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Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model. Cecal ligation and puncture (CLP) surgery was used to establish polymicrobial sepsis in mice. Mice depleted of gut microbiota by an antibiotic cocktail (ABX) exhibited a significantly higher level of mortality than controls. As determined by metabolomics analysis, ABX treatment has depleted many metabolites, and subsequent supplementation with l-rhamnose (rhamnose, Rha), a bacterial carbohydrate metabolite, exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis, which in turn improved organ damage and mortality. Mechanistically, rhamnose binds directly to and activates the solute carrier family 12 (potassium-chloride symporter), member 4 (SLC12A4) in macrophages and promotes phagocytosis by activating the small G-proteins, Ras-related C3 botulinum toxin substrate1 (Rac1) and cell division control protein 42 homolog (Cdc42). Interestingly, rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients. In conclusion, by identifying SLC12A4 as the host interacting protein, we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

Introduction Recently, NLR family pyrin domain containing 3 (NLRP3) and pyroptosis have been reported to be involved in traumatic brain injury-induced acute lung injury (TBI-ALI). Studies have shown that triggering receptor expressed on myeloid cells-1 (TREM-1) may be one of the upstream molecules regulating NLRP3/pyroptosis, and 5-hydroxytryptamine type 3-receptor (5-HT3R) antagonists can inhibit NLRP3/pyroptosis. However, the role of TRME-1 in TBI- ALI, the therapeutic effect of 5-HT3R inhibition on TBI-ALI and its mechanism are still unclear. Therefore, this study aimed to evaluate the protective effect of ondansetron, a 5-HT3 inhibitor, on TBI-ALI, and to explore whether the underlying mechanism is related to the regulation of TREM-1. Material and methods A TBI-ALI rat model was constructed via lateral fluid percussion (LFP) brain injury, and either TREM-1 inhibitor (LP17) or ondansetron was administered as needed. Results TBI induced NLRP3 inflammasome, pyroptosis, and TREM-1 activation in rat lung tissues in a time-dependent manner. Inhibition of TREM-1 activity attenuated TBI-ALI; this is evident from reduced pathological scores, wet/dry ratios, and bronchoalveolar lavage fluid protein levels and alleviated NLRP3 inflammasome/pyroptosis. In addition, ondansetron reduced NLRP3 inflammasome/pyroptosis and alleviated TBI-ALI. Moreover, ondansetron reduced TREM-1 activation in macrophages and lung tissue. Conclusions Ondansetron alleviated TBI-ALI. In terms of mechanism, TREM-1 promotes TBI-ALI via the NLRP3-related pyroptosis pathway, and the protective effect of ondansetron on TBI-ALI may be related to the inhibition of TREM-1.

Abstract Introduction Sepsis is a severe disease with a complex pathogenesis and is an important factor in the mortality of patients in intensive care units (ICUs). The administration of vitamin C and its combination treatment in sepsis was not supported by the results of multiple randomized controlled clinical trials. However, the efficacy of a higher vitamin C dose in treating patients with sepsis remains unclear. Therefore, the effectiveness of administering a larger dosage of vitamin C to patients with sepsis remains unclear. Methods and Analysis The Clinical Efficacy of Megadose Vitamin C in Sepsis (CEMVIS) trial is a multicenter, single-blind, randomized, placebo-controlled trial with 234 individuals with sepsis. The following adult patients will be enrolled: those with procalcitonin (PCT) ≥ 2 ng/mL and sepsis 3.0 diagnostic criteria. Patients will be randomly assigned to receive 12 g vitamin C or the same volume of 5% glucose injection intravenously pumped every 12 h for 4 days or up to the moment they are discharged from ICU. The primary outcome will be the mortality within 28 days. Secondary outcomes will mainly include protection and support of organ functions, improvement in inflammatory status, and length of ICU stay. Moreover, adverse events and serious adverse events will be meticulously recorded. Ethics This study was approved by the Clinical Ethics Committee of Zhujiang Hospital of Southern Medical University (2020-KY-069-05). The trial results will be published in peer-reviewed journals or at national or international conferences. Trial registration clinicaltrials.gov, NCT05194189, Registered 3 January 2022, URL: https://www.clinicaltrials.gov .

Abstract Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.

