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Abstract Research on the impact of financial agglomeration on CO2 emissions is a vital avenue for advancing CO2 emissions reduction and aligning with the Sustainable Development Goals set forth by the United Nations. However, few studies have investigated the dynamic spatial spillover effect of financial agglomeration on CO2 emissions, and the concepts of “time inertia” and “spatial spillover effect” about CO2 emissions have received limited attention. To address this gap, we used provincial panel data from 30 provinces in China from 2006 to 2019. We employed the entropy method to measure the level of financial accumulation, constructed a dynamic spatial Durbin model, and analyzed the “time inertia” and “spatial spillover effects” of CO2 dioxide emissions in Chinese provinces. Additionally, we explored the dynamic spatial spillover effects of financial agglomeration on CO2 emissions. We examined the transmission mechanism of the impact of financial agglomeration on CO2 emissions through energy consumption and technology market development. The results show that CO2 emissions exhibit significant “time inertia” and “space spillover” effects and considerable regional differences. Financial agglomeration levels positively impact reducing CO2 emissions in the short and long term. Through two intermediary paths of energy consumption and technology market development, financial agglomeration can indirectly reduce CO2 emissions. Our research effectively provides information and serves as a decision-making reference for policy planning related to CO2 emissions reduction, especially in countries with high CO2 emissions, particularly developing nations.

Abstract β-Hydroxybutyrate (β-OHB), the primary ketone body, is a bioactive metabolite that acts as both an energy substrate and a signaling molecule. Recent studies found that β-OHB inhibits the production of pro-inflammatory cytokines in macrophages, but its underlying molecular mechanisms have not yet been fully elucidated. Lysine β-hydroxybutyrylation (Kbhb), a post-translational modification mediated by β-OHB, plays a key role in regulating the expression and activity of modified proteins. However, whether macrophages undergo protein Kbhb and whether Kbhb modification regulates macrophage polarization remains largely unknown. In this study, treatment with β-OHB and ketone ester significantly decreased the lipopolysaccharide (LPS)-induced enhancement of the M1 phenotype of mouse bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and peritoneal macrophages (PMs) in vitro and in vivo. Moreover, β-OHB treatment induced global protein Kbhb, which is associated with the regulation of macrophage M1 polarization. Proteome-wide Kbhb analysis in β-OHB-treated BMDMs revealed 3469 Kbhb modification sites within 1549 proteins, among which interleukin-12-responding proteins were significantly upregulated. Our results indicated that β-OHB regulated M1 macrophage polarization by inducing Kbhb modification of the signal transducer and activator of transcription 1 (STAT1) K679 site, which inhibited its LPS-induced phosphorylation and transcription. Altogether, our study demonstrated the presence of a widespread Kbhb landscape in the β-OHB-treated macrophages and provided novel insights into the anti-inflammatory effects of β-OHB.

Abstract Background Mentoring’s success in nurturing professional identity formation (PIF) has been attributed to its ability to build personalised and enduring mentoring relationships. However, beyond functioning as communities of practice (CoPs) supporting socialisation processes, how mentoring integrates programme values and instils a shared identity amongst mentees remains unclear. The need for personalised guidance and timely attention to a mentee’s unique needs in evolving mentoring relationships point to the critical role of support mechanisms (‘mentoring support’). We conducted a systematic scoping review (SSR) studying “What is known about mentoring support’s role in nurturing PIF?”. Methods Adopting PRISMA-ScR guidelines, this SSR was guided by the Systematic Evidence-Based Approach (SEBA). Independent searches were carried out on publications featured between 1st January 2000 and 30th June 2023 in PubMed, Embase, ERIC and Scopus databases. The Split Approach saw concurrent, independent thematic and content analyses of the included articles. The Jigsaw Perspective combined complementary themes and categories, creating broader themes/categories. The subsequent Funnelling Process formed key domains that platformed the synthesis of the discussion. Results Two thousand three hundred forty-one abstracts were reviewed, 323 full-text articles were appraised and 151 articles were included and analysed. The key domains identified were (1) definitions and roles; (2) personalisation; (3) shepherding; and (4) PIF. Conclusion The success of mentoring in PIF lies in its ability to blend role modelling, supervision, mentoring, coaching and teaching, with self-care, guided reflection, apprenticeship and assessment to meet the individual needs of the mentee and their changing circumstances. Blending the contents of the mentoring umbrella emphasises the critical role of the mentor and host organisation in supporting mentor training, communications, support and assessment mechanisms. Mentee engagement and its active role in support measures complement the CoP-like mentoring programme’s use of blending mentoring support to advance the socialisation process. These insights reflect a complex interactive process scaffolding the development of mentoring relationships and PIF. The effect of the mentoring umbrella on clinical practice requires further study.

