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Background: SAKI is a common and serious complication of sepsis, contributing significantly to high morbidity and mortality, especially in patients requiring RRT. Early identification of high-risk patients enables timely interventions and improvement in clinical outcomes. The objective of this study was to develop and validate a predictive model for in-hospital mortality in patients with SAKI receiving RRT. Methods: Patients with SAKI receiving RRT from the MIMIC-IV database were retrospectively enrolled and randomly assigned to either the training cohort or the testing cohort in a 7:3 ratio. LASSO regression and Boruta algorithm were utilized for feature selection. Subsequently, three machine learning models—CART, SVM and LR—were constructed, and their predictive efficacy was assessed using a comprehensive set of performance indicators. Feature importance analysis was performed to determine the contribution of each feature to a model's predictions. Finally, DCA was employed to evaluate the clinical utility of the prediction models. Additionally, a clinical nomogram was developed to facilitate the interpretation and visualization of the LR model. Results: A total of 1663 adults were ultimately enrolled and randomly allocated into the training cohort (n = 1164) or the testing cohort (n = 499). Twenty-eight variables were evaluated for feature selection, with eight ultimately retained in the final model: age, MAP, RR, lactate, Cr, PT-INR, TBIL and CVP. The LR model demonstrated commendable performance, exhibiting robust discrimination in both the training cohort (AUROC: 0.73 (95% CI 0.70–0.76); AUPRC: 0.75 (95% CI 0.72–0.79); accuracy: 0.66 (95% CI 0.63–0.68)) and the testing cohort (AUROC: 0.72 (95% CI 0.68-0.76); AUPRC: 0.73 (95% CI 0.67–0.79); accuracy: 0.65 (95% CI 0.61–0.69)). Furthermore, there was good concordance between predicted and observed values in both the training cohort (χ2 = 4.41, p = 0.82) and the testing cohort (χ2 = 4.16, p = 0.84). The results of the DCA revealed that the LR model provided a greater net benefit compared to other prediction models. Conclusions: The LR model exhibited superior performance in predicting in-hospital mortality in patients with SAKI receiving RRT, suggesting its potential utility in identifying high-risk patients and guiding clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Sepsis‐associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H2) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H2 on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics. Methods: A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H2 for 1 h at 1 and 6 h post‐surgery, respectively. The 7‐day survival rate was recorded. Cognitive function was assessed using the Y‐maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC‐1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy. Results: Inhalation of 67% H2 improved the 7‐day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H2 inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis‐related factors (PGC‐1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels. Conclusions: Inhalation of high concentration (67%) of H2 in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

Objective: It is well known that glucose and lipid metabolism disorders and insulin resistance are common in sepsis, which affect the occurrence and prognosis of multiple organ dysfunction in septic patients. Previous study reported the predictive value of triglyceride-glucose index (TyG), a clinical indicator for insulin resistance, in postoperative delirium patients. However, it remains unclear whether the TyG index is a novel predictive biomarker for sepsis-associated delirium. The aim of this study is to explore the relationship between TyG index and the risk of delirium in patients with sepsis. Methods: Adult septic patients were identified from the MIMIC-IV database and divided into four groups based on the mean value of TyG. The primary outcome was the incidence of delirium. The association between TyG and the risk of developing delirium was evaluated by restricted cubic spline (RCS), multivariate logistic regression and subgroup analysis. Propensity Score Matching (PSM) method was used to balance the baseline data. Results: A total of 3,331 septic patients were included in the analysis, and further divided into four groups: Q1 (TyG ≤ 8.67), Q2 (8.67 < TyG ≤ 9.08), Q3 (9.08 < TyG ≤ 9.61), and Q4 (TyG > 9.61). The RCS curves demonstrated a non-linear positive relationship between TyG index and the risk of developing delirium, and an optimal cut-of value 9.09 was recommended. After balancing the baseline information by PSM, patients in the TyG > 9.09 group had a significant higher incidence of delirium compared with those in the TyG ≤ 9.09 group. In logistic regression analysis, TyG > 9.09 was significantly associated with lower risk of developing delirium in both original cohort (OR 1.54–1.78, all P < 0.001) and the PSM cohort (OR 1.41–1.48, all P < 0.001). No association was found between the TyG index and mortality (all P > 0.05). In subgroup analysis, our findings were consistent (all OR > 1 in all subgroups). Conclusion: Our study demonstrated an independent association between TyG index and increased risk of delirium in septic patients, indicating that TyG index can serve as a biomarker for delirium in sepsis. [ABSTRACT FROM AUTHOR]