Abstract Electrochemical chlorine evolution reaction is of central importance in the chlor-alkali industry, but the chlorine evolution anode is largely limited by water oxidation side reaction and corrosion-induced performance decay in strong acids. Here we present an amorphous CoOxCly catalyst that has been deposited in situ in an acidic saline electrolyte containing Co2+ and Cl- ions to adapt to the given electrochemical condition and exhibits ~100% chlorine evolution selectivity with an overpotential of ~0.1 V at 10 mA cm−2 and high stability over 500 h. In situ spectroscopic studies and theoretical calculations reveal that the electrochemical introduction of Cl- prevents the Co sites from charging to a higher oxidation state thus suppressing the O-O bond formation for oxygen evolution. Consequently, the chlorine evolution selectivity has been enhanced on the Cl-constrained Co-O* sites via the Volmer-Heyrovsky pathway. This study provides fundamental insights into how the reactant Cl- itself can work as a promoter toward enhancing chlorine evolution in acidic brine.

Abstract The increase of lactate is an independent risk factor for patients with sepsis-induced acute kidney injury (SAKI). However, whether elevated lactate directly promotes SAKI and its mechanism remain unclear. Here we revealed that downregulation of the deacetylase Sirtuin 3 (SIRT3) mediated the hyperacetylation and inactivation of pyruvate dehydrogenase E1 component subunit alpha (PDHA1), resulting in lactate overproduction in renal tubular epithelial cells. We then found that the incidence of SAKI and renal replacement therapy (RRT) in septic patients with blood lactate ≥ 4 mmol/L was increased significantly, compared with those in septic patients with blood lactate < 2 mmol/L. Further in vitro and in vivo experiments showed that additional lactate administration could directly promote SAKI. Mechanistically, lactate mediated the lactylation of mitochondrial fission 1 protein (Fis1) lysine 20 (Fis1 K20la). The increase in Fis1 K20la promoted excessive mitochondrial fission and subsequently induced ATP depletion, mitochondrial reactive oxygen species (mtROS) overproduction, and mitochondrial apoptosis. In contrast, PDHA1 activation with sodium dichloroacetate (DCA) or SIRT3 overexpression decreased lactate levels and Fis1 K20la, thereby alleviating SAKI. In conclusion, our results show that PDHA1 hyperacetylation and inactivation enhance lactate overproduction, which mediates Fis1 lactylation and exacerbates SAKI. Reducing lactate levels and Fis1 lactylation attenuate SAKI.

If and how non-bonding ligands mediate the electronic states of metal sites is interesting yet remains to be explored. Here the authors show that a non-covalent phenanthroline can promote the population of Co4+ and induce polaron-like Co sites for improved water oxidation.

Background and aims Esmolol is a common short-acting drug to control ventricular rate. This study aimed to evaluate the association between use of esmolol and mortality in critically ill patients. Methods This is a retrospective cohort study from MIMIC-IV database containing adult patients with a heart rate of over 100 beats/min during the intensive care unit (ICU) stay. Multivariable Cox proportional hazard models and logistic regression were used to explore the association between esmolol and mortality and adjust confounders. A 1:1 nearest neighbor propensity score matching (PSM) was performed to minimize potential cofounding bias. The comparison for secondary outcomes was performed at different points of time using an independent t -test. Results A total of 30,332 patients were reviewed and identified as critically ill. There was no significant difference in 28-day mortality between two groups before (HR = 0.90, 95% CI = 0.73-1.12, p = 0.343) and after PSM (HR = 0.84, 95% CI = 0.65-1.08, p = 0.167). Similar results were shown in 90-day mortality before (HR = 0.93, 95% CI = 0.75-1.14, p = 0.484) and after PSM (HR = 0.85, 95% CI = 0.67-1.09, p = 0.193). However, esmolol treatment was associated with higher requirement of vasopressor use before (HR = 2.89, 95% CI = 2.18-3.82, p 0.05). Conclusion Esmolol treatment was associated with reduced heart rate and lowered DBP and MAP, which may increase vasopressor use and fluid balance at the timepoint of 24 hours in critically ill patients during ICU stay. However, after adjusting for confounders, esmolol treatment was not associated with 28-day and 90-day mortality.