Abstract Background Identification and validation of potential biomarkers could facilitate the identification of pulmonary arterial hypertension (PAH) and thus aid to study their roles in the disease process. Methods We used the isobaric tag for relative and absolute quantitation approaches to compare the protein profiles between the serum of PAH patients and the controls. Bioinformatics analyses and enzyme-linked immunosorbent assay (ELISA) identification of PAH patients and the controls were performed to identify the potential biomarkers. The receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic performance of these potential biomarkers. Mendelian randomization (MR) analysis further clarified the relationship between the potential biomarkers and PAH. Additionally, the expression levels of the potential biomarkers were further validated in two PAH animal models (monocrotaline-PH and Sugen5416 plus hypoxia-PH) using ELISA and reverse transcription-quantitative PCR (RT-qPCR). Results We identified significant changes in three proteins including heparanase (HPSE), gelsolin (GSN), and hepatocyte growth factor activator (HGFA) in PAH patients. The ROC analysis showed that the areas under the curve of HPSE, GSN, and HGFA in differentiating PAH patients from controls were 0.769, 0.777, and 0.964, respectively. HGFA was correlated with multiple parameters of right ventricular functions in PAH patients. Besides proteomic analysis, we also used MR method to demonstrate the causal link between genetically reduced HGFA levels and an increased risk of PAH. In subsequent validation study in PAH animal models, the mRNA expression levels of HGFA in the lung tissues were significantly lower in PAH rat models than in controls. In the rat models, serum levels of HGFA were lower compared to the control group and showed a negative correlation with right ventricular systolic pressure. Conclusion The study demonstrated that HGFA might be a promising biomarker for noninvasive detection of PAH.

Abstract Background The effects of restrictive versus liberal transfusion strategies in critically ill patients with traumatic brain injury (TBI) and anemia, particularly in adult patients with moderate to severe TBI, remain inconclusive. Therefore, this systematic review and meta-analysis aim to evaluate the comparative impact of restrictive and liberal red blood cell transfusion strategies among critically ill adult patients with moderate to severe TBI. Methods We conducted a search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from their inception through October 20, 2024, to identify randomized controlled trials that compared restrictive (transfusions at a hemoglobin level of ≤ 7 g/dL) and liberal (transfusions at a hemoglobin level of ≤ 9–10 g/dL) transfusion strategies in adult patients with TBI. The primary outcome was mortality, with secondary outcomes including an unfavorable neurological outcome at six months, as determined by the Glasgow Outcome Scale (GOS

Abstract Saccharomyces boulardii (S. boulardii) is a fungal probiotic used to treat digestive disorders. However, the mechanism(s) by which S. boulardii affects the small intestine remains unclear. Here, we aimed to explore the effects of S. boulardii on the small intestine and the underlying mechanisms in mice with loperamide-induced constipation. While S. boulardii administration did not fully reverse the alterations in loperamide-induced defecation parameters, it altered the small intestinal floral composition toward a community conducive to alleviate constipation. Moreover, S. boulardii up-regulated the expression of tyrosine-protein kinase Kit (c-Kit), aquaporin 3 (AQP3), interleukin (IL)-10, myosin light chain kinase (MLCK), and phosphorylated myosin light chain 20 (P-MLC20), while concurrently down-regulating the expression levels of inducible nitric oxide synthase (iNOS), p65, and IL-17 A. These alterations indicate a discernible effect of small intestinal water reabsorption, inflammatory factor levels, and smooth muscle contraction. Saccharomyces boulardii also positively regulated small intestinal metabolite levels, such as fructose 6-phosphate, dihomo-alpha-linolenic acid, and 3-(4-hydroxyphenyl) lactate, and participated in metabolic pathways such as arginine biosynthesis, linoleic acid metabolism, and protein digestion and absorption. While not fully reversing defecation changes, Saccharomyces boulardii alters intestinal flora, up-regulates key proteins affecting water reabsorption and inflammation, and positively influences metabolic pathways. Our study provides serves as a basis for further studies on the application of S. boulardii in the treatment of intestinal disorders.

