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Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine’s protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis.

BackgroundSepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear.MethodsGenetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes.ResultsOur MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype.ConclusionOur MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.

Cognitive impairment is an important component of non motor symptoms in Parkinson's disease (PD), and if not addressed in a timely manner, it can easily progress to dementia. However, no effective method currently exists to completely prevent or reverse cognitive impairment associated with PD. We therefore aimed to investigate the therapeutic effect of near-infrared region II light (NIR-II) region illumination on cognitive impairment in PD through behavioral experiments (water maze and rotary rod) and multiple fluorescence immunohistochemistry techniques. The 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced group was compared with the MPTP- untreated rat group, showing a significant reduction in escape latency and significant increase in the fall latency in the MPTP-treated group. The horizontal analysis results indicated that NIR-II phototherapy improved the learning and cognitive abilities as well as coordination and balance abilities of rats. Post-treatment, the MPTP rats showed significantly shortened, escape latency, prolonged target quadrant residence time, and prolonged fall latency compared with pre-treatment. The longitudinal analysis results reaffirmed that NIR-II phototherapy improved the learning and cognitive abilities as well as coordination and balance abilities of rats. The multiple fluorescence immunohistochemistry analysis trend plot showed that the activated microglia and astrocytes in the hippocampus were highest in MPTP-induced PD untreated group, moderate in MPTP-induced PD treatment group, and lowest in the control group. Our data indicates that NIR-II illumination improves learning and cognitive impairment as well as coordination and balance abilities in PD rats by downregulating the activation of microglia and astrocytes in the hippocampus.

BackgroundAcute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.MethodsEmploying a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.ResultsOur investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis.ConclusionThis study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Large volumes of Early Mesozoic intermediate to basic igneous rocks related to the evolution of the Paleo-Tethys Ocean are exposed in the East Kunlun Orogenic Belt (EKOB). The petrography, geochemistry, and results of zircon U-Pb dating of Defusheng intermediate to basic rocks from the eastern segment of the EKOB are presented in this report. Zircon U–Pb dating of the intermediate to basic rocks yields ages of 239–245 Ma (Middle Triassic). Defusheng intermediate to basic rocks have low TiO2 contents (0.80–1.47 wt.%) and widely varying MgO (3.14–6.08 wt.%), and are enriched in large ion lithophile elements and light rare earth elements, having a geochemical composition similar to that of island arc basalts. The variation diagrams of major elements indicate that the Defusheng intermediate to basic rocks underwent fractional clinopyroxene and olivine crystallization. Depletion of the high-field-strength elements Nb, Ta, and Ti may have been caused by the mantle wedge having been infiltrated by fluids derived from the subducted slab. The Defusheng intermediate to basic rocks represent magmatic records of the Early Mesozoic oceanic crust subduction in Eastern Kunlun. This indicates that the final closure of the Paleo-Tethyan Ocean and the beginning of collisional orogeny occurred after the Middle Triassic.

To ensure the accuracy of state of charge (SOC) and state of health (SOH) estimation for battery packs while minimizing the amount of pre-experiments required for aging modeling and the scales of computation for online management, a decisive-cell-based estimation method with training-free characteristic parameters and a dynamic-weighted estimation strategy is proposed in this paper. Firstly, to reduce the computational complexity, the state estimation of battery packs is summed up to that of two decisive cells, and a new selection approach for the decisive cells is adopted based on the detection of steep voltage changes. Secondly, two novel ideas are implemented for the state estimation of the selected cells. On the one hand, a set of characteristic parameters that only exhibit local curve shrinkage with aging is chosen, which keeps the corresponding estimation approaches away from training. On the other hand, multiple basic estimation approaches are effectively combined by their respective dynamic weights, which ensures the estimation can maintain a good estimation accuracy under various load profiles. Finally, the experimental results show that the new method can quickly correct the initial setting deviations and have a high estimation accuracy for both the SOC and SOH within 2% for a series battery pack consisting of cells with obvious inconsistency.

Drought and salt stresses, the major environmental abiotic stresses in agriculture worldwide, affect plant growth, crop productivity, and quality. Therefore, developing crops with higher drought and salt tolerance is highly desirable. This study reported the isolation, biological function, and molecular characterization of a novel maspardin gene, OsMas1, from rice. The OsMas1 protein was localized to the cytoplasm. The expression levels of OsMas1 were up-regulated under mannitol, PEG6000, NaCl, and abscisic acid (ABA) treatments in rice. The OsMas1 gene was introduced into the rice cultivar Zhonghua 11 (wild type, WT). OsMas1-overexpression (OsMas1-OE) plants exhibited significantly enhanced salt and drought tolerance; in contrast, OsMas1-interference (OsMas1-RNAi) plants exhibited decreased tolerance to salt and drought stresses, compared with WT. OsMas1-OE plants exhibited enhanced hypersensitivity, while OsMas1-RNAi plants showed less sensitivity to exogenous ABA treatment at both germination and post-germination stages. ABA, proline and K+ contents and superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and photosynthesis activities were significantly increased. In contrast, malonaldehyde (MDA), hydrogen peroxide (H2O2), superoxide anion radical (O2-·), and Na+ contents were significantly decreased in OsMas1-OE plants compared with OsMas1-RNAi and WT plants. Overexpression of OsMas1 up-regulated the genes involved in ABA signaling, proline biosynthesis, reactive oxygen species (ROS)-scavenging system, photosynthesis, and ion transport under salt and drought stresses. Our results indicate that the OsMas1 gene improves salt and drought tolerance in rice, which may serve as a candidate gene for enhancing crop resistance to abiotic stresses.

