Search

Abstract A light (GeV mass) long-lived (cτ around dozens of millimeters) CP-odd scalar can be readily predicted in new physics models. In this work we investigate the Higgs decay into such a light scalar plus a Z-boson and take the aligned two-Higgs-doublet model (2HDM) as an example. This light long-lived scalar, with the dominant decay to tau leptons, will fly over a distance from the production point and present a displaced vertex in an Inner Detector of a generally purposed experiment like ATLAS or CMS. In our study we focus on the LHC experiment and perform Monte Carlo simulations for the signal and backgrounds. We demonstrate some benchmark points for the aligned 2HDM and find the signal to be detectable when the luminosity is accumulated to 300 fb −1. So our study suggests an experimental search for this process in the ongoing LHC.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging global infectious disease with a high mortality rate. Clinicians lack a convenient tool for early identification of critically ill SFTS patients. The aim of this study was to construct a simple and accurate nomogarm to predict the prognosis of SFTS patients. Methods We retrospectively analyzed the clinical data of 372 SFTS patients collected between May 2015 and June 2023, which were divided 7:3 into a training set and an internal validation set. We used LASSO regression to select predictor variables and multivariable logistic regression to identify independent predictor variables. Prognostic nomograms for SFTS were constructed based on these factors and analysed for concordance index, calibration curves and area under the curve (AUC) to determine the predictive accuracy and consistency of the model. Results In the training set, LASSO and multivariate logistic regression analyses showed that age, SFTSV RNA, maximum body temperature, pancreatitis, gastrointestinal bleeding, pulmonary fungal infection (PFI), BUN, and PT were independent risk factors for death in SFTS patients. There was a strong correlation between neurological symptoms and mortality (P

Abstract Pantropical climate interactions across ocean basins operate on a wide range of timescales and can improve the accuracy of climate predictions. Here, we show in observations that Central Pacific (CP) El Niño-like sea surface temperature (SST) anomalies have coevolved with tropical South Atlantic SST anomalies on a quasi-decadal (~10-year) timescale over the past seven decades. During the austral autumn–winter season, decadal warm SSTs in the tropical CP effectively induce tropical SST cooling in the South Atlantic, mainly by strengthening the South Atlantic subtropical anticyclone via an extratropical atmospheric wave teleconnection in the southern hemisphere. Partially coupled pacemaker simulations corroborate the observational findings, indicating that tropical CP decadal SSTs play a primary pacing role, while Atlantic feedback is of secondary importance throughout the study period. Our results suggest that the tropical CP could be an important source of decadal predictability for tropical South Atlantic SST and the surrounding climate.

Objective: To investigate the protective effect of fermented Lycium barbarum polysaccharides (FLBP) on the intestine in an aging mouse model. Methods: The aging model was established by continuous subcutaneous injection of 1 000 mg/(kg mb · d) D-galactose in the back of the neck, followed by gavage of low (150 mg/(kg mb · d)) and high (300 mg/(kg mb · d)) doses of FLBP. After 10 weeks, body mass, organ indexes, serum inflammatory markers and anti-inflammatory indicators including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 levels, intestinal permeability, intestinal barrier damage biomarkers such as lipopolysaccharide (LPS) and lipopolysaccharide binding protein (LBP) contents, the histological structure of the colon, colonic mucin 2 (Muc2) expression, intestinal flora composition and fecal short-chain fatty acid contents were detected and analyzed. Results: High-dose FLBP antagonized D-galactose-induced growth retardation and thymus atrophy, decreased the serum levels of TNF-α, IL-1β and IL-6 and significantly increased serum IL-10 levels in the aging mice (P < 0.05). Furthermore, FLBP significantly ameliorated colonic barrier damage in mice, as evidenced by a significant decrease in intestinal permeability, LPS and LBP contents (P < 0.05), alterations in colonic tissue structure, and a significant increase in MUC2 secretion (P < 0.05). Meanwhile, FLBP regulated the gut microbiota composition by changing the α- and β-diversity, increasing the relative abundance of the beneficial bacteria norank_f_Muribaculaceae and Lactobacillus, and decreasing the relative abundance of the harmful bacteria Atopostipes and Jeotgalicoccus, and increasing the fecal contents of acetic acid, propionic acid, valeric acid and isobutyric acid significantly (P < 0.05). Conclusion: High-dose FLBP reduced circulating pro-inflammatory cytokine levels and enhanced anti-inflammatory function in aging mice, which might be related to improving colonic barrier function, regulating the intestinal flora composition, and increasing the levels of beneficial SCFAs in the intestinal tract of mice. This study provides a theoretical reference for the application of FLBP as a functional food ingredient for intestinal health.

Abstract More recently, increased studies have revealed that antioxidants can cure osteoporosis by inhibiting oxidative stress. Tauroursodeoxycholic acid (TUDCA) and Selenium (Se) have been confirmed to possess potent anti-oxidative effects and accelerate bone regeneration. In addition, very little is currently known about the effects of a combination with Se and TUDCA on bone defects in osteoporotic states. We, therefore, aimed to assess the protective effect of combination with Se and TUDCA on bone regeneration and investigate the effect and underlying mechanisms. When MC3T3-E1 was cultured in the presence of H2H2, Se, TUDCA and Se/TUDCA therapy could increase the matrix mineralization and promote expression of anti-oxidative stress markers in MC3T3-E1, while reducing intracellular reactive oxygen species (ROS) and mitochondrial ROS levels. Meanwhile, silent information regulator type 1 (SIRT1) was upregulated in response to Se, TUDCA and Se/TUDCA exposures in H2H2 treated-MC3T3-E1. In the OVX rat model, Se, TUDCA and Se/TUDCA showed a clear positive effect against impaired bone repair in osteoporosis. The results above demonstrate that Se/TUDCA exhibits superior efficacy in both cellular and animal experiments, as compared to Se and TUDCA. In conclusion, combination with Se and TUDCA stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis. Graphical abstract The release of TUDCA and Se during the degradation of Se/TUDCA can improve the local bone repair ability. At the same time, it can also inhibit cell ROS, and ultimately greatly promote local bone repair.