The automation degree of sealing technology in coal mine is insufficient, and the automatic directional drilling rig can improve the automation degree of sealing. A colloidal slip with double friction force for automatic directional drilling machine is designed to solve the problem that the clamping device of automatic directional drilling machine is bad. Two kinds of colloidal structures are proposed to realize the difference of friction between active drill pipe jointing and unjointing, and to ensure the smooth jointing of drill pipe. Using the nonlinear finite element method, Mooney-Rivlin strain energy function was used to describe the mechanical properties of colloid, and the simulation of colloid clamping hole sealer was carried out. The working friction of colloid of different materials was obtained, and the rationality of the two structural colloids was verified. The influence of the compression amount of adhesive strip on the surface of the colloid on the stress of the hole sealer was studied. The effect of the number of adhesive strips on the colloidal surface on the axial friction force was investigated. The results show that natural rubber and polyurethane rubber are reasonable as colloidal materials, the compression of rubber strips is 0.9 mm, and the number of rubber strips is 3.

Abstract Background Mesenchymal stem cells (MSCs) are multipotent stem cells that are under investigation for use in clinical trials because they are capable of self-renewal and differentiating into different cell types under defined conditions. Nonetheless, the therapeutic effects of MSCs have been constrained by low engraftment rates, cell fusion, and cell survival. Various strategies have been explored to improve the therapeutic efficacy of MSCs, with platelet-derived growth factor (PDGF)-BB emerging as a promising candidate. To enhance our comprehension of the impact of PDGF-BB on the gene expression profile and chromosomal accessibility of MSCs, RNA-sequencing and analysis of chromatin accessibility profiles were conducted on three human primary MSCs in culture, both with and without stimulation by PDGF-BB. Results Integrative analysis of gene expression and chromatin accessibility demonstrated that PDGF-BB treatment modified the chromatin accessibility landscape, marking regions for activation or repression through the AP-1 family transcription factors TEAD, CEBP, and RUNX2. These changes in AP-1 transcription factor expression, in turn, led to cell proliferation and differentiation potential towards osteoblasts, adipocytes, or chondrocytes. The degree of MSC differentiation varies among cells isolated from different donors. The presence of an enrichment of exosome-related genes is also noted among all the differentially expressed genes. Conclusions In conclusion, the observed changes in AP-1 transcription factor expression not only induced cellular proliferation and differentiation, but also revealed variations in the degree of MSC differentiation based on donor-specific differences. Moreover, the enrichment of exosome-related genes among differentially expressed genes suggests a potential significant role for PDGF-BB in facilitating intercellular communication.

Owing to their exceptional piezoelectric effects, piezoelectric materials play a crucial role in high-end technologies and contribute significantly to the national economy. Bismuth layer-structured ferroelectrics (BLSFs) possess high Curie temperatures, making them a focal point of research in high-temperature piezoelectric sensor devices. However, their poor piezoelectric performance and low direct-current (DC) electrical resistivity hinder their effective deployment in high-temperature applications. To overcome these shortcomings, we employed composition optimization by partially substituting bismuth ions with rare-earth praseodymium ions. This approach enhances the piezoelectric performance and improves the DC electrical resistivity by preventing the loss of volatile bismuth ions and stabilizing the bismuth oxide layer (Bi2O2)2+, thereby reducing the concentration of oxygen vacancies. Consequently, we achieved a large piezoelectric constant d33 of 23.5 pC/N in praseodymium-substituted Bi5Ti3FeO15, which is three times higher than that of pure Bi5Ti3FeO15 (7.1 pC/N), along with a high Curie temperature TC of 778 °C. Additionally, the optimal composition of 4 mol% praseodymium-substituted Bi5Ti3FeO15 exhibits good thermal stability of electromechanical coupling characteristics up to 300 °C. This study holds promise for a wide array of high-temperature piezoelectric applications and has the potential to accelerate the development of high-temperature piezoelectric sensor technologies.

Abstract Evidence shows that inflammatory responses play an essential role in the development of brain metastases (BM). The goal of this meta-analysis was to critically evaluate the literature regarding the use of the neutrophil to lymphocyte ratio (NLR) to predict the prognosis of patients with BM to help clinicians institute early interventions and improve outcomes. We conducted systematic review and meta-analysis, utilizing data from prominent databases, including PubMed, Cochrane Library and China National Knowledge Infrastructure databases. Our inclusion criteria encompassed studies investigating the studies that assessed the association between NLR and overall survival (OS). We included 11 articles, with 2629 eligible patients, to evaluate the association between NLR and OS. High NLR was significantly associated with shorter OS, with a pooled hazard ratio (HR) of 1.82 (95% CI 1.57–2.11). Subgroup analysis revealed that this association was consistent across different regions, with HRs of 2.03 (95% CI 1.67–2.46) in Asian populations and 1.58 (95% CI 1.35–1.84) in non-Asian populations. Additionally, in a subgroup analysis based on NLR cut-off values, patients with NLR ≥ 3 had an HR of 1.69 (95% CI 1.46–1.96), while those with NLR

