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Background: In heart failure (HF), mitochondrial dysfunction and metabolic remodeling lead to a reduction in energy productivity and aggravate cardiomyocyte injury. Supplementation with α-ketoglutarate (AKG) alleviated myocardial hypertrophy and fibrosis in mice with HF and improved cardiac insufficiency. However, the myocardial protective mechanism of AKG remains unclear. We verified the hypothesis that AKG improves mitochondrial function by upregulating NAD+ levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes. Methods: In vivo, 2% AKG was added to the drinking water of mice undergoing transverse aortic constriction (TAC) surgery. Echocardiography and biopsy were performed to evaluate cardiac function and pathological changes. Myocardial metabolomics was analyzed by liquid chromatography‒mass spectrometry (LC‒MS/MS) at 8 weeks after surgery. In vitro, the expression of SIRT1 or PINK1 proteins was inhibited by selective inhibitors and siRNA in cardiomyocytes stimulated with angiotensin II (AngII) and AKG. NAD+ levels were detected using an NAD test kit. Mitophagy and ferroptosis levels were evaluated by Western blotting, qPCR, JC-1 staining and lipid peroxidation analysis. Results: AKG supplementation after TAC surgery could alleviate myocardial hypertrophy and fibrosis and improve cardiac function in mice. Metabolites of the malate-aspartate shuttle (MAS) were increased, but the TCA cycle and fatty acid metabolism pathway could be inhibited in the myocardium of TAC mice after AKG supplementation. Decreased NAD+ levels and SIRT1 protein expression were observed in heart of mice and AngII-treated cardiomyocytes. After AKG treatment, these changes were reversed, and increased mitophagy, inhibited ferroptosis, and alleviated damage in cardiomyocytes were observed. When the expression of SIRT1 was inhibited by a selective inhibitor and siRNA, the protective effect of AKG was suppressed. Conclusion: Supplementation with AKG can improve myocardial hypertrophy, fibrosis and chronic cardiac insufficiency caused by pressure overload. By increasing the level of NAD+, the SIRT-PINK1 and SIRT1-GPX4 signaling pathways are activated to promote mitophagy and inhibit ferroptosis in cardiomyocytes, which ultimately alleviates cardiomyocyte damage. [ABSTRACT FROM AUTHOR]

Hemodynamic management is crucial in patients with acute pancreatitis. Central venous pressure (CVP) is widely used to assess volume status. Our aim was to determine the optimal time window for obtaining CVP measurements to prevent adverse outcomes in patients. This study utilized data from the Medical Information Mart for Intensive Care (MIMIC) IV database. The primary outcome under investigation was the 28-day mortality, while secondary outcomes included 90-day mortality and 1-year mortality. To categorize the study population, a CVP waiting time of 12 hours was employed as the grouping criterion, followed by the utilization of Cox regression analysis to compare the outcomes between the 2 groups. Our study included a total of 233 patients, among whom 154 cases (66.1%) underwent CVP measurements within 12 hours after admission to the Intensive Care Unit (ICU). Univariate and multivariate Cox regression analyses revealed a significantly increased risk of 28-day mortality in patients from the delayed CVP monitoring group compared to those who underwent early CVP measurements (HR = 2.87; 95% CI: 1.35-6.13; P = .006). Additionally, consistent results were observed for the risks of 90-day mortality (HR = 1.91; 95% CI: 1.09-3.35; P = .023) and 1-year mortality (HR = 1.84; 95% CI: 1.09-3.10; P = .023). In the ICU, an extended waiting time for CVP measurements in patients with acute pancreatitis was associated with an increased risk of 28-day mortality., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Whether early dietary fiber intake in septic patients is associated with a better clinical prognosis remains unclear, especially the time and the amount. Therefore, we assessed the association between early dietary fiber intake and clinical outcomes in septic patients by examining an extensive database., Methods: We conducted a retrospective cohort study using data from the MIMIC IV 2.1 database, focusing on consecutive septic patients requiring mechanical ventilation in medical or mixed medical-surgical ICUs. We collected patient demographics and nutritional data. Dietary fiber amounts were calculated according to enteral nutrition instructions from manufacturers within the first 72 h after admission. After adjusting for covariates, we employed restricted cubic spline (RCS) regression to investigate the relationship between fiber intake (FI) and 28-day mortality. Patients were categorized into three groups based on their fiber index (FI) within 72 h of admission: low fiber index (LFI) group when FI was < 3 g/(%), medium fiber index (MFI) group when FI ranged from 3 to 35 g(%), and high fiber index (HFI) group when FI ≥ 35 g(%). Univariate and multivariate Cox proportional hazards regression models were utilized to assess the association between early FI and 28-day mortality. We ultimately employed Kaplan-Meier (KM) curves and log-rank test visually represent the association between FI and 90-day mortality. The second outcomes include ICU-acquired infections and the hospital and ICU death, length of hospital and ICU stay, and length of mechanical ventilation., Results: Among 1057 subjects, 562 (53.2%) were male, with a median age of 64.8 years (IQR 53.4-75.2). We observed a J-shaped relationship between FI and 28-day mortality. The MFI group exhibited the lowest 28-day mortality [adjusted HR 0.64 (0.45-0.91), p = 0.013] and the lowest rate of hospital mortality [adjusted OR 0.60 (0.39-0.93), p = 0.022], with no statistically significant differences noted in the HFI group when compared to the LFI group. Similar patterns were observed for 60-day and 90-day mortality. However, no statistically significant differences were observed in other secondary outcomes after adjusting for covariates., Conclusion: Early medium fiber index intake improved 28-day mortality and lower hospital mortality in septic M/SICU patients on mechanical ventilation., (© 2023. The Author(s).)