Abstract Analysing non-stationarity in runoff and sediment load is crucial for effective water resource management in the Dongting Lake basin amid climate change and human impacts. Using the Mann-Kendall test, Generalized Additive Models for Location, Scale, and Shape framework, and Random Forest models, we evaluated non-stationarity and its drivers in the annual runoff and annual sediment load series at eight hydrological stations from 1961 to 2021. These stations include three inflow sites at the Jingjiang Three Outlets (Ouchi, Songzi, and Hudu Rivers), four inflow sites in the Four Rivers basin (Xiang, Zi, Yuan, and Li Rivers), and one outflow site at Chenglingji. Results revealed a significant decrease in annual runoff at the Three Outlets and Chenglingji, while the Four Rivers basin showed no significant trend. The non-stationary models with multiple physically-based covariates better captured non-stationarity compared to single covariate models. Annual rainfall was a key contributor to annual runoff in the Four Rivers basin, while reservoir storage capacity played a more dominant role in the Three Outlets. At Chenglingji station, both factors significantly influenced annual runoff. For annual sediment load, reservoir storage capacity emerged as the most critical factor across all regions. These findings provide a basis for improving runoff and sediment regulation in the Dongting Lake basin.

The family Proalidae Harring & Myers, 1924, includes four genera and 53 species, distributed across all eight biogeographic realms and inhabiting various environments, including freshwater, saltwater and terrestrial environments. The genus Proales, the largest within Proalidae, encompasses 41 species characterised by diverse morphological traits. In Korea, the presence of Proalidae has been documented with five known species: Bryceella perpusilla Wilts, Martínez Arbizu & Ahlrichs, 2010, B. stylata (Milne, 1886), B. tenella (Bryce, 1897), Proales fallaciosa Wulfert, 1937 and Proalinopsis caudatus (Collins, 1872).A new species, Proales amplus sp. nov., is the 42nd species within the genus Proales. This species exhibits unique morphological characteristics in the trophi, particularly in the epipharynx, which are distinctive enough to prevent misidentification with other Proales species. The habitus of the new species bears some resemblance to P. phaeopis Myers, 1933, sharing features, such as an elongated and fusiform body, two eyespots, a single foot pseudosegment, two short toes and the absence of a dorsal papilla between the toes. However, the epipharynx of the two species is markedly different. The unique epipharynx characteristic of this new species is unparalleled within the genus Proales.

Abstract Purpose The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. Methods Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed. Results In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P

Abstract The Atlantic Niño, a primary climatic variability mode in the equatorial Atlantic Ocean, exhibits pronounced variability not only in boreal summer but also in winter. However, the role of the winter Atlantic Niño in trans-basin interactions remains underexplored compared to its summer counterpart. Through analysis of observational reanalysis data since the mid-twentieth century, here we found that the winter Atlantic Niño significantly influences the development of El Niño–Southern Oscillation (ENSO), surpassing the impact of summer Atlantic Niño, with a longer lead time. This effect is reasonably captured in the CMIP6 Historical simulations from a multi-model ensemble perspective. Further analysis of the global warming scenario projects that the influence of winter Atlantic Niño on ENSO will persist into the future, in contrast to the reduced impact of summer Atlantic Niño. Therefore, these findings underscore the importance of further investigating the winter Atlantic Niño to gain a comprehensive understanding of trans-basin interactions and their future changes.

Abstract The Hewlett Packard Enterprise–Cray EX Frontier is the world’s first and fastest exascale supercomputer, hosted at the Oak Ridge Leadership Computing Facility in Tennessee, United States. Frontier is a significant electricity consumer, drawing 8–30 MW; this massive energy demand produces significant waste heat, requiring extensive cooling measures. Although harnessing this waste heat for campus heating is a sustainability goal at Oak Ridge National Laboratory (ORNL), the 30 °C–38 °C waste heat temperature poses compatibility issues with standard HVAC systems. Heat pump systems, prevalent in residential settings and some industries, can efficiently upgrade low-quality heat to usable energy for buildings. Thus, heat pump technology powered by renewable electricity offers an efficient, cost-effective solution for substantial waste heat recovery. However, a major challenge is the absence of benchmark data on high-performance computing (HPC) heat generation and waste heat profiles. This paper reports power demand and waste heat measurements from an ORNL HPC data centre, aiming to guide future research on optimizing waste heat recovery in large-scale data centres, especially those of HPC calibre.

Abstract Background Our previous study has demonstrated a decreased colonic CD8+CD39+ T cells, enrichment of granzyme A (GZMA), was found in pediatric-onset colitis and inflammatory bowel disease (IBD) characterized by impaired intestinal barrier function. However, the influence of GZMA on intestinal barrier function remains unknown. Methods Western blotting(WB), real-time PCR (qPCR), immunofluorescence (IF) and in vitro permeability assay combined with intestinal organoid culture were used to detect the effect of GZMA on intestinal epithelial barrier function in vivo and in vitro. Luciferase, immunoprecipitation (IP) and subcellular fractionation isolation were performed to identify the mechanism through which GZMA modulated intestinal epithelial barrier function. Results Herein, we, for the first time, demonstrated that CD8+CD39+ T cells promoted intestinal epithelial barrier function through GZMA, leading to induce Occludin(OCLN) and Zonula Occludens-1(ZO-1) expression, which was attributed to enhanced CDX2-mediated cell differentiation caused by increased glutathione peroxidase 4(GPX4)-induced ferroptosis inhibition in vivo and in vitro. Mechanically, GZMA inhibited intestinal epithelial cellular PDE4B activation to trigger cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation, initiating GPX4 transactivity. In addition, endogenous PKA interacted with CREB, and this interaction was enhanced in response to GZMA. Most importantly, administration of GZMA could alleviate DSS-induced colitis in vivo. Conclusion These findings extended the novel insight of GZMA contributed to intestinal epithelial cell differentiation to improve barrier function, and enhacement of GZMA could be a promising strategy to patients with IBD.

The focus of this article lies in the existence of global mild solutions for Hilfer fractional stochastic evolution equations (HFSEEs) on the positive semi-axis (0,+∞) with a derivative order greater than 32 and less than 2. A significant challenge, which also presents novelty here, is to extend the generalized Ascoli–Arzela (A–A) theorem established in Zhou and He (2022) to the stochastic case under the associated sine family {S(t)}t≥0 not necessary compact. Then, by relying on our newly established generalized A–A theorem, standard stochastic analysis theory and Schauder’s fixed point principle, we derive the existence of global mild solutions for the addressed system. Finally, we demonstrate the feasibility of our obtained results through an illustrative example.