BackgroundPrevious studies have shown that dexmedetomidine (DEX) may be associated with reduced vasopressor requirements in septic shock patients, however, long-term DEX-only sedation in reducing vasopressor requirements is still controversial.MethodsA retrospective study was conducted among patients with septic shock on mechanical ventilation using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was the ratio of norepinephrine equivalent dose to mean arterial pressure (NEq/MAP) in the first 72 h after DEX or other sedatives for sedation. The secondary outcomes were key organ function parameters, 28-day mortality, and 90-day mortality. Univariate, propensity score matching (PSM), and generalized linear mixed model (GLMM) analyses were performed.ResultsDEX was associated with decreased NEq/MAP in the first 72 h (difference = 0.05, 95% CI = –0.02–0.08, p = 0.002) after adjusting for confounders in the GLMM analysis. The DEX group was also associated with a lower heart rate, cardiac output (CO), lactate level, aspartate transaminase (AST) level, and higher PaO2/FiO2 ratio (p

It is a new advertising marketing method for commodity companies to use vloggers to endorse their products, and to influence consumers' attitudes and decisions. In view of this phenomenon, there are few studies on the relationship between vloggers and consumers, and this study aims to explore how the persuasive strategies used by vloggers to promote products influence consumers' purchase intentions. Based on the concepts of Aristotle's persuasion theory, this study extracts two specific persuasive approaches, “two-sided messages” and “emotional appeal,” to explore consumers' perceptions of them and the effectiveness of these two strategies. At the same time, para-social interaction and perceived value as intermediary factors are also included in the study for further discussion. The study empirically analyzed a sample of 511 questionnaires from participants who had purchased products recommended by vloggers and came to the following conclusions: (1) vloggers can enhance consumers' purchase intention by adopting two-sided messages persuasion when promoting products; (2) vloggers' emotional persuasion can enhance consumers' purchase intention; (3) as an intermediary variable, para-social interaction plays a more obvious role in vloggers' persuasion by appealing to emotions. The audience can have common feelings with vloggers, and they are more connected with each other, thus increasing their willingness to buy; (4) Perceived value, as an intermediary variable, plays a more obvious role in vloggers' persuasion with the two-sided messages. The two-sided messages can show vloggers' credibility and more abundant information about products, so that consumers have a positive perception of product value, and the direct persuasion effect of the two-sided messages is greater. Based on the results of the study, this paper helps vloggers to adopt different persuasive approaches for different types of audiences, choose the proper marketing methods, attract the potential customers, and achieve such purposes as enriching product marketing forms and increasing market share.

Background: Recombinant human thrombopoietin (rhTPO) is reported to stimulate platelet production and increase peripheral platelet counts; it is primarily used to manage chemotherapy-induced thrombocytopenia and idiopathic thrombocytopenic purpura. However, the effect of rhTPO in patients with pneumonia and thrombocytopenia remains uncertain.Objective: To assess the association of rhTPO and platelet counts in ICU patients with pneumonia and thrombocytopenia.Materials and Methods: A retrospective cohort study was performed in the ICU department, Nanfang Hospital, Southern Medical University, Guangzhou, China. From January 2016 to April 2021, patients with pneumonia and thrombocytopenia were allocated to two groups—the rhTPO and no-rhTPO groups—according to whether they received rhTPO treatment or not during their ICU stay. Demographical and clinical data were collected and analyzed using statistical software; p < 0.05 was considered statistically significant.Results: Out of 327 patients, 149 were in the rhTPO group and 178 were in the no-rhTPO group. Within the first 7 days, platelet counts increased more for patients in the rhTPO group compared with those in the no-rhTPO group (99.21 ± 102.613 vs. 2.08 ± 43.877, p = 0.000). The clinical recovery rate of platelets increased within 7 days (65.8 vs. 18.5%, p = 0.000) and, after 7 days of enrollment, hemorrhagic scores decreased more apparently in the rhTPO group (2.81 ± 2.856 vs. 1.16 ± 2.123, p = 0.000). Further, bleeding events ceased in 66.7% of the patients in the rhTPO group compared with 37.3% of the patients in the no-rhTPO group (p = 0.000). Less red-blood-cells transfusions were needed in the rhTPO group (3.639 ± 4.630 vs. 5.818 ± 6.858, p = 0.009). Furthermore, through logistic regression, rhTPO administration was found to be an independent indicator that affected the platelet recovery rate within 7 days.Conclusion: This study finds that rhTPO administration is associated with increased platelet counts, alleviated bleeding, and reduced blood transfusion. For patients with pneumonia and thrombocytopenia, rhTPO may be an effective therapeutic drug; however, more RCT trails are needed to confirm our observation.