Background: As the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surges amid the coronavirus disease 2019 (COVID-19) pandemic, there is limited comorbidities data associated with viral shedding time (VST). We aimed to investigate the effect of comorbidities on VST in asymptomatic and mild patients with omicron. Methods: A multi-center, retrospective, observational study was conducted from March 12, 2022 to May 24, 2022 in Shanghai. The analysis was adjusted for patients’ baseline demographic, using log-rank test and logistic regression model. Results: The study enrolled 198,262 subjects. The median duration of viral shedding time (VST) was 8.29 days. The number of cumulative viral shedding events was significantly lower in the chronic obstructive pulmonary disease (COPD), hyperlipidemia, diabetes, urinary system disease, and cardiocerebrovascular disease than in the no corresponding comorbidities group. Patients with comorbidities had a lower incidence of viral shedding, and the most significant independent risk factor is COPD (aOR 1.78, 95% CI: 1.53–2.08, p

The simultaneous high-capacity and fast removal of radioactive barium ion (Ba2+) from nuclear wastewater is necessary but still faces large challenge. In this study, a novel adsorbent containing sulfonic group, MOF-808-SO3H, was prepared based on the oxidation of –SH group. Characterizations confirm the successful introduction of –SO3H, good porosity, and stability of the material. The adsorbent exhibits excellent capture ability for Ba2+ due to strong hard acid-base and electrostatic interactions, with the adsorption capacity of 152.0 mg g−1 and fast equilibrium adsorption time, superior to other reported materials. Optimal pH was found to be almost neutral and temperature cannot affect the adsorption largely. Besides, the irreversible adsorption was demonstrated and thereby the secondary pollution may be avoided. Therefore, our work provides an efficient adsorbent for capturing Ba2+ irreversibly, and proposes a feasible strategy for constructing adsorbents with simultaneous high adsorption capacity and fast kinetics.

Crop growth stages are integral components of plant phenology and are of significant ecological and agricultural importance. While the use of remote sensing methods for phenology identification in cropland ecosystems has been extensively explored in previous studies, the focus has often been on land surface phenology, primarily related to the start and end of the growing season. In contrast, the monitoring of crop growth within an agronomic framework has been limited, particularly in the context of recently developed solar-induced chlorophyll fluorescence (SIF) data. Additionally, some critical growth stages have not received adequate attention or evaluation. This study aims to assess the utility of SIF data, collected from both ground and satellite measurements, for identifying critical crop growth stages within the realm of remote sensing phenological estimation. A comparative analysis was conducted using enhanced vegetation index (EVI) data at the Shangqiu site in the North China Plain from 2018 to 2022. Both SIF and EVI time-series data, obtained from ground and satellite sources, undergo a comprehensive phenological estimation framework encompassing pre-processing, modeling, and transition characterization. This approach involves reconciling time-series phenological patterns with crop growth stages, revealing the necessity of redefining the mapping relationship between these two fundamental concepts. After preprocessing the time-series data, the framework incorporates the phenological modeling process employing two double logistic models and a spline model for comparison. Additionally, it includes phenological transition characterization using four different methods. Consequently, each input dataset undergoes an assessment, resulting in 12 sets of estimations, which are compared to select the ideal estimation portfolio for identifying the growth stages of maize and winter wheat. Our findings highlight the efficacy of SIF data in accurately identifying the growth stages of maize and winter wheat, achieving remarkable results with an R-square exceeding 0.9 and an RMSE of less than 1 week for key growth stages (KGSs). Notably, SIF data demonstrate superior accuracy, robustness, and sensitivity to phenological events when compared to EVI data. This study establishes an estimation portfolio utilizing SIF data, involving the Gu model, a double logistic model, as the preferred phenological modelling method together with various compositing methods and transition characterization methods, suitable for most KGSs. These findings create opportunities for future research aimed at enhancing and standardizing crop growth stage identification using remote sensing data for a wide range of KGSs.

The lack of innovative standards for biosafety in synthetic biology is an unresolved policy gap that limits many potential applications in synthetic biology. We argue that a massive support for standardization in biosafety is required for synthetic biology to flourish.

Background: Evidence indicates that chronic stress promotes progression of colorectal liver metastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood. Methods: To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-α) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy. Results: CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-β1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM. Conclusion: MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.

Abstract The third isoform of the Na+–Ca2+ exchanger (NCX3) is crucial for a physiological fine-tuning of the Ca2+ fluxes in excitable tissues. In this view, the NCX3 accounts for the aberrant Ca2+ influx seen during neuronal excitotoxicity, such as in Alzheimer’s disease (AD). However, little is known about NCX3 regulation and functional properties. Withania somnifera (L.) Dunal (W. somnifera), a traditional indigenous plant widely recognized for having numerous medicinal values, was undertaken to determine its potential therapeutic benefit against aggregated Aβ1–42-induced NCX3 dysregulation and the thereof cognition impairment in 5xFAD mice. The undertaken sourced dried roots of authenticated W. somnifera physicochemical compositional tests satisfied standards of pharmacognostic quality, and further phytochemical analysis of the roots methanol extract revealed the roots constitute several antioxidants. Following an intra-gastric gavage administration of synthesized W. somnifera roots methanolic extract from postnatal day 30 (P30) to P75, in vivo cognitional studies and then neurochemical examinations of the NCX3 expression level, Aβ plaque deposition, and antioxidant activities in the AD-associated brain regions of 4-month-old 5xFAD mice suggests that the oxidative stress normalizing effects of W. somnifera constituents, operating on the NCX3, may have a therapeutic role in the improvement of cognition in AD.