[Objective] Energy transition is a key path to achieving China’s carbon peaking and carbon neutrality goals, and exploring the impact of energy transition on the urban-rural income gaps can provide a scientific basis for realizing equity in the transition. [Methods] Based on the panel data of 108 cities at the prefecture level and above in the Yangtze River Economic Belt from 2010 to 2020, this study employed spatial analysis and fixed-effects model to analyze the characteristics of the temporal and spatial change of energy transition and urban-rural income gaps, and to reveal the correlation between the two and their regional heterogeneity of this relationship. [Results] (1) The performance level of energy transition of cities in the Yangtze River Economic Belt shows an overall upward trend, and the energy transition index values of provincial capital cities has remained at a high level for a long time. At the same time, urban-rural income gaps have been narrowing year by year, showing a pattern of high in the west and low in the east. (2) The relationship between energy transition and urban-rural income gaps in cities in the Yangtze River Economic Belt was U-shaped. With the improvement of the performance level of energy transition, urban-rural income gaps showed the characteristic of decreasing and then increasing. (3) There was a significant difference in the relationship between energy transition and urban-rural income gaps in cities in the upper, middle, and lower reaches of the Yangtze River, with the upstream showing an inverted U-shaped relationship and the middle reaches showing a U-shaped relationship, and the downstream showing no significant correlation. This suggests that the energy transition paths of cities in the upstream region were gradually moving towards a fair direction, while the opposite was true in the midstream region, and that urban and rural residents in the downstream region were less sensitive to the socioeconomic effects caused by energy transition. [Conclusion] Therefore, diversified energy transition policies should be formulated in accordance with the actual development of the upstream, midstream and downstream, so as to effectively prevent the negative impacts of the transition and actively promote the just energy transition and the balanced development of urban and rural regions.

Iron is essential in various life processes, and its imbalance is closely related to disorders in multiple systems such as the nervous, cardiovascular, and immune systems, as well as many chronic diseases such as infections and cancer. Therefore, accurately assessing the status of iron in the body is of great significance for both basic and clinical research. The gold standard for iron status is still bone marrow stainable iron, but its actual application is very limited due to its invasive sampling and high cost. Other traditional biomarkers such as serum iron, ferritin, and related composite indicators are all affected to varying degrees by factors such as inflammation, age, and circadian fluctuations, but they also have their own suitable application scenarios. However, biomarkers that can fully assess iron status are far from perfect, leading to inaccurate diagnosis and treatment of iron imbalance in many cases. Although new biomarkers such as hepcidin, reticulocyte hemoglobin content, and erythroferrone have emerged, and with the rapid advancement of high-throughput technologies, multi-omics may help diagnose iron status in the future, more exploration and mining are still needed to expand the widespread and rational application of these potential markers. This article reviews the research progress of iron biomarkers, aiming to provide more references and directions for future related research.

Pattern recognition is critical to map data handling and their applications. This study presents a model that combines the Shape Context (SC) descriptor and Graph Convolutional Neural Network (GCNN) to classify the patterns of interchanges, which are indispensable parts of urban road networks. In the SC-GCNN model, an interchange is modeled as a graph, wherein nodes and edges represent the interchange segments and their connections, respectively. Then, a novel SC descriptor is implemented to describe the contextual information of each interchange segment and serve as descriptive features of graph nodes. Finally, a GCNN is designed by combining graph convolution and pooling operations to process the constructed graphs and classify the interchange patterns. The SC-GCNN model was validated using interchange samples obtained from the road networks of 15 cities downloaded from OpenStreetMap. The classification accuracy was 87.06%, which was higher than that of the image-based AlexNet, GoogLeNet, and Random Forest models.

Abstract Background The utilization of ultrapure dialysate has been shown to decrease dialysate contamination and mitigate inflammatory responses. The central dialysate delivery system (CDDS) has the potential to attain a level of purity similar to ultrapure dialysate. Nevertheless, there is limited research examining the impact of CDDS on inflammation in comparison to single-patient dialysis fluid delivery system(SPDDS). This study aims to investigate the effects of CDDS utilizing ultrapure dialysate on ameliorating the microinflammatory state in hemodialysis patients. Method A retrospective cohort clinical study enrolled a total of 125 hemodialysis patients, with 58 patients from the CDDS unit and 67 patients from the SPDDS unit. Each participant was monitored for a period of 6 months, and the repeated measurement data was analyzed using a generalized linear mixed models (GLMM). Results The average age of the studty cohort was 56.22 ± 12.64 years. The GLMM analysis showed a significant time*group interaction effect on hs-CRP changes over the follow-up period (β = -1.966, FTime* CDDS group = 13.389, P

Abstract Background The Medium and Long-Term Plan for the Prevention and Treatment of Chronic Diseases (2017–2025) in China has highlighted the importance of reducing fat, sodium, and sugar in foods. However, front-of-pack labeling, which enables consumers to assess the health levels of prepackaged foods, is lacking in China. In response to the Zhejiang Provincial Health Commission’s request, we sought to develop a method for efficiently evaluating the health level of prepackaged foods. Methods Through a comprehensive literature review, we established a systematic framework: the Prepackaged Foods Healthiness Ranking Index (PHRI). We determined specific threshold values and grading criteria and conducted two rounds of Delphi survey to refine the index. Using a measurement dataset, we aimed to determine the optimal limit values for assessing the health level of prepackaged foods in real-world settings. Results After two rounds of Delphi surveys, the PHRI underwent multiple revisions until consensus among experts was reached. The final decision regarding the upper limit values set 30% Nutrient Reference Values as the limit for solid foods and 15% Nutrient Reference Values for liquid foods. The calculation of PHRI values was successfully implemented with the dataset, in accord with current nutrition awareness and real-world conditions. Conclusions The PHRI provides a valuable tool for assessing the healthiness of prepackaged foods. This front-of-pack labeling system provides a convenient method for evaluating the nutritional quality of prepackaged foods. Ultimately, the PHRI has the potential to contribute to advancements in health policy, practice, and education in China.