ObjectiveTo investigate the clinical efficacy and safety of flow diverter device (FDD) in the treatment of tandem aneurysms in the internal carotid artery.Materials and methodsThis study was a retrospectively observational study involving two neurointerventional centers. Sixteen Patients with tandem aneurysms in the internal carotid artery treated with FDD and Digital Subtraction Angiography (DSA) follow-up in Huashan Hospital Affiliated with Fudan University and Jing’an District Central Hospital Affiliated with Fudan University from 2020.08 to 2023.12 were included. The outcomes included the angiographic occlusion rate of aneurysms, complications, and the modified Rankin Scale score. The risk factors of complete occlusion of tandem aneurysms were explored by logistic regression analysis.ResultsA total of 38 aneurysms were included, including 21 aneurysms of 8 patients in the Pipeline Embolization Device (PED) group and 17 aneurysms of 8 patients in the Tubridge Flow Diverter (TFD) group. A total of 16 FDD stents were implanted, 8 in each PED and TFD group, with a technical success rate of 100%. The median value of maximum aneurysm diameter (Dmax) was 4.27 (3.57–5.41) mm. Among them, 28 aneurysms had a maximum diameter of

Abstract Colorectal cancer (CRC) cells display remarkable adaptability, orchestrating metabolic changes that confer growth advantages, pro‐tumor microenvironment, and therapeutic resistance. One such metabolic change occurs in glutamine metabolism. Colorectal tumors with high glutaminase (GLS) expression exhibited reduced T cell infiltration and cytotoxicity, leading to poor clinical outcomes. However, depletion of GLS in CRC cells has minimal effect on tumor growth in immunocompromised mice. By contrast, remarkable inhibition of tumor growth is observed in immunocompetent mice when GLS is knocked down. It is found that GLS knockdown in CRC cells enhanced the cytotoxicity of tumor‐specific T cells. Furthermore, the single‐cell flux estimation analysis (scFEA) of glutamine metabolism revealed that glutamate‐to‐glutathione (Glu‐GSH) flux, downstream of GLS, rather than Glu‐to‐2‐oxoglutarate flux plays a key role in regulating the immune response of CRC cells in the tumor. Mechanistically, inhibition of the Glu‐GSH flux activated reactive oxygen species (ROS)‐related signaling pathways in tumor cells, thereby increasing the tumor immunogenicity by promoting the activity of the immunoproteasome. The combinatorial therapy of Glu‐GSH flux inhibitor and anti‐PD‐1 antibody exhibited a superior tumor growth inhibitory effect compared to either monotherapy. Taken together, the study provides the first evidence pointing to Glu‐GSH flux as a potential therapeutic target for CRC immunotherapy.

Abstract Alzheimer's Disease (AD) is a neurodegenerative condition characterized by the accumulation and deposition of amyloid‐β (Aβ) aggregates in the brain. Despite a wealth of research on the toxicity of Aβ and its role in synaptic damage, the mechanisms facilitating Aβ clearance are not yet fully understood. However, microglia, the primary immune cells of the central nervous system, are known to maintain homeostasis through the phagocytic clearance of protein aggregates and cellular debris. In this study, RNA sequencing analysis and live cell functional screens are employed to uncover microglial genetic modifiers related to AD. Lyzl4 is identified, which encodes a c‐type lysozyme‐like enzyme primarily localized to microglial lysosomes, as a gene significantly upregulated in AD microglia with aging and propose that Lyzl4 upregulation acts as a positive regulator of Aβ clearance. Furthermore, it is found that Lyzl4 overexpression boosts Aβ clearance both in vitro and in vivo, underscoring its potential for mitigating Aβ burden. These novel insights position Lyzl4 as a promising therapeutic target for Alzheimer's disease, paving the way for further exploration into potential AD treatments.