Syntrichia caninervis is the dominant species of biological soil crust in the desert, including the Gurbantunggut Desert in China. It is widely distributed in drylands and considered to be a new model of vegetative desiccation tolerance moss. Here, we cloned an ATG8 gene from S. caninervis and confirmed its function under multiple abiotic stresses, both in situ and in Physcomitrium patens . The results showed that the ScATG8 gene encoded a protein with a highly conserved ATG8 functional domain. ScATG8 gene was increasingly expressed under different abiotic stresses. Under desiccation stress, the overexpression of ScATG8 enhanced the tolerance of S. caninervis and its ability to scavenge ROS. In addition, ScATG8 overexpression promoted the growth of P. patens under multiple stress conditions. Thus, ScATG8 may be a multifunctional gene, and it plays a critical role in the survival of S. caninervis under various abiotic stresses. Our results provide new insights into the function of ATG8 in enabling desiccation tolerance and open up more possibilities for subsequent plant molecular breeding and the mining of the resistance genes of S. caninervis and other moss species.

Huangjiu is known for its unique aroma, primarily attributed to its high concentration of β-phenylethanol (ranging from 40 to 130 mg/L). Phenylalanine aminotransferase Aro9p and phenylpyruvate decarboxylase Aro10p are key enzymes in the β-phenylethanol synthetic pathway of Saccharomyces cerevisiae HJ. This study examined the enzymatic properties of these two enzymes derived from S. cerevisiae HJ and S288C. After substrate docking, Aro9p HJ (-24.05 kJ/mol) and Aro10p HJ (-14.33 kJ/mol) exhibited lower binding free energies compared to Aro9p S288C (-21.93 kJ/mol) and Aro10p S288C (-12.84 kJ/mol). ARO9 and ARO10 genes were heterologously expressed in E. coli BL21. Aro9p, which was purified via affinity chromatography, showed inhibition by l-phenylalanine (L-PHE), but the reaction rate V max (Aro9p HJ : 23.89 μmol·(min∙g) -1 ) > Aro9p S288C : 21.3 μmol·(min∙g) -1 ) and inhibition constant K i values (Aro9p HJ : 0.28 mol L -1 >Aro9p S288C 0.26 mol L -1 ) indicated that Aro9p from S. cerevisiae HJ was more tolerant to substrate stress during Huangjiu fermentation. In the presence of the same substrate phenylpyruvate (PPY), Aro10p HJ exhibited a stronger affinity than Aro10p S288C . Furthermore, Aro9p HJ and Aro10p HJ were slightly more tolerant to the final metabolites β-phenylethanol and ethanol, respectively, compared to those from S288C. The study suggests that the mutations in Aro9p HJ and Aro10p HJ may contribute to the increased β-phenylethanol concentration in Huangjiu . This is the first study investigating enzyme tolerance mechanisms in terms of substrate and product, providing a theoretical basis for the regulation of the β-phenylethanol metabolic pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Different microorganisms can produce different proteases, which can adapt to different industrial requirements such as pH, temperature, and pressure. Salt-tolerant proteases (STPs) from microorganisms exhibit higher salt tolerance, wider adaptability, and more efficient catalytic ability under extreme conditions compared to conventional proteases. These unique enzymes hold great promise for applications in various industries including food, medicine, environmental protection, agriculture, detergents, dyes, and others. Scientific studies on microbial-derived STPs have been widely reported, but there has been little systematic review of microbial-derived STPs and their application in high-salt conventional soybean fermentable foods. This review presents the STP-producing microbial species and their selection methods, and summarizes and analyzes the salt tolerance mechanisms of the microorganisms. It also outlines various techniques for the isolation and purification of STPs from microorganisms and discusses the salt tolerance mechanisms of STPs. Furthermore, this review demonstrates the contribution of modern biotechnology in the screening of novel microbial-derived STPs and their improvement in salt tolerance. It highlights the potential applications and commercial value of salt-tolerant microorganisms and STPs in high-salt traditional soy fermented foods. The review ends with concluding remarks on the challenges and future directions for microbial-derived STPs. This review provides valuable insights into the separation, purification, performance enhancement, and application of microbial-derived STPs in traditional fermented foods., (© 2023. The Author(s).)