Abstract Determination of high sulfur content in sulfide minerals is crucial for various applications, including geochemistry, mining, and environmental monitoring. While inductively coupled plasma optical emission spectrometry (ICP-OES) is the preferred method for sulfur analysis, conventional sample preparation techniques often fall short when dealing with high sulfur concentrations. This study investigated optimized digestion conditions for accurate sulfur determination in sulfide minerals using ICP-OES. We employed anti-corrosion acid digestion bombs, an aqua regia–hydrofluoric acid system, and a digestion temperature of 180 °C, achieving exceptional results. Certified reference material recoveries ranged from 99.9 to 100.5%, with relative standard deviations between 0.42 and 0.84%. These results demonstrate the high accuracy and precision of the method. The optimized digestion protocol presented in this study provides a robust and reliable approach for accurate sulfur analysis in sulfide minerals, particularly for high concentrations.

The human leukocyte antigen (HLA) system, which is part of the major histocompatibility complex (MHC) plays a vital role in immune responses by differentiating between itself and foreign cells and antigens. The significant diversity of alleles affects disease susceptibility and immune responses within different populations. Specifically, the HLA-A and HLA-DRB1 alleles are associated with various immune-related diseases, and understanding the frequency and haplotype associations of these alleles is vital for genetic and immunological research. To investigate the distribution of these characteristics in Koreans, we isolated peripheral blood mononuclear cells (PBMCs) from blood samples donated by volunteers at the Seoul Central Blood Bank and performed HLA typing on 790 samples. Our study found that the HLA-A and HLA-DRB1 alleles are widely distributed within the Korean population, with HLA-A*24:02 (21.7%) and HLA-DRB1*09:01 (9.9%) being the most frequent. Significant haplotype associations between specific HLA-A and HLA-DRB1 alleles were identified using the Chi-square test, suggesting that certain genetic combinations may influence disease onset. This insight could contribute to the development of predictive and preventative strategies for various diseases. The unique genetic characteristics of the Korean population highlight the importance of studying the HLA allele and the haplotype distributions in this group as key indicators for understanding disease susceptibility.

Buckwheat and other grains have become influential in sustainable agriculture and food security owing to climate change. However, subpar storage conditions can result in the deterioration of the nutritional value and active components of buckwheat, making storage quality a significant research subject. This study examined common buckwheat (CB) and Tartary buckwheat (TB) stored at 4 °C, 30 °C, and 55 °C from 0 to 6 months to assess storage quality and its relationship to the preservation of active components. The results of agglomerative hierarchical clustering (AHC) and principal component analysis (PCA) showed that as storage temperature and time increased, both CB and TB exhibited the following differences: significant alterations in color due to an increase in browning index (B.I.), higher acidity from accelerated acid production at high temperatures, and a decrease in total phenolics, flavonoid content, and antioxidant capacity due to thermal degradation of functional components. In the storage quality assessment, no alteration in microstructure or degradation in components was detected after exposure to all times and temperatures, and the content of the primary bioactive compound, rutin, was CB (16.57–27.81 mg/100 g d.w.) and TB (707.70–787.58 mg/100 g d.w.), demonstrating buckwheat’s resistance to microbial contamination. Storage temperature significantly impacts buckwheat’s quality and bioactive components, making it an important element in establishing a sustainable food supply chain.

Objective To explore the influencing factors of incision infection in elderly patients with traumatic limb fracture after surgery, and to construct a nomographic model. Methods A total of 360 elderly patients with traumatic limb fracture who received surgical treatment in the First Affiliated Hospital of Chengdu Medical College from May 2021 to September 2023 were selected as the study subjects and divided into the modeling group (n = 252) and the verification group (n = 108) by the computer random number table. LASSO regression and logistic regression were used to analyze the influencing factors of postoperative incision infection, and column line diagrams were constructed according to the influencing factors, and the predictive performance and effect of the risk prediction model were evaluated by ROC curve and calibration curve. Results Twenty-seven research variables were included in the LASSO regression model for screening, and two models were constructed based on minimum values and standardization. Model 1 included 12 variables, including body mass index (BMI), use of steel plate, diabetes, drainage tube placement time, incision type, operation time, incision length, the ratio of peripheral blood C-reactive protein to albumin (CAR), serum procalcitonin (PCT)/albumin (ALB), interleukin-6 (IL-6), neutrophil to lymphocyte ratio (NLR), and serum erythrocyte sedimentation rate (ESR) three days after operation. Seven variables were included in model 2, including diabetes, drainage tube placement time, and peripheral blood CAR, PCT/ ALB, IL-6, NLR, ESR 3 days after surgery. The logistic regression analysis models were constructed with the dependent variable of whether the incision infection occurred after surgery, and the variables screened by LASSO regression in model 1 and model 2 as independent variables. The results of model 1 showed that BMI ≥28 kg/ m2, combined with diabetes, incision type Ⅲ, operation time, incision length, use of steel plate, placement time of drainage tube ≥ 6 days, and peripheral blood CAR, PCT/ ALB, IL-6, NLR, ESR 3 days after surgery were independent risk factors for postoperative incision infection in elderly patients with traumatic limb fracture (P < 0.05) . The results of model 2 showed that the combination of diabetes, the placement time of drainage tube ≥6 days and the peripheral blood CAR, PCT/ ALB, IL-6, NLR, ESR 3 days after operation were independent risk factors for postoperative incision infection in elderly patients with traumatic limb fracture (P < 0.05) . The area under the ROC curve of Model 1 in the modeling and validation groups was respectively 0.949 (95% CI: 0.898 - 1.000) and 0.981 (95% CI: 0.956 - 1.000), respectively. The results of the Hosmer Lemeshow test for Model 1 in the modeling and validation groups showed that the model did not deviate from a perfect fit, and the consistency of the calibration curve was good. The area under the ROC curve of Model 2 in the modeling and validation groups was respectively 0.882 (95% CI: 0.787 - 0.977) and 0.921 (95% CI: 0.843 - 1.000), respectively. Furthermore, the Hosmer Lemeshow test of Model 2 in the modeling and validation groups showed that the model deviated from a perfect fit and the consistency of the calibration curve was poor. Conclusion BMI, combined diabetes, incision type, operation time, incision length, use of steel plate, placement time of drainage tube, CAR, PCT/ ALB, IL-6, NLR and ESR of peripheral blood 3 days after operation are the influencing factors of postoperative incision infection in elderly patients with traumatic limb fracture.