Summary: Background: Pulmonary embolism (PE) as a preventable and potentially fatal noncommunicable disease was believed to have a lower incidence in Asian populations compared to Western populations. However, the incidence and mortality rates of PE in China and the impact of venous thromboembolism (VTE) prevention system constructions on PE still lack nationwide evidence. Methods: For this nationwide hospital-based observational study, we used data from the National Hospital Quality Monitoring System (HQMS) and public database in China. We estimated the incidence and in-hospital mortality rates of PE by age group, sex, and regions of geographical and socioeconomic level. VTE prevention and management system constructions were quantified by geographical density. We then calculated the incidence and mortality rates in different conditions of VTE prevention and management system construction. Findings: During the 12 months period between January and December 2021, a total number of 200,112 PE patients and 14,123 deaths were recorded from 5101 hospitals in the HQMS database. The incidence of PE was 14.19 (200,112, 95% CI 14.13–14.26) per 100,000 population and the mortality rate was 1.00 (95% CI 0.99–1.02) per 100,000 population. The incidence of PE was higher in male patients (14.43 per 100,000 population) than in female patients (13.95 per 100,000 population). Disparities of incidence and mortality rates were shown within age groups and geographical regions. The incidence and mortality rates of PE showed decreasing trend with increasing geographical density of VTE-related facilities and VTE prevention system developments. Interpretation: China had a substantially large number of PE patients. The incidence and mortality rates of PE showed disparities in terms of sex, age, and geography. The incidence and mortality rates of PE decrease across regions with increasing levels of socioeconomic development, potentially influenced by the existing VTE prevention and management systems. Optimizing the health policies and healthcare investment in VTE prevention may help reduce the disease burden of PE. Funding: CAMS Innovation Fund for Medical Sciences (CIFMS) (2023-I2M-A-014); National High Level Hospital Clinical Research Funding (2022-NHLHCRF-LX-01-0108); National Key Research and Development Program of China (2023YFC2507200); Discipline-Innovation and Talent-Introduction Program for Colleges and Universities (111 Plan, B23038).

Background: Colorectal adenomas (CAs) represent a significant global health issue, particularly in China, where lifestyle modifications have contributed to their increased prevalence. These adenomas are precursors to colorectal cancer. While high-fiber diets have been shown to decrease risk, the implications of food-specific serum immunoglobulin G reactivity (FSsIgGR) on CAs remain uncertain and warrant further investigation. Objectives: To investigate the association between FSsIgGR and the occurrence of CAs in the Chinese population, assess the mediating influence of body mass index (BMI), and offer insights into potential prevention strategies. Design: A retrospective cross-sectional study. Methods: This study is based on 8796 individuals who underwent colonoscopy at the Second Medical Center of Chinese PLA General Hospital from 2017 to 2021. We examined the relationship between FSsIgGR and CAs using logistic regression, controlling for various confounders. Interaction effects were explored through subgroup analysis. We addressed missing data using multiple imputation and confirmed the robustness of our findings through sensitivity analysis. The role of BMI as a mediator was quantified using structural equation modeling. Results: The cohort comprised 2703 patients diagnosed with CAs and 6093 polyp-free controls, with an average age of 50.1 years, of whom 70.1% were male. The analysis revealed a significant inverse association between FSsIgGR and the incidence of CAs (adjusted odds ratio = 0.97; 95% confidence interval: 0.95–0.99; p

ABSTRACT Objective Preeclampsia (PE) is a multifaceted medical condition that manifests during pregnancy, characterized by hypertension and damage to multiple organs. In PE, the placenta's impaired functionality leads to continuous hypoxia in placental tissues, which is considered the primary cause of the condition. Inhibition of hypoxia‐induced injury in trophoblast cells presents a potential therapeutic strategy for PE. Edaravone (EDA) is a potent antioxidant with proven efficacy against various diseases and injuries, yet its impact on PE requires further exploration. Methods Placenta tissues from pregnant women, with or without PE, were collected, and levels of hypoxia‐inducible factor (HIF‐1α), P‐AKT, AKT, and PI3K proteins were analyzed using Western blotting. An in vitro anoxia model was established by treating the human trophoblast cell line HTR‐8/SVneo with cobalt chloride (CoCl2). Standard techniques were employed to measure proliferation, apoptosis, and reactive oxygen species (ROS) production rates in the anoxic cells, with and without EDA treatment. Results HIF‐1α, P‐AKT, AKT, and PI3K protein levels were significantly elevated in the placenta of the PE group compared with the control group. EDA mitigated the CoCl2‐induced decrease in HTR‐8/SVneo cell viability and reduced apoptosis and ROS production. Furthermore, EDA counteracted the activation of the PI3K/AKT pathway in CoCl2‐treated trophoblasts. Conclusion EDA protected trophoblasts against hypoxic injury by inhibiting the PI3K/AKT pathway, suggesting that it may serve as a promising therapeutic option for PE.

