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Cardiovascular disease is a significant cause of death in humans. Various models are necessary for the study of cardiovascular diseases, but once cellular and animal models have some defects, such as insufficient fidelity. As a new technology, organoid has certain advantages and has been used in many applications in the study of cardiovascular diseases. This article aims to summarize the application of organoid platforms in cardiovascular diseases, including organoid construction schemes, modeling, and application of cardiovascular organoids. Advances in cardiovascular organoid research have provided many models for different cardiovascular diseases in a variety of areas, including myocardium, blood vessels, and valves. Physiological and pathological models of different diseases, drug research models, and methods for evaluating and promoting the maturation of different kinds of organ tissues are provided for various cardiovascular diseases, including cardiomyopathy, myocardial infarction, and atherosclerosis. This article provides a comprehensive overview of the latest research progress in cardiovascular organ tissues, including construction protocols for cardiovascular organoid tissues and their evaluation system, different types of disease models, and applications of cardiovascular organoid models in various studies. The problems and possible solutions in organoid development are summarized.

Abstract Objective To analyzed the safety and efficacy of percutaneous nephrolithotomy (PCNL) in lateral decubitus position and prone position for upper ureteral calculi. Methods Databases including PubMed, Springer, ScienceDirect, Wiley Online Library, CNKI, CSPD and VIP were searched for clinical controlled studies involved with lateral decubitus position and prone position PCNL from their establishment to November 2023.Studies were enrolled according to inclusion and exclusion criteria. the dates were compared by Review Manager 5.4 software. Results seven studies were eligible, including 807 cases. The Meta-analysis showed that, blood loss and perioperative complication rate of lateral decubitus position PCNL group were significantly different from those of the prone position PCNL group (P 0.05).Conclusions The lateral decubitus position can reduce blood loss and perioperative complication rate. The lateral decubitus position PCNL is safe and effective for upper ureteral calculi which was deserved clinical popularizing use.

Introduction: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and it significantly increases the risk of cardiovascular complications and morbidity, even with appropriate treatment. Tissue remodeling has been a significant topic, while its systematic transcriptional signature remains unclear in AF. Objectives: Our study aims to systematically investigate the molecular characteristics of AF at the cellular-level. Methods: We conducted single-nuclei RNA-sequencig (snRNA-seq) analysis using nuclei isolated from the left atrial appendage (LAA) of AF patients and sinus rhythm. Pathological staining was performed to validate the key findings of snRNA-seq. Results: A total of 30 cell subtypes were identified among 80, 592 nuclei. Within the LAA of AF, we observed a specific subtype of dedifferentiated cardiomyocytes (CMs) characterized by reduced expression of cardiac contractile proteins (TTN and TRDN) and heightened expression of extracellular-matrix related genes (COL1A2 and FBN1). Transcription factor prediction analysis revealed that gene expression patterns in dedifferentiated CMs were primarily regulated by CEBPG and GISLI. Additionally, we identified a distinct subtype of endothelial progenitor cells (EPCs) demonstrating elevated expression of PROM1 and KDR, a population decreased within the LAA of AF. Epicardial adipocytes disclosed a reduced release of the anti-inflammatory and anti-fibrotic factor PRG4, and an augmented secretion of VEGF signals targeting CMs. Additionally, we noted accumulation of M2-like macrophages and CD8+ T cells with high pro-inflammatory score in LAA of AF. Furthermore, the analysis of intercellular communication revealed specific pathways related to AF, such as inflammation, extracellular matrix, and vascular remodeling signals. Conclusions: This study has discovered the presence of dedifferentiated CMs, a decrease in endothelial progenitor cells, a shift in the secretion profile of adipocytes, and an amplified inflammatory response in AF. These findings could offer crucial insights for future research on AF and serve as valuable references for investigating novel therapeutic approaches for AF.

Abstract The Islamist group ISIS has been particularly successful at recruiting Westerners as terrorists. A hypothesized explanation is their simultaneous use of two types of propaganda: Heroic narratives, emphasizing individual glory, alongside Social narratives, which emphasize oppression against Islamic communities. In the current study, functional MRI was used to measure brain responses to short ISIS propaganda videos distributed online. Participants were shown 4 Heroic and 4 Social videos categorized as such by another independent group of subjects. Persuasiveness was measured using post-scan predictions of recruitment effectiveness. Inter-subject correlation (ISC) was used to measure commonality of brain activity time courses across individuals. ISCs in ventral striatum predicted rated persuasiveness for Heroic videos, while ISCs in mentalizing and default networks, especially in dmPFC, predicted rated persuasiveness for Social videos. This work builds on past findings that engagement of the reward circuit and of mentalizing brain regions predicts preferences and persuasion. The observed dissociation as a function of stimulus type is novel, as is the finding that intersubject synchrony in ventral striatum predicts rated persuasiveness. These exploratory results identify possible neural mechanisms by which political extremists successfully recruit prospective members and specifically support the hypothesized distinction between Heroic and Social narratives for ISIS propaganda.

BackgroundIncreasing evidence suggests that the CXC chemokine receptor 6 (CXCR6) is involved in tumor progression and the regulation of tumor immunity. However, its role in muscle-invasive bladder cancer (MIBC) remains largely unexplored.MethodsData from 391 MIBC patients in the TCGA, 212 patients from GEO, 131 patients from our center, 195 patients in the IMvigor210 cohort, and single-cell RNA sequencing (scRNA-seq) data from 9 bladder cancer patients (GSE222315) were analyzed. Additionally, data from the GEPIA 2, TISCH2, TIMER2.0, and UALCAN platforms were utilized to investigate the prognostic and immunotherapeutic significance of CXCR6 in MIBC.ResultsWe observed that CXCR6 expression was significantly reduced in bladder cancer tumors and correlated with tumor stage and grade. Low CXCR6 expression was associated with poor recurrence-free survival (RFS) and overall survival (OS) in the TCGA cohort, a finding validated in both the meta-GEO dataset and our center’s cohort. Multivariate analysis confirmed that low CXCR6 expression was an independent predictor of poor OS and RFS. A nomogram incorporating CXCR6 expression and other independent prognostic factors was developed to accurately predict 3- and 5-year OS. Gene set enrichment analysis indicated that immune activation-related pathways were significantly enriched in tumors with high CXCR6 expression. CIBERSORT analysis revealed that CXCR6 expression was positively correlated with CD8+ T cells, CD4+ T cells, activated NK cells, M1 macrophages, and activated dendritic cells in TCGA, findings further validated by TIMER2.0. scRNA-seq data showed that CXCR6 was predominantly expressed in T and NK cells and facilitated T/NK-myeloid interaction via the CXCR6-CXCL16 axis. Importantly, CXCL16+ macrophages and dendritic cells recruited CXCR6+ T and NK cells, which exhibited enhanced cytotoxicity, thereby amplifying anti-tumor immunity. Clinically, in the IMvigor210 immunotherapy cohort, higher CXCR6 expression was associated with improved anti-PD-L1 therapeutic outcomes.ConclusionOur findings highlight CXCR6 as a critical biomarker for predicting prognosis and immunotherapeutic response in MIBC.