Circulating nucleosome levels are commonly elevated in physiological and pathological conditions. Their potential as biomarkers for diagnosing and prognosticating sepsis remains uncertain due, in part, to technical limitations in existing detection methods. This scoping review explores the possible role of nucleosome concentrations in the diagnosis, prognosis, and therapeutic management of sepsis. A comprehensive literature search of the Cochrane and Medline libraries from 1996 to 1 February 2024 identified 110 potentially eligible studies, of which 19 met the inclusion criteria, encompassing a total of 39 SIRS patients, 893 sepsis patients, 280 septic shock patients, 117 other ICU control patients, and 345 healthy volunteers. The enzyme-linked immunosorbent assay [ELISA] was the primary method of nucleosome measurement. Studies consistently reported significant correlations between nucleosome levels and other NET biomarkers. Nucleosome levels were higher in patients with sepsis than in healthy volunteers and associated with disease severity, as indicated by SOFA and APACHE II scores. Non-survivors had higher nucleosome levels than survivors. Circulating nucleosome levels, therefore, show promise as early markers of NETosis in sepsis, with moderate diagnostic accuracy and strong correlations with disease severity and prognosis. However, the available evidence is drawn mainly from single-center, observational studies with small sample sizes and varied detection methods, warranting further investigation. [ABSTRACT FROM AUTHOR]

Background: Approximately 40 to 60% of patients with sepsis develop sepsis-induced cardiomyopathy (SIC), which is associated with a substantial increase in mortality. We have found that molecular hydrogen (H2) inhalation improved the survival rate and cardiac injury in septic mice. However, the mechanism remains unclear. This study aimed to explore the regulatory mechanism by which hydrogen modulates autophagy and its role in hydrogen protection of SIC. Methods: Cecal ligation and puncture (CLP) was used to induce sepsis in adult C57BL/6J male mice. The mice were randomly divided into 4 groups: Sham, Sham + 2% hydrogen inhalation (H2), CLP, and CLP + H2 group. The 7-day survival rate was recorded. Myocardial pathological scores were calculated. Myocardial troponin I (cTnI) levels in serum were detected, and the levels of autophagy- and mitophagy-related proteins in myocardial tissue were measured. Another four groups of mice were also studied: CLP, CLP + Bafilomycin A1 (BafA1), CLP + H2, and CLP + H2 + BafA1 group. Mice in the BafA1 group received an intraperitoneal injection of the autophagy inhibitor BafA1 1 mg/kg 1 h after operation. The detection indicators remained the same as before. Results: The survival rate of septic mice treated with H2 was significantly improved, myocardial tissue inflammation was improved, serum cTnI level was decreased, autophagy flux was increased, and mitophagy protein content was decreased (P < 0.05). Compared to the CLP + H2 group, the CLP + H2 + BafA1 group showed a decrease in autophagy level and 7-day survival rate, an increase in myocardial tissue injury and cTnI level, which reversed the protective effect of hydrogen (P < 0.05). Conclusion: Hydrogen exerts protective effect against SIC, which may be achieved through the promotion of autophagy and mitophagy. [ABSTRACT FROM AUTHOR]

A correction notice was issued for an article titled "The impact of the new acute respiratory distress syndrome (ARDS) criteria on Berlin criteria ARDS patients: a multicenter cohort study" published in BMC Medicine. The correction addresses errors in the number of patients in different groups and the descriptions in the figures. The authors have acknowledged these mistakes and provided the correct information for clarity. The correction was authored by Lina Zhao, Fuhong Su, Nannan Zhang, Hening Wu, Yuehao Shen, Haiying Liu, Xuguang Li, Yun Li, and Keliang Xie. [Extracted from the article]

Background: ACT001 is a potent anti-inflammatory small-molecule drug. However, the single cell and spatial molecular basis of pyroptosis and whether ACT001 exerts a therapeutic effect by preventing pyroptosis on acute lung injury (ALI) remains unclear., Methods: The bioinformatics approach was employed to identify single cell and spatial landscape of nucleotide-binding domains and leucine-rich repeat protein 3 (NLRP3)-dependent pyroptosis in lipopolysaccharide (LPS) and influenza virus-induced ALI. Molecular docking was performed to elucidate the relationship between ACT001 and NLRP3. LPS-induced ALI mice model was established. Histopathological analysis and bronchoalveolar lavage fluid collection were conducted to investigate the anti-inflammatory and protective effects. In vitro experiments were also performed on bone marrow-derived macrophages to explore the effect of ACT001 on the balance of mitochondrial fusion and fission protein., Results: Single cell transcriptomic and spatial transcriptomic analysis predicted that NLRP3-dependent pyroptosis significantly correlated with the development of ALI both in single cell and spatial distribution. Molecular docking provided a stable and reliable docking between ACT001 and NLRP3. ACT001 improved the 7-day survival of mice by approximately 50% over the loading dose of LPS-induced ALI. ACT001 (5 uM) attenuated the disruption of mitochondrial integrity and reactive oxygen species. Further, ACT001 reduced the overexpression of the mitochondrial fission protein DRP1 without affecting fusion protein Mitofusin2 levels. Moreover, ACT001 exerted a similar protective effect of suppressing pyroptosis as the DRP1-inhibitor Mdivi-1., Conclusions: Our study revealed that pyroptosis genes were highly expressed in single-cell and spatial mapping along the first week of ALI occurrence. ACT001 attenuates ALI by reducing the NLRP3-dependent pyroptosis and balancing mitochondrial fission and fusion., Competing Interests: The authors have declared that no conflicts of interest exist. We acknowledge that no AI has been applied to this paper.

