the best discrimination, with a change in AUC of 0.042 and a fraction of new information of 0.219. CONCLUSIONS: Preoperative N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T both improved the prediction for cardiovascular events after noncardiac surgery in addition to clinical evaluation, with their combination providing maximal predictive information.

Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice.

BACKGROUND: Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled. METHODS: To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit. RESULTS: Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy. CONCLUSION: The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.

Preoperative risk prediction models for acute kidney injury after noncardiac surgery: an independent external validation cohort study.

BACKGROUND: Numerous models have been developed to predict acute kidney injury (AKI) after noncardiac surgery, yet there is a lack of independent validation and comparison among them. METHODS: We conducted a systematic literature search to review published risk prediction models for AKI after noncardiac surgery. An independent external validation was performed using a retrospective surgical cohort at a large Chinese hospital from January 2019 to October 2022. The cohort included patients undergoing a wide range of noncardiac surgeries with perioperative creatinine measurements. Postoperative AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Model performance was assessed in terms of discrimination (area under the receiver operating characteristic curve, AUROC), calibration (calibration plot), and clinical utility (net benefit), before and after model recalibration through intercept and slope updates. A sensitivity analysis was conducted by including patients without postoperative creatinine measurements in the validation cohort and categorising them as non-AKI cases. RESULTS: Nine prediction models were evaluated, each with varying clinical and methodological characteristics, including the types of surgical cohorts used for model development, AKI definitions, and predictors. In the validation cohort involving 13,186 patients, 650 (4.9%) developed AKI. Three models demonstrated fair discrimination (AUROC between 0.71 and 0.75); other models had poor or failed discrimination. All models exhibited some miscalibration; five of the nine models were well-calibrated after intercept and slope updates. Decision curve analysis indicated that the three models with fair discrimination consistently provided a positive net benefit after recalibration. The results were confirmed in the sensitivity analysis. CONCLUSIONS: We identified three models with fair discrimination and potential clinical utility after recalibration for assessing the risk of acute kidney injury after noncardiac surgery.

Novel tripeptide RKH derived from Akkermansia muciniphila protects against lethal sepsis.

OBJECTIVE: The pathogenesis of sepsis is complex, and the sepsis-induced systemic proinflammatory phase is one of the key drivers of organ failure and consequent mortality. Akkermansia muciniphila (AKK) is recognised as a functional probiotic strain that exerts beneficial effects on the progression of many diseases; however, whether AKK participates in sepsis pathogenesis is still unclear. Here, we evaluated the potential contribution of AKK to lethal sepsis development. DESIGN: Relative abundance of gut microbial AKK in septic patients was evaluated. Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) injection were employed to establish sepsis in mice. Non-targeted and targeted metabolomics analysis were used for metabolites analysis. RESULTS: We first found that the relative abundance of gut microbial AKK in septic patients was significantly reduced compared with that in non-septic controls. Live AKK supplementation, as well as supplementation with its culture supernatant, remarkably reduced sepsis-induced mortality in sepsis models. Metabolomics analysis and germ-free mouse validation experiments revealed that live AKK was able to generate a novel tripeptide Arg-Lys-His (RKH). RKH exerted protective effects against sepsis-induced death and organ damage. Furthermore, RKH markedly reduced sepsis-induced inflammatory cell activation and proinflammatory factor overproduction. A mechanistic study revealed that RKH could directly bind to Toll-like receptor 4 (TLR4) and block TLR4 signal transduction in immune cells. Finally, we validated the preventive effects of RKH against sepsis-induced systemic inflammation and organ damage in a piglet model. CONCLUSION: We revealed that a novel tripeptide, RKH, derived from live AKK, may act as a novel endogenous antagonist for TLR4. RKH may serve as a novel potential therapeutic approach to combat lethal sepsis after successfully translating its efficacy into clinical practice.

Gut microbiota-derived succinate aggravates acute lung injury after intestinal ischaemia/reperfusion in mice.