Abstract Background Fluid therapy is a cornerstone in the treatment of sepsis. Recently, the guidelines have recommended the combined administration that using crystalloids plus albumin for septic patients, but the optimal timing for albumin combined is still unclear. The objective of this study was to investigate the association of timing of albumin combined with 28-day mortality in patients with sepsis. Methods We involved septic patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database, and these patients were categorized into crystalloids group (crystalloids alone) and early combination group (crystalloids combined albumin at 0–24 h). The primary outcome was 28-day mortality. We used propensity score matching (PSM) to adjust confounding and restricted mean survival time (RMST) analysis was conducted to quantify the beneficial effect on survival due to the combination group. Results We categorized 6597 and 920 patients in the “crystalloids alone” and “early combination”, respectively. After PSM, compared to the crystalloids group, the combination group was associated with the increased survival among 28-day (increased survival: 3.39 days, 95% CI 2.53–4.25; P

Heat stroke (HS) is a severe condition characterized by increased morbidity and high mortality. Acute liver injury (ALI) is a well-documented complication of HS. The tumor suppressor p53 plays an important role in regulation of mitochondrial integrity and mitophagy in several forms of ALI. However, the role of p53-regulated mitophagy in HS-ALI remains unclear. In our study, we discovered the dynamic changes of mitophagy in hepatocytes and demonstrated the protective effects of mitophagy activation on HS-ALI. Pretreatment with 3-MA or Mdivi-1 significantly exacerbated ALI by inhibiting mitophagy in HS-ALI mice. Consistent with the animal HS-ALI model results, silencing Parkin aggravated mitochondrial damage and apoptosis by inhibiting mitophagy in HS-treated normal human liver cell line (LO2 cells). Moreover, we described an increase in the translocation of p53 from the nucleus to the cytoplasm, and cytosolic p53 binds to Parkin in LO2 cells following HS. p53 overexpression using a specific adenovirus or Tenovin-6 exacerbated HS-ALI through Parkin-dependent mitophagy both in vivo and in vitro, whereas inhibition of p53 using siRNA or PFT-α effectively reversed this process. Our results demonstrate that cytosolic p53 binds to Parkin and inhibits mitophagy by preventing Parkin’s translocation from the cytosol to the mitochondria, which decreases mitophagy activation and leads to hepatocyte apoptosis in HS-ALI. Overall, pharmacologic induction of mitophagy by inhibiting p53 may be a promising therapeutic approach for HS-ALI treatment.

BackgroundThe effectiveness of melatonin and its analogs in preventing postoperative delirium (POD) following cardiac surgery is controversial. The purpose of this systematic review and meta-analysis was to confirm the benefits of melatonin and its analogs on delirium prevention in adults who underwent cardiac surgery.MethodsWe systematically searched the PubMed, Cochrane Library, Web of Science, Embase, and EBSCOhost databases, the last search was performed in October 2021 and repeated before publication. The controlled studies were included if investigated the impact of melatonin and its analogs on POD in adults who underwent cardiac surgery. The primary outcome was the incidence of delirium. The Stata statistical software 17.0 was used to perform this study.ResultsThis meta-analysis included eight randomized controlled trials (RCTs) and two cohort studies with a total of 1,714 patients. The results showed that melatonin and ramelteon administration were associated with a significantly lower incidence of POD in adults who underwent cardiac surgery (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.29–0.74; P = 0.001). The subgroup analyses confirmed that melatonin 3 mg (OR, 0.37; 95% CI, 0.18–0.76; P = 0.007) and 5 mg (OR, 0.34; 95% CI, 0.21–0.56; P < 0.001) significantly reduced the incidence of POD.ConclusionMelatonin at dosages of 5 and 3 mg considerably decreased the risk of delirium in adults who underwent cardiac surgery, according to our results. Cautious interpretation of our results is important owing to the modest number of studies included in this meta-analysis and the heterogeneity among them.Systematic Review RegistrationPROSPERO registration number: CRD42021246984.

Abstract Our previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.

Cardiovascular disease (CVD) is a group of systemic disorders threatening human health with complex pathogenesis, among which mitochondrial energy metabolism reprogramming has a critical role. Mitochondria are cell organelles that fuel the energy essential for biochemical reactions and maintain normal physiological functions of the body. Mitochondrial metabolic disorders are extensively involved in the progression of CVD, especially for energy-demanding organs such as the heart. Therefore, elucidating the role of mitochondrial metabolism in the progression of CVD is of great significance to further understand the pathogenesis of CVD and explore preventive and therapeutic methods. In this review, we discuss the major factors of mitochondrial metabolism and their potential roles in the prevention and treatment of CVD. The current application of mitochondria-targeted therapeutic agents in the treatment of CVD and advances in mitochondria-targeted gene therapy technologies are also overviewed.