The edge reconstruction of two‐dimensional (2D) materials is significant for the stability, properties, and applications. Significant progress has been made in understanding the edge reconstruction of 2D materials. Herein, an overview of the latest theoretical and experimental advances on edge reconstruction of α‐phase phosphorene nanoribbon and IV–VI group binary compounds MX (M = Ge, Sn; X = S, Se), focusing on the mechanism, stability, physical, and chemical properties of the edge reconstructions is provided. The status, challenges, and contradictions in experiments and theory are addressed and the progress in edge reconstruction of α‐phase puckered 2D materials as well as the effects of edge reconstruction on physicochemical properties are systematically introduced. A novel tube‐like edge reconstruction is suggested to be universal for α‐phase puckered monolayers. While ZZ(U) edge can be another important reconstruction in bilayer. Beyond the review, the edge structures of phosphorene have odd–even layered oscillations are also proposed. The edge terminations can affect the exfoliation mechanism and electronic, transport properties. Interesting, unique U‐edge, which has been verified by experiment, exhibits nearly edgeless electronic and thermal transport, which is beneficial for ultrafast microelectronics.

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three vesicular glutamate transporters (Slc17a7 (Vglut1), Slc17a6 (Vglut2), and Slc17a8 (Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA-derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.

IntroductionPoor graft function (PGF), characterized by myelosuppression, represents a significant challenge following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with human cytomegalovirus (HCMV) being established as a risk factor for PGF. However, the underlying mechanism remains unclear. Bone marrow endothelial progenitor cells (BM-EPCs) play an important role in supporting hematopoiesis and their dysfunction contributes to PGF development. We aim to explore the effects of CMV on BM-EPCs and its underlying mechanism.MethodsWe investigated the compromised functionality of EPCs derived from individuals diagnosed with HCMV viremia accompanied by PGF, as well as after infected by HCMV AD 169 strain in vitro, characterized by decreased cell proliferation, tube formation, migration and hematopoietic support, and increased apoptosis and secretion of TGF-β1.ResultsWe demonstrated that HCMV-induced TGF-β1 secretion by BM-EPCs played a dominant role in hematopoiesis suppression in vitro experiment. Moreover, HCMV down-regulates Vitamin D receptor (VDR) and subsequently activates p38 MAPK pathway to promote TGF-β1 secretion by BM-EPCs.DiscussionHCMV could infect BM-EPCs and lead to their dysfunction. The secretion of TGF-β1 by BM-EPCs is enhanced by CMV through the activation of p38 MAPK via a VDR-dependent mechanism, ultimately leading to compromised support for hematopoietic progenitors by BM EPCs, which May significantly contribute to the pathogenesis of PGF following allo-HSCT and provide innovative therapeutic strategies targeting PGF.

Heat performance and internal pressure loss are important reference standards in solar air heaters (SAH). In order to solve the problem of too large a pressure loss in SAH, an innovative SAH with sinusoidal baffles was proposed on the basis of folded baffle and semi-circular baffle air heaters. A computational fluid dynamics (CFD) simulation calculation was performed for the SAH with sinusoidal baffles, and the relevant parameters, such as the heat collection efficiency and the pressure loss, were analyzed. The results showed that the sinusoidal baffle had a better heat collection performance and a smaller pressure loss compared to the folded baffle and the semi-circular baffle. A sinusoidal baffle can further improve the thermal performance of SAH. The simulation calculation of wave lengths for sinusoidal baffles revealed that when the wavelength value was 200 mm, the SAH had the best heat collection effect, and the heat collection efficiency was 64.49%. On the basis of determining the wavelength, the wave height of the sinusoidal baffle was studied. When the wave height was 30 mm, the minimum pressure loss of the SAH was 17.51 Pa, and the maximum heat collection efficiency was 64.91%. Analyses and research on the Reynolds number of the air inlet showed that as the Reynolds number increased, the collection efficiency and internal pressure loss gradually increased, while the outlet temperature decreased. The curve fitting of the imported Reynolds number and the pressure loss showed that the accuracy of pressure loss fitting curve is 0.997. Research on a double-layer SAH showed that the cross different inlet (CDI) had the best collector performance. This research has a high practicality and can provide a theoretical basis for winter air heating.

Abstract Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung’s development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

Abstract Based on a total of 1,590 listed non-financial firms on the Taiwan Stock Exchange and the Taipei Exchange (formerly the Over The Counter securities market) covering the period of 2007~2020, this study examines whether firm's performance on Corporate Social Responsibility (CSR) is affected by corporate board gender diversity. Based on the Upper Echelons Theory, the Agency Theory and the Resource Dependence Theory, increasing the number of female director to achieve higher level of gender diversity brings forth traits such as compassion, kindness, helpfulness, empathy, interpersonal sensitivity, a willingness to nurture, and a greater concern for others' well-being. These traits help firms form policies that prioritize stakeholders' welfare. Moreover, board gender diversity corresponds to a more diverse and broad background, understanding and experience of business operations, enabling firms to better understand where the key interest groups they face are and what they value. This allows firms to make more effective and better-performing decision in CSR. Through correlation analysis and multiple regression estimation, the principal outcome shows that greater degree of board gender diversity is associated with better CSR performance, confirming the hypothesis that a more gender diversified board enhances the efficiency of monitoring and advising function of board and then forming corporate strategies and implementations toward a better stakeholders’ management.

ObjectiveTo determine the function of miR-125a-5p in laryngeal squamous cell carcinoma (LSCC), its correlation with radiation sensitivity, and the underlying regulatory mechanism.Materials and methodsWe conducted the analysis on the correlation between miR-125a-5p and head and neck squamous cell carcinoma (HNSCC) using data obtained from The Cancer Genome Atlas (TCGA). The putative gene targeted by miR-125a-5p has been identified as HK2, while the expression levels of miR-125a-5p and HK2 were measured in laryngeal cancer tissues and cells using RT-PCR. MiR-125a-5p and HK2 were introduced into the lentiviral vector and the vector was used to transfect AMC-HN-8 cells. The roles of miR-125a-5p and HK2 in LSCC and on radiosensitivity were determined by evaluating cell growth, examining colony formation, analyzing flow cytometry, and utilizing the single hit multi-target model. Western blotting was used to measure H2AX and rH2AX levels in the DNA damage response (DDR) pathway. The validation of the interaction between miR-125a-5p and HK2 was conducted through the dual-luciferase assay. To further confirm the association between miR-125a-5p and HK2, as well as its influence on radiosensitivity, rescue experiments were performed.ResultsThe expression of miR-125a-5p is downregulated in LSCC, while upregulating its expression could suppress cell growth, induce apoptosis, and enhance radiosensitivity. Additionally, HK2 exhibited high expression in LSCC and the biological function was opposite to miR-125a-5p. Western blotting analysis revealed that miR-125a-5p increased rH2AX levels and decreased H2AX levels, conversely, HK2 had the opposite effect on miR-125a-5p. These findings suggested that HK2 may serve as the target gene of miR-125a-5p. The double luciferase assay confirmed the binding of HK2 to miR-125a-5p, and rescue trials confirmed the role of miR-125a-5p in regulating the effects and radiation sensitivity of LSCC by targeting HK2 via the DDR pathway.ConclusionBy targeting HK2 and impacting the DDR pathway, miR-125a-5p has been found to inhibit cellular proliferation, enhance apoptosis, and heighten radiosensitivity in LSCC.