INTRODUCTION: Acute lung injury (ALI) is a major cause of morbidity and mortality after intestinal ischaemia/reperfusion (I/R). The gut microbiota and its metabolic byproducts act as important modulators of the gut-lung axis. This study aimed to define the role of succinate, a key microbiota metabolite, in intestinal I/R-induced ALI progression. METHODS: Gut and lung microbiota of mice subjected to intestinal I/R were analysed using 16S rRNA gene sequencing. Succinate level alterations were measured in germ-free mice or conventional mice treated with antibiotics. Succinate-induced alveolar macrophage polarisation and its effects on alveolar epithelial apoptosis were evaluated in succinate receptor 1 (Sucnr1)-deficient mice and in murine alveolar macrophages transfected with Sucnr1-short interfering RNA. Succinate levels were measured in patients undergoing cardiopulmonary bypass, including intestinal I/R. RESULTS: Succinate accumulated in lungs after intestinal I/R, and this was associated with an imbalance of succinate-producing and succinate-consuming bacteria in the gut, but not the lungs. Succinate accumulation was absent in germ-free mice and was reversed by gut microbiota depletion with antibiotics, indicating that the gut microbiota is a source of lung succinate. Moreover, succinate promoted alveolar macrophage polarisation, alveolar epithelial apoptosis and lung injury during intestinal I/R. Conversely, knockdown of Sucnr1 or blockage of SUCNR1 in vitro and in vivo reversed the effects of succinate by modulating the phosphoinositide 3-kinase-AKT/hypoxia-inducible factor-1α pathway. Plasma succinate levels significantly correlated with intestinal I/R-related lung injury after cardiopulmonary bypass. CONCLUSION: Gut microbiota-derived succinate exacerbates intestinal I/R-induced ALI through SUCNR1-dependent alveolar macrophage polarisation, identifying succinate as a novel target for gut-derived ALI in critically ill patients.

Microbiota-derived tryptophan metabolites indole-3-lactic acid is associated with intestinal ischemia/reperfusion injury via positive regulation of YAP and Nrf2.

BACKGROUND: Lactobacillus has been demonstrated to serve a protective role in intestinal injury. However, the relationship between Lactobacillus murinus (L. murinus)-derived tryptophan metabolites and intestinal ischemia/reperfusion (I/R) injury yet to be investigated. This study aimed to evaluate the role of L. murinus-derived tryptophan metabolites in intestinal I/R injury and the underlying molecular mechanism. METHODS: Liquid chromatograph mass spectrometry analysis was used to measure the fecal content of tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. Immunofluorescence, quantitative RT-PCR, Western blot, and ELISA were performed to explore the inflammation protective mechanism of tryptophan metabolites in WT and Nrf2-deficient mice undergoing intestinal I/R, hypoxia-reoxygenation (H/R) induced intestinal organoids. RESULTS: By comparing the fecal contents of three L. murinus-derived tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. We found that the high abundance of indole-3-lactic acid (ILA) in the preoperative feces was associated with better postoperative intestinal function, as evidenced by the correlation of fecal metabolites with postoperative gastrointestinal function, serum I-FABP and D-Lactate levels. Furthermore, ILA administration improved epithelial cell damage, accelerated the proliferation of intestinal stem cells, and alleviated the oxidative stress of epithelial cells. Mechanistically, ILA improved the expression of Yes Associated Protein (YAP) and Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) after intestinal I/R. The YAP inhibitor verteporfin (VP) reversed the anti-inflammatory effect of ILA, both in vivo and in vitro. Additionally, we found that ILA failed to protect epithelial cells from oxidative stress in Nrf2 knockout mice under I/R injury. CONCLUSIONS: The content of tryptophan metabolite ILA in the preoperative feces of patients is negatively correlated with intestinal function damage under CPB surgery. Administration of ILA alleviates intestinal I/R injury via the regulation of YAP and Nrf2. This study revealed a novel therapeutic metabolite and promising candidate targets for intestinal I/R injury treatment.

Gut microbiota dysbiosis is associated with sepsis-induced cardiomyopathy in patients: A case-control study.

BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.

Carbon Dots as Potential Therapeutic Agents for Treating Non-Alcoholic Fatty Liver Disease and Associated Inflammatory Bone Loss.

