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Abstract Kidney diseases represent a diverse range of conditions that compromise renal function and structure which characterized by a progressive deterioration of kidney function, may ultimately necessitate dialysis or kidney transplantation as end-stage treatment options. This review explores the complex landscape of kidney diseases, highlighting the limitations of existing treatments and the pressing need for innovative strategies. The paper delves into the role of extracellular vesicles (EVs) as emerging biomarkers and therapeutic agents in the context of kidney pathophysiology. Urinary extracellular vesicles (uEVs), in particular, offer a non-invasive means of assessing renal injury and monitoring disease progression. Additionally, mesenchymal stem cell-derived EVs (MSC-EVs) are examined for their immunomodulatory and tissue repair capabilities, presenting a promising avenue for novel therapeutic interventions. And discusses the potential of engineering EVs to enhance their targeting and therapeutic efficacy. This paper systematically integrates the latest research findings and aims to provide a comprehensive overview of the role of EVs in kidney disease, providing cutting-edge insights into their potential as a diagnostic and therapeutic tool.

Groundwater is an important water supply source in Xining City. Previous works have found that iron-rich groundwater limits water development and utilization. However, few studies focus on the distribution characteristics and mechanism of iron-rich groundwater in different types of aquifers in Xining City. Based on the hydrochemical data of 144 groundwater samples, combined with the geological and hydrogeological conditions, the distribution characteristics and influencing factors of iron content in groundwater in different aquifers were analyzed by methods of statistics and geostatistics. The results show that the exceeding standard ratio of iron in groundwater of unconsolidated sediments aquifer (Area Ⅰ) is 27. 85%, which is 1. 6 times and 2. 7 times higher than that of clastic rocks fissure-pore aquifer (Area Ⅱ) and bedrock aquifer (Area Ⅲ), respectively. The proportion of iron-rich groundwater (concentration greater than 0. 3 mg/L) in construction land area is significantly higher than in areas with other land use types. The redox environment and human activities (such as industrial wastewater, domestic sewage, and infiltration of iron-rich river water) may be the main factors affecting the increase of iron content in groundwater in Area I. In addition to the redox environment, Agricultural nitrogen fertilizer use and domestic sewage discharge are also important factors affecting iron-rich groundwater in Area Ⅱ. The iron-rich groundwater in Area Ⅲ is mainly controlled by redox conditions. On the regional scale, the distribution of iron-rich groundwater presents in bands or spots along the river. The iron deposits releasing in the primary strata and human activities (industrial wastewater) are the main source of iron ions in the shallow groundwater in the study area. The migration and enrichment of iron in groundwater are mainly controlled by redox conditions, and affected by the runoff condition, without relation to pH and salt effect. This study can provide scientific basis for urban water environment management in Xining City and similar arid and semi-arid areas.

Abstract Background With global climate change, the health threats of ambient high temperature have received widespread attention. However, latest spatio-temporal patterns of the non-communicable diseases (NCDs) burden attributable to high temperature have not been systematically reported. We aimed to analyze vulnerable areas and populations based on a detailed profile for the NCDs burden attributable to high temperature globally. Methods We obtained data from the Global Burden of Diseases (GBD) Study (2019) to describe the temporal and spatial patterns of NCDs burden attributable to high temperature globally from 1990–2019. Then we analyzed the differences by region, sex, and socio-demographic index (SDI). Finally, the age‑period‑cohort (APC) model was utilized to explore the age, period, and cohort effects of NCDs mortality caused by high temperature. Results In 2019, the number of deaths and Disability-adjusted life years (DALYs) from high-temperature-related NCDs was about 150,000 and 3.4 million globally, of which about 70% were in South Asia and North Africa and Middle East, and the burden was higher in men. Among 204 countries and territories, the highest age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were observed in Oman and United Arab Emirates, respectively. The global burden showed an upward trend from 1990 to 2019, with an EAPC of 3.66 (95%CI: 3.14–4.18) for ASMR and 3.68 (95%CI: 3.16-4.21) for ASDR. Cardiovascular diseases were the main contributors to the global burden of high-temperature-related NCDs in 2019. The age and period effect in APC model showed an increasing trend globally. There was a significant negative correlation between SDI and both ASMR (r = -0.17) and ASDR (r = -0.20) from 1990 to 2019. Conclusion There was an increasing trend of the global burden of high-temperature-related NCDs. The burden was likely to be higher in males and the elderly, as well as in countries and regions with less economically and socially developed and in tropical climates. Surveillance and prevention measures should be implemented with a focus on these vulnerable areas and susceptible populations.

Abstract Polymeric-based dielectric materials hold great potential as energy storage media in electrostatic capacitors. However, the inferior thermal resistance of polymers leads to severely degraded dielectric energy storage capabilities at elevated temperatures, limiting their applications in harsh environments. Here we present a flexible laminated polymer nanocomposite where the polymer component is confined at the nanoscale, achieving improved thermal-mechanical-electrical stability within the resulting nanocomposite. The nanolaminate, consisting of nanoconfined polyetherimide (PEI) polymer sandwiched between solid Al2O3 layers, exhibits a high energy density of 18.9 J/cm3 with a high energy efficiency of ~ 91% at elevated temperature of 200°C. Our work demonstrates that nanoconfinement of PEI polymer results in reduced diffusion coefficient and constrained thermal dynamics, leading to a remarkable increase of 37°C in glass-transition temperature compared to bulk PEI polymer. The combined effects of nanoconfinement and interfacial trapping within the nanolaminates synergistically contribute to improved electrical breakdown strength and enhanced energy storage performance across temperature range up to 250°C. By utilizing the flexible ultrathin nanolaminate on curved surfaces such as thin metal wires, we introduce an innovative concept that enables the creation of a highly efficient and compact metal-wired capacitor, achieving substantial capacitance despite the minimal device volume.

Abstract Hyperuricemia is associated with an increased risk of gout, hypertension, diabetes, and cardiovascular diseases. Most mammals maintain normal serum uric acid (SUA) via urate oxidase (Uox), an enzyme that metabolizes poorly-soluble UA to highly-soluble allantoin. In contrast, Uox became a pseudogene in humans and apes over the long course of evolution. Here we demonstrate an atavistic strategy for treating hyperuricemia based on endogenous expression of Uox in hepatocytes mediated by mRNA (mUox) loaded with an ionizable lipid nanoparticle termed iLAND. mUox@iLAND allows effective transfection and protein expression in vitro. A single dose of mUox@iLAND lowers SUA levels for several weeks in two female murine models, including a novel long-lasting model, which is also confirmed by metabolomics analysis. Together with the excellent safety profiles observed in vivo, the proposed mRNA agent demonstrates substantial potential for hyperuricemia therapy and the prevention of associated conditions.