Air-to-air membrane-energy exchangers have been widely used in green buildings as passive energy-recovery technologies for energy conservation and carbon reduction. An air-to-air membrane-energy exchanger conserves building energy by forcing the indoor exhaust air and unconditioned fresh air to exchange heat and moisture. As a critical performance indicator, the energy-exchange efficiency is primarily determined by the core. To improve energy-saving performance, many studies have been conducted to analyze and enhance the efficiency of air-to-air membrane-energy exchanger cores by manufacturing, testing, modeling, and comparing different cores. However, few studies have investigated the uncertainty introduced by the manufacturing and testing processes (most related research only studied the uncertainty of the sensible efficiency), which means that some positive results of those controlled trials are possibly owing to the manufacturing tolerance or testing errors, rather than real technical progress. This study addresses this problem by quantifying the efficiency uncertainty caused by manufacturing and testing processes. Three cores were produced using the same manufacturing process and materials, followed by identical experimental tests on their sensible, latent, and enthalpy efficiencies. Comparison results suggest that even when all variables are controlled, the differential enthalpy efficiency of two “identical” cores still vary from 0 % to 2 %. Variance of repetitive testing results of a certain core can afford an enthalpy efficiency of 4 % owing to a non-ideal experimental procedure. When manufacturing tolerances and experimental errors are considered simultaneously, the differential sensible efficiency among multiple “identical” cores is within 0–5%, whereas latent efficiency data in winter shows a significant variation of 5–10 % for “identical” cores. The contributions and conclusions of this study are as follows. The efficiency uncertainty caused by manufacturing and testing processes is non-negligible, particularly in latent efficiency. This phenomenon could alert researchers and engineers in this field to conduct repetitive manufacturing and testing while trying to modify/test/compare air-to-air membrane-energy exchanger cores. Because this study is based on a limited number of cores, the quantitative results of this study should be considered a non-universal reference, and a systematic benchmark must be established in the future.

To determine the optimal baffle's type (longitudinal and transverse baffles) and the number of baffles, two computational fluid dynamics (CFD) models for solar air heaters (SAHs) were developed by using ''ANSYS Fluent'' software. The computational results closely aligned with the experimental data. As the width of the air channel in SAHs with transverse baffles was narrower than in those with longitudinal baffles under the same number of baffles, the heat transfer coefficient of SAHs with transverse baffles was greater than those with longitudinal baffles. Thus, for the airflow rate (m˙) range of 0.013 kg s−1 to 0.078 kg s−1, SAHs with transverse baffles exhibited 2.34 %–6.97 % higher collection efficiency compared to those with longitudinal baffles. An analysis of the impact of the number of transverse baffles (N) on the flow and heat transfer characteristics in SAHs revealed that both the size and intensity of the vortex zones increased with an increase in N, thereby influencing the heat transfer between the air and the absorber plate. Specifically, among the studied values of N (2, 4, 6, and 8), at = 0.026 kg s−1, N = 4 achieved the peak effective efficiency at 54.32 %. Conversely, for m˙ = 0.039 kg s−1, 0.052 kg s−1, 0.065 kg s−1, and 0.078 kg s−1, the highest effective efficiency was observed at N = 6, with values of 60.03 %, 63.78 %, 64.39 %, and 64.38 %, respectively.

Clusters, an aggregation of several to thousands of atoms, molecules, or ions, are the building blocks of novel functional materials by atomic manufacturing and exhibit excellent applications in catalysis, quantum information, and nanomedicine. The evolution of cluster structures has been studied for many years. Many effective structural search methods, such as genetic algorithm, basin‐hopping, and so on, have been developed. However, the efficient execution of these methods relies on precise energy calculators, such as density functional theory (DFT) calculations. Up to now, limited by computational methods and capabilities, the researches mainly focus on free‐standing clusters, which are different from clusters in practical applications. Recently, the rapid development of big data‐driven machine learning is expected to replace DFT for high‐precision large‐scale computing. In this review, the present cluster search methods and challenges currently faced have been summarized. It is proposed that the development of artificial intelligence has the potential to solve some practical problems including the structural and properties evolution of clusters in complex environment, causing revolutionary developments in the fields of catalysis, quantum information, and nanomedicine based on clusters.

Abstract Wind power supply chains are evolving as markets expand to reach climate goals. With the largest installed wind power capacity globally, China must deal with increasing composite turbine waste and anticipate its associated costs. Here we predict the quantity and composition of wind turbine blade waste based on historic deployment. A high-resolution database containing 14 turbine capacities (150–5500 kilowatts) was compiled based on 104 turbine models. The environmental and financial costs of waste treatment options were evaluated using a bottom-up approach. Based on current installations and future projections, 7.7 to 23.1 million tonnes of blade waste will be generated in China by 2050. Technologies exist to recycle glass fibre from blade waste, but these solutions vary in level of maturity and are not always commercially available, cost-competitive, or environmentally sustainable. Our findings can inform decision-makers in governments and industry on the pathways to carbon neutrality.

Tin-based Babbitt alloys are a widely used bearing bushing material which have good comprehensive properties. However, problems such as high-temperature softening and insufficient bearing capacity occur during their use, so the optimization of tin-based Babbitt alloys has become a research hotspot. In this paper, ZChSnSb11-6 alloy was mainly prepared by the gravity casting method, and different amounts of Zn were added to the alloy (the mass fraction values were 0 wt.%, 0.05 wt.%, 0.1 wt.%, 0.15 wt.%, and 0.2 wt.%, respectively). Through the hardness test, the tensile test, the friction and wear test, and the microstructure observation of the prepared alloy, the influence of Zn on the organization and properties of the ZChSnSb11-6 alloy was analyzed. The results show that the size of the SnSb hard phase changed with the increasing content of Zn. The size of the hard phase of the SnSb tended to increase first and then decrease, and the number of phase particles increased first and then decreased, resulting in changes in performance. Through comparison, it was learned that the addition of Zn can effectively improve the hardness, tensile strength, yield strength, and wear resistance of the alloy, but the elongation rate was reduced. When the Zn content was 0.1 wt.%, the hardness value of the alloy reached the maximum value, 25.82 HB, which increased by 7.3% when compared with the sample without Zn. The hardness of the Zn, 0.15 wt.%, is close to that of the Zn, 0.1 wt.%. Compared to the sample without Zn, the tensile strength and elongation of the alloy were maximized at a Zn content of 0.15 wt.%. Compared to the sample without the Zn, the tensile strength was increased by 21.29%, and the elongation rate was increased by 46%. An analysis showed that the alloy has good comprehensive mechanical properties when the Zn content is 0.15 wt.%.

Renewable energy promotes the sustainable development of the environmental protection industry (EPI) and the economy. Meanwhile, the EPI provides various technologies and services for renewable energy, which is an important guarantee for the renewable energy market. This paper combines the DY and BK spillover indexes to discuss the cross-market risk contagion effect between EPI and renewable energy market from the perspective of time-frequency spillover. The results show that: (1) The spillover effect between the EPI and renewable energy market is cyclical from the perspective of frequency domain, and the total market spillover is dominated by high-frequency spillover. And the risk contagion has the characteristics of time-varying and vulnerability from the perspective of time domain. (2) The net spillover effect shows that the EPI plays the role of a net exporter in different frequency domains, the solar energy and the hydro market play more roles as risk receivers, and the role of the wind energy market is frequently converted. (3) The risk spillover network structure shows that EPI acts as an important node in the cross-market risk contagion path. Driven by EPI, the short-term risk transmission follows the path of “EPI-biomass energy-other four renewable energy markets”, and the medium and long-term follows the path of “EPI-wind energy-other four renewable energy markets”.

BackgroundGastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, with its etiology attributed to a complex interplay of genetic, dietary, environmental factors, and infections such as Helicobacter pylori. Despite the known risk factors, the role of gut microbiota in the development of gastric cancer remains insufficiently explored. This study aims to elucidate the causal relationship between gut microbiota and gastric cancer using a two-sample Mendelian Randomization (MR) approach.MethodsUtilizing genome-wide association study (GWAS) summary data from the MiBioGen consortium and gastric cancer datasets, we selected instrumental variables for MR analysis based on their association with specific microbiota. We employed several MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and others, to estimate the causal effects of gut microbiota diversity on the risk of developing gastric cancer.ResultsOur analysis identified significant associations between certain gut microbiota and gastric cancer risk. Specifically, taxa such as Clostridium sensustricto1 (OR = 0.540, 95%CI: 0.354–0.823, p = 0.004), Actinomycetales (OR = 0.756, 95%CI: 0.613–0.932, p = 0.009), Selenomonadales (OR = 0.816, 95%CI: 0.666–1.000, p < 0.05), Negativicutes (OR = 0.816, 95%CI: 0.666–1.000, p < 0.05), Rikenellaceae (OR = 0.863, 95%CI: 0.746–0.999, p = 0.048) were found to have a protective effect against gastric cancer. Conversely, an increased risk of gastric cancer was associated with the abundance of Roseburia (OR = 1.342, 95%CI: 1.071–1.681, p = 0.011), Family XI (OR = 1.132, 95%CI: 1.012–1.267, p = 0.030), and Eubacterium brachy group (OR = 1.207, 95%CI: 1.074–1.355, p = 0.002). The findings were robust across various MR methods and were not driven by any single SNP, indicating a genuine causal relationship.ConclusionOur studies have shown that there is a causal relationship between intestinal flora and gastric cancer at the genetic level. Clostridium sensustricto1, Actinomycetales, Rikenellaceae, Selenomonadales, Negativicutes, and Actinomycetaceae as having a protective role against GC, while Roseburia, Family XI, and Eubacterium brachy group were associated with an increased risk.

Abstract Background Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD. Methods We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings. Results Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD. Conclusions Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.

Abstract Based on a total of 1,590 listed non-financial firms on the Taiwan Stock Exchange and the Taipei Exchanges covering the period of 2007 ~ 2020, this study examines whether a firm's capital structure is affected by its corporate social responsibility (CSR) performance. While existing research has explored the impact of a firm’s CSR performance on various financial and non-financial consequences, this study argues that firm engaging in CSR is putting greater emphasis on the financial and bankruptcy risks arising from the use of debt financing and to maintain firm’s sustainability, firm with better CSR performance tends to reduce the use of debt. Through descriptive statistics, correlation analysis and multiple regression estimation, principal outcome shows that firm with better CSR performance tends to use less debt financing and inter-temporally reduce the use of debt.

Computer-aided design usually gives inspirations and has become a vital strategy to develop novel pesticides through reconstructing natural lead compounds. Patulin, an unsaturated heterocyclic lactone mycotoxin, is a new natural PSII inhibitor and shows significant herbicidal activity to various weeds. However, some evidence, especially the health concern, prevents it from developing as a bioherbicide. In this work, molecular docking and toxicity risk prediction are combined to construct interaction models between the ligand and acceptor, and design and screen novel derivatives. Based on the analysis of a constructed patulin–Arabidopsis D1 protein docking model, in total, 81 derivatives are designed and ranked according to quantitative estimates of drug-likeness (QED) values and free energies. Among the newly designed derivatives, forty-five derivatives with better affinities than patulin are screened to further evaluate their toxicology. Finally, it is indicated that four patulin derivatives, D3, D6, D34, and D67, with higher binding affinity but lower toxicity than patulin have a great potential to develop as new herbicides with improved potency.

The distribution of energetic ion flux in the ring current region, such as a meteorological cumulonimbus cloud, stores up the particle energy for a geomagnetic substorm. It is helpful to study the geomagnetic substorm mechanism by using a lunar base ENA imaging simulation of the dynamic evolution of the ring current, and establishing the corresponding relationship between key node events of the substorm. Based on the previous observation experience and our simulation results of the dynamic evolution of the ring current, we propose a macroscopic model of substorms related to the dynamic evolution of ring currents and present the possibility of confirming the causal sequence of some of those critical node events of substorms with the lunar base ENA imaging measurement. IBEX, operating in the ecliptic plane, may even give examples of the telemetry of ring current ion fluxes through ENA measurements during substorms/quiets.

Abstract Background V domain Immunoglobulin suppressor of T cell activation (VISTA) has been proved to be a novel immune checkpoint molecule that positively regulates T cell infiltration in several malignancies. However, the clinical impact of VISTA on muscle-invasive bladder cancer (MIBC) patients remains relatively obscure. Methods This study enrolled 135 MIBC patients from Zhongshan Hospital (ZSHS) and 391 patients from The Cancer Genome Atlas (TCGA) to examine the VISTA expression and immune contexture based on immunohistochemistry (IHC) staining and CIBERSORT algorithm. Additionally, IMvigor210 Cohort included 195 bladder-derived urothelial carcinoma patients to evaluate the efficacy of immunotherapy. Kaplan-Meier curve and Cox regression analyses were conducted to assess clinical outcomes. Results MIBC patients with high VISTA+ immune cells (ICs) possessed poor overall survival and inferior therapeutic responsiveness to adjuvant chemotherapy (ACT), but superior responsiveness to PD-L1 inhibitor. VISTA+ ICs infiltration shaped an immunoevasive context featured by regulatory T cells (Tregs), M2 macrophages, mast cells and exhausted CD8+ T cells infiltration, with increased interleukin 10 (IL-10), transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ), but also elevated T-cell immunoglobulin mucin-3 (TIM-3), lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and ITIM domain (TIGIT), which was also mainly presented in basal-squamous and luminal-infiltrated subtypes of MIBC. Conclusion VISTA+ ICs infiltration could be an independent predictor to identify poor prognosis and therapeutic responses (PD-L1 blockade and ACT) in MIBC patients, which was associated with immunoevasive contexture. The novel immune checkpoint VISTA might be utilized as a candidate treatment biomarker in MIBC patients.

Abstract Introduction The purpose of this study was to assess the efficacy and safety of fractional CO2 laser combined with halometasone cream in patients with moderate-to-severe chronic hand eczema (CHE). Methods A prospective, single-center, parallel-group, open-label randomized trial including 67 patients with moderate-to-severe CHE was carried out. Patients were randomly assigned to group A (n = 33, fractional CO2 laser once every 4 weeks 1–2 times and halometasone cream twice daily for 8 weeks) or group B (n = 34, halometasone cream alone twice daily for 8 weeks). The primary endpoint was the proportion of patients achieving treatment success at week 12 in each group. Secondary endpoints included differences between groups in the change of hand eczema severity index (HECSI), patient global assessment (PaGA), dermatology life quality index (DLQI), and quality of life in hand eczema questionnaire (QOLHEQ) from baseline to week 12. Relapse rate and adverse effects were also recorded. Results A total of 29 patients in each group completed the trial. At week 12, the treatment success rate was 62.1% (18/29) in group A and 27.6% (8/29) in group B (p = 0.009). At week 12, HECSI, PaGA, DLQI, and QOLHEQ all decreased compared with baseline in both groups (p

With the rapid development of deep learning technology in recent years, convolutional neural networks have gained remarkable progress in SAR ship detection tasks. However, noise interference of the background and inadequate appearance features of small-scale objects still pose challenges. To tackle these issues, we propose a small ship detection algorithm for SAR images by means of a coordinate-aware mixed attention mechanism and spatial semantic joint context method. First, the coordinate-aware mixed attention mechanism innovatively combines coordinate-aware channel attention and spatial attention to achieve coordinate alignment of mixed attention features. In this way, attention with finer spatial granularity is conducive to strengthening the focusing ability on small-scale objects, thereby suppressing the background clutters accurately. In addition, the spatial semantic joint context method exploits the local and global environmental information jointly. The detailed spatial cues contained in the multi-scale local context and the generalized semantic information encoded in the global context are used to enhance the feature expression and distinctiveness of small-scale ship objects. Extensive experiments are conducted on the LS-SSDD-v1.0 and the HRSID dataset. The results with an average precision of 77.23% and 90.85% on the two datasets show the effectiveness of the proposed methods.