Nonalcoholic fatty liver disease (NAFLD) has emerged as one of the most significant metabolic diseases worldwide and is associated with heightened systemic inflammation, which has been shown to foster the development of extrahepatic complications. So far, there is no definitive, effective, and safe treatment for NAFLD. Although antidiabetic agents show potential for treating NAFLD, their efficacy is significantly limited by inadequate liver accumulation at safe doses and unwanted side effects. Herein, we demonstrate that pharmacologically active carbon dots (MCDs) derived from metformin can selectively accumulate in the liver and ameliorate NAFLD by activating hepatic PPARα expression while maintaining an excellent biosafety. Interestingly, MCDs can also improve the function of extrahepatic organs and tissues, such as alleviating alveolar inflammatory bone loss, in the process of treating NAFLD. This study proposes a feasible and safe strategy for designing pharmacologically active MCDs to target the liver, which regulates lipid metabolism and systemic inflammation, thereby treating NAFLD and its related extrahepatic complications.

Coded aperture-based compressive data page for optical data storage.

In an era of data explosion, optical data storage provides an alternative solution for cold data storage due to its energy-saving and cost-effective features. However, its data density is still insufficient for zettabyte-scale cold data storage. Here, a coded aperture-based compressive data page with a compression ratio of ≤0.125 is proposed. Based on two frameworks-weighted nuclear norm minimization (WNNM) and alternating direction method of multipliers (ADMM)-the decoded quality of the compressive data page is ensured by utilizing sparsity priors. In experiments, compressive data pages of a monochromatic photo-array, full-color photo, and dynamic video are accurately decoded.

Acute Kidney Injury After General Thoracic Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: The clinical importance of postoperative acute kidney injury (AKI) in patients undergoing general thoracic surgery is unclear. We aimed to systematically review the incidence, risk factors, and prognostic implications of AKI as a complication after general thoracic surgery. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from January 2004 to September 2021. Observational or interventional studies that enrolled ≥50 patients undergoing general thoracic surgery and reported postoperative AKI defined using contemporary consensus criteria were included for meta-analysis. RESULTS: Thirty-seven articles reporting 35 unique cohorts were eligible. In 29 studies that enrolled 58,140 consecutive patients, the pooled incidence of postoperative AKI was 8.0% (95% confidence interval [CI]: 6.2-10.0). The incidence was 3.8 (2.0-6.2) % after sublobar resection, 6.7 (4.1-9.9) % after lobectomy, 12.1 (8.1-16.6) % after bilobectomy/pneumonectomy, and 10.5 (5.6-16.7) % after esophagectomy. Considerable heterogeneity in reported incidences of AKI was observed across studies. Short-term mortality was higher (unadjusted risk ratio: 5.07, 95% CI: 2.99-8.60) and length of hospital stay was longer (weighted mean difference: 3.53, 95% CI: 2.56-4.49, d) in patients with postoperative AKI (11 studies, 28,480 patients). Several risk factors for AKI after thoracic surgery were identified. CONCLUSIONS: AKI occurs frequently after general thoracic surgery and is associated with increased short-term mortality and length of hospital stay. For patients undergoing general thoracic surgery, AKI may be an important postoperative complication that needs early risk evaluation and mitigation.

Bioinformatic Analysis of lncRNA Mediated CeRNA Network in Intestinal Ischemia/Reperfusion Injury.