Abstract Background Obstructive sleep apnea (OSA) and osteoporosis (OP) are prevalent diseases in the elderly. This study aims to reveal the clinical association between OSA and OP and explore potential crosstalk gene targets. Methods Participants diagnosed with OSA in the National Health and Nutrition Examination Survey (NHANES) database (2015–2020) were included, and OP was diagnosed based on bone mineral density (BMD). We explored the association between OSA and OP, and utilized multivariate logistic regression analysis and machine learning algorithms to explore the risk factors for OP in OSA patients. Overlapping genes of comorbidity were explored using differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Random Forest (RF) methods. Results In the OSA population, the weighted prevalence of OP was 7.0%. The OP group had more females, lower body mass index (BMI), and more low/middle-income individuals compared to the non-OP group. Female gender and lower BMI were identified as independent risk factors for OP in OSA patients. Gene expression profiling revealed 8 overlapping differentially expressed genes in OP and OSA patients. KCNJ1, NPR3 and WT1-AS were identified as shared diagnostic biomarkers or OSA and OP, all of which are associated with immune cell infiltration. Conclusion This study pinpointed female gender and lower BMI as OP risk factors in OSA patients, and uncovered three pivotal genes linked to OSA and OP comorbidity, offering fresh perspectives and research targets.

Highlights Asymmetrically coordinated Co–N4–O sites on N-doped carbon nanofiber were prepared. Co–O coordination along the axial direction led to enhanced dielectric polarization loss. Multifunctional films were developed for practical application in harsh environments.

Abstract Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients’ therapy response and prognosis.

The coastal areas of the lower reaches of Oujiang River Basin are rich in groundwater resources. However, the unsustainable exploitation and utilization of groundwater have led to significant changes in the groundwater environment. Understanding the characteristics and genesis of groundwater salinization is crucial for preventing its deterioration and ensuring sustainable utilization. In this study, a comprehensive approach combining the ion ratio method, mineral saturation index method and multivariate statistical analysis was employed to investigate the hydrochemical characteristics and main controlling factors in the study area. The findings reveal that: (1) Groundwater samples in study area exhibit a neutral to slightly alkaline pH. The predominant chemical types of unconfined water are HCO3-Ca·Na, HCO3·Cl-Na·Ca and HCO3·SO4-Ca·Na, while confined water mainly exhibits Cl·HCO3-Na and Cl-Na types. (2) Salinity coefficients indicate an increase in salinity from unconfined to confined water. TDS, Na+ and Cl– concentrations show an increasing trend from mountainous to coastal areas in unconfined water, while confined water displays variability in TDS, Na+ and Cl– concentrations. (3) Groundwater salinity is mainly influenced by water-rock interactions, including the dissolution of halite and gypsum, cation exchange, and seawater intrusion etc. Additionally, human activities and carbonate dissolution contribute to salinity in unconfined water. Seawater intrusion is identified as the primary factor leading to higher salinity in confined water compared to unconfined water, with increasing cation exchange and seawater interaction observed from unconfined to confined water.

Abstract Programmed death‐ligand 1 (PD‐L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC‐1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC‐1 is positively correlated with PD‐L1 in human CRC specimens. SRC‐1 deficiency significantly inhibits PD‐L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8+ T cells. Genetic ablation of SRC‐1 in mice also decreases PD‐L1 expression in AOM/DSS‐induced murine CRC. These results suggest that tumor‐derived SRC‐1 promotes CRC immune escape by enhancing PD‐L1 expression. Mechanistically, SRC‐1 activated JAK‐STAT signaling by inhibiting SOCS1 expression and coactivated STAT3 and IRF1 to enhance PD‐L1 transcription as well as stabilized PD‐L1 protein by inhibiting proteasome‐dependent degradation mediated by speckle type POZ protein (SPOP). Pharmacological inhibition of SRC‐1 improved the antitumor effect of PD‐L1 antibody in both subcutaneous graft and AOM/DSS‐induced murine CRC models. Taken together, these findings highlight a crucial role of SRC‐1 in regulating PD‐L1 expression and targeting SRC‐1 in combination with PD‐L1 antibody immunotherapy may be an attractive strategy for CRC treatment.

With rapid urbanization, the conflicts between economic development and environmental protection have become increasingly complex and exhibit multiscale characteristics. Constructing a green space ecological network (EN) is an effective approach to alleviate urban ecological issues and maintain regional ecological security. However, traditional EN research often focuses on a single scale, neglecting multiscale nesting and collaborative optimization of landscape elements, particularly the importance of spatial granularity. To address this deficiency, this study proposed a multiobjective, multiscale nested green space EN framework for Chengdu, China. Using landscape pattern index fitting functions, morphological spatial pattern analysis, the connectivity index, circuit theory, hydrological analysis model, scale nesting, and hierarchical transmission theories, a multiscale coupled synergistic and hierarchical optimization regional green space ecological security pattern (ESP) was developed. Analysis of the derived results revealed the following. ① With increasing granularity, the landscape pattern indices showed overall increasing, overall decreasing, and overall fluctuating trends. The optimal granularity threshold for large, medium, and small scales was 9, 6, and 3 m, respectively. ② Overall, 92, 66, and 88 ecological sources; 403, 278, and 321 ecological corridors; 72, 77, and 47 pinch points; 96, 94, and 88 barriers; and 182, 120, and 87 ecological nodes were identified in the city, central city, and old city areas, respectively. ③ The ENs demonstrated reasonable hierarchical nesting characteristics, essential for interscale material and energy circulation. There were 9 overlapping ecological sources with total area of 18.34 km2 and 47 overlapping corridors with total length of 53.37 km. These overlapping areas were key regions for ensuring stability in the overall regional ESP and continuity in biological processes, and should be given priority protection. In addition, there were also 19 overlapping pinch points, 12 overlapping barriers, and 4 ecological nodes that accounted for 26.39 %, 24.68 %, and 40.43 % of the total pinch points; 12.50 %, 12.77 %, and 13.64 % of the total barriers; and 2.20 %, 3.33 %, and 4.60 % of the total ecological nodes in the city area, central city area, and old city area, respectively. The high overlap of ecological strategic points across scales indicated cross-scale continuity of biological processes. ④ Enhancing the habitat quality of land types such as forest land, green spaces, grassland, and water bodies is crucial for restoration of ecological corridors and strategic points. Constructing a multiscale hierarchical linkage framework and formulating cross-scale pattern optimization and coordination schemes can effectively address ecological issues. The multiscale nested and synergistic green space ESP, constructed from the “source–corridor–strategic-point–network” framework, enhances the connectivity of regional landscape elements, increases energy flow efficiency, and strengthens spatial stability. The results provide methodological support for strategic policymaking focused on ecological spatial governance of an urban ecological protection at multiple levels.