To identify the risk factors related to the patient's 28-day mortality, we retrospectively reviewed the records of patients with intra-abdominal infections admitted to the ICU of Nanfang Hospital, Southern Medical University from 2011 to 2018. Multivariate Cox proportional hazard regression analysis was used to identify independent risk factors for mortality. Four hundred and thirty-one patients with intra-abdominal infections were analyzed in the study. The 28-day mortality stepwise increased with greater severity of disease expression: 3.5% in infected patients without sepsis, 7.6% in septic patients, and 30.9% in patients with septic shock (p < 0.001). In multivariate analysis, independent risk factors for 28-day mortality were underlying chronic diseases (adjusted HR 3.137, 95% CI 1.425–6.906), high Sequential Organ Failure Assessment (SOFA) score (adjusted HR 1.285, 95% CI 1.160–1.424), low hematocrit (adjusted HR 1.099, 95% CI 1.042–1.161), and receiving more fluid within 72 h (adjusted HR 1.028, 95% CI 1.015–1.041). Compared to the first and last 4 years, the early use of antibiotics, the optimization of IAT strategies, and the restriction of positive fluid balance were related to the decline in mortality of IAIs in the later period. Therefore, underlying chronic diseases, high SOFA score, low hematocrit, and receiving more fluid within 72 h after ICU admission were independent risk factors for patients' poor prognosis.

Objectives: Our ex vivo study was designed to determine the sequestration of teicoplanin, tigecycline, micafungin, meropenem, polymyxin B, caspofungin, cefoperazone sulbactam, and voriconazole in extracorporeal membrane oxygenation (ECMO) circuits.Methods: Simulated closed-loop ECMO circuits were prepared using 2 types of blood-primed ECMO. After the circulation was stabilized, the study drugs were injected into the circuit. Blood samples were collected at 2, 5, 15, 30 min, 1, 3, 6, 12, and 24 h after injection. Drug concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Control groups were stored at 4°C after 3, 6, 12, and 24 h immersing in a water bath at 37°C to observe spontaneous drug degradation.Results: Twenty-six samples were analyzed. The average drug recoveries from the ECMO circuits and control groups at 24 h relative to baseline were 67 and 89% for teicoplanin, 100 and 145% for tigecycline, 67 and 99% for micafungin, 45 and 75% for meropenem, 62 and 60% for polymyxin B, 83 and 85% for caspofungin, 79 and 98% for cefoperazone, 75 and 87% for sulbactam, and 60 and 101% for voriconazole, respectively. Simple linear regression showed no significant correlation between lipophilicity (r2 = 0.008, P = 0.225) or the protein binding rate (r2 = 0.168, P = 0.479) of drugs and the extent of drug loss in the ECMO circuits.Conclusions: In the two ECMO circuits, meropenem and voriconazole were significantly lost, cefoperazone was slightly lost, while tigecycline and caspofungin were not lost. Drugs with high lipophilicity were lost more in the Maquet circuit than in the Sorin circuit. This study needs more in vivo studies with larger samples for further confirmation, and it suggests that therapeutic drug concentration monitoring should be strongly considered during ECMO.

Anaerobic glycolysis is the process by which glucose is broken down into pyruvate and lactate and is the primary metabolic pathway in sepsis. The pyruvate dehydrogenase complex (PDHC) is a multienzyme complex that serves as a critical hub in energy metabolism. Under aerobic conditions, pyruvate translocates to mitochondria, where it is oxidized into acetyl-CoA through the activation of PDHC, thereby accelerating aerobic oxidation. Both phosphorylation and acetylation affect PDHC activity and, consequently, the regulation of energy metabolism. The mechanisms underlying the protective effects of PDHC in sepsis involve the regulation on the balance of lactate, the release of inflammatory mediators, the remodeling of tricarboxylic acid (TCA) cycle, as well as on the improvement of lipid and energy metabolism. Therapeutic drugs that target PDHC activation for sepsis treatment include dichloroacetate, thiamine, amrinone, TNF-binding protein, and ciprofloxacin. In this review, we summarize the recent findings regarding the metabolic regulation of PDHC in sepsis and the therapies targeting PDHC for the treatment of this condition.