INTRODUCTION: Recently, accumulating studies have reported the roles of competitive endogenous RNA (ceRNA) networks in ischemia/reperfusion (I/R) injury in several organs, including the liver, kidney, heart, brain, and intestine. However, the functions and mechanisms of long noncoding RNAs (lncRNAs)-which serve as ceRNA networks in intestinal I/R injury-remain elusive. METHODS: RNA expression data were retrieved from the National Center for Biotechnology Information-Gene Expression Omnibus database. Differentially expressed microRNAs (miRNAs) (miDEGs) were explored between the sham and intestinal I/R injury samples. Next, targeted lncRNAs and messenger RNAs in the database were matched based on miDEGs. Hub ceRNA networks were constructed and visualized via Cytoscape. Intersection analysis was performed to screen mDEGs between two datasets. Finally, the vital nodes of the ceRNA networks were validated by quantitative PCR. RESULTS: A total of 189 miDEGs were identified. Forty miRNAs were found to be associated with 240 predicted target genes from miRWalk 3.0. The ceRNA network was constructed with 10 miRNAs, including the 1700020114Rik/mmu-miR-7a-5p/Klf4 axis. Furthermore, the expression of lncRNA 1700020114Rik (P < 0.05) and messenger RNA Klf4 (P < 0.01) was markedly decreased in mouse models of intestinal I/R injury, whereas the expression level of mmu-miR-7a-5p was significantly increased (P < 0.05). CONCLUSIONS: The results provide novel insights into the molecular mechanism of ceRNA networks in intestinal I/R injury and highlight the potential of the 170002700020114Rik/mmu-miR-7a-5p/Klf4 axis in the prevention and treatment of intestinal I/R injury.

Sex-Specific Associations Between Preoperative Hemoglobin and Outcomes After Major Noncardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Preoperative anemia is an established risk factor for morbidity and mortality after surgery. Men and women have different hemoglobin concentrations and are at different risks of postoperative complications. However, sex-stratified analysis on the association between preoperative hemoglobin and outcomes after noncardiac surgery has been limited in previous studies. METHODS: This was a retrospective cohort study of adult patients undergoing elective major noncardiac surgery in a large academic hospital. The primary outcome was a collapsed composite of postoperative mortality or cardiovascular, renal, pulmonary, and infectious complications during hospitalization. Sex-specific univariable associations between preoperative hemoglobin and the composite outcome were visualized using moving-average and cubic-spline smoothing plots. Multivariable regression models adjusting for patient demographics, comorbidities, medication uses, laboratory tests, and anesthesia/surgery features were used to estimate confounder-adjusted associations. Restricted cubic spline and piecewise linear functions were used to assess the possible nonlinear relationships between preoperative hemoglobin and the outcomes. The interaction between patient sex and hemoglobin on outcomes was assessed using a likelihood-ratio test. RESULTS: We included 22,550 patients, with 6.7% (622 of 9268) of women and 9.7% (1293 of 13,282) of men developing the primary outcome. Lower preoperative hemoglobin was associated with a higher incidence of the primary composite outcome in both men and women. Nonlinearity for the association was not statistically significant in either women ( P = .539) or men ( P = .165). The multivariable-adjusted odds ratios per 1 g/dL increase in hemoglobin were 0.93 (95% confidence interval [CI], 0.87-0.98; P = .013) for women and 0.94 (95% CI, 0.90-0.97; P < .001) for men, with no interaction by sex ( Pinteraction = .923). No hemoglobin thresholds were confirmed at which the associations with the primary outcome changed significantly. CONCLUSIONS: Low preoperative hemoglobin was associated with a higher risk of complications or mortality after elective noncardiac surgery in both men and women. No differences in the strength of associations between sexes were found. Further studies are needed to assess whether these associations are linear or there are sex-specific thresholds of preoperative hemoglobin concentrations below which postoperative risks begin to increase.

Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy.

BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.

Association between cumulative duration of deep anesthesia and postoperative acute kidney injury after noncardiac surgeries: a retrospective observational study.