Objective: This study aimed to assess whether β-blockers are associated with mortality in patients with sepsis., Method: We conducted a retrospective cohort study of patients with sepsis using the Medical Information Market for Intensive Care (MIMIC)-IV and the emergency intensive care unit (eICU) databases. The primary outcome was the in-hospital mortality rate. The propensity score matching (PSM) method was adopted to reduce confounder bias. Subgroup and sensitivity analyses were performed to test the stability of the conclusions., Results: We included a total of 61,751 patients with sepsis, with an overall in-hospital mortality rate of 15.3% in MIMIC-IV and 13.6% in eICU. The inverse probability-weighting model showed that in-hospital mortality was significantly lower in the β-blockers group than in the non-β-blockers group [HR = 0.71, 95% CI: 0.66-0.75, p  < 0.001 in MIMIC-IV, and HR = 0.48, 95% CI: 0.45-0.52, p  < 0.001 in eICU]. In subgroups grouped according to sex, age, heart rate, APSIII, septic shock, and admission years, the results did not change., Conclusion: β-blocker use is associated with lower in-hospital mortality in patients with sepsis, further randomized trials are required to confirm this association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Kong, Bao, Yang, Chen, Zheng, Xiong, Wen and Zhang.)

VPS34 is well-known to be the unique member of the class III phosphoinositide 3-kinase (PI3K) family, forming VPS34 complex 1 and complex 2, which are involved in several key physiological processes. Of note, VPS34 complex 1 is an important node of autophagosome generation, which controls T cell metabolism and maintains cellular homeostasis through the autophagic pathway. And, VPS34 complex 2 is involved in endocytosis as well as vesicular transport, and is closely related to neurotransmission, antigen presentation and brain development. Due to the two important biological functions of VPS34, its dysregulation can lead to the development of cardiovascular disease, cancer, neurological disorders, and many types of human diseases by altering normal human physiology. Thus, in this review, we not only summarize the molecular structure and function of VPS34, but demonstrate the relationships between VPS34 and human diseases. Moreover, we further discuss the current small molecule inhibitors targeting VPS34 based upon the structure and function of VPS34, which may provide an insight into the future targeted drug development., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Silver is an important precious metal with superior ductility, electrical and thermal conductivity, photosensitivity, and antibacterial properties. However, without proper recycling and treatment, silver emissions may pose a threat to the human health and subsistence environment due to their toxicity. Therefore, it is environmentally and economically important to recover Ag from waste electronic equipment and anode slime. Herein, carboxyl functionalized modified magnetic nanoparticles (Fe 3 O 4 @3-phenylglutaricacid nanoparticles) were designed and prepared to obtain the low-cost magnetic pitch-based HCP adsorbents (MPHCP and P-MPHCP). The novelty of present work is that superior adsorption capacity and magnetic responsiveness of adsorbent can be obtained by a simple one-step Friedel-Crafts reaction with very low-cost raw material. The maximum Ag + adsorption capacity of MPHCP and P-MPHCP were 321 and 353 mg/g, respectively. The adsorption was completed within a short duration of 15 min for MPHCP and P-MPHCP at an initial Ag + concentration of 100 mg/L. Moreover, the most selective is P-MPHCP wherein Ag + is α = 61 times more selective than Pb 2+ at a concentration of 100 mg/L.The adsorption capacity of MPHCP and P-MPHCP towards Ag + still maintains above 89% after ten cycles of adsorption-desorption. This study not only provides new guidance for the development of porous polymeric adsorbents but also provides technical feasibility for the field of recovery and reutilization of precious metals, which has a very extensive practical application prospect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Enterococcus gallinarum, a gut pathobiont, is an opportunistic pathogen that carries the risk of antibiotic resistance in the clinic and has been proven to drive autoimmunity in both mice and humans. Screening for novel bacteriophages targeting Enterococcus gallinarum is expected to provide a promising strategy for controlling such infections or regulating related chronic diseases. In the present study, we isolated a novel lytic Enterococcus gallinarum phage, Phi&#95;Eg&#95;SY1, which presents favourable thermostability and pH stability. Further assays indicated that Phi&#95;Eg&#95;SY1 can efficiently adsorb and lyse the host bacteria in vitro. Genomic and phylogenetic analyses suggested that Phi&#95;Eg&#95;SY1 does not contain virulence or lysogeny genes and presents a novel unassigned evolutionary lineage among the related dsDNA phages. Phi&#95;Eg&#95;SY1 is therefore considered to be suitable for further applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Diabetic chronic wound is a worldwide medical burden related to overdosed methylglyoxal (MGO) synthesis, which is the major precursor of glycation of proteins and DNA and is related to the dysfunction of dermal cells thus leading to chronic refractory wounds. Previous studies proved that earthworm extract accelerates diabetic wound healing and possesses cell proliferation and antioxidative effects. However, the effects of earthworm extract on MGO-damaged fibroblasts, the inner mechanisms of MGO-induced cell damage and the functional components in earthworm extract are still poorly understood. Firstly, we evaluated the bioactivities of the earthworm extract PvE-3 on the diabetic wound model and the diabetic related cell damage model. Then the mechanisms were investigated through transcriptomics, flow cytometry and fluorescence probe. The results revealed that PvE-3 promoted diabetic wound healing and protected fibroblast function in cell-damaged conditions. Meanwhile, the high-throughput screening implied the inner mechanisms of diabetic wound healing and PvE-3 cytoprotection effect were involved in the muscle cell function, the cell cycle regulation and the mitochondrial transmembrane potential depolarization. The functional glycoprotein isolated from PvE-3 possessed EGF-like domain which had a strong binding affinity with EGFR. The findings provided references to explore the potential treatments of diabetic wound healing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jie Bai reports financial support was provided by Foundation for Innovative Research Groups of the National Natural Science Foundation of China. Shouying Du reports financial support was provided by Fundamental Research Funds for the Central Universities., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Marine sediments are one of the largest habitats on Earth, and their unique ecology, such as high salinity, high pressure, and hypoxia, may activate certain silent genes in marine microbes, resulting in microbes, enzymes, active products, and specific metabolic pathways that can adapt to these specific ecological environments. Marine sediment-derived microorganisms and their bioactive metabolites are of great significance and have potential commercial development prospects for food, pharmaceutical, chemical industries, agriculture, environmental protection and human nutrition and health. In recent years, although there have been numerous scientific reports surrounding marine sediment-derived microorganisms and their bioactive metabolites, a comprehensive review of their research progress is lacking. This paper presents the development and renewal of traditional culture-dependent and omics analysis techniques and their application to the screening of marine sediment-derived microorganisms producing bioactive substances. It also highlights recent research advances in the last five years surrounding the types, functional properties and potential applications of bioactive metabolites produced by marine sediment-derived microorganisms. These bioactive metabolites mainly include antibiotics, enzymes, enzyme inhibitors, sugars, proteins, peptides, and some other small molecule metabolites. In addition, the review ends with concluding remarks on the challenges and future directions for marine sediment-derived microorganisms and their bioactive metabolites. The review report not only helps to deepen the understanding of marine sediment-derived microorganisms and their bioactive metabolites, but also provides some useful information for the exploitation and utilization of marine microbial resources and the mining of new compounds with potential functional properties., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The relationship between serum creatinine and type 2 diabetes is limited. We aimed to investigate the association of baseline serum creatinine and new-onset type 2 diabetes in Chinese population. This retrospective cohort study was conducted using data from the health screening program in China. The population were divided into four groups based on serum creatinine levels, and the outcome of interest was the occurrence of a diabetic event. Cox proportional risk model was used to assess the independent effect of baseline serum creatinine level on future diabetes risk. Sensitivity and subgroup analysis were used to verify the reliability of the results. After an average follow-up of 3.12 years, among 201,298 individuals aged ≥ 20 years, 3389 patients developed diabetes. Compared with participants in quartile 2-4 (> 51.6umol/L for female, > 71.8umol/L for male,), a significantly higher risk of new-onset Type 2 Diabetes (OR, 1.15; 95%CI: 1.07-1.23) was found in those in quartile 1 (< 51.6umol/L for female, < 71.8umol/L for male). Moreover, Similar results were found in various subgroups stratified by age, BMI, TG, TC, FPG and family history group. Low serum creatinine is independently associated with increased risk of type 2 diabetes in Chinese adults. It was also stable in various subgroups stratified., (© 2023. The Author(s).)