Abstract Rationale, aims, and objectives Hospital‐acquired pressure injuries (HAPI) prolong hospital stays and are an important health problem worldwide. The aim of this study was to assess the frequency of and risk factors for intensive care unit (ICU)‐acquired pressure injuries (IAPI) on the sacrum in critically ill patients in China. Methods We performed a multicenter, cross‐sectional survey of IAPI on the sacrum in 23 adult ICUs in 19 hospitals in China. Data for 421 critically ill patients were collected on December 13, 2019, and January 13, 2020, including patient characteristics, physiological, and clinical information. Logistic regression was used to analyze the risk factors for IAPI on the sacrum in the ICU. Results Forty‐one patients presented sacrum pressure injuries in the ICU, with a frequency of 9.74%. Risk factors that significantly increased the risk of IAPI on the sacrum were lower body mass index (BMI, odds ratio [OR] = 1.115, confidence interval [CI]: 1.011‐1.229, P = .029), chronic obstructive pulmonary disease (COPD, OR = 3.183, CI: 1.261‐8.037, P = .014), multiple organ dysfunction syndrome (MODS, OR = 2.670, CI: 1.031‐6.903, P = .043), and a lower Braden risk score (OR = 1.409, CI: 1.197‐1.659, P

NiFe and CoFe layered double hydroxides are among the most active electrocatalysts for the alkaline oxygen evolution reaction. Here, by combining operando experiments and rigorous DFT calculations, the authors unravel their active phase, the reaction center and the catalytic mechanism.

Recent studies have shown that autophagy upregulation can attenuate sepsis-induced acute kidney injury (SAKI). The tumor suppressor p53 has emerged as an autophagy regulator in various forms of acute kidney injury (AKI). Our previous studies showed that p53 acetylation exacerbated hemorrhagic shock-induced AKI and lipopolysaccharide (LPS)-induced endothelial barrier dysfunction. However, the role of p53-regulated autophagy in SAKI has not been examined and requires clarification. In this study, we observed the dynamic changes of autophagy in renal tubular epithelial cells (RTECs) and verified the protective effects of autophagy activation on SAKI. We also examined the changes in the protein expression, intracellular distribution (nuclear and cytoplasmic), and acetylation/deacetylation levels of p53 during SAKI following cecal ligation and puncture (CLP) or LPS treatment in mice and in a LPS-challenged human RTEC cell line (HK-2 cells). After sepsis stimulation, the autophagy levels of RTECs increased temporarily, followed by a sharp decrease. Autophagy inhibition was accompanied by an increased renal tubular injury score. By contrast, autophagy agonists could reduce renal tubular damage following sepsis. Surprisingly, the expression of p53 protein in both the renal cortex and HK-2 cells did not significantly change following sepsis stimulation. However, the translocation of p53 from the nucleus to the cytoplasm increased, and the acetylation of p53 was enhanced. In the mechanistic study, we found that the induction of p53 deacetylation, due to either the resveratrol/quercetin -induced activation of the deacetylase Sirtuin 1 (Sirt1) or the mutation of the acetylated lysine site in p53, promoted RTEC autophagy and alleviated SAKI. In addition, we found that acetylated p53 was easier to bind with Beclin1 and accelerated its ubiquitination-mediated degradation. Our study underscores the importance of deacetylated p53-mediated RTEC autophagy in future SAKI treatments.

Summary: Carbon-based supercapacitors (SCs) are important electrochemical energy storage devices and are often used in electronic equipment that generates a magnetic field. However, whether the magnetic field affects the charge storage of SCs is unknown. Here, we discover that applying an external magnetic field to carbon-based SCs can induce capacitance change in both aqueous acidic and alkaline electrolytes but not in neutral electrolytes. We further show that, in KOH electrolytes, the competition between the driving force caused by the Lorentz force and the damping force related to the electrolyte conductivity plays a crucial role in affecting the OH− transport under the magnetic field. In H2SO4 electrolytes, the third paramagnetic force generated by the paramagnetic H+ under the magnetic field hinders the H+ transport in addition to the above forces. A quantitative relationship among the limiting current density at the electrode-electrolyte interface, the intensity of the magnetic field, and the concentration and viscosity of electrolytes can therefore be established.

Melatonin reportedly alleviates sepsis-induced multi-organ injury by inducing autophagy and activating class III deacetylase Sirtuin family members (SIRT1–7). However, whether melatonin attenuates small-intestine injury along with the precise underlying mechanism remain to be elucidated. To investigate this, we employed cecal ligation and puncture (CLP)- or endotoxemia-induced sepsis mouse models and confirmed that melatonin treatment significantly prolonged the survival time of mice and ameliorated multiple-organ injury (lung/liver/kidney/small intestine) following sepsis. Melatonin partially protected the intestinal barrier function and restored SIRT1 and SIRT3 activity/protein expression in the small intestine. Mechanistically, melatonin treatment enhanced NF-κB deacetylation and subsequently reduced the inflammatory response and decreased the TNF-α, IL-6, and IL-10 serum levels; these effects were abolished by SIRT1 inhibition with the selective blocker, Ex527. Correspondingly, melatonin treatment triggered SOD2 deacetylation and increased SOD2 activity and subsequently reduced oxidative stress; this amelioration of oxidative stress by melatonin was blocked by the SIRT3-selective inhibitor, 3-TYP, and was independent of SIRT1. We confirmed this mechanistic effect in a CLP-induced sepsis model of intestinal SIRT3 conditional-knockout mice, and found that melatonin preserved mitochondrial function and induced autophagy of small-intestine epithelial cells; these effects were dependent on SIRT3 activation. This study has shown, to the best of our knowledge, for the first time that melatonin alleviates sepsis-induced small-intestine injury, at least partially, by upregulating SIRT3-mediated oxidative-stress inhibition, mitochondrial-function protection, and autophagy induction.