BACKGROUND: Bispectral index (BIS) is a processed electroencephalography monitoring tool and is widely used in anesthetic depth monitoring. Deep anesthesia exposure may be associated with multiple adverse outcomes. However, the relationship between anesthetic depth and postoperative acute kidney injury (AKI) remains unclear. We sought to determine the effect of BIS-based deep anesthesia duration on postoperative AKI following noncardiac surgery. METHODS: This retrospective study used data from the Vital Signs DataBase, including patients undergoing noncardiac surgeries with BIS monitoring. The BIS values were collected every second during anesthesia. Restricted cubic splines and logistic regression were used to assess the association between the cumulative duration of deep anesthesia and postoperative AKI. RESULTS: 4774 patients were eligible, and 129 (2.7%) experienced postoperative AKI. Restricted cubic splines showed that a cumulative duration of BIS < 45 was nonlinearly associated with postoperative AKI (P-overall = 0.033 and P-non-linear = 0.023). Using the group with the duration of BIS < 45 less than 15 min as the reference, ORs of postoperative AKI were 2.59 (95% confidence interval [CI]:0.60 to 11.09, p = 0.200) in the 15-100 min group, and 4.04 (95%CI:0.92 to 17.76, p = 0.064) in the ≥ 100 min group after adjusting for preoperative and intraoperative covariates in multivariable logistic regression. CONCLUSIONS: The cumulative duration of BIS < 45 was independently and nonlinearly associated with the risk of postoperative AKI in patients undergoing noncardiac surgery.

Trend analysis of dependence between rainfall and storm tides in coastal cities.

Compound flooding from rainfall and storm tides is prone to occur in coastal cities. The identification of them is essential for controlling urban flooding. First, the dependence between rainfall and storm tides is quantified by Kendall's τ, Spearman's ρ, and tail dependence coefficient. Then, a bivariate copula-based probability distribution model is built to calculate the joint and conditional probability of rainfall and storm tides. Finally, MK and SQMK methods are employed to detect the trends of the dependence and joint probability. The results show that: (1) The dependence between strong rainfall and corresponding storm tides is much higher than that of small rainfall and storm tides, and the effect of tropical cyclones may be one of the reasons. (2) The dependence between rainfall and storm tides is the largest in October and the smallest in July. More attention should be paid to the compound flooding caused by rainfall and storm tides in October for Haikou. (3) The upper tail dependence coefficient of the rainfall and storm tides is significantly greater than the lower tail dependence coefficient and exhibits a significant positive trend. The results can provide additional insights into the effect of rainfall and storm tides for coastal flood management.

Characterization and seasonal variation in biofilms attached to leaves of submerged plant.

The microorganisms and functional predictions of leaf biofilms on submerged plants (Vallisneria natans (Val)) and in water samples (surface water (S) and bottom water (B)) in different seasons were evaluated in this study. S and B groups had 3249 identical operational taxonomic units (OTUs) (50.03%), while the Val group only had 1201 (18.49%) unique OTUs. There was significant overlap between microbial communities of S and B groups in the same season, while Val group showed the greater diversity. The dominant microbial clades were Proteobacteria (18.2-47.3%), Cyanobacteria (3.74-39.3%), Actinobacteria (1.64-29.3%), Bacteroidetes (1.31-21.7%), and Firmicutes (1.10-15.72%). Furthermore, there was a significant relationship between total organic carbon and the distribution of microbial taxa (p = 0.047), and TN may have altered the status of Cyanobacteria by affecting its biological nitrogen fixation capacity and reproductive capacity. The correlation network analysis results showed that the whole system consisted of 249 positive correlations and 111 negative correlations, indicating strong interactions between microbial communities. Functional predictions indicated that microbial functions were related to seasonal variation. These findings would guide the use of submerged plants to improve the diversity and stability of wetland microbial communities.

The regulatory role of NLRX1 in innate immunity and human disease.

Nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) initially appeared in the public view as a cytoplasmic pathogen recognition receptor (PRR) that plays an important role in innate immunity. NLRX1 is currently the only NLR known to be located in mitochondria through a mechanism presumed to be associated with its special N-terminal domain, and it establishes a novel connection between mitochondrial function and disease pathophysiology. NLRX1 functions as a negative regulator of the body's inflammatory response. Concurrently, the role of NLRX1 in regulating mitochondrial autophagy and metabolism has also been confirmed. Based on accumulating evidence, NLRX1 is involved in the occurrence and development of various diseases, including autoimmune diseases and inflammatory diseases. Research on the roles of NLRX1 in cancer, nervous system diseases and metabolic diseases has also undergone qualitative advances. However, according to current research, the function of NLRX1 is controversial, and the opposite effect has even been observed. This new study suggests that this phenomenon may be related to the specific localization of NLRX1 in cells. To date, the biological function of NLRX1 has not been comprehensively explored, but studies have introduced some new directions. For example, some recent studies have shown that NLRX1 affects pyroptosis. In this review, we summarize existing research results on NLRX1, facilitating explorations of the potential mechanism of NLRX1 and the development of new treatment strategies.