BackgroundRe-resection is recommended for patients with incidental gallbladder carcinoma (iGBC) at T1b stage and above. It is unclear whether continuation of laparoscopic re-resection (CLR) for patients with intraoperatively detected iGBC (IDiGBC) is more beneficial to short- and long-term clinical outcomes than with conversion to radical extensive-resection (RER).MethodsThis single-centre, retrospective cohort study of patients with iGBC was conducted between June 2006 and August 2021. Patients who underwent immediate reresection for T1b or higher ID-iGBC were enrolled. Propensity score matching (PSM) was used to match the two groups (CLR and RER) of patients, and differences in clinical outcomes before and after matching were analyzed.ResultA total of 102 patients with ID-iGBC were included in this study. 58 patients underwent CLR, and 44 underwent RER. After 1:1 propensity score matching, 56 patients were matched to all baselines. Patients in the RER group had a lower total postoperative complication rate, lower pulmonary infection rate, and shorter operation time than those in the CLR group did. Kaplan-Meier analysis showed that the overall survival rate of patients who underwent CLR was significantly lower than that of patients who underwent RER. Multivariate analysis showed that CLR, advanced T stage, lymph node positivity, and the occurrence of postoperative ascites were adverse prognostic factors for the overall survival of patients.ConclusionPatients with ID-iGBC who underwent RER had fewer perioperative complications and a better prognosis than those who underwent CLR. For patients with ID-iGBC, conversion to radical extensive-resection appears to be a better choice.

This study aimed to investigate the neuroprotective effects of Zanthoxylum alkylamides (ZAs) in a mouse model of Alzheimer’s disease (AD) induced by D-galactose/aluminum chloride (D-gal/AlCl3). ZAs improved cognitive function, increased body weight, food intake, water consumption and organ indices, antioxidant enzymes activities in both the serum and brain tended normal conditions, while the malondialdehyde (MDA) concentration was reduced. The levels of the inflammatory cytokines were significantly reduced. Histopathological revealed that ZAs repaired damaged brain tissue. Transcriptomic revealed ZAs regulated Shh, Ptch1, Smo, and Gli1 gene expression to mitigate apoptosis. Metabolomic revealed ZAs regulated the levels of arachidonic acid, 5-hydroxyindoleacetic acid, docosahexaenoic acid, and cholesterol. Integrated omics analysis revealed that ZAs can activate the Shh/Ptch1/Smo signaling pathway to affect nerve cell proliferation and improve neuronal dysfunction. This study provides biomarkers for AD and reveals the signaling pathways through which ZAs ameliorate AD in mice, providing a potential treatment strategy for AD.

Abstract Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

Abstract Background Influenza is an acute respiratory infection caused by influenza virus. Maxing Shigan Decoction (MXSGD) is a commonly used traditional Chinese medicine prescription for the prevention and treatment of influenza. However, its mechanism remains unclear. Method The mice model of influenza A virus pneumonia was established by nasal inoculation. After 3 days of intervention, the lung index was calculated, and the pathological changes of lung tissue were detected by HE staining. Firstly, transcriptomics technology was used to analyze the differential genes and important pathways in mouse lung tissue regulated by MXSGD. Then, real-time fluorescent quantitative PCR (RT-PCR) was used to verify the changes in mRNA expression in lung tissues. Finally, intestinal microbiome and intestinal metabolomics were performed to explore the effect of MXSGD on gut microbiota. Results The lung inflammatory cell infiltration in the MXSGD group was significantly reduced (p

Abstract Background Colorectal cancer (CRC) is the 3rd most common malignancy with the liver being the most common site of metastases. The recurrence rate of colorectal liver metastases (CRLM) after liver resection (LR) is notably high, with an estimated 40% of patients experiencing recurrence within 6 months. In this context, we conducted a meta-analysis to synthesize and evaluate the reliability of evidence pertaining to prognostic factors associated with early recurrence (ER) in CRLM following LR. Methods Systematic searches were conducted from the inception of databases to July 14, 2023, to identify studies reporting prognostic factors associated with ER. The Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess risk-of-bias for included studies. Meta-analysis was then performed on these prognostic factors, summarized by forest plots. The grading of evidence was based on sample size, heterogeneity, and Egger’s P value. Results The study included 24 investigations, comprising 12705 individuals, during an accrual period that extended from 2007 to 2023. In the evaluation of risk-of-bias, 22 studies were rated as low/moderate risk, while two studies were excluded because of high risk. Most of the studies used a postoperative interval of 6 months to define ER, with 30.2% (95% confidence interval [CI], 24.1–36.4%) of the patients experiencing ER following LR. 21 studies were pooled for meta-analysis. High-quality evidence showed that poor differentiation of CRC, larger and bilobar-distributed liver metastases, major hepatectomy, positive surgical margins, and postoperative complications were associated with an elevated risk of ER. Additionally, moderate-quality evidence suggested that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA199), lymph node metastases (LNM) of CRC, and a higher number of liver metastases were risk factors for ER. Conclusion This review has the potential to enhance the efficacy of surveillance strategies, refine prognostic assessments, and guide judicious treatment decisions for CRLM patients with high risk of ER. Additionally, it is essential to undertake well-designed prospective investigations to examine additional prognostic factors and develop salvage therapeutic approaches for ER of CRLM.

Abstract Background Zoonotic viruses cause substantial public health and socioeconomic problems worldwide. Understanding how viruses evolve and spread within and among wildlife species is a critical step when aiming for proactive identification of viral threats to prevent future pandemics. Despite the many proposed factors influencing viral diversity, the genomic diversity and structure of viral communities in East Africa are largely unknown. Results Using 38.3 Tb of metatranscriptomic data obtained via ultradeep sequencing, we screened vertebrate-associated viromes from 844 bats and 250 rodents from Kenya and Uganda collected from the wild. The 251 vertebrate-associated viral genomes of bats (212) and rodents (39) revealed the vast diversity, host-related variability, and high geographic specificity of viruses in East Africa. Among the surveyed viral families, Coronaviridae and Circoviridae showed low host specificity, high conservation of replication-associated proteins, high divergence among viral entry proteins, and frequent recombination. Despite major dispersal limitations, recurrent mutations, cocirculation, and occasional gene flow contribute to the high local diversity of viral genomes. Conclusions The present study not only shows the landscape of bat and rodent viromes in this zoonotic hotspot but also reveals genomic signatures driven by the evolution and dispersal of the viral community, laying solid groundwork for future proactive surveillance of emerging zoonotic pathogens in wildlife. Video Abstract

Background: Cancer-associated cachexia is a multi-organ disorder associated with progressive weight loss due to a variable combination of anorexia, systemic inflammation and excessive energy wasting. Considering the importance of immunoregulation in cachexia, it still lacks a complete understanding of the immunological mechanisms in cachectic progression. Aim of review: Our aim here is to describe the complex immunoregulatory system in cachexia. We summarize the effects and translational potential of the immune system on the development of cancer-associated cachexia and we attempt to conclude with thoughts on precise and integrated therapeutic strategies under the complex immunological context of cachexia. Key Scientific Concepts of Review: This review is focused on three main key concepts. First, we highlight the inflammatory factors and additional mediators that have been identified to modulate this syndrome. Second, we decipher the potential role of immune checkpoints in tissue wasting. Third, we discuss the multilayered insights in cachexia through the immunometabolic axis, immune-gut axis and immune-nerve axis.