Strain and support effects play a crucial role in heterogeneous catalysis, which has been intensively studied over metal-based catalysts. In contrast, there is little discussion about the two effects in oxide systems. In this work, using an ultrathin ZnO film as an example, we investigate strain and support effects on the structure and surface reactivity of oxide catalysts through density functional theory calculations. Our results suggest that tensile strain increases the surface reactivity of ZnO films as indicated by enhanced CO and NH3 adsorptions and compressive strain renders an early phase transition from an inert graphene-like phase to a more reactive wurtzite-like phase. The support (Au, Pt, and Ru) can promote the phase transition and surface reactivity concurrently, which exhibits a larger effect on the reactivity than the strain. The support effect can be ascribed to the increasing rumple and polarization of ZnO films through the strong ZnO–substrate interaction, which enhances the surface reactivity. The insight helps us to develop advanced oxide-based catalysts through the strain and/or substrate engineering.

A near-isogenic line (NIL) DC90 which was generated by introgressing a wild rice (Oryza rufipogon Griff.) locus CTS-12 into the 9311(Oryza sativa L. ssp. indica) background confers chilling tolerance phenotype. Here, our pilot trials showed that chilling tolerance was positively correlated with abscisic acid (ABA) biosynthesis. To understand how CTS-12 mediated the ABA-dependent multi-levels of regulation, the integration of transcriptomic and metabolomic profiling using the two-way orthogonal projections to latent structures (O2PLS) and discriminant analysis (OPLS-DA) modeling was performed to investigate the mechanisms underlying chilling tolerance. Our results revealed that metabolic shifts, including the activation of stachyose biosynthesis, amino acid metabolism pathways, phenylpropanoid/flavonoid biosynthesis, ABA biosynthesis, and perturbation of glycolysis, occurred under chilling treatment; in the recovery period, glutamate-related pathways, β-alanine biosynthesis and degradation, and serotonin biosynthesis pathways were differentiated between 9311 and DC90. Particularly, the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs), including galactinol, β-alanine, glutamate, naringenin, serotonin, ABA, and LOC_Os03g44380 (9-cis-epoxycarotenoid dioxygenase 3, OsNCED3), might be involved in the chilling tolerance variation of 9311 and DC90. CRISPR/Cas9-edited OsNCED3 resulted in chilling sensitive of japonica rice ZH11, demonstrating the involvement of ABA pathway in chilling stress response. In addition, chilling tolerance of rice was associated with the balance of water uptake and loss that was modulated by stomatal movement under chilling stress. Therefore, we speculated that the CTS-12-mediated ABA signaling pathway leads to transcriptional regulation of chilling-responsive genes and, in turn, triggers metabolic shifts to coordinately regulate the stomatal movement of guard cells. The results of this study improve our understanding of the multilevel regulation of wild rice in response to chilling stress.

This investigation was performed to verify whether lncRNA CRNDE sponging miR-181a-5p was involved with sepsis-relevant inflammatory dysfunctions. Aggregately 136 sepsis patients and 151 healthy people were recruited, and their fasting peripheral blood was gathered to detect expressions of CRNDE and miR-181a-5p. In addition, THP-1 cells were transfected with si-CRNDE, miR-181a-5p mimic, pcDNA3.1-TLR4 and si-TLR4, and then sepsis-specific inflammatory cytokines within the cells were quantified. The sponging relationships between CRNDE and miR-181a-5p, as well as between miR-181a-5p and TLR4, were ascertained by means of luciferase reporter gene assay. The experimental results revealed that over-expressed CRNDE and under-expressed miR-181a-5p were associated with shortened lifespan of sepsis patients. Mechanically, si-CRNDE-1 and miR-181a-5p mimic were able to reverse the promoting effects of LPS on production of NF-kB, TNF-α, IL-1β and IL-6 by THP-1 cells. Moreover, the expressional change of miR-181a-5p in THP-1 cells was in part owing to its being sponged by CRNDE. Lastly, TLR4, subjected to targeted modification of miR-181a-5p, was capable of disturbing the contribution of CRNDE and miR-181a-5p to THP-1 cells’ release of NF-kB, TNF-α, IL-1β and IL-6. Collectively, the CRNDE/miR-181a-5p/TLR4 axis seemed to have potential in modifying sepsis-related inflammatory pathogenesis, which offered a direction for sepsis diagnosis and treatment.