Objective To assess the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2-I) on cardiac remodeling and prognosis in type 2 diabetes mellitus (T2DM) patients presenting with acute myocardial infarction (AMI). Methods In this single-center retrospective active-comparator study, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2021 and 2023 were enrolled. Patients were divided into SGLT2-I users and non-SGLT2-I users based on discharge medications. The primary endpoint was the left ventricular remodeling index (LVRI), defined as the relative change in LV end-diastolic volume after six months. The secondary outcomes included major adverse cardiovascular events (MACE), comprising all-cause mortality, hospitalization for heart failure, nonfatal MI, and nonfatal stroke. Results The study comprised 423 T2DM AMI patients(with or without ST-segment elevation), with 239 SGLT2-I users and 184 non-SGLT2-I users. At six months, LVRI was significantly lower in the SGLT2-I users compared to the non-SGLT2-I users (3.49 ± 19.71 vs 7.06 ± 15.15, P = .042). The non-SGLT2-I users exhibited a higher prevalence of positive LVR (LVRI > 0%) (64.67% vs 50.63%, P = .004) and pathological LVR (LVRI > 20%) (19.57% vs 12.13%, P = .036). Multivariate logistic regression indicated that SGLT2-I was associated with a reduced risk of LVR (OR 0.6; 95%CI 0.38-0.97; P = .035). During a mean follow-up of 25 ± 8 months, Kaplan-Meier analysis demonstrated a lower rate of MACE-free survival in the non-SGLT2-I users ( P = .005). Conclusions SGLT2-I protects against LVR and lowers the risk of adverse cardiovascular outcomes in T2DM AMI patients.

Regulated necrosis (necroptosis) and apoptosis are important biological features of ischemia-reperfusion (I/R) injury. However, the molecular mechanisms underlying myocardial necroptosis remain elusive. Leucine rich repeat containing G protein-coupled receptor 6 (LGR6) has been reported to play important roles in various cardiovascular disease. In this study, we aimed to determine whether LGR6 suppresses I/R-induced myocardial necroptosis and the underlying molecular mechanisms. We generated LGR6 knockout mice and used ligation of left anterior descending coronary artery to produce an in vivo I/R model. The effects of LGR6 and its downstream molecules were subsequently identified using RNA sequencing and CHIP assays. We observed significantly downregulated LGR6 expression in hearts post myocardial I/R and cardiomyocytes post hypoxia and reoxygenation (HR). LGR6 deficiency promoted and LGR6 overexpression inhibited necroptosis and acute myocardial injury after I/R. Mechanistically, in vivo and in vitro experiments suggest that LGR6 regulates the expression of STAT2 and ZBP1 by activating the Wnt signaling pathway, thereby inhibiting cardiomyocyte necroptosis after HR. Inhibiting STAT2 and ZBP1 effectively alleviated the aggravating effect of LGR6 deficiency on myocardial necroptosis after I/R. Furthermore, activating LGR6 with RSPO3 also effectively protected mice from acute myocardial I/R injury. Our findings reveal that RSPO3-LGR6 axis downregulates the expression of STAT2 and ZBP1 through the Wnt signaling pathway, thereby inhibiting I/R-induced myocardial injury and necroptosis. Targeting the RSPO3-LGR6 axis may be a potential therapeutic strategy to treat myocardial I/R injury.

Accumulating evidence has revealed that chronic unresolved inflammation can cause significant tissue damage and can be a key mediator of advanced heart failure (HF). Resolvin (Rv) D2, a member of specialized pro-resolving lipid mediators (SPMs), plays a protective role in various diseases by facilitating resolution. However, whether RvD2 participates in the pathogenesis of HF is still unclear. Our study demonstrated that RvD2 treatment mitigated cardiac remodeling and improved cardiac function in HF mice induced by pressure overload. The absence of G protein-coupled receptor 18 (GPR18), an endogenous receptor for RvD2, abolished the beneficial effects of RvD2 on HF. Additionally, RvD2 inhibited inflammatory responses and Ly6Chigh macrophage polarization during both early and late inflammatory stages involved in HF. Further investigation revealed that bone marrow transplantation from Gpr18 deficient mice into WT mice blocked the protective effects of RvD2 in HF mice. Moreover, Gpr18 deficiency impeded RvD2's capacity to downregulate inflammatory responses and Ly6Chigh macrophage polarization. Consistent with experiments in vivo, RvD2 treatment in bone marrow-derived macrophages (BMDMs) reduced inflammatory responses through its receptor GPR18. Mechanistically, RvD2 suppressed the phosphorylation of STAT1 and NF-κB p65, and the effects of RvD2 were reversed by the application of STAT1 or NF-κB p65 agonists in BMDMs. In conclusion, RvD2/GPR18 axis improved cardiac remodeling and function in pressure overload-induced HF mice by modulating macrophage phenotype via STAT1 and NF-κB p65 pathways. Our findings underscore the anti-inflammatory potential of RvD2/GPR18 axis, suggesting that RvD2/GPR18 axis may be a potential strategy for the treatment of HF.