Abstract Background Though programmed cell death‐ligand 1 (PD‐L1) has been used in predicting the efficacy of immune checkpoint blockade (ICB), it is insufficient as a single biomarker. As a key effector of an intrinsically mutagenic microhomology‐mediated end joining (MMEJ) pathway, DNA polymerase theta (POLQ) was overexpressed in various malignancies, whose expression might have an influence on genomic stability, therefore altering the sensitivity to chemotherapy and immunotherapy. Methods A total of 1304 patients with muscle‐invasive bladder cancer (MIBC) from six independent cohorts were included in this study. The Zhongshan Hospital (ZSHS) cohort (n = 134), The Cancer Genome Atlas (TCGA) cohort (n = 391), and the Neo‐cohort (n = 148) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n = 234) and the UNC‐108 cohort (n = 89) were used for the assessment of immunotherapeutic response. In addition, the relationship between POLQ and the immune microenvironment was assessed, and GSE32894 (n = 308) was used only for the evaluation of the immune microenvironment. Results We identified POLQhigh PD‐L1high patients could benefit more from immunotherapy and platinum‐based chemotherapy. Further analysis revealed that high POLQ expression was linked to chromosome instability and higher tumor mutational burden (TMB), which might elicit the production of neoantigens. Further, high POLQ expression was associated with an active tumor immune microenvironment with abundant infiltration of immune effector cells and molecules. Conclusions The study demonstrated that high POLQ expression was correlated with chromosome instability and antitumor immune microenvironment in MIBC, and the combination of POLQ and PD‐L1 could be used as a superior companion biomarker for predicting the efficacy of immunotherapy.

Summary: Recent studies have demonstrated the pivotal involvement of endocannabinoids in regulating learning and memory, but the conclusions obtained from different paradigms or contexts are somewhat controversial, and the underlying mechanisms remain largely elusive. Here, we show that JZL195, a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase, can enhance the performance of mice in a contextual fear conditioning task and increase the time spent in open arms in the elevated zero maze (EZM). Although the effect of JZL195 on fear memory could not be inhibited by antagonists of cannabinoid receptors, the effect on the EZM seems to be mediated by CB1R. Simultaneously, hippocampal neurons are hyperactive, and theta oscillation power is significantly increased during the critical period of memory consolidation upon treatment with JZL195. These results suggest the feasibility of targeting the endocannabinoid system for the treatment of various mental disorders.

Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent low-grade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA. The cytotoxicity of DZ2002 was evaluated using the MTT assay on bone marrow-derived macrophages. The inhibitory impact of DZ2002 during the process of osteoclastogenesis was assessed using TRAP staining, analysis of bone resorption pits, and F-actin ring formation. Mechanistic insights were derived from qPCR and Western blot analyses. Through the intra-articular injection of monosodium iodoacetate (MIA), an experimental rat model of OA was successfully instituted. This was subsequently accompanied by a series of assessments including Von Frey filament testing, analysis of weight-bearing behaviors, and micro-CT imaging, all aimed at assessing the effectiveness of DZ2002. The findings emphasized the effectiveness of DZ2002 in mitigating osteoclastogenesis induced by M-CSF/RANKL, evident through a reduction in TRAP-positive OCs and bone resorption. Moreover, DZ2002 modulated bone resorption-associated gene and protein expression (CTSK, CTR, Integrin β3) via the MEK/ERK pathway. Encouragingly, DZ2002 also alleviates MIA-induced pain, cartilage degradation, and bone loss. In conclusion, DZ2002 emerges as a potential therapeutic contender for OA, as evidenced by its capacity to hinder in vitro M-CSF/RANKL-induced osteoclastogenesis and mitigate in vivo osteoarthritis progression. This newfound perspective provides substantial support for considering DZ2002 as a compelling agent for osteoarthritis intervention.

Objective KDM6A, a representative tumour suppressor gene with sex bias, is frequently altered in urothelial carcinoma (UC). The specific impacts of KDM6A mutations on gender-based clinical outcomes in UC remain poorly understood.Methods and analysis We enrolled 2438 patients with UC from seven independent real-world cohorts possessing comprehensive clinical and genomic data. Point mutations and homozygous deletions of KDM6A are categorised as KDM6AMut. We assessed the correlation between gender disparities in relation to KDM6A status and clinical outcomes, as well as genomic and immunological profiles.Results KDM6A mutations were identified in 679 of the 2306 patients with UC (29.4%), with 505 of 1768 (28.6%) in men and 174 of 538 (32.3%) in women. KDM6A mutations correlated with enhanced overall survival exclusively in male patients but were linked to improved outcomes following adjuvant chemotherapy only in female patients. Concerning immunotherapeutic responses, KDM6AMut male patients displayed the most favourable clinical outcomes, whereas KDM6AMut female patients demonstrated the least favourable outcomes. Independent of gender variations, KDM6AMut patients exhibited heightened androgen receptor and diminished oestrogen receptor 1 filtered regulon activity. Additionally, KDM6AMut male patients showed increased infiltration of T cells, cytotoxic T cells and NK cells with enriched neoantigens, in contrast to KDM6AMut female patients who manifested a more pronounced angiogenesis signature.Conclusion Our findings offer preliminary clinical evidence accentuating KDM6A alterations as a promising prognostic and predictive biomarker while elucidating the gender disparities observed in patients with UC.

Neuroinflammation plays a key role in the pathogenesis of post-cardiac arrest (CA) brain injury. Innate immune cells sense a variety of danger signals through pattern-recognition receptors and evoke rapidly after ischemic challenge, triggering inflammatory responses and amplifying brain damage. A programmed cell death (PCD) pathway is activated after ischemic and/or inflammatory stimuli, leading to the elimination of the damaged cells. However, PCD also regulates inflammatory responses flexibly. The present review aimed to summarize the mechanisms of inflammatory responses, including the biology of immune cells, the innate immune recognition that initiates the inflammation, and the immunomodulatory effects of PCD following CA. Promising therapeutic approaches of targeting inflammatory responses to alleviate brain injury and improve neurological outcomes after CA are also reviewed.

The nephrite belt in the Altun Mountain–Western Kunlun Mountain region, which extends about 1300 km in Xinjiang, NW China, is the largest nephrite deposit in the world. The Qiemo region in the Altun Mountains is a crucial nephrite-producing area in China, with demonstrated substantial prospects for future exploration. While existing research has extensively investigated secondary nephrite deposits in the Karakash River and native black nephrite deposits in Guangxi Dahua, a comprehensive investigation of black nephrite from original deposits in Xinjiang is lacking. Margou black-toned nephrite was recently found in primary deposits in Qiemo County, Xinjiang; this makes in-depth research on the characteristics of this mine necessary. A number of technical analytical methods such as polarizing microscopy, Ultra-Deep Three-Dimensional Microscope, electron microprobe, back-scattered electron image analysis, X-ray fluorescence, and inductively coupled plasma mass spectrometry were employed for this research. An experimental test was conducted to elucidate the chemical and mineralogical composition, further clarifying the genetic types of the black and black cyan nephrite from the Margou deposit in Qiemo, Xinjiang. The results reveal that the nephrite is mainly composed of tremolite–actinolite, characterized by Mg/(Mg + Fe2+) ratios ranging from 0.86 to 1.0. Minor minerals include diopside, epidote, pargasite, apatite, zircon, pyrite, and magnetite. Bulk-rock rare earth element (REE) patterns exhibit distinctive features, such as negative Eu anomalies (δEu = 0.00–0.17), decreasing light REEs, a relatively flat distribution of heavy REEs, and low total REE concentrations (1.6–38.9 μg/g); furthermore, the Cr (6–21 μg/g) and Ni (2.5–4.5 μg/g) contents are remarkably low. The magmatic influence of granite appears to be a fundamental factor in the genesis of the magnesian skarn hosting Margou nephrite. The distinctive black and black cyan colors are attributed to heightened iron content, mainly associated with FeO (0.08~6.29 wt.%). Analyses of the chemical composition allow Margou nephrite to be classified as typical of magnesian skarn deposits.