In previous studies, an allodiploid lineage (WR-F1-F5) was established by the distant hybridization of white crucian carp (Carassius cuvieri, WCC, ♀) and red crucian carp (Carassius auratus red var., RCC, ♂), an allodiploid fish (WR-II) was produced by WR-F1 (♀) × WCC (♂). In this study, the nutrients in the muscle and ovary of WR-II and its parents (WCC, RCC, and WR) were investigated, including protein, fat, amino acid, docosahexaenoic acid (DHA), moisture, and ash. The results showed that the protein content of WR-II in muscle and ovary (17.90 % and 25.60 % respectively) was higher than that of WR, and was significantly higher than that of WCC and RCC (p

BackgroundObesity represents a significant risk factor for the development of metabolic abnormalities. However, it is not inevitable that all individuals with obesity will develop these disorders. Selenium has been demonstrated to play a role in maintaining metabolic homeostasis in vivo, with the ability to regulate relevant signaling pathways involved in glucose and lipid metabolism processes. Previous studies have indicated that selenium concentrations in obese individuals are higher than those reported in the general population. These findings the question of whether altered selenium concentrations may act as important triggers for accelerating metabolic imbalances in the obese population. The aim of this study was to examine the potential correlation between serum selenium concentrations and the risk of developing metabolic abnormalities in individuals with obesity.MethodsThe present study included 6,125 participants from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) who were aged between 20 and 80 years, with a body mass index (BMI) of 30 kg/m2 or greater, and met the inclusion and exclusion criteria. Weighted generalized linear regression analyses were conducted to evaluate the associations between serum selenium concentrations and the conversion of metabolically healthy obesity (MHO) to metabolically unhealthy obesity (MUO). A generalized additive model (GAM) and a two-piecewise linear regression model were employed to investigate the saturation threshold effect between selenium and MUO. The correlation between different selenium concentration intervals and metabolic diseases was evaluated by categorizing selenium concentrations according to the saturation threshold. Furthermore, this study investigated the correlation between serum selenium and lipid concentrations in obese females and between serum selenium and blood pressure in obese males.ResultsThe weighted prevalence of MUO in the study population was 48.35%. After rigorous adjustment for sociodemographic, physical, and laboratory test covariates, the weighted odds ratio (OR) of MUO increased by 44% for every 1 µM increase (approximately 78.74 µg) in the serum selenium concentration (weighted OR=1.44; 95% CI=1.09 - 1.91; P=0.018). Second, GAM analysis and saturation threshold analyses revealed an inverted U-shaped relationship between serum selenium and metabolic abnormalities in males, with a corresponding inflection point (K) of 2.82 µM. When the serum selenium concentration was below the K-value, the effects of serum selenium were mainly on blood pressure, especially diastolic blood pressure (DBP) (weighted β: 3.34; 95% CI= 0.25 - 6.44; P=0.038). Conversely, the correlation between the serum selenium concentrations and metabolic homeostasis imbalance in females was linear. When the selenium concentration exceeded 2.12 µM, the increase in selenium content was accompanied by increases in total cholesterol (TC, weighted β=0.54, 95% CI=0.32 - 0.76; P=0.000) and triglyceride (TG, weighted β=0.51, 95% CI=0.27 - 0.75; P=0.000) concentrations.ConclusionsThe findings of our study indicate that selenium supplementation strategies for individuals with obesity should be tailored to the sex of the individual. In females, serum selenium concentration above the saturation threshold primarily facilitates the transition from MHO to MUO by influencing alterations in serum lipid metabolism. Maintaining selenium concentrations below the threshold levels is highly important for preventing the conversion of MHO to MUO. In males, serum selenium concentrations above the threshold were found to be effective in preventing an elevation in blood pressure, particularly in improving systolic blood pressure (SBP). Nevertheless, serum selenium concentrations below the threshold are linked to an increased risk of hypertension in obese individuals, particularly those with elevated diastolic blood pressure (DBP). Further research is needed to elucidate the optimal serum selenium concentration that exerts deleterious effects on blood pressure.

BackgroundRecent evidence indicates that inflammation plays a major role in the pathogenesis and progression of CCA. This meta-analysis seeks to evaluate the prognostic implications of preoperative inflammatory markers, specifically NLR, PLR, and LMR, in patients with eCCA. By focusing on these preoperative biomarkers, this study aims to provide valuable insights into their prognostic value and potential utility in clinical practice.MethodsFor this analysis, comprehensive searches were conducted in PubMed, Embase, and Web of Science databases from inception to May 2024. The primary outcomes of interest focused on the association between the levels of NLR, PLR, and LMR and the prognosis of eCCA patients. Statistical analyses were conducted using STATA 17.0 software.ResultsThe meta-analysis, involving 20 retrospective studies with 5553 participants, revealed significant correlations between preoperative biomarkers and the prognosis of eCCA patients. Elevated NLR, PLR, and decreased LMR levels were extensively studied regarding overall survival (OS) in eCCA patients. Elevated NLR was an independent predictor of poor OS (HR 1.86, p < 0.001), similar to elevated PLR (HR 1.76, p < 0.001), while decreased LMR predicted poor OS (HR 2.16, p < 0.001). Subgroup analyses based on eCCA subtypes and curative surgery status showed consistent results.ConclusionsIn conclusion, our study emphasizes the clinical significance of assessing NLR, PLR, and LMR preoperatively to predict patient prognosis. Elevated NLR and PLR values, along with decreased LMR values, were linked to poorer overall survival (OS). Large-scale prospective cohort studies are required to confirm their independent prognostic value in eCCA.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024551031.

Abstract Although capacitive deionization (CDI) technology has been studied intensively for more than 20 years, its commercialization remains in the initial stage, which is partly caused by the insufficient knowledge exchange between academia and industry. This concept reviews multiple scaling‐up efforts in the CDI technology for treating real water streams, following a case‐by‐case fashion. While the cell architecture in pilot scales is limited to the membrane CDI, highlighting the necessary role of ion‐exchange components during scaling‐ups, different ways of electrode stacking, i. e., monopolar and bipolar, are available. The performance indicators of these CDI systems when treating real water streams are summarized to gain insights into industrial practices. Importantly, key discrepancies in cell components and performances between pilot‐scale and lab‐scale studies are emphasized. The main challenges in large‐scale CDI systems for industrial purposes are discussed, providing hints for a better integration of research and applications.