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. Methods and design The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. Conclusions As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. Registration Number in ClinicalTrials.gov NCT05311072.

Abstract This study aimed to establish a machine learning (ML) model for predicting hepatic metastasis in esophageal cancer. We retrospectively analyzed patients with esophageal cancer recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2020. We identified 11 indicators associated with the risk of liver metastasis through univariate and multivariate logistic regression. Subsequently, these indicators were incorporated into six ML classifiers to build corresponding predictive models. The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. A total of 17,800 patients diagnosed with esophageal cancer were included in this study. Age, primary site, histology, tumor grade, T stage, N stage, surgical intervention, radiotherapy, chemotherapy, bone metastasis, and lung metastasis were independent risk factors for hepatic metastasis in esophageal cancer patients. Among the six models developed, the ML model constructed using the GBM algorithm exhibited the highest performance during internal validation of the dataset, with AUC, accuracy, sensitivity, and specificity of 0.885, 0.868, 0.667, and 0.888, respectively. Based on the GBM algorithm, we developed an accessible web-based prediction tool (accessible at https://project2-dngisws9d7xkygjcvnue8u.streamlit.app/ ) for predicting the risk of hepatic metastasis in esophageal cancer.

Objective To explore the influencing factors the combination of acute renal tubular injury （ARTI） in patients with idiopathic membranous nephropathy （IMN） in a multi-ethnic area of Guangxi. Methods From April 2013 to October 2021, 155 patients with IMN diagnosed by renal biopsy and hospitalized at Hechi People's Hospital were recruited. They were assigned into two groups of with ARTI （n = 43） and without （n = 112）. Results Multifactorial Logistic analysis revealed that serum β2 microglobulin （β2-MG） was independently associated with ARTI in IMN patients （OR = 1.06, 95%CI: 1.01 to 1.12, P = 0.014）. AUC value for ROC curve analysis of serum β2 microglobulin for diagnosing ARTI was 0.748. An optimal threshold value of 2.65 mg/L corresponded to a sensitivity of 81.4% and a specificity of 58.04%. According to serum β2 microglobulin level, they were assigned into three groups of low, medium and high. The odds of ARTI spiked 5.01 and 22.89 folds in medium and high groups as compared with low group. And the results of trend test indicated that the odds of ARTI in IMN patients increased with a rising serum β2 microglobulin concentration （P＜0.001）. Stratified interaction test analysis revealed an interaction between serum β2 microglobulin and ARTI in IMN patients among gender, differential degrees of hypoproteinemia and ethnicity （P for interaction ＜0.05）. Conclusion Serum β2 microglobulin is independently associated with ARTI in IMN patients. And an interaction exists between gender, differential levels of hypoproteinemia and ethnicity.

ABSTRACT Objective To investigate the differences in headache and comorbidity symptoms between migraine patients with negative and positive food specific IgG antibodies, and explore the correlation between these symptoms with food specific IgG antibodies. Methods A total of 129 migraine patients were enrolled. Seven questionnaires were used to gather information regarding the symptoms of migraine, gastrointestinal, depression, anxiety, and sleep. Serum specific IgG antibodies against 14 kinds of food were detected using enzyme‐linked immunosorbent assays. Results Patients with migraine diagnosis who had positive food specific IgG antibodies had significantly worse headaches, gastrointestinal and anxiety symptoms, compared to the patients with negative IgG antibodies. Patients with more IgG positive foods and higher total positive IgG concentration generally had worse migraine conditions, anxiety, depression, and gastrointestinal symptoms. Conclusion The effect of food specific IgG antibodies on severity of migraine and its comorbidities were antibody‐quantity and IgG‐concentration dependent. Future studies are warranted to explore the mechanism underlying such relationship.