Abstract Background Although the patient survival rate for many malignancies has been improved with immune checkpoint inhibitors (ICIs), some patients experience various immune-related adverse events (irAEs). IrAEs impact several organ systems, including the kidney. With anti-programmed cell death protein 1 (PD-1) therapy (pembrolizumab), kidney-related adverse events occur relatively rarely compared with other irAEs. However, the occurrence of AKI usually leads to anti-PD-1 therapy interruption or discontinuation. Therefore, there is an urgent need to clarify the mechanisms of renal irAEs (R-irAEs) to facilitate early management. This study aimed to analyse the characteristics of peripheral blood mononuclear cells (PBMCs) in R-irAEs. Methods PBMCs were collected from three patients who developed R-irAEs after anti-PD-1 therapy and three patients who did not. The PBMCs were subjected to scRNA-seq to identify cell clusters and differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses were performed to investigate the most active biological processes in immune cells. Results Fifteen cell clusters were identified across the two groups. FOS, RPS26, and JUN were the top three upregulated genes in CD4+ T cells. The DEGs in CD4+ T cells were enriched in Th17 differentiation, Th1 and Th2 cell differentiation, NF-kappa B, Nod-like receptor, TNF, IL-17, apoptosis, and NK cell-mediated cytotoxicity signaling pathways. RPS26, TRBV25-1, and JUN were the top three upregulated genes in CD8+ T cells. The DEGs in CD8+ T cells were enriched in Th17 cell differentiation, antigen processing and presentation, natural killer cell-mediated cytotoxicity, the intestinal immune network for IgA production, the T-cell receptor signalling pathway, Th1 and Th2 cell differentiation, the phagosome, and cell adhesion molecules. Conclusions In conclusion, R-irAEs are associated with immune cell dysfunction. DEGs and their enriched pathways identified in CD4+ T cells and CD8+ T cells play important roles in the development of renal irAEs related to anti-PD-1 therapy. These findings offer fresh perspectives on the pathogenesis of renal damage caused by anti-PD-1 therapy.

Abstract Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.

Abstract Purpose This study aimed to develop a Quality of Life (QOL) assessment scale for older patients with Neuro-co-Cardiological Diseases (NCCD) and to evaluate the reliability and validity of the scale. Method The study participants were derived from the Elderly Individuals with NCCD Registered Cohort Study (EINCCDRCS), a multicenter registry of patients with NCCD. The preliminary testing of the questionnaire was conducted among 10 older individuals aged 65 years and older who had NCCD and were recruited from the registry. Other patients who met the inclusion criteria participated in the field testing. After verifying the unidimensionality, local independence, and monotonicity assumptions of the scale, we employed the Rasch model within Item Response Theory framework to assess the quality of the scale through methods including internal consistency, criterion validity, Wright map, and item functioning differential. Subsequently, we assessed the construct validity of the scale by combining exploratory factor analysis with confirmatory factor analysis. Results Based on well-validated scales such as the short-form WHOQOL-OLD, HeartQOL, IQCODE, and SF-36, an original Neuro-co-Cardiological Diseases Quality of Life scale (NCCDQOL) was developed. 196 individuals from the EINCCDRCS were included in the study, with 10 participating in the preliminary testing and 186 in the field testing. Based on the results of the preliminary testing, the original questionnaire was refined through item deletion and adjustment, resulting in an 11-item NCCDQOL questionnaire. The Rasch analysis of the field testing data led to the removal of 21 misfitting individuals. The NCCDQOL demonstrated a four-category structure, achieved by combining two response categories. This structure aligned with the assumptions of unidimensionality, local independence, and monotonicity. The NCCDQOL also exhibited good validity and reliability. Conclusion The revised NCCDQOL questionnaire demonstrated good reliability and validity in the Rasch model, indicating promising potential for clinical application.

Abstract The Atlantic meridional overturning circulation is an important component of the climate system because of its role in the heat transport. Its strength is sensitive to the surface density but mechanisms of the effect of Southern Ocean freshwater anomalies are relatively unknown. Here, we investigate the impact of Antarctic ice sheet meltwater on the Atlantic meridional overturning circulation using an earth system model of intermediate complexity. The meltwater over the Pacific sector of the Southern Ocean is transported to the east and, after passing the Drake Passage, travels northward reaching the North Atlantic. Furthermore, Southern Ocean cooling induces a northward shift of the Intertropical Convergence Zone, leading to more precipitation in the tropical Atlantic. Consequently, the reduced salinity weakens the Atlantic meridional overturning circulation. Additional experiments, in which the duration period of freshwater hosing was varied while keeping its total amount constant, indicate that the amplitude and the duration of the meltwater play crucial roles in determining the degree of reduction in Atlantic meridional overturning circulation.

Dryas octopetala L. var. asiatica (Nakai) Nakai 1918 is a dwarf shrub that mainly grow in alpine and arctic zones of the Northern Hemisphere, representing an endemic variety in Asia. In the present study, the complete chloroplast (cp) genome of D. octopetala var. asiatica was first characterized and used for its phylogenetic analysis. The cp genome span 158,271 bp with an overall GC content of 36.5%. A total of 129 genes were identified, including 84 protein-coding genes (PCGs), 37 tRNA genes, and 8 rRNA genes. In addition, repetitive sequences and microsatellites were detected within this species. Phylogenetic analysis involving 39 cp genomes from Rosaceae family indicated that D. octopetala var. asiatica was sister to the clade of Amygdaloideae. This study contributes fundamental insights into the cp genome of Dryas octopetala var. asiatica, which will have expanded its use in photosynthesis and evolutionary study.

Abstract Background/objectives The hemoglobin glycation index (HGI) has been demonstrated to serve as a substitute for the individual bias in glycosylated hemoglobin A1c (HbA1c). Our objective was to assess the correlation between HGI and cardiovascular (CV) outcomes in patients with diabetes and coronary artery disease (CAD). Subjects/methods We sequentially recruited 11921 patients with diabetes and CAD at Fuwai Hospital. The patients were categorized into five groups based on their HGI quintiles, ranging from Q1 to Q5. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), which included CV death and nonfatal myocardial infarction. Results During the median 3-year follow-up, 327 (2.7%) MACEs were observed. A U-shaped relationship between HGI and 3-year MACEs was demonstrated by restricted cubic spline (RCS) after multivariable adjustment (nonlinear P = 0.014). The Kaplan-Meier curves demonstrated that the Q2 group had the lowest risk of MACE (P = 0.006). When comparing the HGI Q2 group, multivariable Cox regression models showed that both low (Q1) and high (Q4 or Q5) HGI were linked to a higher risk of MACEs (all P