Sepsis is a major cause of mortality among critical patients. Acute kidney injury (AKI) is the common complication in patients with sepsis, characterized by rapid deterioration of renal function. The purpose of this study is to assess the impact of inhaling high concentration hydrogen on septic mice with AKI and to examine the involvement of mitochondria in this process. High concentration hydrogen does not cause hypoxia and can alleviate AKI and improve 7-day survival in septic mice. Inflammatory factors are markedly elevated in the serum and renal tissues in CLP group which are dramatically down-regulated by hydrogen. The activities of both antioxidant enzymes are significantly reduced after CLP, whereas hydrogen markedly increases the activities of SOD and CAT. MMP is found to be significantly lower in CLP group whereas this effect is reversed by hydrogen. The trend of ATP content in renal tissues corresponded with that of MMP. There is a substantial downregulation of PGC-1α, Nrf2, and TFAM protein in CLP group. Drp1 expression is significantly higher in CLP group compared to Sham group, while the opposite trend is observed for MFN2. Hydrogen can reverse these changes. Inhalation of high concentration hydrogen can improve acute kidney injury, 7-day survival, inflammatory response and oxidative stress in septic mice. The mechanism may be related to inhibit renal mitochondrial fission and promote mitochondrial fusion and biogenesis., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: superparamagnetic ferroferric oxide (Fe 3 O 4 ) nanoparticles can be extensively functionalized for applications in drug enrichment and separation. Their high magnetic responsiveness and controllable surface modification enable rapid drug enrichment and separation under external magnetic fields. This study aimed to enhance the application potential of superparamagnetic Fe 3 O 4 nanoparticles in the field of drug enrichment and separation by functionalizing these nanoparticles to improve their biocompatibility and targeting capabilities., Methods: superparamagnetic Fe 3 O 4 nanoparticles functionalized with dopamine were synthesized using benzyl alcohol as the solvent and iron acetylacetonate as the precursor. The dopamine-functionalized superparamagnetic iron oxide nanoparticles were used to analyze protein enrichment and separation. Characterization of the nanoparticles was conducted, including analysis of particle size distribution, Zeta potential, and fluorescence spectra using a fluorescence spectrophotometer., Results: the Fe 3 O 4 nanoparticles maintained high magnetism from the original material and exhibited uniform particle size distribution and stable Zeta potential. The saturation magnetization of dopamine-functionalized superparamagnetic Fe 3 O 4 nanoparticles showed no significant difference compared to before coating, indicating minimal influence of dopamine on the internal magnetic core of the nanoparticles. The Fe 3 O 4 nanoparticles demonstrated good biocompatibility and stability., Conclusion: functionalization of superparamagnetic Fe 3 O 4 nanoparticles significantly enhances their efficiency in drug enrichment and separation processes, suggesting broad applications in the pharmaceutical industry., (© 2024. The Author(s).)

The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is critical for cancer cell proliferation and immune cell phenotypes, but whether it can contribute to macrophage inflammatory responses remains unclear. In this study, we show that MTHFD2 was upregulated by LPS in murine macrophages upon activation of the TLR4-MyD88-IKKα/β-NF-κB signaling pathway. MTHFD2 significantly attenuated LPS-induced macrophage proinflammatory cytokine production through its enzymatic activity. Notably, ablation of myeloid MTHFD2 rendered mice more sensitive to septic shock and CCl4-induced acute hepatitis. Mechanistically, MTHFD2 restrained IKKα/β-NF-κB activation and macrophage inflammatory phenotype by scavenging reactive oxygen species through the generation of NADPH. Our study reveals MTHFD2 as a "self-control" mechanism in macrophage-mediated inflammatory responses., (Copyright © 2024 by The American Association of Immunologists, Inc.)