Ofloxacin (OFL) with high biological activity and antimicrobial degradation is a kind of the typical high concentration and environmental risk antibiotics in rural sewage. In this paper, a combined rural sewage treatment facility based on anaerobic baffled reactor and integrated constructed wetlands was built and the removal performance, pathway and mechanism for OFL and conventional pollutants were evaluated. Results showed that the OFL and TN removal efficiency achieved 91.78 ± 3.93 % and 91.44 ± 4.15 %, respectively. Sludge adsorption was the primary removal pathway of OFL. Metagenomics analysis revealed that Proteobacteria was crucial in OFL removal. baca was the dominated antibiotic resistance genes (ARGs). Moreover, carbon metabolism with a high abundance was conductive to detoxify OFL to enhance system stability and performance. Co-occurrence network analysis further elucidated that mutualism was the main survival mode of microorganisms. Denitrifers Microbacterium, Geobacter and Ignavibacterium, were the host of ARGs and participated in OFL biodegradation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Higher alcohols (HAs) and acetate esters (AEs) produced by yeasts are two important volatile flavor substances in fermented alcoholic beverages (FABs). To improve the FABs overall quality, lab-scale huangjiu brewing and systematic evaluation were performed using 171 Saccharomyces cerevisiae strains. Finally, two S. cerevisiae strains that produced lower HAs and higher AEs were obtained and named jiangnan1# and jiangnan3#, respectively. The results of production-scale huangjiu fermentation indicated that HAs produced by jiangnan1# sample decreased by 24.99 %, and AEs produced by jiangnan1# increased by 36.35 %. Sensory evaluation showed that the acidic taste, honey aroma attribute intensity were higher in 85# huagnjiu, and the fruity aroma attribute intensity was higher in jiangnan1# huangjiu (P < 0.01). Moreover, urea and ethyl carbamate produced by jiangnan1# strain were degraded by 13.89 % and 45.51 % compared with those of the control strain 85#, indicating the positive effects of jiangnan1# strain on health and safety. Thus, the obtained S. cerevisiae strains in this study can better enhance the flavor and improve the drinking safety and comfort of huangjiu., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Fried licorice is obtained by frying licorice without using any auxiliary materials, and it is widely used both as food and medicine in China. To explore the influence of licorice origin on the quality of fried licorice, a method based on fingerprinting and chemometrics was developed. Twenty batches of licorice were selected from four locations. The reference chromatograms of each location were established via similarity analysis. Chemometric methods, such as cluster, principal component, and orthogonal partial least squares discriminant analyses were used to evaluate the changes in the composition of fried licorice, predict its origin, and reflect its quality. Mass spectrometry was used to identify the chemical components. Finally, an origin prediction function was established via discriminant analysis to trace the origin of licorice. The model was demonstrated to be stable, reliable, and accurate in predicting licorice origin and to provide a reference for origin traceability., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To assess the effect of intra-aortic balloon pump (IABP) on in-hospital mortality in patients with cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation (ECPR)., Methods: A retrospective study was performed on 696 patients with intra-hospital cardiac arrest undergoing ECPR from Samsung Medical Center in Korea between January 2004 and December 2013. According to whether IABP was used, the patients were divided into ECPR group and ECPR+IABP group. Cox regression and propensity score matching (PSM) were used to examine the correlation between IABP usage and in-hospital mortality, and standardized mean difference (SMD) was used to check the degree of PSM. Survival analysis of in-hospital mortality was performed by the Kaplan-Meier method, and further analyzed by the Log-Rank test. Using the propensity score as weights, multiple regression model and inverse probability weighting (IPW) model were used for sensitivity analysis. In-hospital mortality, extracorporeal membrane oxygenation (ECMO) withdrawal success rate and neurological function prognosis were compared between the two groups., Results: A total of 199 patients with cardiac arrest undergoing ECPR were included, including 120 males and 79 females, and the average age was (60.0±16.8) years. Thirty-one patients (15.6%) were treated with ECPR and IABP, and 168 patients (84.4%) only received ECPR. The total hospitalized mortality was 68.8% (137/199). The 1 : 1 nearest neighbor matching algorithm was performed with the 0.2 caliper value. The following variables were selected to generate propensity scores, including age, gender, race, marital status, insurance, admission type, service unit, heart rate, mean arterial pressure, respiratory rate, pulse oxygen saturation, white blood cell count. After the propensity score matching, 24 pairs of patients were successfully matched, with the average age of (63.0±12.8) years, including 31 males and 17 females. The in-hospital mortality was 72.6% (122/168) and 48.4% (15/31) in the ECPR group and the ECPR+IABP group [hazard ratio (HR) = 0.48, 95% confidence interval (95%CI) was 0.28-0.82, P = 0.007]. Multiple regression model, adjusted propensity score, PSM and IPW model showed that the in-hospital mortality in the ECPR+IABP group was significantly lower compared with the ECPR group (HR = 0.44, 0.50, 0.16 and 0.49, respectively, 95%CI were 0.24-0.79, 0.28-0.91, 0.06-0.39 and 0.31-0.77, all P < 0.05). The combined application of IABP could improve the ECMO withdrawal success rate [odds ratio (OR) = 8.95, 95%CI was 2.72-29.38, P < 0.001] and neurological prognosis (OR = 4.06, 95%CI was 1.33-12.40, P = 0.014) in adult cardiac arrest patients., Conclusions: In patients with cardiac arrest using ECPR, the combination of IABP was independently associated with lower in-hospital mortality, higher ECMO withdrawal success rate and better neurological prognosis.