Abstract Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

The utilization of Bacillus sp. for the production of bio-CaCO3 in concrete crack repair and strength enhancement has attracted considerable attention. However, microbial-induced calcium carbonate precipitation (MICP) has yet to be explored as a precedent with activated sludge. Here calcium sourced from concrete slurry waste (CSW) and carbon from sludge microbial β-oxidation under alkaline were used to generate micro/nano CaCO3. The results indicate that the main crystalline form of the generated precipitated particles is calcite, with a particle size ranging from 0.7 to 10 μm. Minimal heavy metals were found in the supernatant following settling. And at the optimum pH of 8.5–9, carbon capture reached 743 mg L−1, and CaCO3 production reached 1,191 mg L−1, and dominant phylum were Proteobacteria and Bacteroidota, with Thauera being a prevalent genus adept in β-oxidation. Mass balance analysis showed that alkali promotes microbial β-oxidation of organisms to produce CO2 and facilitate storage. Thus, the alkaline regulation of metabolism between microbe and CSW provides a novel way of sludge to initiate MICP. HIGHLIGHTS Utilizing concrete slurry waste as a calcium source and sludge β-oxidation as a carbon source can successfully produce bio-CaCO3.; pH 8.5–9 is the optimal alkaline control for Thauera to be the dominant genus undergoing β-oxidation to produce CO2.; Bio-CaCO3 is a 0.7–10 μm calcite particle, which is an excellent material for repairing concrete.; There is no risk of heavy metal leakage during operation.;

Abstract Background We aimed to explore the impact of adherence to Life’s Simple 7 (LS7) metrics on risk of obstructive sleep apnea (OSA), and the impact of inflammation on the association, in adults in the United States. Methods Data from 13,825 community-dwelling adults aged ≥ 20 years recruited in the National Health and Nutrition Examination Surveys (NHANES) 2005–2008, 2015–2018 was analyzed. The LS7 score was calculated based on the AHA definition of LS7 metrics. The diagnosis of OSA was based on self-reported symptoms of sleep disturbance using a standard questionnaire. The Multivariable Apnea Prediction (MAP) Index score was also calculated to assess the risk of OSA. Log-binominal regression and negative binomial regression were performed to estimate the associations between LS7 and OSA and MAP index, with odds ratios (ORs) and prevalence ratios (PRs) and their 95% confidence intervals (CIs) calculated. Mediation analysis was performed to estimate the mediating effects of inflammatory indicators on the associations. Results A total of 4473 participants (32.4%) had OSA, and the mean MAP index was 0.39. In fully adjusted log-binominal regression models, with total score 8, respectively (P for trend 8, respectively (P for trend

Abstract There is limited research on risk factors for chronic endometritis regarding reproductive history and clinical symptoms. Thus, this nested case–control study identified risk factors for chronic endometritis in women who have undergone hysteroscopy. Endometrial tissue sections were obtained from 502 women with intrauterine disorders who underwent hysteroscopy. Chronic endometritis was diagnosed via CD138 immunostaining. The women were divided into two groups: 271 women without chronic endometritis and 231 women with chronic endometritis. The prevalence of chronic endometritis was 46%. Univariate logistic regression revealed that prolonged menstruation and intermenstrual bleeding were associated with chronic endometritis, and subsequent multivariate logistic regression analyses showed that these were further independently associated. With univariable logistic regression, the gravidity and abortion history were correlated with chronic endometritis; however, no significant correlation was found with the adjusted odds ratio (OR) of 0.74 (95% confidence interval [CI] 0.46–1.19) or 0.76 (95% CI 0.58–1.11), respectively. No significant correlation was found between caesarean section history and the rates of chronic endometritis. No significant difference was found in all other variables between the three groups with > 5, ≤ 5 plasma cells and in a unknown group. Prolonged menstruation and intermenstrual bleeding were risk factors associated with chronic endometritis. Chronic endometritis should be considered and CD138 immunohistochemical examination should be recommended in women with these symptoms.

Abstract The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.

Abstract In the realm of natural supersymmetric models, higgsinos are typically the lightest electroweakinos. In gauge-mediated supersymmetry breaking models, the lightest higgsino-dominated particles decay into a Z-boson or a Higgs boson (h), along with an ultra-light gravitino ( $$\tilde{G}$$ G ~ ) serving as the lightest supersymmetric particle (LSP). This scenario suggests a significant non-resonant hh production. Basing on the recent global fitting results of the $$\tilde{G}$$ G ~ -EWMSSM (MSSM with light electroweakinos and an eV-scale gravitino as the LSP) performed by the GAMBIT collaboration, which support a higgsino-dominated electroweakino as light as 140 GeV, we develop two simplified models to evaluate their detection potential at the high-luminosity LHC (HL-LHC) with $$\sqrt{s} = 14~\textrm{TeV}$$ s = 14 TeV and an integrated luminosity of $$3000~\textrm{fb}^{-1}$$ 3000 fb - 1 . The first model examines the processes where heavier higgsino-dominated states decay into soft W/Z bosons, while the second focuses on direct decays of all three higgsino-dominated electroweakinos into W/Z/h plus a $$\tilde{G}$$ G ~ . Our study, incorporating both models and their distinct decay channels, utilizes detailed Monte Carlo simulations for signals and standard model backgrounds. We find that the HL-LHC can probe higgsinos up to 575 GeV, potentially discovering or excluding the natural SUSY scenario in the context of a gravitino LSP. Further, we reinterpret this discovery potential using the GAMBIT global fit samples, and find that the entire parameter space of $$|\mu | \le 500~\textrm{GeV}$$ | μ | ≤ 500 GeV with an electroweak fine-tuning measure ( $$\Delta _{\textrm{EW}}$$ Δ EW ) under 100 in $$\tilde{G}$$ G ~ -EWMSSM is accessible at the HL-LHC.

Owing to their limited accuracy and narrow applicability, current antimicrobial peptide (AMP) prediction models face obstacles in industrial application. To address these limitations, we developed and improved an AMP prediction model using Comparing and Optimizing Multiple DEep Learning (COMDEL) algorithms, coupled with high-throughput AMP screening method, finally reaching an accuracy of 94.8% in test and 88% in experiment verification, surpassing other state-of-the-art models. In conjunction with COMDEL, we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro, ultimately increasing AMPs yields to a range of 0.5–2.1 g/L within hours. Moreover, by multi-omics analysis using COMDEL, we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible probiotics. Following this, we developed a microdroplet sorting approach and successfully screened three L. plantarum mutants, each showing a twofold increase in antimicrobial ability, underscoring their substantial industrial application values.

BackgroundBacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. ObjectiveTo understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. MethodsThree subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO2), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min−1, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO2 concentration and total bacterial count. ResultsThe pass rates were 100.0% for airborne total bacteria count, PM2.5, and PM10 in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO2, but 0% for humidity. The overall median (P25, P75) total bacteria count was 177 (138,262) CFU·m−3. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P

Abstract Background Idiopathic short stature (ISS) is characterized by short stature with unknown causes. Recent studies showed different gut microbiota flora and reduced fecal short-chain fatty acids in ISS children. However, the roles of the microbiome and metabolites in the pathogenesis of ISS remains largely unknown. Methods We recruited 51 Chinese subjects, comprising 26 ISS children and 25 normal-height control individuals. Untargeted metabolomics was performed to explore the fecal metabolic profiles between groups. A shotgun metagenomic sequencing approach was used to investigate the microbiome at the strains level. Mediation analyses were done to reveal correlations between the height standard deviation (SD) value, the gut microbiome and metabolites. Results We detected marked differences in the composition of fecal metabolites in the ISS group, particularly a significant increase in erucic acid and a decrease in spermidine, adenosine and L-5-Hydroxytryptophan, when compared to those of controls. We further identified specific groups of bacterial strains to be associated with the different metabolic profile. Through mediation analysis, 50 linkages were established. KEGG pathway analysis of microbiota and metabolites indicated nutritional disturbances. 13 selected features were able to accurately distinguish the ISS children from the controls (AUC = 0.933 [95%CI, 79.9–100%]) by receiver operating characteristic (ROC) analysis. Conclusion Our study suggests that the microbiome and the microbial-derived metabolites play certain roles in children’s growth. These findings provide a new research direction for better understanding the mechanism(s) underlying ISS.

Abstract Intrahepatic accumulation dominates organ distribution for most nanomedicines. However, obscure intrahepatic fate largely hampers regulation on their in vivo performance. Herein, PEGylated liposomal doxorubicin is exploited to clarify the intrahepatic fate of both liposomes and the payload in male mice. Kupffer cells initiate and dominate intrahepatic capture of liposomal doxorubicin, following to deliver released doxorubicin to hepatocytes with zonated distribution along the lobule porto-central axis. Increasing Kupffer cells capture promotes doxorubicin accumulation in hepatocytes, revealing the Kupffer cells capture-payload release-hepatocytes accumulation scheme. In contrast, free doxorubicin is overlooked by Kupffer cells, instead quickly distributing into hepatocytes by directly crossing fenestrated liver sinusoid endothelium. Compared to free doxorubicin, liposomal doxorubicin exhibits sustained metabolism/excretion due to the extra capture-release process. This work unveils the pivotal role of Kupffer cells in intrahepatic traffic of PEGylated liposomal therapeutics, and quantitively describes the intrahepatic transport/distribution/elimination process, providing crucial information for guiding further development of nanomedicines.

Amorphophallus paeoniifolius (Dennst.) Nicolson, 1885, often known as elephant foot yam, is a tropical tuber crop that originates from south-east Asia and belongs to the Araceae family. It is known for its high production potential and popularity as a medicinal plant. However, the phylogeny and genes for this species are still unavailable. In this study, the first complete chloroplast genome of A. paeoniifolius was reported and phylogenetic analysis was conducted with Araceae species. The chloroplast genome was 176,258 bp in length with 34.80% overall GC content and includes a large single-copy (LSC) region (93,951 bp), a small single-copy (SSC) region (15,013 bp), and a pair of inverted repeat (IRs) regions (33,647 bp). The chloroplast genome has 130 genes, which include 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. A maximum-likelihood (ML) phylogenetic analysis indicated that all Amorphophallus species formed a single monophyletic clade with a high bootstrap value and A. paeoniifolius was closely related to A. konjac, A. albus, A. krausei, and A. titanum. The chloroplast genome reported in this study will be useful for further taxonomic and evolutionary studies of Amorphophallus.

Abstract Iodine-129, which is a promising tracer for dating old groundwater, has been used as a tracer for deep upwelling groundwater. The nuclide is expected to be one of the key factors for site selection for high-level radioactive waste disposal, which is a global societal issue. The pre-anthropogenic 129I/127I ratio for marine iodine is (1.50 ± 0.15) × 10−12, which could be considered the initial value for 129I dating. This study identifies the challenges in groundwater age dating using 129I/127I. We measured the ratios of 129I/127I and 81Kr/Kr and concentration of 4He in groundwater from boreholes on the northern coast of Japan. The 129I dating results were not coincident with the other groundwater dating results. The iodine in the groundwater was inferred to be released in situ from marine organisms in sediments of various ages. We estimated that the primordial iodine ratio originating from seawater was ~ 1 × 10–13 (8 × 10–14 ~ 2 × 10–13). The groundwater age deduced from the 129I/127I ratio using this value agrees with other groundwater dating results.

Background: Hepatic immune tolerance might contribute to the development of therapeutic resistance to immunotherapy. However, addressing this issue is challenging since the efficacy of immunotherapy in the context of liver metastasis (LM) remains poorly studied. Here, we aimed to establish an LM common immune feature (LMCIF) score to quantify the characteristics of LM immunotolerance across cancer types for assisting clinical disease management. Methods: Large-scale clinical data were collected to identify the prognosis of LM. Multi-omics datasets of metastatic cancers with LM special immune-related pathways (LMSIPs) from the Molecular Signatures Database (MSigDB) were used to obtain an LMCIF cluster. Based on differential expression genes (DEGs), a novel LMCIF score for the LMCIF cluster was constructed. In addition, multi-omics, and immunohistochemistry (IHC) data from the public and in-house cohorts were used to explore the features of LM, and LMCIF score. Results: Patients with LM had a worse prognosis and significantly lower infiltration of immune cells than patients with metastasis to other organs when analyzed with combined clinical and RNA sequencing data. After extracting the LMCIF cluster from 373 samples by utilizing 29 LMSIPs and validating them in a microarray cohort, an LMCIF score was established to confirm the role of the immunosuppressive environment as a contributor to the poor prognosis of LM across cancer types. Moreover, this LMCIF score could be used to predict the immune response of cancer patients undergoing immunotherapy. Finally, we identified that the majority of the 31 LMCIF genes exhibited a negative correlation with TME cells in LM patients, one of them, KRT19, which possessed the strongest positive correlation with LMCIF score, was confirmed to have an immunosuppressive effect through IHC analysis. Conclusions: Our results suggest that LM across cancer types share similar immunological profiles that induce immunotolerance and escape from immune monitoring. The novel LMCIF score represents a common liver metastasis immune cluster for predicting immunotherapy response, the results of which might benefit clinical disease management.

