BMAL1 alleviates myocardial damage in sepsis by activating SIRT1 signaling and promoting mitochondrial autophagy.

BACKGROUND: Brain and muscle arnt-like protein-1 (BMAL1) deficiency is associated with myocardial dysfunction and suppressed sirtuin 1 (SIRT1). However, whether BMAL1 promotes mitophagy via SIRT1 to alleviate myocardial injury in sepsis remains unknown. METHODS: An in vitro myocardial injury model was established using lipopolysaccharide (LPS)-treated H9C2 cells. Knockdown or overexpression of genes was performed using plasmid transfection. Gene and protein expression was assessed by qRT-PCR and Western blot, respectively. Cell proliferation was evaluated using cell counting kit-8, and cellular apoptosis and reactive oxygen species (ROS) levels were analyzed using flow cytometry. An in vivo myocardial injury model of sepsis was established by cecal ligation and puncture in rats. Myocardial function was characterized by analyzing the damage-associated proteins, inflammatory factors, ejection fraction, and fraction shortening. RESULTS: sgBMAL1 significantly decreased BMAL1 levels and remarkably increased the sensitivity of H9C2 cells to LPS stimulation, consequently enhancing LPS-induced apoptosis, inflammation, and ROS levels. These effects were further attenuated by BMAL1 overexpression. BMAL1 knockdown inhibited the expression of SIRT1 and mitophagy-associated proteins. SIRT1 overexpression reversed the enhancement of shBMAL1 on cell proliferation and inflammation. In the rat model of sepsis, BMAL1 overexpression decreased the myocardial injury-associated proteins to recover the myocardial function and suppressed inflammatory activities by promoting mitophagy via SIRT1. CONCLUSION: BMAL1 enhances mitophagy dependent on SIRT1, thereby alleviating myocardial injury in sepsis.

Spread of antibiotic resistance genes in drinking water reservoirs: Insights from a deep metagenomic study using a curated database.

The exploration of antibiotic resistance genes (ARGs) in drinking water reservoirs is an emerging field. Using a curated database, we enhanced the ARG detection and conducted a comprehensive analysis using 2.2 Tb of deep metagenomic sequencing data to determine the distribution of ARGs across 16 drinking water reservoirs and associated environments. Our findings reveal a greater diversity of ARGs in sediments than in water, underscoring the importance of extensive background surveys. Crucial ARG carriers-specifically Acinetobacter, Pseudomonas, and Mycobacterium were identified in drinking water reservoirs. Extensive analysis of the data uncovered a considerable concern for drinking water safety, particularly in regions reliant on river sources. Mobile genetic elements have been found to contribute markedly to the propagation of ARGs. The results of this research suggest that the establishment of drinking water reservoirs for supplying raw water may be an effective strategy for alleviating the spread of water-mediated ARGs.

Influence of voluntary action and outcome valence on the sense of agency.

Recent studies have revealed that people might experience a lessened sense of agency for negative consequences by claiming that they were obeying orders. However, little is known about the cognitive neural mechanism behind the reduced sense of agency when individuals are forced to inflict physical harm on others. This study adopted temporal estimation tasks to investigate the internal mechanism of voluntary action on the sense of agency and the moderating effect of outcome valence as measured by event-related potentials (ERPs). In the temporal estimation task, participants were asked to make trade-offs of monetary gains for themselves against painful electric stimuli experienced by strangers, subjectively estimated the perceptual temporal interval between keypress actions (i.e., free or coercive actions) and consequent outcomes (i.e., positive or negative tones) and rated the feeling of control. The results showed that perceived temporal interval was shorter for positive tones compared with negative tones in the coercive condition, and induced more negative N1 and N300 amplitudes, which indicated that the implicit sense of agency was higher. However, the explicit sense of agency was stronger in the free condition than in the coercive condition, which was not influenced by outcome valence. We discuss the implications of utilizing positive feedback and free choice as significant strategies for those experiencing the abnormal sense of agency.

Correlation of HMGB1, TLR2 and TLR4 with left ventricular diastolic dysfunction in sepsis patients.

Left ventricular diastolic dysfunction (LVDD) is a common consequence of sepsis due to dysregulated inflammatory responses. Here we aim to investigate high mobility group box 1 (HMGB1), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) as serum biomarkers to assess LVDD risk of patients with sepsis. We recruited 120 patients with sepsis, among which 52 had ultrasonically confirmed LVDD and 68 were without LVDD. Blood samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to analyse levels of HMGB1, TLR2 and TLR4 in serum. Multivariate analysis was performed to assess the odds ratio of the serum biomarkers. Spearman's correlation analysis was conducted to evaluate the correlation between the serum biomarkers to B-type natriuretic peptide (BNP) and cardiac troponin I (cTnl) levels and the ratios of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e' ratios) in ultrasound. Receiver operating curve was used to measure the sensitivity and specificity of HMGB1, TLR2 and TLR4 individually and in combination as diagnostic markers. Elevated HMGB1, TLR2 and TLR4 had significant values in predicting LVDD suggested by high odds ratio (all P < .05). A significant correlation was found between these values and cTnl, the current gold standard for LVDD analysis. HMGB1, TLR2 and TLR4 also showed a high diagnostic sensitivity and specificity in ROC analysis. HMGB1, TLR2 and TLR4 are potentially valuable in predicting LVDD risk among patients with sepsis, providing additional tools with the capability of potentially assisting the clinical management of patients with sepsis.

[Effect of admission mode of septic patients in intensive care unit on acute kidney injury and prognosis].