Background: Sepsis is a leading cause of mortality worldwide. Septic shock is a subtype of sepsis in which the underlying cardiovascular and cellular/metabolic disorders are profound enough to increase mortality significantly. We sought to investigate the association between soluble cluster of differentiation-73 (sCD73) and the incidence of septic shock in severe sepsis patients., Methods: This cross-sectional study included 588 Finnish patients with severe sepsis or septic shock from the Finnish Acute Kidney Injury (FINNAKI) study. The primary exposure of interest was baseline level of sCD73. The outcome was the incidence of septic shock. Multivariable logistic regression analyses were performed to assess the independent association between sCD73 and the incidence of septic shock., Results: The average age of 588 participants was 62±16 years, and 65.14% of the patients were male. The average sCD73 was 5.11 (interquartile range, 3.30, 8.25) ng/mL. The incidence of sepsis shock was 429 (72.96%). In the multivariate logistic regression model, sCD73 was negatively associated with septic shock. After multiple adjustments (for age, gender, lactate, the Sequential Organ Failure Assessment score, systolic heart failure, emergency admission, operative admission, and acute kidney injury within 12 h), a 1 ng/mL increment in sCD73 was associated with a 5% lower incidence of septic shock [odds ratio (OR) =0.95; 95% confidence interval (CI): 0.92, 0.98; P<0.001]., Conclusions: We found that sCD73 was negatively correlated with septic shock. Higher sCD73 was associated with a lower incidence of septic shock., Keywords: Septic shock; severe sepsis; soluble cluster of differentiation-73 (sCD73); inflammation; phosphatidylinositol 3-kinase/Akt signaling (PI3K/Akt signaling)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-371/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: To establish a nomogram prediction model for the prognosis of patients with septic cardiomyopathy (SCM) based on afterload-corrected cardiac performance (ACP), in order to identify septic patients with poor outcomes and treatment., Methods: The data of patients admitted to the department of critical medicine of the Second Affiliated Hospital of Guangzhou Medical University from June 2016 to June 2019 were analyzed. All patients were monitored by pulse indication continuous cardiac output (PiCCO) monitor more than 24 hours and diagnosed as SCM with ACP less than 80%. The predictors of 30-day death risk of SCM patients were screened by univariate Cox regression analysis. Multivariate Cox regression analysis was used to establish the prediction model for 30-day death risk of SCM patients, which was displayed by the nomogram. Finally, the discrimination and calibration of the model were analyzed by receiver operator characteristic curve (ROC curve) and consistency index (C-index)., Results: A total of 102 patients with SCM were included and the 30-day mortality was 60.8% (62 cases). Among 102 patients with SCM, 57 patients (55.9%) had mild impairment of cardiac function (60% ≤ ACP < 80%), and the 30-day mortality was 43.9% (25/57); 39 patients (38.2%) had moderate impairment of cardiac function (40% ≤ ACP < 60%), and the 30-day mortality was 79.5% (31/39); 6 patients (5.9%) had severe impairment of cardiac function (ACP < 40%), and the 30-day mortality was 100% (6/6). There was significantly difference in mortality among the three groups (χ 2 = 24.156, P < 0.001). The potential risk factors for 30-day death of SCM patients screened by univariate Cox regression analysis were included in multivariate Cox regression analysis. The results showed that the independent risk factors for 30-day death of SCM patients were acute physiology and chronic health evaluation II [APACHE II, risk ratio (HR) = 1.031, 95% confidence interval (95%CI) was 1.002-1.061, P = 0.039], vasoactive inotropic score (VIS, HR = 1.003, 95%CI was 1.001-1.005, P = 0.012), continuous renal replacement therapy (CRRT; HR = 2.106, 95%CI was 1.089-4.072, P = 0.027), and ACP (HR = 0.952, 95%CI was 0.928-0.977, P < 0.001). The nomogram model was established based on the above independent risk factors and age, and the area under the curve (AUC) was 0.865 (95%CI was 0.795-0.935), P < 0.001; C-index was 0.797 (95%CI was 0.747-0.847), P > 0.05., Conclusions: The nomogram model based on age, APACHE II score, VIS score, CRRT and ACP has a certain clinical reference significance for the prediction of 30-day mortality of SCM patients. The discrimination and calibration are good, however, further verification is needed.