Summary: Background: Glibenclamide alleviates brain edema and improves neurological outcomes in experimental models of stroke. We aimed to assess whether glibenclamide improves functional outcomes in patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Methods: In this randomized, double-blind, placebo-controlled trial, patients with acute ischemic stroke were recruited to eight academic hospitals in China. Patients were eligible if they were aged 18–74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4–25, and had been treated with rtPA within 4.5 h of symptom onset. We used web-based randomization (1:1) to allocate eligible participants to the glibenclamide or placebo group, stratified according to endovascular treatment and baseline stroke severity. Glibenclamide or placebo was taken orally or via tube feeding at a loading dose of 1.25 mg within 10 h after symptom onset, followed by 0.625 mg every 8 h for 5 days. The primary outcome was the proportion of patients with good outcomes (modified Rankin Scale of 0–2) at 90 days, assessed in all randomly assigned patients who had been correctly diagnosed and had begun study medication. The study is registered with ClinicalTrials.gov, NCT03284463, and is closed to new participants. Findings: Between January 1, 2018, and May 28, 2022, 305 patients were randomly assigned, of whom 272 (142 received glibenclamide and 130 received placebo) were included in the primary efficacy analysis. 103 (73%) patients in the glibenclamide group and 94 (72%) in the placebo group had a good outcome (adjusted risk difference 0.002, 95% CI −0.098 to 0.103; p = 0.96). 12 (8%) patients allocated to glibenclamide and seven (5%) patients allocated to placebo died from any cause at 90 days (p = 0.35). The number and type of adverse events were similar between the two groups. There were no drug-related adverse events and no drug-related deaths. Interpretation: The addition of glibenclamide to thrombolytic therapy did not increase the proportion of patients who achieved good outcomes after stroke compared with placebo, but it did not lead to any safety concerns. Funding: Southern Medical University and Nanfang Hospital.

Energy storage and renewable energy sources are critical for addressing the growing global energy demand and reducing the negative environmental impacts of fossil fuels. Carbon nanomaterials are extensively explored as high reliable, reusable, and high‐density mechanical energy storage materials. In this context, machine learning techniques, specifically machine learning potentials (MLPs), are employed to explore the elastic properties of 1D carbon nanowires (CNWs) as a promising candidate for mechanical energy storage applications. The study focuses on the elastic energy storage properties of these CNWs, utilizing MLPs trained with data from first‐principles molecular dynamics simulations. It is found that these materials exhibit an exceptionally high tensile elastic energy storage capacity, with a maximum storage density ranging from 2262 to 2680 kJ kg−1. Furthermore, it is discovered that some CNWs exhibit a superior torsional energy storage capacity compared to their tensile energy storage capacity. Overall, this research demonstrates the effectiveness of machine learning‐based computational approaches in accelerating the exploration and optimization of novel materials. It also highlights the potential of CNWs as promising candidates for future energy storage applications.

Introduction and Objectives: In hepatocellular carcinoma (HCC), the prognosis of patients with microvascular invasion (MVI) is poor. Therefore, in this study, we established and evaluated the performance of a novel nomogram to predict MVI in patients with HCC. Materials and Methods: We retrospectively obtained clinical data of 497 patients with HCC who underwent hepatectomy at Liaoning Cancer Hospital from November 1, 2018, to November 4, 2021. The patients (n = 497) were randomized in a 7:3 ratio into the training cohort (TC, n = 349) and the validation cohort (VC, n = 148). We performed Least Absolute Shrinkage and Selection Operator (LASSO) and univariate as well as multivariate logistic regression analyses (ULRA, MRLA) on patients in the TC to identify factors independently predicting MVI. Results: Preoperative FIB-4, AFU, AFP levels, liver cirrhosis, and non-smooth tumor margin were independent risk factors for preoperative MVI prediction. The C-index of the TC, VC, and the entire cohort was 0.846, 0.786, and 0.829, respectively. The calibration curves demonstrated the outstanding agreement between predicted MVI incidences by our model and the actual MVI risk. Decision curve analysis (DCA) confirmed the significance of our predictive model in clinical settings. The Kaplan−Meier (KM) survival curve showed that the recurrence-free survival (RFS) and overall survival (OS) of patients in the high-MVI risk group were poor compared to those in the low-MVI risk group. Conclusions: We constructed and evaluated the performance of the novel nomogram for predicting MVI risk. Our predictive model could adequately predict MVI risk and aid clinicians in selecting appropriate therapeutic strategies for patients.

The study aimed to compare the differences in organic fractions transformation, humus components and bacterial community dynamics during manure composting from different sources, and to identify the key biotic and abiotic factors driving the humification process. Five types of manure [pig manure (PM), cow dung (CD), sheep manure (SM), chicken manure (CM), and duck manure (DM)] were used as raw materials for 30 days composting. The results showed the obvious difference of organic fractions decomposition with more cellulose degradation in CD and SM composting and more hemicellulose degradation in PM and CM composting. Composting of PM and CD contained significantly higher humus fractions than the other composts. Fluorescence spectra indicated that SM composting tended to form structurally stable humic acid fractions, while CM and DM tended to form structurally complex fulvic acid fractions. Pearson correlation analysis showed that humification process of composts in category A (PM, CD) with higher humification degree than category B (SM, CM, and DM) was positively correlated with lignin and hemicellulose degradation. Bioinformatics analysis found that Lysinibacillus promoted the degradation of hemicellulose and the conversion of fulvic to humic acid in the composts of category A, and in category B, Thermobifida, Lactobacillus, and Ureibacillus were key genera for humic acid formation. Network analysis indicated that bacterial interaction patterns had obvious differences in composting with different humus and humification levels.

This paper studies the phase and gain control dependencies of a variable gain amplifier (VGA) and a vector interpolator phase shifter (VIPS) within a 20 GHz beamforming receiver. First, the mechanisms of gain control and phase variation in a classic current-steering VGA are analyzed and design techniques are proposed such that the gain-dependent phase variations (GDPV) introduced by the amplifiers are well balanced. Second, similar analysis is performed to evaluate GDPV within a vector interpolator, where we show how the same techniques only partially apply due to the cross-coupling structure of the interpolator’s VGAs. We evaluate our techniques within a 20 GHz beamforming receiver IC realized in GlobalFoundries 45 nm RFSOI. Very low GDPV is observed within the VGA, with less than 0.3-deg. root-mean squared phase variation for a 9 dB gain control, whereas the VIPS achieves worst-case GDPV of 14 deg. The full beamformer channel achieves 29 dB gain, 2.2-2.4 dB noise figure, −26 dBm input 1 dB compression and consumes 111 mW. Based on these results, improvements to the interpolator are proposed and validated through simulation. The result is a near-ideal Cartesian interpolator that has less than 2-deg. GDPV and very low crosstalk between the VGAs.