ObjectiveThis study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections. The study seeks to address the gaps identified in the latest guidelines regarding the optimal use of different corticosteroid types and to provide recommendations for clinical practice.Data SourcesThis study conducted a comprehensive search of Medline, Embase, and the Cochrane Central Register of Controlled Trials, covering the period from inception until 22 June 2023. Randomized clinical trials for corticosteroid use among adults with SCAP were collected.Study SelectionTwo researchers independently assessed study eligibility based on titles and abstracts, with any disagreements resolved through discussion or consultation with a third researcher.Data ExtractionTwo researchers independently collected and clarified study details, with a third researcher adjudicating in case of disputes.Data SynthesisThe data from 13 randomized clinical trials involving 2,495 patients, were analyzed using a random-effects model. Eleven trials were assessed as low risk, while two were assessed as high risk. Trials were rated as having low bias risk. Results, presented as risk ratios (RR) with a 95% confidence interval (CI), indicated that hydrocortisone outperformed prednisolone (RR 0.35; 95% CI 0.10–0.94), methylprednisolone (RR 0.41; 95% CI 0.15–0.89), and placebo (RR 0.35; 95% CI 0.16–0.59) in reducing 30-day mortality. A rankogram plot suggested that hydrocortisone had the highest probability of being the most effective treatment for this outcome within the analyzed group.ConclusionIn this network meta-analysis, while hydrocortisone showed greater efficacy than prednisolone, methylprednisolone, and placebo in reducing 30-day mortality in patients with SCAP, further Randomized Controlled Trials (RCTs) are required to confirm these findings before drawing definitive conclusions.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438389, identifier CRD42023438389.

BackgroundSince the emergence of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), millions of lives have been lost, posing formidable challenges to healthcare systems worldwide. Our study aims to conduct a meta-analysis to evaluate the efficacy of vitamin C supplementation in reducing in-hospital mortality rates and shortening the length of ICU or hospital stays among patients diagnosed with COVID-19.MethodsA comprehensive systematic review and meta-analysis was conducted, sourcing data from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Our analysis focused on randomized clinical trials comparing the efficacy of vitamin C supplementation with standard care in adult COVID-19 patients.ResultsThrough meticulous examination of 11 clinical trials, our meta-analysis found that vitamin C supplementation did not reduce in-hospital mortality rates in COVID-19 patients compared to those receiving standard care (Risk Ratio [RR] = 0.85; 95% Confidence Interval [CI]: 0.62–1.17; p = 0.31). Similarly, the analysis indicated no significant difference in the length of ICU stays between both cohorts. Additionally, the occurrence of other adverse events was found to be similar across both groups treated with vitamin C supplementation and standard care (all p > 0.05).ConclusionVitamin C supplementation did not reduce in-hospital mortality or ICU stay durations in patients with COVID-19. The interpretation of these findings is limited by the small number of available studies and participants, which affects the strength of the conclusions.Clinical trial registrationIdentifier CRD42024497474.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia due to multiple etiological factors. In diabetics, lipid accumulation may cause lipid peroxidation and cell membrane lipid oxidation, leading to cellular injuries and triggering dysfunctions. Lipid accumulation may also lead to kidney injury in diabetics, such as glomerulosclerosis, tubular injury and loss of podocytes. As a water-soluble low molecular glycoprotein, apolipoprotein C3 (APOC3) is an important factor in the regulation of human lipid metabolism. It is closely involved in the development of diabetes mellitus and related complications through insulin resistance, lipid metabolism disorders, inflammation and oxidative stress. This review summarized the role and mechanism of APOC3 in diabetes and diabetic kidney disease.

There is a lack of comprehensive evaluation on the impact of ESG rating differences on the green transformation of energy enterprises in the transition era. This study leverages data from companies listed on the Shanghai Stock Exchange in China, applying double machine-learning algorithms to precisely estimate the causal relationship between variations in ESG ratings and the green transition efficiency of energy companies. The research shows that the difference in ESG ratings of third-party rating agencies significantly promotes the efficiency of green transformation of energy enterprises. This paper also studies the influencing factors of this effect: First, ESG rating differences significantly promote the improvement of green transition efficiency of energy enterprises; Second, the positive effect is more pronounced in energy companies with more balanced board structures. Finally, energy companies with high capital market attention can also contribute to this positive impact. Through the mechanism test, this paper finds that enterprise green innovation is an important mechanism for ESG rating divergence to positively promote the efficiency of energy enterprises’ green transformation. Furthermore, this paper analyzes the impact of ESG rating on enterprises from the perspective of market cognition and short-term behavior, which provides a new perspective for analyzing the practice of enterprises pursuing long-term transformation. The study also calls for a more sober reflection on the trend toward ESG in society.