ABSTRACT Klebsiella pneumoniae is an important opportunistic pathogen that causes a variety of infections. It is critical for bacteria to maintain metal homeostasis during infection. By using an isogenic mntP deletion mutant of K. pneumoniae strain NTUH-K2044, we found that MntP was a manganese efflux pump. Manganese increased the tolerance to oxidative stress, and oxidative stress could increase the intracellular manganese concentration. In oxidative stress, the mntP deletion mutant exhibited significantly higher sensitivity to manganese. Furthermore, iron could increase the tolerance of the mntP deletion mutant to manganese. Inductively coupled plasma mass spectrometry analysis revealed that the mntP deletion mutant had higher intracellular manganese and iron concentrations than wild-type and complementary strains. These findings suggested that iron could increase manganese tolerance in K. pneumoniae. This work elucidated the role of MntP in manganese detoxification and Mn/Fe homeostasis in K. pneumoniae.IMPORTANCEMetal homeostasis plays an important role during the process of bacterial infection. Herein, we revealed that MntP was involved in intracellular manganese homeostasis. Manganese promoted resistance to oxidative stress in Klebsiella pneumoniae. Furthermore, we demonstrated that the mntP deletion mutant exhibited significantly lower survival under manganese and H2O2 conditions. Oxidative stress increased the intracellular manganese content of the mntP deletion mutant. MntP played a critical role in maintaining intracellular manganese and iron concentrations. MntP contributed to manganese detoxification and Mn/Fe homeostasis in K. pneumoniae.

Histone demethylase JMJD2D (also known as KDM4D) can specifically demethylate H3K9me2/3 to activate its target gene expression. Our previous study has demonstrated that JMJD2D can protect intestine from dextran sulfate sodium (DSS)-induced colitis by activating Hedgehog signaling; however, its involvement in host defense against enteric attaching and effacing bacterial infection remains unclear. The present study was aimed to investigate the role of JMJD2D in host defense against enteric bacteria and its underlying mechanisms. The enteric pathogen Citrobacter rodentium (C. rodentium) model was used to mimic clinical colonic infection. The responses of wild-type and JMJD2D-/- mice to oral infection of C. rodentium were investigated. Bone marrow chimeric mice were infected with C. rodentium. JMJD2D expression was knocked down in CMT93 cells by using small hairpin RNAs, and Western blot and real-time PCR assays were performed in these cells. The relationship between JMJD2D and STAT3 was studied by co-immunoprecipitation and chromatin immunoprecipitation. JMJD2D was significantly up-regulated in colonic epithelial cells of mice in response to Citrobacter rodentium infection. JMJD2D-/- mice displayed an impaired clearance of C. rodentium, more body weight loss, and more severe colonic tissue pathology compared with wild-type mice. JMJD2D-/- mice exhibited an impaired expression of IL-17F in the colonic epithelial cells, which restricts C. rodentium infection by inducing the expression of antimicrobial peptides. Accordingly, JMJD2D-/- mice showed a decreased expression of β-defensin-1, β-defensin-3, and β-defensin-4 in the colonic epithelial cells. Mechanistically, JMJD2D activated STAT3 signaling by inducing STAT3 phosphorylation and cooperated with STAT3 to induce IL-17F expression by interacting with STAT3 and been recruited to the IL-17F promoter to demethylate H3K9me3. Our study demonstrates that JMJD2D contributes to host defense against enteric bacteria through up-regulating IL-17F to induce β-defensin expression.

Objective To analyze the correlation between the distribution interval of minipool nucleic acid testing(NAT) positive CT value and the resolution rate, so as to improve the retest model and reduce residual risk of blood transfusion. Methods The resolution testing results by Cobas S201 system of our blood center from January 2017 to December 2021 were retrospective analyzed, and the retest model was developed based on the distribution interval of CT values. For minipool NAT HBV positive samples from March 2022 to March 2023, synchronous detection was conducted by Cobas S201 and Panther detection system, and the detection results were statistically analyzed. Results From 2017 to 2021, 474 were minipool NAT positive, among which 324 were HBV positive, accounting for 68.35%. From 2017 to 2020, the proportion of HBV positive per year was significantly higher than that of HCV and HIV(P40, with the resolution rate at 95.8%, 56.5% and 14.8% respectively(P40, 36

Abstract BRCA2-mutated carriers have a high lifetime risk of breast cancer (BC), an early age of onset, and an increased risk of other cancers (including ovarian, pancreatic, and prostate cancer). Almost 70–80% of BRCA2-mutated BC are estrogen receptor (ER)-positive, which is a particular type of ER-positive BC that differs from sporadic ER-positive BC. This article reviews the clinicopathological features, treatment, and prognosis of ER-positive and BRCA2-mutated BC to provide a reference for clinical decision-making.

Abstract Objective The outbreak of the COVID-19 pandemic has drawn attention from all sectors of society to the level of public health services. This study aims to investigate the level of public health service supply in the four major regions of Guangdong Province, providing a basis for optimizing health resource allocation. Methods This article uses the entropy method and panel data of 21 prefecture-level cities in Guangdong Province from 2005 to 2021 to construct the evaluation index system of public health service supply and calculate its supply index. On this basis, the standard deviation ellipse method, kernel density estimation, and Markov chain are used to analyze the spatiotemporal evolution trend of the public health service supply level in Guangdong Province. The Dagum Gini coefficient and panel regression model are further used to analyze the relative differences and the key influencing factors of difference formation. Finally, the threshold effect model is used to explore the action mechanism of the key factors. Results Overall, the level of public health service supply in Guangdong Province is on an upward trend. Among them, polarization and gradient effects are observed in the Pearl River Delta and Eastern Guangdong regions; the balance of public health service supply in Western Guangdong and Northern Mountainous areas has improved. During the observation period, the level of public health services in Guangdong Province shifted towards a higher level with a smaller probability of leapfrogging transition, and regions with a high level of supply demonstrated a positive spillover effect. The overall difference, intra-regional difference and inter-regional difference in the level of public health service supply in Guangdong Province during the observation period showed different evolutionary trends, and spatial differences still exist. These differences are more significantly positively affected by factors such as the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate. Under different economic development threshold values, the degree of fiscal decentralization and urbanization rate both have a double threshold effect on the role of public health service supply level. Conclusion The overall level of public health service supply in Guangdong Province has improved, but spatial differences still exist. Key factors influencing these differences include the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate, all of which exhibit threshold effects. It is suggested that, in view of the actual situation of each region, efforts should be made to build and maintain their own advantages, enhance the spatial linkage of public health service supply, and consider the threshold effects of key factors in order to optimize the allocation of health resources.

The protection control system determines the operation safety of wind turbines. The peak shaving controller can protect wind turbines by mitigating the thrust peak near the rated wind speed. However, the traditional controller is designed in the form of a look-up table, which leads to limitations in stability and regulation capability. Therefore, an improved strategy based on model predictive control is proposed to enhance the performance of peak shaving regulation. During each control period, the allowable pitch range is improved by solving the optimization problem in real-time. Firstly, the traditional peak shaving controller is introduced and analyzed in detail. Then, a peak shaving strategy based on model predictive control is put forward for thrust peak protection by providing additional pitch action. The controller is established in a closed-loop control framework by solving an open-loop optimization problem. Finally, systematic simulations are implemented based on a high fidelity model in Bladed. As a result, it is demonstrated that the strategy can reduce the thrust peak to the safe range at the expense of acceptable output power. In addition, the proposed controller can relieve the alternating load in the peak shaving range and mitigate fatigue loads of key components.