Short-term load forecasting is generally applied in power system real-time dispatching and day-ahead generation planning, which is of great significance for power system economic dispatching and safe operation of the system. Many researches on short-term load forecasting using smart models have been conducted at home and abroad. However, how to obtain the optimal structure and parameters accurately and quickly poses a challenge to short-term load forecasting, because the prediction performance of smart forecasting methods is more easily affected by the structure and parameters of the method, and the personality difference of the prediction object itself makes it difficult for the parameters to be reused. Aiming at this problem, a tree-structured Parzen estimator (TPE)-based boosting short-term load forecasting method is proposed. The results show that the proposed method can achieve rapid optimization of structure and parameters, which is verified in the application in short-term load forecasting of a southern province in China to improve the prediction accuracy.

Abstract This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for treating chronic hepatitis B (CHB), and explore combined RNA interference (RNAi) and immune modulatory modalities for better viral control. Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and evaluated. The lipid nanoparticle (LNP) formulation was optimized by adopting HO-PEG2000-DMG lipid and modifying the molar ratio of traditional polyethylene glycol (PEG) lipid in LNP prescriptions. The efficacy and safety of this formulation in delivering siHBV (tLNP/siHBV) along with the mouse IL-2 (mIL-2) mRNA (tLNP/siHBVIL2) were evaluated in the rAAV-HBV1.3 mouse model. A siRNA combination (terms “siHBV”) with a genotypic coverage of 98.55% was selected, chemically modified, and encapsulated within an optimized LNP (tLNP) of high efficacy and security to fabricate a therapeutic formulation for CHB. The results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA (up to 3log10 reduction; vs PBS) in dose- and time-dependent manners at single-dose or multi-dose frequencies, with satisfactory safety profiles. Further studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus, via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4+ and CD8+ T cell responses by expressed mIL-2 protein. By adopting tLNP as nucleic acid nanocarriers, the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV, thus offering a promising translational therapeutic strategy for treating CHB.

Abstract Climate change mitigation through negative CO2 emissions has been recognized as a crucial strategy to combat global warming. However, its potential effects on terrestrial productivity and agricultural activities remain uncertain. In this study, we utilized large ensemble simulations with an Earth system model of full complexity to investigate the response of Gross Primary Production (GPP) to CO2 forcings. Our findings reveal a significant asymmetry in the GPP response to CO2 ramp-up and symmetric ramp-down model experiments, especially in Europe, suggesting that GPP declines rapidly as CO2 levels decrease. Remarkably, during the CO2 removal period, the North Atlantic Sea surface temperature experienced cooling due to a delayed recovery of the Atlantic Meridional Overturning Circulation (AMOC). This cooling led to precipitation and soil moisture deficits, resulting in a rapid reduction in GPP. This asymmetry in GPP response holds consistent across multi-model simulations. These results underscore the potential implications of delayed recovery in ocean circulation, which could unexpectedly accelerate terrestrial GPP reduction. These insights are crucial for policymakers, aiding them in projecting agricultural activity and formulating targeted GPP control policies specific to the European region.

This study sought to determine the effects of rosemary leaf powder (RP) on laying performance, egg quality, serum indices, gut barrier function, and cecal microbiota and metabolites of late-phase laying hens. A total of 84 “Jing Tint 6” laying hens at 65-week old were randomly divided into 2 groups and fed either a basal diet (CON) or a basal diet supplemented with 0.3% RP. Our study revealed that RP improved the Haugh unit and decreased yolk n-6/n-3 polyunsaturated fatty acid (PUFA) ratio of laying hens, increased serum superoxide dismutase (SOD), jejunal activities of SOD and catalase (CAT), and jejunal zonula occludens-1 (ZO-1) expression, as well as decreased serum tumor necrosis factor-α (TNF-α) level and jejunal TNF-α mRNA expression. Rosemary leaf powder markedly enhanced (P

We study radiative transfer in participating binary stochastic mixtures in two dimensions (2D) by developing an accurate and efficient simulation tool. For two different sets of physical parameters, 2D benchmark results are presented, and it is found that the influence of the stochastic mixture on radiative transfer is clearly parameter-dependent. Our results confirm that previous multidimensional results obtained in different studies are basically consistent, which is interpreted in terms of the relationship between the photon mean free path lp and the system size L. Nonlinear effects, including those due to scattering and radiation–material coupling, are also discussed. To further understand the particle size effect, we employ a dimensionless parameter lp/L, from which a critical particle size can be derived. On the basis of further 2D simulations, we find that an inhomogeneous mix is obtained for lp/L > 0.1. Furthermore, 2D material temperature distributions reveal that self-shielding and particle–particle shielding of radiation occur, and are enhanced when lp/L is increased. Our work is expected to provide benchmark results to verify proposed homogenized models and/or other codes for stochastic radiative transfer in realistic physical scenarios.

This study examines the impact of political connections on charitable giving by private enterprises in China in the business environment context. The study constructs a nested structure model and empirically analyzes 1,426 sample enterprises from the 13th China Private Enterprise Survey (2018) data using stata15.1 software. The findings indicate that the business environment influences political connections, charitable giving, and their interaction. Political connections at the individual level of enterprise owners and core managers partly have a positive impact on the charitable giving of Chinese private enterprises. At the enterprise level, the formation of political connections, including the establishment of party organizations, cost-sharing, and receiving government subsidies, also enhances charitable giving. Additionally, certain attributes of private enterprises and entrepreneurs, such as age, year-on-year growth in net profit, and total bank loans, positively influence their charitable giving. However, a high debt-to-asset ratio may adversely affect a company’s charitable giving. These insights are invaluable for local entrepreneurs, authorities, and policymakers in understanding how to effectively conduct charitable giving within specific business and political environments. Academically, this study contributes to the corporate sociology literature by offering new perspectives and data support for future research.