Purpose: Acute kidney injury (AKI) occurs in more than half of intensive care unit patients. Effective prevention and treatment strategies for AKI remain limited. We aimed to assess AKI-related mortality in patients with diabetes who were metformin and non-metformin users., Materials and Methods: We included patients with AKI and type 2 diabetes (T2DM) from the Medical Information Mart for Intensive Care database. The 30-day mortality, neutrophil-to-lymphocyte ratio, and length of hospital stay were compared between patients with and without metformin prescriptions. We used multivariable Cox proportional hazards regression, propensity score analysis, and an inverse probability-weighting model to ensure the robustness of our findings., Results: We included 4328 patients with AKI and T2DM (998 and 3330 patients were metformin and non-metformin users, respectively). The overall 30-day mortality was 14.2% (613/4328); it was 15.7% (523/3330) and 9.0% (90/998) for non-metformin and metformin users, respectively. In the inverse probability-weighting model, metformin use was associated with 37% lower 30-day mortality (HR = 0.63, 95% CI: 0.50-0.80, p < 0.0001)., Conclusions: Metformin use may be associated with reduced risk-adjusted mortality in patients with AKI and T2DM. Further randomized controlled trials are needed to clarify this association., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Fundamental researches have shown that soluble CD73 (sCD73) can inhibit inflammatory response and limit excessive tissue damage caused by continuous immune cell activation. A Finnish prospective, observational study of acute kidney injury (FINNAKI) showed no association between sCD73 and 90-day mortality in sepsis patients. Clinical data of this study was used for secondary analysis to explore whether the relationship between sCD73 and 90-day mortality was consistent in septic shock and non-septic shock patients., Methods: The FINNAKI study was a prospective, observational cohort study conducted in 17 intensive care units (ICUs) in Finland from September 1st, 2011 to February 1st, 2012. Sepsis/septic shock was defined according to Sepsis-1 definition. Demographic characteristics, treatment, comorbidities and 90-day mortality of the patients were analyzed. To evaluate the difference (interaction test) between the relationship of sCD73 and 90-day mortality in septic shock and non-septic shock patients, likelihood ratio test was used to integrate the product term (sCD73×septic shock or non-septic shock) into multivariable Logistic regression. Sensitivity analysis was performed with the definition of Sepsis-3. The interaction between sCD73 and 90-day mortality in patients with septic shock and non-septic shock were verified by generalized additive model (GAM)., Results: A total of 588 patients with severe sepsis/septic shock were enrolled. 164 patients died in 90 days, and the 90-day mortality was 27.89%. Based on the Sepsis-1 definition, there were 159 non-septic shock patients and 429 septic shock patients. Compared with the non-septic shock patients, lactate (Lac) level, sequential organ failure assessment (SOFA) score, fluid balance on the first day, and ratio of mechanical ventilation, 12-hour acute kidney injury (AKI), renal replacement therapy (RRT), and postoperative ICU transition in the septic shock patients were significantly increased and the proportion of emergency admission to ICU was significantly decreased. Based on the Sepsis-3 definition, there were 383 non-septic shock patients and 205 septic shock patients; the results of clinical data analysis between the two groups were similar to those based on Sepsis-1. Based on Sepsis-1, there was no significant difference in 90-day mortality between non-septic shock and septic shock patients [23.90% (38/159) vs. 29.37% (126/429), P > 0.05]. However, based on Sepsis-3, the 90-day mortality of patients with septic shock was significantly higher than that of patients with non-septic shock [37.56% (77/205) vs. 22.72% (87/383), P < 0.01]. Multivariate Logistic regression analysis and interaction test showed that after adjusting all confounding factors (except the number of complications) in non-sepsis shock and sepsis shock patients, sCD73 and 90-day mortality were significantly different in both Sepsis-1 and Sepsis-3. The P values for interaction tests were 0.046 and 0.027, respectively. In patients with non-septic shock, sCD73 tended to be positively associated with 90-day mortality [Sepsis-1: odds ratio (OR) = 1.46, 95% confidence interval (95%CI) was 0.99-2.13, P = 0.053; Sepsis-3: OR = 1.34, 95%CI was 1.02-1.74, P = 0.034]. In septic shock patients, sCD73 tended to be negatively associated with 90-day mortality (Sepsis-1: OR = 0.91, 95%CI was 0.69-1.20, P = 0.494; Sepsis-3: OR = 0.80, 95%CI was 0.55-1.17, P = 0.249). The results of GAM model validation were consistent with the results of Logistic regression equation cross validation., Conclusions: The relationship between sCD73 and 90-day mortality is significantly different from patients with non-sepsis shock and sepsis shock. In patients with non-sepsis shock, sCD73 is trend to positively associated with 90-day mortality, and there is a negative trend between sCD73 and 90-day mortality in patients with septic shock.