BackgroundAmoxicillin (AMX) is among the most prescribed and the best tolerated antimicrobials worldwide. However, it can occasionally trigger severe cutaneous adverse reactions (SCAR) with a significant morbidity and mortality. The genetic factors that may be relevant to AMX-induced SCAR (AMX-SCAR) remain unclear. Identification of the genetic risk factor may prevent patients from the risk of AMX exposure and resume therapy with other falsely implicated drugs.MethodologyFour patients with AMX-SCAR, 1,000 population control and 100 AMX-tolerant individuals were enrolled in this study. Both exome-wide and HLA-based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between AMX and risk HLA proteins.ResultsCompared with AMX-tolerant controls, a significant association of HLA-B*15:01 with AMX-SCAR was validated [odds ratio (OR) = 22.9, 95% confidence interval (CI): 1.68–1275.67; p = 7.34 × 10−3]. Moreover, 75% carriers of HLA-B*15:01 in four patients with AMX-SCAR, and the carrier frequency of 10.7% in 1,000 control individuals and 11.0% in 100 AMX-tolerant controls, respectively. Within HLA-B protein, the S140 present in all cases and demonstrated the strongest association with AMX-SCAR [OR = 53.5, p = 5.18 × 10−4]. Molecular docking results also confirmed the interaction between AMX and S140 of the HLA-B protein, thus eliminating the false-positive results during in association analysis.ConclusionOur findings suggest that genetic susceptibility may be involved in the development of AMX-SCAR in Han Chinese. However, whether the HLA-B variants observed in this study can be used as an effective genetic marker of AMX-induced SCAR still needs to be further explored in larger cohort studies and other ethnic populations.

BackgroundHepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for elderly patients with HCC after surgery.MethodWe retrospectively analyzed HCC patients over 65 years old who underwent hepatectomy from 2015 to 2018, and randomly divided them into training cohort and validation cohort in a ratio of 3:1. Univariate Cox regression was used to screen the risk factors related to prognosis. Prognostic variables were further selected by least absolute shrinkage and selection operator regression model (LASSO) and multivariate Cox regression to identify the predictors of overall survival (OS) and disease-free survival (DFS). These indicators were then used to construct a predictive nomogram. The receiver operating characteristic curve (ROC curve), calibration curve, consistency index (C-index) and decision analysis curve (DCA) were used to test the predictive value of these independent prognostic indicators.ResultA total of 188 elderly HCC patients who underwent hepatectomy were enrolled in this study. The independent prognostic indicators of OS included albumin (ALB), cancer embolus, blood loss, viral hepatitis B, total bilirubin (TB), microvascular invasion, overweight, and major resection. The independent prognostic indicators of DFS included major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion. In the training cohort, the ROC curve showed that the predictive values of these indicators for OS and DFS were 0.827 and 0.739, respectively, while in the validation cohort, they were 0.798 and 0.694. The calibration curve nomogram exhibited good prediction for 1-year, 2-year, and 3-year OS and DFS. Moreover, the nomogram models exhibited superior performance compared to the T-staging suggested by C-index and DCA.ConclusionThe nomogram established in this study demonstrate commendable predictive efficacy for OS and DFS in elderly patients with HCC after hepatectomy.Core Tip: The purpose of this retrospective study is to screen the risk factors of survival and recurrence in elderly patients with HCC after hepatectomy. The nomogram included cancer embolus, viral hepatitis B, overweight, major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion as predictors. The calibration curve of this nomogram was good, indicating credible predictive value and clinical feasibility.

Corona Virus Disease 2019 (COVID-19) is a highly prevalent and potent infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until now, the world is still endeavoring to develop new ways to diagnose and treat COVID-19. At present, the clinical prevention and treatment of COVID-19 mainly targets the spike protein on the surface of SRAS-CoV-2. However, with the continuous emergence of SARS-CoV-2 Variants of concern (VOC), targeting the spike protein therapy shows a high degree of limitation. The Nucleocapsid Protein (N protein) of SARS-CoV-2 is highly conserved in virus evolution and is involved in the key process of viral infection and assembly. It is the most expressed viral structural protein after SARS-CoV-2 infection in humans and has high immunogenicity. Therefore, N protein as the key factor of virus infection and replication in basic research and clinical application has great potential research value. This article reviews the research progress on the structure and biological function of SARS-CoV-2 N protein, the diagnosis and drug research of targeting N protein, in order to promote researchers’ further understanding of SARS-CoV-2 N protein, and lay a theoretical foundation for the possible outbreak of new and sudden coronavirus infectious diseases in the future.

Cells constitute the fundamental units of living organisms. Investigating individual differences at the single-cell level facilitates an understanding of cell differentiation, development, gene expression, and cellular characteristics, unveiling the underlying laws governing life activities in depth. In recent years, the integration of single-cell manipulation and recognition technologies into detection and sorting systems has emerged as a powerful tool for advancing single-cell research. Raman cell sorting technology has garnered attention owing to its non-labeling, non-destructive detection features and the capability to analyze samples containing water. In addition, this technology can provide live cells for subsequent genomics analysis and gene sequencing. This paper emphasizes the importance of single-cell research, describes the single-cell research methods that currently exist, including single-cell manipulation and single-cell identification techniques, and highlights the advantages of Raman spectroscopy in the field of single-cell analysis by comparing it with the fluorescence-activated cell sorting (FACS) technique. It describes various existing Raman cell sorting techniques and introduces their respective advantages and disadvantages. The above techniques were compared and analyzed, considering a variety of factors. The current bottlenecks include weak single-cell spontaneous Raman signals and the requirement for a prolonged total cell exposure time, significantly constraining Raman cell sorting technology’s detection speed, efficiency, and throughput. This paper provides an overview of current methods for enhancing weak spontaneous Raman signals and their associated advantages and disadvantages. Finally, the paper outlines the detailed information related to the Raman cell sorting technology mentioned in this paper and discusses the development trends and direction of Raman cell sorting.

Pien Tze Huang (PZH), a class-1 nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Single-cell isolation stands as a critical step in single-cell studies, and single-cell ejection technology based on laser induced forward transfer technology (LIFT) is considered one of the most promising methods in this regard for its ability of visible isolating single cell from complex samples. In this study, we improve the LIFT technology and introduce optical vortex laser-induced forward transfer (OV-LIFT) and flat-top laser-induced forward transfer (FT-LIFT) by utilizing spatial light modulator (SLM), aiming to enhance the precision of single-cell sorting and the cell’s viability after ejection. Experimental results demonstrate that applying vortex and flat-top beams during the sorting and collection process enables precise retrieval of single cells within diameter ranges of 50 μm and 100 μm, respectively. The recovery rates of Saccharomyces cerevisiae and Escherichia coli DH5α single cell ejected by vortex beam are 89 and 78%, by flat-top beam are 85 and 57%. When employing Gaussian beam sorting, the receiving range extends to 400 μm, with cultivation success rates of S. cerevisiae and E. coli DH5α single cell are 48 and 19%, respectively. This marks the first application of different mode beams in the ejection and cultivation of single cells, providing a novel and effective approach for the precise isolation and improving the viability of single cells.