Preoperative fasting confers protection against intestinal ischaemia/reperfusion injury by modulating gut microbiota and their metabolites in a mouse model.

BACKGROUND: Intestinal ischaemia/reperfusion (I/R) injury is a grave surgical event with high morbidity and mortality. Preoperative fasting might confer protection against intestinal I/R injury by altering the composition of gut microbiota and their respective metabolites. METHODS: An intestinal I/R mouse model was established and subjected to preoperative fasting for 24 h or fed ad libitum. Intestinal I/R injury was assessed using histological examination and survival analysis. Faecal samples were collected for 16S rDNA sequencing and metabolomic analysis. Faecal transplantation of fasted and non-fasted mice and humans was conducted to evaluate the effects of gut microbiota on intestinal I/R. Murine small intestinal cells wecre subjected to oxygen and glucose deprivation/reoxygenation as an in vitro I/R model. RESULTS: Preoperative fasting protected against intestinal I/R injury and improved survival in mice (P<0.001). In addition, 16S rDNA sequencing revealed that preoperative fasting increased the diversity and restructured the composition of the gut microbiota after intestinal I/R. Mice that received microbiota from fasted mice and humans showed less intestinal damage than those that received microbiota from fed subjects. Metabolomic analysis showed that the profiles of gut microbial metabolites differed between fasted and fed groups. Specifically, the concentration of petroselinic acid was significantly higher in the fasted group (P=0.009). Treatment of intestinal I/R mice with petroselinic acid alleviated intestinal injury in vivo and decreased cell apoptosis by mediating AMP-activated protein kinase-mammalian target of rapamycin-P70S6K signaling in vitro. CONCLUSIONS: Preoperative fasting protected against intestinal I/R injury by modulating gut microbiota and petroselinic acid, suggesting a novel therapeutic strategy.

MicroRNA-26b-5p Targets DAPK1 to Reduce Intestinal Ischemia/Reperfusion Injury via Inhibition of Intestinal Mucosal Cell Apoptosis.

BACKGROUND: Emerging evidence has suggested that miRNAs are important regulators of intestinal I/R injury, but their function in this context remains elusive. AIMS: To evaluate the role of miR-26b-5p in intestinal I/R injury. METHODS: We utilized in vivo murine models of intestinal I/R and in vitro Mode-K cell-based models of oxygen and glucose deprivation/reperfusion (OGD/R) to examine the function of miR-26b-5p in intestinal I/R injury. The expression of miR-26b-5p in intestinal mucosa and Mode-K cell was detected by RT-PCR. HE staining and Chiu's score were used to evaluate intestinal mucosa injury severity. Apoptosis was detected by TUNEL stain, flow cytometry, and western blot. TargetScan and StarBase prediction algorithms were applied to predict putative target genes of miR-26b-5p and validated by luciferase reporter analyses. RESULTS: We found that the expression of miR-26b-5p in intestinal mucosa was markedly decreased during I/R injury. We additionally found miR-26b-5p overexpression to markedly disrupt intestinal I/R- or OGD/R-induced injury in vivo and in vitro, whereas inhibiting this miRNA had an adverse impact and resulted in increased intestinal tissue injury and Mode-K cell damage. From a mechanistic perspective, miR-26b-5p was predicted to target DAPK1, which was related to cellular apoptosis. Luciferase reporter assay results confirmed that miR-26b-5p directly targets DAPK1 in Mode-K cells, thereby suppressing OGD/R-induced cell apoptosis. CONCLUSION: Our findings show that miR-26b-5p may prevent intestinal I/R injury via targeting DAPK1 and inhibiting intestinal mucosal cell apoptosis, suggesting that this miRNA may be a viable target for the treatment of intestinal I/R injury.