Abstract Background Brain injury is the main cause of high mortality and disability after successful cardiopulmonary resuscitation (CPR) from sudden cardiac arrest (CA). The transient receptor potential M4 (TRPM4) channel is a novel target for ameliorating blood–brain barrier (BBB) disruption and neuroinflammation. Herein, we tested whether flufenamic acid (FFA), which is reported to block TRPM4 with high potency, could confer neuroprotection against brain injury secondary to CA/CPR and whether its action was exerted by blocking the TRPM4 channel. Methods Wild-type (WT) and Trpm4 knockout (Trpm4 −/− ) mice subjected to 10-min CA/CPR were randomized to receive FFA or vehicle once daily. Post-CA/CPR brain injuries including neurologic deficits, survival rate, histological damage, edema formation, BBB destabilization and neuroinflammation were assessed. Results In WT mice subjected to CA/CPR, FFA was effective in improving survival and neurologic outcome, reducing neuropathological injuries, attenuating brain edema, lessening the leakage of IgG and Evans blue dye, restoring tight junction protein expression and promoting microglia/macrophages from the pro-inflammatory subtype toward the anti-inflammatory subtype. In comparison to WT mice, Trpm4 −/− mice exhibited less neurologic deficiency, milder histological impairment, more BBB integrity and more anti-inflammatory microglia/macrophage polarization. As expected, FFA did not provide a benefit of superposition compared with vehicle in the Trpm4 −/− mice after CA/CPR. Conclusions FFA mitigates BBB breach and modifies the functional status of microglia/macrophages, thereby improving survival and neurologic deficits following CA/CPR. The neuroprotective effects occur at least partially by interfering with the TRPM4 channel in the neurovascular unit. These results indicate the significant clinical potential of FFA to improve the prognosis for CA victims who are successfully resuscitated.

Summary: Giant cell myocarditis (GCM) is a rare, usually rapidly progressive, and potentially fatal disease. Detailed inflammatory responses remain unknown, in particular the formation of multinucleate giant cells. We performed single-cell RNA sequencing analysis on 15,714 Cd45+ cells extracted from the hearts of GCM rats and normal rats. NETosis has been found to contribute to the GCM process. An inhibitor of NETosis, GSK484, alleviated GCM inflammation in vivo. MPO (a marker of neutrophils) and H3cit (a marker of NETosis) were expressed at higher levels in patients with GCM than in patients with DCM and healthy controls. Imaging mass cytometry analysis revealed that immune cell types within multinucleate giant cells included CD4+ T cells, CD8+ T cells, neutrophils, and macrophages but not B cells. We elucidated the role of NETosis in GCM pathogenesis, which may serve as a potential therapeutic target in the clinic.

Alternaria alternata is the main pathogenic fungus of postharvest black spots in fruits and vegetables. This study aimed to explore the antifungal activity of methionine on A. alternata in vitro and to reveal related antifungal mechanisms through a metabolomics analysis. The results showed that the inhibitory effects of L-methionine (Met) treatment on mycelium growth, spore germination, and the germ tube elongation of A. alternata were enhanced with an increase in the Met concentration, but the inhibitory effects decreased when the Met concentration was higher than 50 mmolL−1. The results of propidium iodide staining and scanning electron microscopy showed that the Met treatment damaged the plasma membrane integrity of the A. alternata spores and caused an irreversible deformation of mycelium. In addition, after the Met treatment, the leakage of electrolytes, nucleic acid, and proteins in the A. alternata cells was significantly higher than that in the control group, indicating that the Met treatment increased the permeability of the cell membranes. Eighty-one different metabolites, divided into seven categories, were identified through the metabolomics analysis, including forty-three downregulated metabolites and thirty-eight upregulated metabolites. Among them, these differential metabolites were mainly involved in amino acid synthesis and metabolism, the pentose phosphate pathway, and the TCA cycle. Therefore, the antifungal effect of the Met treatment on A. alternata was mainly to damage the integrity of the cell membranes, make nucleic acid and protein contents leak, and affect the TCA cycle, carbohydrate metabolism, amino acid synthesis metabolism, and the metabolic pathways associated with cell membrane biosynthesis. Thus, the growth and development of A. alternata were inhibited. The research enriched the investigation of the effect of the antifungal mechanism of Met treatment on A. alternata and provided a theoretical basis for the application of Met to prevent and treat postharvest black spots in fruits and vegetables.

The adsorption of proteins onto surfaces significantly impacts biomaterials, medical devices, and biological processes. This study aims to provide insights into the irreversible adsorption process of multiprotein complexes, particularly focusing on the interaction between anti-His6 IgG antibodies and the His6-tagged P2X2 receptor. Traditional approaches to understanding protein adsorption have centered around kinetic and thermodynamic models, often examining individual proteins and surface coverage, typically through Molecular Dynamics (MD) simulations. In this research, we introduce a computational approach employing Autodesk Maya 3D software for the investigation of multiprotein complexes’ adsorption behavior. Utilizing Atomic Force Microscopy (AFM) imaging and Maya 3D-based mechanical simulations, our study yields real-time structural and kinetic observations. Our combined experimental and computational findings reveal that the P2X2 receptor–IgG antibody complex likely undergoes absorption in an ‘extended’ configuration. Whereas the P2X2 receptor is less adsorbed once is complexed to the IgG antibody compared to its individual state, the opposite is observed for the antibody. This insight enhances our understanding of the role of protein–protein interactions in the process of protein adsorption.

Electric spring (ES) can suppress the voltage fluctuation caused by large-scale grid-connected renewable energy sources. However, ES can only work within a certain range of gird voltage fluctuations. This means, if the grid voltage fluctuates greatly, the ES will expose to the risk of off-limit failure. Focusing on this problem, the steady-state operating range and the failure mechanism of ES are analyzed. Then the influence of changes in critical load target voltage on the operating range of ES is analyzed. After that, a calculation method for critical load target voltage based on a two-port impedance model of ES is proposed, which can expand the operation range of the ES through optimal adjustment of the critical load target voltage effectively. Finally, a simulation model of the three-phase ES is built, and the detailed simulation results verify the validity of the proposed method.

α-amylase inhibitors (α-AI) are a kind of active substances which show inhibitory activities to human, insect pancreas and saliva. α-AI can reduce blood glucose index in human body and kill insects, thus widely used in medicine and agriculture. This review summarizes the source, structure and action mechanisms of protein and non-protein-based α-AI, focuses on the mechanisms from the view of structure-function relationship. The applications of α-AI in disease prevention, agricultural production and plant protection are also summarized. This review may provide new insights into the comprehensive exploitation and application of α-AI from different sources.

Abstract Background Caryopteris mongholica Bunge is a rare broad-leaved shrub distributed in the desert and arid regions of Mongol and North China. Due to land reclamation, natural habitat deterioration and anthropogenic activities in recent years, the wild resources have sharply reduced. To effectively protect and rationally use it, we investigated the genetic diversity and population structure from 18 populations across the range of C. mongholica in China by reduced representation sequencing technology. Results We found the overall average values of observed heterozygosity (Ho), expected heterozygosity (He), and average nucleotide diversity (π) were 0.43, 0.35 and 0.135, respectively. Furthermore, the NM17 population exhibited higher genetic diversity than other populations. The phylogenetic tree, principal component analysis (PCA) and structure analysis showed the sampled individuals clustered into two main groups. The NM03 population, with individuals clustered in both groups, may be a transitional population located between the two groups. In addition, most genetic variation existed within populations (90.97%) compared to that among the populations (9.03%). Interestingly, geographic and environmental distances were almost equally important to the observed genetic differences. Redundancy analysis (RDA) identified optical radiation (OR), minimum temperature (MIT) and mean annual precipitation (MAP) related variables as the most important environment factors influencing genetic variation, and the importance of MIT was also confirmed in the latent factor mixed models (LFMM). Conclusions The results of this study facilitate research on the genetic diversity of C. mongholica. These genetic features provided vital information for conserving and sustainably developing the C. mongholica genetic resources.