ABSTRACTThe nucleocapsid protein of SARS-CoV-2 plays significant roles in viral assembly, immune evasion, and viral stability. Due to its immunogenicity, high expression levels during COVID-19, and conservation across viral strains, it represents an attractive target for antiviral treatment. In this study, we identified and characterized a single-stranded DNA aptamer, N-Apt17, which effectively disrupts the liquid-liquid phase separation (LLPS) mediated by the N protein. To enhance the aptamer’s stability, a circular bivalent form, cb-N-Apt17, was designed and evaluated. Our findings demonstrated that cb-N-Apt17 exhibited improved stability, enhanced binding affinity, and superior inhibition of N protein LLPS; thus, it has the potential inhibition ability on viral replication. These results provide valuable evidence supporting the potential of cb-N-Apt17 as a promising candidate for the development of antiviral therapies against COVID-19.IMPORTANCEVariants of SARS-CoV-2 pose a significant challenge to currently available COVID-19 vaccines and therapies due to the rapid epitope changes observed in the viral spike protein. However, the nucleocapsid (N) protein of SARS-CoV-2, a highly conserved structural protein, offers promising potential as a target for inhibiting viral replication. The N protein forms complexes with genomic RNA, interacts with other viral structural proteins during virion assembly, and plays a critical role in evading host innate immunity by impairing interferon production during viral infection. In this investigation, we discovered a single-stranded DNA aptamer, designated as N-Apt17, exhibiting remarkable affinity and specificity for the N protein. Notably, N-Apt17 disrupts the liquid-liquid phase separation (LLPS) of the N protein. To enhance the stability and molecular recognition capabilities of N-Apt17, we designed a circular bivalent DNA aptamer termed cb-N-Apt17. In both in vivo and in vitro experiments, cb-N-Apt17 exhibited increased stability, enhanced binding affinity, and superior LLPS disrupting ability. Thus, our study provides essential proof-of-principle evidence supporting the further development of cb-N-Apt17 as a therapeutic candidate for COVID-19.

Summary: Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.

Abstract Background Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5‐year survival rate. Method Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely‐targeted metabolomics by UPLC‐MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. Results A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p

To investigate the chemical composition and interfunctional differences among the endosperm of Gleditsia species seeds (EGS), this study was conducted to determine the metabolic profiles in three EGSs based on the metabolomics approach of UPLC–ESI–MS/MS. A total of 505 metabolites were identified, of which 156 metabolites of EGS were annotated as pharmaceutical ingredients for six human diseases. A total of 110, 146, and 104 metabolites showed different accumulation patterns in the three control groups, LEGS vs. MEGS, LEGS vs. SEGS, and MEGS vs. SEGS, respectively. The metabolic profiles of EGSs differed significantly, and KEGG annotation and enrichment analyses indicated aminoacyl-tRNA biosynthesis as the key metabolic pathway of EGSs. This study enriches the understanding of the chemical composition of EGSs and provides theoretical support for the development and application of EGSs.

Abstract Prostate cancer is the second incidence of malignant tumors in men worldwide. Its incidence and mortality are increasing year by year. Enhanced expression of Cav1 in prostate cancer has been linked to both proliferation and metastasis of cancer cells, influencing disease progression. Dysregulation of the Cav1 gene shows a notable association with prostate cancer. Nevertheless, there is no systematic review to report about molecular signal mechanism of Cav1 and drug treatment in prostate cancer. This article reviews the structure, physiological and pathological functions of Cav1, the pathogenic signaling pathways involved in prostate cancer, and the current drug treatment of prostate cancer. Cav1 mainly affects the occurrence of prostate cancer through AKT/mTOR, H-RAS/PLCε, CD147/MMPs and other pathways, as well as substance metabolism including lipid metabolism and aerobic glycolysis. Baicalein, simvastatin, triptolide and other drugs can effectively inhibit the growth of prostate cancer. As a biomarker of prostate cancer, Cav1 may provide a potential therapeutic target for the treatment of prostate cancer.

Highlights This is the largest case series and case review of traumatic neuroma in the abdominal cavity. We conclude and update the clinical and epidemiological characteristics of TN in the abdominal cavity. We assessed and discussed the management of TN in the abdominal cavity, especially TBN.

The supra-permafrost water is a vital water source to support the ecosystem and an important link in maintaining the hydrothermal cycle in the permafrost area. Under the intensification of climate change, scientific understanding of the effect of permafrost degradation on the supra-permafrost water is of great significance to water resources and ecological protection. Focusing on the hydrological effects of permafrost degradation in the source areas of the Yellow River, this study analyzed the degradation characteristics of permafrost, and revealed the response of the depth of groundwater level and recharge process of the supra-permafrost water to the permafrost degradation, on the basis of the temperature and moisture content of frozen soil at typical monitoring points and the runoff change at the Huangheyan Hydrologic Station. The results show that the average temperature increased 0.42 °C at the 0−2.4 m profile of the monitoring point from 2010 to 2020. The depth of the upper interface of the permafrost reduced from 2.1m to 2.5 m, with an average decrease rate of 4cm/a. After 2018, the depth of supra-permafrost water level reduced from less than 0.9 m to 0.9−1.8 m. The permafros degradation led to the runoff process in the melting period of active layer (May−October) being advanced, the ratio of extreme value being reduced，and the runoff hydrograph in January being more prominent. Ground temperature is the dominant factor in controlling the changes of depth of the supra-permafrost water. Under the condition of warm and humid climate change, Permafrost degradation would change the dynamic characteristics of the water above the frozen layer and its hydraulic relationship with surface water, affecting the hydrological and ecological processes in the source area of the Yellow River.

Abstract This paper presents comprehensive research of the advantages and applicability of various concrete carbonation detection methods. Employing a combination of Phenolphthalein indicator (PI), Thermogravimetric analysis (TGA), X-ray phase analysis (XRD), Fourier transform infrared spectroscopy (FTIR), and Quantitative calcium carbonate analysis (CA), a detailed comparison to determine the carbonation depth in the partial carbonation zone of concrete specimens is conducted. Among the quantitative analysis methods, CA measures CaCO3 content based on chemical reactions, while TGA obtains the concentration distribution of Ca(OH)2 and CaCO3. Among qualitative analysis methods, XRD tested the intensity distribution of Ca(OH)2 and CaCO3, while FTIR traced the characteristic peaks of C-O functional groups in a specific spectral range to determine the depth of carbonation of concrete. Results indicate that the depth of carbonation values measured by CA, TGA, XRDA, and FTIR are 2–3 times higher than those measured by PI. This research may provide valuable insights for the design of carbonation detection in concrete.