Objective: To investigate the relationship between 1-hour lactate (1 h Lac) and 30-day mortality in critical care patients in intensive care unit (ICU)., Methods: A retrospective, observational cohort study was performed with adult critical patients (age ≥ 16 years old) having lactate records within 1 hour after ICU admission from Medical Information Mart for Intensive Care-III database (MIMIC-III). According to the 1 h Lac level, the patients were divided into three groups: < 2 mmol/L, 2-4 mmol/L, and > 4 mmol/L groups. The baseline characteristics were analyzed. Multivariable Logistic regression analysis was performed to assess the association between 1 h Lac and 30-day mortality. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of 1 h Lac for 30-day mortality, and Kaplan-Meier survival curve was performed according to the best cut-off value. In addition, sensitivity analysis was carried out for each classification variable., Results: A total of 3 969 ICU patients were included, with 673 died in 30 days, and the total mortality was 16.95%. There were 1 664, 1 588, 717 patients in Lac < 2 mmol/L, 2-4 mmol/L and > 4 mmol/L group, respectively. There were significant differences in age, ICU duration, ICU type, heart rate, leukocyte count, hemoglobin, creatinine, sequential organ failure score (SOFA), ventilator application, vasoactive drug use and main diagnosis among the three groups. Multivariable Logistic regression analysis showed that a 1 mmol/L increment in Lac was associated with 0.24 times higher risk of 30-day mortality [odds ratio (OR) = 1.24, 95% confidence interval (95%CI) was 1.19-1.29, P < 0.000 1]. ROC curve analysis showed that the area under ROC curve (AUC) of 1 h Lac for predicting 30-day mortality of severe patients was 0.694 (95%CI was 0.669-0.718). The cut-off value was 3.35 mmol/L with sensitivity of 0.499 and specificity of 0.779, whilst positive likelihood ratio was 2.260, and negative likelihood ratio was 0.643. According to the cut-off value of 1 h Lac, the patients were divided into high lactate group (≥ 3.35 mmol/L) and low lactate group (< 3.35 mmol/L). In the two subgroups, 30-day mortality was 31.58% (336/1 064) and 11.60% (337/2 905), respectively. The Kaplan-Meier survival curve showed that the 30-day cumulative survival rate of high lactate group was significantly lower than that of low lactate group (Log-rank test: χ 2 = 247.72, P < 0.000 1). Multiple Logistic regression analysis showed that the 30-day mortality rate of high lactate group was 2.34 times that the level of low lactate group (OR = 2.34, 95%CI was 1.90-2.88, P < 0.000 1), after the adjustment of age, time of admission, type of ICU, hemoglobin, leukocyte count, use of vasopressor, use of ventilator and main diagnosis of patients. Stratified analysis showed that the relationship between 1 h Lac and 30-day mortality was stable., Conclusions: 1 h Lac is associated with 30-day mortality in critical care patients. The risk of death was significantly increased in critically ill patients with 1 h Lac higher than 3.35 mmol/L.

In an effort to facilitate the discovery of new, improved inhibitors of the metallo--lactamases (MBLs), a new, interactive website called MBLinhibitors.com was developed. Despite considerable efforts from the science community, there are no clinical inhibitors of the MBLs, which are now produced by human pathogens. The website, MBLinhibitors.com, contains a searchable database of known MBL inhibitors, and inhibitors can be searched by chemical name, chemical formula, chemical structure, Simplified Molecular-Input Line-Entry System (SMILES) format, and by the MBL on which studies were conducted. The site will also highlight a "MBL Inhibitor of the Month", and researchers are invited to submit compounds for this feature. Importantly, MBLinhibitors.com was designed to encourage collaboration, and researchers are invited to submit their new compounds, using the "Submit" function on the site, as well as their expertise using the "Collaboration" function. The intention is for this site to be interactive, and the site will be improved in the future as researchers use the site and suggest improvements. It is hoped that MBLinhibitors.com will serve as the one-stop site for any important information on MBL inhibitors and will aid in the discovery of a clinically useful MBL inhibitor., Competing Interests: References

Novel Ag 3 PO 4 /Bi 2 WO 6 heterostructured materials with enhanced visible-light catalytic performance were successfully synthesized by assembly combined with a hydrothermal treatment. The microstructures, morphologies, and optical properties of the prepared samples were characterized by multiple techniques. The irregular Ag 3 PO 4 nanospheres dispersed on the surface of Bi 2 WO 6 nanoflakes, and their catalytic performances were evaluated via the degradation of organic pollutants including rhodamine B (RB), methylene blue (MB), crystal violet (CV), methyl orange (MO), and phenol (Phen) under visible-light irradiation. The resulting Ag 3 PO 4 /Bi 2 WO 6 heterostructured materials displayed higher photocatalytic activity than that of either pure Bi 2 WO 6 or Ag 3 PO 4 . The enhanced photocatalytic activity was due to the good formation of heterostructures, which could not only broaden the spectral response range to visible light but also effectively promoted the charge separation. Meanwhile, the reasonable photoreactive plasmonic Z-scheme mechanism was carefully investigated on the basic of the reactive species scavenging tests, photoelectrochemical experiments, and photoluminescence (PL) spectrum. In addition, the excellent photostability of Ag 3 PO 4 /Bi 2 WO 6 was obtained, which Ag formed at the early photocatalytic reaction acted as the charge transmission-bridge to restrain the further photoreduction of Ag 3 PO 4 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)