Summary: Ischemia reperfusion injury (IRI), often related to surgical procedures, is one of the important causes of acute kidney injury (AKI). To decipher the dynamic process of AKI caused by IRI (with prolonged ischemia phase), we performed single-cell RNA sequencing (scRNA-seq) of clinically relevant IRI murine model with different ischemic intervals. We discovered that Slc5a2hi proximal tubular cells were susceptible to AKI and highly expressed neutral amino acid transporter gene Slc6a19, which was dramatically decreased over the time course. With the usage of mass spectrometry–based metabolomic analysis, we detected that the level of neutral amino acid isoleucine dropped off in AKI mouse plasma metabolites. And the reduction of plasma isoleucine was also verified in patients with cardiac surgery–associated acute kidney injury (CSA-AKI). The findings advanced the understanding of dynamic process of AKI and introduced reduction of isoleucine as a potential biomarker for CSA-AKI.

Introduction: Hypertensive nephropathy is characterized by glomerular and tubulointerstitial damage, but we know little about changes in cell-specific gene expression in the early stages of hypertensive kidney injury, which usually has no obvious pathological changes. Methods: We performed unbiased single-cell RNA sequencing of rat kidney samples from hypertensive kidney injury to generate 10602 single-cell transcriptomes from 2 control and 2 early stage of hypertensive kidney injury samples. Results: All major cell types of the kidney were represented in the final dataset. Side-by-side comparisons showed that cell type-specific changes in gene expression are critical for functional impairment of glomeruli and tubules and activation of immune cells. In particular, we found a significantly reduced gene expression profile of maintaining vascular integrity in glomerular cells of hypertensive kidney injury. Meanwhile, the expression of genes associated with oxidative stress injury and fibrosis in the renal tubules and collecting ducts was elevated, but the degree of tubular cells response to injury differed between parts. We also found a signature of immune cell infiltration in hypertensive kidney injury. Discussion/Conclusion: Exploring the changes of gene expression in hypertension-injured kidneys may be helpful to identify the early biomarkers and signal pathways of this disease. Our data provide rich resources for understanding the pathogenesis of hypertensive renal injury and formulating effective treatment strategies.

Postharvest cherry tomatoes are prone to senescence, decay and nutrient loss during the storage period owing to microbial invasion and their own metabolism. In this work, postharvest cherry tomatoes were treated with a composite coating of 1% chitosan and 1% curdlan, and the characteristics of postharvest cherry tomatoes during storage were investigated. Compared to control samples, after 21 d of storage under ambient conditions, the cherry tomatoes treated with the chitosan and curdlan coatings showed less rottenness, less weight loss, a lower respiration rate, reduced ethylene production, lower malonaldehyde (MDA) content and reduced membrane permeability. After the samples were treated with the composite coating, the activities of free radical scavenging enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were maintained at higher levels; the activities of related disease-resistant enzymes such as chitinase (CHI) and glucanase (GLU) were also maintained at higher levels. The soluble solids, titratable acidity, firmness, vitamin C content, lycopene content and antioxidant activities of postharvest cherry tomatoes treated with the composite coating exhibited higher levels as well. The composite coating of chitosan and curdlan might be a potentially promising method for preserving postharvest cherry tomatoes and other fruits.

Drug–target interactions (DTIs) are considered a crucial component of drug design and drug discovery. To date, many computational methods were developed for drug–target interactions, but they are insufficiently informative for accurately predicting DTIs due to the lack of experimentally verified negative datasets, inaccurate molecular feature representation, and ineffective DTI classifiers. Therefore, we address the limitations of randomly selecting negative DTI data from unknown drug–target pairs by establishing two experimentally validated datasets and propose a capsule network-based framework called CapBM-DTI to capture hierarchical relationships of drugs and targets, which adopts pre-trained bidirectional encoder representations from transformers (BERT) for contextual sequence feature extraction from target proteins through transfer learning and the message-passing neural network (MPNN) for the 2-D graph feature extraction of compounds to accurately and robustly identify drug–target interactions. We compared the performance of CapBM-DTI with state-of-the-art methods using four experimentally validated DTI datasets of different sizes, including human (Homo sapiens) and worm (Caenorhabditis elegans) species datasets, as well as three subsets (new compounds, new proteins, and new pairs). Our results demonstrate that the proposed model achieved robust performance and powerful generalization ability in all experiments. The case study on treating COVID-19 demonstrates the applicability of the model in virtual screening.

IntroductionPostoperative myocardial injury after noncardiac surgery is common and is associated with short- and long-term morbidity and mortality. However, the incidence and risk factors for postoperative acute myocardial injury (POAMI) are currently unknown due to inconsistent definitions.MethodsWe systematically searched PubMed and Web of Science to identify studies that applied the change value of preoperative and postoperative cardiac troponins to define cardiac injury. We estimated the pooled incidence, risk factors, and 30-day and long-term mortality of POAMI in noncardiac patients. The study protocol was registered with PROSPERO, CRD42023401607.ResultsTen cohorts containing 11,494 patients were included for analysis. The pooled incidence of POAMI was 20% (95% CI: 16% to 23%). Preoperative hypertension (OR: 1.47; 95% CI: 1.30 to 1.66), cardiac failure (OR: 2.63; 95% CI: 2.01 to 3.44), renal impairment (OR: 1.66; 95% CI: 1.48 to 1.86), diabetes (OR: 1.43; 95% CI: 1.27 to 1.61), and preoperative beta-blocker intake (OR: 1.65; 95% CI: 1.10 to 2.49) were the risk factors for POAMI. Age (mean difference: 2.08 years; 95% CI: -0.47 to 4.62), sex (male, OR: 1.16; 95% CI: 0.77 to 1.76), body mass index (mean difference: 0.35; 95% CI: -0.86 to 1.57), preoperative coronary artery disease (OR: 2.10; 95% CI: 0.85 to 5.21), stroke (OR: 0.90; 95% CI: 0.50 to 1.59) and preoperative statins intake (OR: 0.65; 95% CI: 0.21 to 2.02) were not associated with POAMI. Patients with POAMI had higher preoperative hsTnT levels (mean difference: 5.92 ng/L; 95% CI: 4.17 to 7.67) and lower preoperative hemoglobin levels (mean difference: -1.29 g/dL; 95% CI: -1.43 to -1.15) than patients without.ConclusionBased on this meta-analysis, approximately 1 in 5 of noncardiac patients develop POAMI. However, the lack of a universally recognized definition for POAMI, which incorporates diverse cardiac biomarkers and patient groups, poses a challenge in accurately characterizing its incidence, risk factors, and clinical outcomes.

4E-BP1 is a tumor suppressor regulating cap-dependent translation that is in turn controlled by mechanistic target of rapamycin (mTOR) or cyclin-dependent kinase 1 (CDK1) phosphorylation. 4E-BP1 serine 82 (S82) is phosphorylated by CDK1, but not mTOR, and the consequences of this mitosis-specific phosphorylation are unknown. Knock-in mice were generated with a single 4E-BP1 S82 alanine (S82A) substitution leaving other phosphorylation sites intact. S82A mice were fertile and exhibited no gross developmental or behavioral abnormalities, but the homozygotes developed diffuse and severe polycystic liver and kidney disease with aging, and lymphoid malignancies after irradiation. Sublethal irradiation caused immature T-cell lymphoma only in S82A mice while S82A homozygous mice have normal T-cell hematopoiesis before irradiation. Whole genome sequencing identified PTEN mutations in S82A lymphoma and impaired PTEN expression was verified in S82A lymphomas derived cell lines. Our study suggests that the absence of 4E-BP1S82 phosphorylation, a subtle change in 4E-BP1 phosphorylation, might predispose to polycystic proliferative disease and lymphoma under certain stressful circumstances, such as aging and irradiation.