BackgroundThis study is to explore the effect of SIRT1 deacetylating inactivation on organ-derived high mobility group box 1 (HMGB1) during the development of severe hemorrhagic shock (HS).MethodsHemorrhagic shock model was reproduced in rats by blood shedding and mimicked in HK-2 cells by hypoxia-reoxygenation (H/R) treatment. The level and acetylation of HMGB1 and the expression and activity of SIRT1 were detected in tissue, serum and cultured cells and supernatant. The deacetylated sites of HMGB1 was determined by Co-IP.ResultsSerum HMGB1 in HS rats was increased but were reduced in multiple organs, especially in kidney tissue, with enhanced HMGB1 acetylation, and reduced deacetylase SIRT1 activity in isolated RTECs. HMGB1 in suspension of H/R-treated HK-2 cells was increased, accompanying with enhanced HMGB1 acetylation, and nuclear-plasma translocation. SIRT1 down-regulated by siRNA aggravated acetylation of HMGB1 and nucleus-to-cytoplasm translocation and resulted in increased HMGB1 in cultured HK-2 suspension. Immunoprecipitation data suggested that SIRT1-indcuced deacetylated sites of HMGB1 were K90 and K177 following H/R. SIRT1 overexpression inhibited the acetylation of HMGB1 and reduced the content of extracellular HMGB1 in H/R-treated HK-2 cells. Inhibiting mutation of SIRT1 restored the acetylation of HMGB1 and HMGB1 content in extracellular suspension. In HS rat model, the neutralization of HMGB1 with antibody could reduce serum HMGB1 and pro-inflammatory cytokine contents, but had no effect on SIRT1 protein expression and activity. Polydatin (PD), a potential SIRT1 agonist, up-regulated SIRT1 activity and inhibited nucleus-to-cytoplasm translocation of HMGB1 in RTECs. Moreover, PD also attenuated RTEC apoptosis, protected renal function, and prolonged survival in HS rats. These beneficial effect of PD is largely blocked by specific inhibition of SIRT1 with Ex527.ConclusionThe acetylation of HMGB1 in K99 and K177 is enhanced during HS due to the downregulation of SIRT1. The nucleus-to-cytoplasm translocation and the release of acetylated HMGB1 from RTECs of kidney might exacerbate the pro-inflammatory effects of HMGB1 during the development of HS.

Sepsis, a dysregulated host response to infection, is a major public health concern. Though experimental and clinical studies relating to sepsis are increasing, the mechanism of sepsis is not completely understood. To date, numerous studies have shown that sirtuins (silent mating type information regulation 2 homolog), which belong to the class III histone deacetylases, may have a varied, or even opposite, effect in the pathogenesis of sepsis. Notably, downstream mechanisms of sirtuins are not fully understood. The sirtuin family consists of sirtuins 1–7; among them, sirtuin 1 (SIRT1) is the most studied one, during the development of sepsis. Furthermore, other sirtuin members are also confirmed to be involved in the regulation of inflammatory or metabolic signaling following sepsis. In addition, sirtuins may interact with each other to form a precise regulatory mechanism in different phases of sepsis. Therefore, in this review, by accumulating data from PubMed, we intend to explain the role of sirtuin in sepsis, which we hope will pave the way for further experimental study and the potential future clinical applications of sirtuins.

Three kinds of nozzles normally used in industrial production are numerically simulated, and the structure of nozzle with the best jetting performance out of the three nozzles is optimized. The R90 nozzle displays the most optimal jetting properties, including the smooth transition of the nozzle’s inner surface. Simulation results of all sample nozzles in this study show that the helix nozzle ultimately displays the best jetting performance. Jetting velocity magnitude along Y and Z coordinates is not symmetrical for the helix nozzle. Compared to simply changing the jetting angle, revolving the jet issued from the helix nozzle creates a grinding wheel on the cleaning surface, which makes not only an impact effect but also a shearing action on the cleaning object. This particular shearing action improves the cleaning process overall and forms a wider, effective cleaning range, thus obtaining a broader jet width.