The 5G flow residence ratio is an important indicator used by communication operators to evaluate the coverage capacity of 5G networks, and it is also an important starting point for the networks’ planning, optimization, maintenance and operation.To ensure user perception, the actual wireless transmission influencing factors, existing network structure and network coordination strategy, etc., need to be considered.The resident capacity of a 5G network in the 3.5 GHz frequency band was evaluated, analyzed and calculated, and the theoretical ultimate value of the 5G traffic resident ratio based on the analysis of network and users’ big data was put forward, which explained the positive relationship between user perception and residence ratio, and provided a reference for the reasonable theoretical ultimate value of 5G traffic resident ratio.

Abstract Background Delayed healing of diabetic cutaneous wounds is one of the most common complications of type 2 diabetes mellitus (T2DM), which can bring great distress to patients. In diabetic patients, macrophages accumulate around skin wounds and produce NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasomes, which in turn undergo pyroptosis and produce inflammatory factors such as interleukin-1β that affect wound healing. Although our previous study revealed that apoptotic extracellular vesicles (ApoEVs) produced from mesenchymal stem cells (MSCs) improve cutaneous wound healing in normal C57BL/6 mice, whether ApoEVs can also improve diabetic wound healing remains unclear. Methods Umbilical cord mesenchymal stem cells (UCMSCs) were cultured in vitro and apoptosis was induced. ApoEVs were extracted and identified and used in a T2DM mouse cutaneous wound model to evaluate the efficacy. The inhibitory effect of ApoEVs on macrophage pyroptosis was verified in vivo and in vitro, and the level of oxidative stress in macrophages was assessed to explore the mechanism by which ApoEVs play a role. Results UCMSC-derived ApoEVs improved skin defect healing in T2DM mice. Moreover, UCMSC-derived ApoEVs inhibited macrophage pyroptosis in T2DM mice in vivo as well as in vitro under high-glucose culture conditions. In addition, we demonstrated that ApoEVs reduce oxidative stress levels, which is a possible mechanism by which they inhibit macrophage pyroptosis. Conclusions Our study confirmed that local application of UCMSC-derived ApoEVs improved cutaneous wound healing in T2DM mice. ApoEVs, as products of MSC apoptosis, can inhibit macrophage pyroptosis and regulate the death process by decreasing the level of oxidative stress.

Abstract Background The optimal timing of surgery after neoadjuvant chemotherapy (NAC) in patients with synchronous colorectal cancer liver metastases (SLM) remains controversial. We plan to analyze whether the choice of different surgical timings will have different effects on the perioperative and oncologic outcomes of patients. Method We retrospectively collected all patients who met the inclusion and exclusion criteria from 2010 to 2020 in West China Hospital. Patients were grouped according to time interval (TI) after NAC to surgery. The perioperative and oncologic outcomes of the two groups were compared after propensity score matching. Univariate and multivariate analyzes were used to screen factors associated with prognosis. Result Among 255 enrolled patients, 188 were matched with comparable baseline (94 each group). Patients in the 6≦TI≦8 group had longer operation time, less intraoperative blood loss, and less postoperative complications than those in the 4≦TI

Improving ferro-piezoelectric properties of niobate-based perovskites is highly desirable for developing eco-friendly high-performance sensors and actuators. Although electro-strain coupling is usually obtained by constructing multiphase boundaries via complex chemical compositions, defect engineering can also create opportunities for novel property and functionality advancements. In this work, a representative tetragonal niobate-based perovskite, i.e., KNbO3, is studied by using first-principles calculations. Two intrinsic types of Nb antisite defect complexes are selected to mimic alkali-deficiency induced excess Nb antisites in experiments. The formation energy, electronic profiles, polarization, and piezoelectric constants are systematically analyzed. It is shown that the structural distortion and chemical heterogeneity around the energetically favorable antisite pair defects, i.e., (NbK4·+KNb4′), lower the crystal symmetry of KNbO3 from tetragonal to triclinic phase, and facilitate polarization emergence and reorientation to substantially enhance intrinsic ferro-piezoelectricity (i.e., spontaneous polarization Ps of 68.2 μC/cm2 and piezoelectric strain constant d33 of 228.3 pC/N) without complicated doping and alloying.

Testicular development and spermatogenesis are tightly regulated by both coding and non-coding genes, with mRNA and lncRNA playing crucial roles in post-transcriptional gene expression regulation. However, there are significant differences in regulatory mechanisms before and after sexual maturity. Nevertheless, the mRNAs and lncRNAs in the testes of Mongolian horses have not been systematically identified. In this study, we first identified the testicular tissues of sexually immature and sexually mature Mongolian horses at the tissue and protein levels, and comprehensively analyzed the expression profiles of mRNA and lncRNA in the testes of 1-year-old (12 months, n = 3) and 10-year-old (n = 3) Mongolian horses using RNA sequencing technology. Through gene expression analysis, we identified 16,582 mRNAs and 2128 unknown lncRNAs that are commonly expressed in both sexually immature and sexually mature Mongolian horses. Meanwhile, 9217 mRNAs (p < 0.05) and 2191 unknown lncRNAs (p < 0.05) were identified as differentially expressed between the two stages, which were further validated by real-time fluorescent quantitative PCR and analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The analysis results showed that genes in the sexually immature stage were mainly enriched in terms related to cellular infrastructure, while genes in the sexually mature stage were enriched in terms associated with hormones, metabolism, and spermatogenesis. In summary, the findings of this study provide valuable resources for a deeper understanding of the molecular mechanisms underlying testicular development and spermatogenesis in Mongolian horses and offer new perspectives for future related research.

Direct contact condensation (DCC) is a phenomenon observed when steam interacts with subcooled water, exhibiting higher heat and mass transfer rates compared to wall condensation. It has garnered significant interest across industries such as nuclear, chemical, and power due to its advantageous characteristics. In the context of pressure-relief tanks, understanding and optimizing the DCC process are critical for safety and efficiency. The efficiency of pressure-relief tanks depends on the amount of steam condensed per unit of time, which directly affects their operational parameters and design. This study focuses on investigating the direct gas–liquid contact condensation process in pressure-relief tanks using computational fluid dynamics (CFD). Through experimental validation and a sensitivity analysis, the study provides insights into the influence of inlet steam parameters and basin temperature on the steam plume characteristics. Furthermore, steady-state and transient calculation models are developed to simulate the behaviour of the pressure-relief tank, providing valuable data for safety analysis and design optimization. There is a relatively high-pressure area in the upper part of the bubble hole of the pressure-relief tube, and the value increases as it is closer to the holes. The steam velocity in the bubbling hole near the 90° elbow position is higher. This study contributes to the understanding of steam condensation dynamics in pressure-relief tanks. When the steam emission and pressure are fixed, the equilibrium temperature increases linearly as the initial temperature increases (where a = 1, b = 20 in y = a x+ b correlation), the equilibrium pressure increases nearly exponentially, and the equilibrium gas volume decreases. When the steam emission and initial temperature are fixed, the equilibrium temperature does not change as the steam discharge pressure increases. The correlations between the predicted equilibrium parameters and the inlet steam parameters and tank temperature provide valuable insights for optimizing a pressure-relief tank design and improving the operational safety in diverse industrial contexts.