OBJECTIVE: To investigate the effect of intensive care unit (ICU) admission model on acute kidney injury (AKI) development and the prognosis in patients with sepsis. METHODS: Patients with sepsis admitted to the ICU of Xinjiang Uygur Autonomous Region People's Hospital from January 2019 to July 2020 were retrospectively analyzed. According to the ICU admission model, the patients were divided into emergency group (first admission or emergency transfer from relevant surgical departments) and delayed group (transferred from the general ward due to disease evolution). Patients were divided into AKI group and non-AKI group according to whether AKI was accompanied. The gender, age, underlying diseases, surgical history, heart rate, laboratory test indicators, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), organ failure and acute complications were collected. The incidence of AKI, 28-day mortality and length of ICU stay were recorded. Univariate and multivariate Logistic regression was used to analyze the risk factors of AKI in patients with sepsis. RESULTS: A total of 185 patients with sepsis were enrolled, including 96 cases in the emergency group and 89 cases in the delayed group. 119 cases of AKI occurred while 66 cases without AKI development. The incidence of AKI within 7 days and the 28-day mortality of patients in the delayed group were significantly higher than those in the emergency group [AKI incidence rate: 77.53% (69/89) vs. 52.08% (50/96), 28-day mortality: 24.72% (22/89) vs. 10.42% (10/96), both P < 0.05], and the length of ICU stay was significantly longer than that of the emergency group (days: 18.70±7.29 vs. 14.56±4.75, P < 0.05). Univariate Logistic analysis showed that there were significant differences in age, diabetes, hypertension, organ failure, heart failure, APACHE II score, SOFA score, white blood cell count (WBC), absolute neutrophil value, platelet count (PLT), blood lactate, total bilirubin, and ICU transferred from general wards between AKI group and non-AKI group. Multivariate Logistic regression analysis showed that transfer from general ward to ICU due to disease evolution was an independent risk factor for AKI in ICU sepsis patients [odds ratio (OR) = 5.165, 95% confidence interval (95%CI) was 3.911-6.823, P < 0.001]. CONCLUSIONS: Septic patients transferred from general ward to ICU due to disease evolution are more likely to develop AKI, and also had a higher mortality and longer ICU stay. It may be an independent risk factor for AKI complicated by patients with sepsis in ICU.

The Neural Basis of Herding Decisions in Enterprise Clustering: An Event-Related Potential Study.

Herding behavior refers to the social phenomenon in which people are intensely influenced by the decisions and behaviors of others in the same group. Although several recent studies have explored the neural basis of herding decisions in people's daily lives (e.g., consumption decisions), the neural processing of herding decisions underlying enterprise behavior is still unclear. To address this issue, this study extracted event-related potentials (ERPs) from electroencephalographic data when participants (i.e., top executives in real enterprises) performed a choice task in which they judged whether to let their enterprises settle in an industrial zone when the occupancy rate of the industrial zone was either low or high. The behavioral results showed that participants had a higher acceptance rate in the high occupancy rate condition than in the low one, suggesting the existence of herding tendency in top executives' business decisions. The ERP results indicated that anticonformity choices induced a larger N2 amplitude than herding choices, demonstrating that participants might experience larger perceived risk and more decision conflict when they processed anticonformity choices. In contrast, we observed that herding choices induced a larger LPP amplitude than anticonformity choices, hinting that participants might experience better evaluation categorization and higher decision confidence when they processed herding choices. Based on these results, this study provides new insights into the neural basis of herding decisions made by top executives in business.

Effect of cadmium accumulation on mineral nutrient levels in vegetable crops: potential implications for human health.

Consumption of vegetables is often the predominant route whereby humans are exposed to the toxic metal Cd. Health impacts arising from Cd consumption may be influenced by changes in the mineral nutrient content of vegetables, which may occur when plants are exposed to Cd. Here, we subjected model root (carrot) and leaf (lettuce) vegetables to soil Cd concentrations of 0.3, 1.5, 3.3, and 9.6 µg g(-1) for 10 weeks to investigate the effect of Cd exposure on Cd accumulation, growth performance, and mineral nutrient homeostasis. The findings demonstrated that Cd accumulation in lettuce (20.1-71.5 µg g(-1)) was higher than that in carrot (3.2-27.5 µg g(-1)), and accumulation exceeded the maximum permissible Cd concentration in vegetables when soil contained more than 3.3 µg g(-1) of Cd. There was a marked hormetic effect on carrot growth at a soil Cd concentration of 3.3 µg g(-1), but increasing the Cd concentration to 9.6 µg g(-1) caused decreased growth in both crops. Additionally, in most cases, there was a positive correlation between Cd and the mineral nutrient content of vegetables, which was due to physiological changes in the plants causing increased uptake and/or translocation. This may suggest a general mechanism whereby the plant compensated for disrupted mineral nutrient metabolism by increasing nutrient supply to its tissues. Increased nutrient levels could potentially offset some risks posed to humans by increased Cd levels in crops, and we therefore suggest that changes in mineral nutrient levels should be included more widely in the risk assessment of potentially toxic metal contamination. Graphical abstract The Cd concentration (µg g-1 in dry matter) in the root, shoot and translocation factor (TF) of Cd from root to shoot in the carrot and lettuce, and the percentage of root Cd to the gross Cd contents (%) in carrot (C) and lettuce (D) exposed to soil Cd (0 (control), 1, 3, and 9 µg g-1) for 70 days. Values are means ± SD (n = 5).