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Abstract Background The relationship between obesity and type 2 diabetes with bone health has always been a topic of debate. The weight-adjusted waist index has become a commonly used indicator for assessing central obesity, fat, and muscle mass. However, currently there is no research reporting the association between weight-adjusted waist index and risk of osteoporosis in populations of type 2 diabetes. Therefore, this study aims to provide new information on the association between weight-adjusted waist index and risk of osteoporosis in type 2 diabetes. Methods This cross-sectional study involved 963 patients with type 2 diabetes who were admitted to the Department of Endocrinology of Cangzhou Central Hospital. Multivariate logistic regression models were used to assess the association between weight-adjusted waist index and osteoporosis. The potential nonlinear association was evaluated. The effects of interaction between subgroups were assessed using the likelihood ratio test. Results Weight-adjusted waist index was positively associated with the risk of osteoporosis, regardless of traditional confounding factors. For each 1 unit increased in weight-adjusted waist index, the risk of osteoporosis increased by 67%. Furthermore, there was a nonlinear relationship between weight-adjusted waist index and osteoporosis. The subgroup analysis did not reveal any significant interactions. Conclusions Our study indicated a positive association between weight-adjusted waist index and the risk of osteoporosis in adult Chinese type 2 diabetes patients, and this relationship was nonlinear.

Abstract According to external pressure theory and reputation theory, reputation-oriented enterprises will experience external pressure as societal attention increases, and enhanced ESG performance can mitigate information asymmetry and boost reputation, thereby signaling to customers the company’s commitment to sustainable development. Based on the data of A-share listed firms in China, this paper manually compiles the detailed information of corporate customers, and explores the relationship between firm’s ESG performance and customer stability using a two-way fixed-effects model. The results show that: (1) Firms with ESG advantages can enhance customer stability, and the higher the ESG score, the more significant the improvement in customer stability; (2) The mechanism test indicates that firms’ ESG performance improves customer stability by strengthening internal and external regulation as well as enhancing corporate reputation; (3) The heterogeneity analysis indicates that in high governance level and small-sized firms, the effect of firms’ ESG performance on customer stability is more significant, and in the ESG sub-test, environmental and social responsibility have a more significant impact on customer stability. This paper provides implications for improving firms’ social responsibility and stabilizing the supply chain.

Abstract Background In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. Methods A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants’ levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin. Results Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47–0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44–0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28–0.59), stroke (OR, 0.44; 95% CI, 0.26–0.74), hypertension (OR, 0.27; 95% CI, 0.14–0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21–0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress. Conclusions In this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.

Abstract Background The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. Methods Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. Results Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. Conclusion Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.

Background: Lung adenocarcinoma (LUAD) is one of the respiratory diseases with high mortality and incidence. As an important angiogenic factor, (Endothelial cell-specific molecule 1) ESM1 plays an important role in the occurrence and development of LUAD. However, the role and molecular mechanism of ESM1 on LUAD metabolic reprogramming and angiogenesis remain unclear. Methods: We used multiple databases to analyze the prognostic significance and potential function of ESM1 in patients with LUAD. The expression of ESM1 in LUAD cells was down-regulated/overexpressed by RNA interference, and the effects of ESM1 on the proliferation, migration, lipid metabolism and angiogenesis of LUAD cells in vitro and in vivo were analyzed using MTT, EdU, wound healing, oil red O, tubule formation, xenograft tumor model and chicken embryo allantoic model. Results: ESM1 is closely associated with poor prognosis in LUAD patients. ESM1 promotes LUAD proliferation, migration, fatty acid synthesis and angiogenesis. It also accelerates the proliferation, migration, lipid synthesis and tubule formation of endothelial cells in the tumor microenvironment in the form of secreted protein. Mechanically, ESM1 can promote the activation of AKT signaling pathway and up-regulate the expression of SCD1 and FASN. Conclusion: Our results suggest that ESM1 promotes the proliferation, migration, lipid reprogramming, and angiogenesis of LUAD cells by activating the AKT signaling pathway, suggesting that ESM1 may be a potential therapeutic target and prognostic marker in LUAD patients.

Sepsis is a syndrome precipitated by immune dysregulation in response to infection, and represents a pivotal factor in global mortality attributed to diseases. The recent consensus delineates sepsis as a perilous state of organ dysfunction arising from the host’s maladaptive reaction to infection. It masks the complexity and breadth of the immune mechanisms involved in sepsis, which is characterized by simultaneous hyperinflammation and immunosuppression. Sepsis is highly correlated with the dysregulation of immune response, which is mainly mediated by various immune cells and their interactions. This syndrome can lead to a plethora of complications, encompassing systemic inflammatory response, metabolic disturbances, infectious shock, MODS, and DIC. Furthermore, more research studies have been conducted on sepsis in the past few years. The pathological characteristics of sepsis have been improved or treated by targeting signaling pathways like NF-B, JAK–STAT, PI3K-Akt, and p38-MAPK. Combined drug therapy is better than single drug therapy for sepsis. This article will review the latest progress in the pathogenesis and treatment of sepsis.

Summary: Selecting a suitable photocatalyst to establish the Z-scheme heterojunction which is accompanied by effective photogenerated hole and electron separation, is one of the advantageous strategies for efficient photocatalytic solar energy conversion. Therefore, we prepared a ZnIn2Se4 nanoparticles photocatalyst to build a double Z-scheme heterojunction with mixed-phase TiO2 nanofibers, boosting photocatalytic solar fuel preparation. The result of X-ray photoelectron spectroscopy confirmed the existence of interfacial chemical bonds and internal electric fields. The interfacial Ti-Se bond is regarded as a channel and the internal electric field serves as the driving force for electron transfer. And the composite photocatalyst exhibits a great hydrogen evolution rate of 0.11 mmol g−1 h−1. From a forward-working perspective, this work proposes a ZnIn2Se4 nanoparticles photocatalyst for efficient solar fuel conversion, promoting the application of bimetallic selenide photocatalyst in the field of photocatalysis.

Abstract Objective To compare the application of sequential embryo transfer, cleavage embryo transfer, and blastocyst transfer combined with intrauterine perfusion in frozen–thawed embryo transfer cycles in patients with recurrent implantation failure to provide a reference for reproductive clinicians. Methods The 166 patients who underwent frozen–thawed embryo transfer due to recurrent implantation failure in the reproductive center from January 2021 to March 2022 were retrospectively analyzed. According to the different embryos transferred, they were divided into cleavage embryo transfer groups (72 cases in Group A), blastocyst transfer group (29 cases in Group B), and sequential transfer group (65 cases in Group C). All three groups were treated with intrauterine perfusion 5 days before embryo transfer. The general data and clinical pregnancy outcome indicators, such as embryo implantation rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, twin rate, were compared among the three groups. Results The embryo implantation rate (53.1%), clinical pregnancy rate (76.9%), ongoing pregnancy rate (67.7%) and live birth rate(66.15%) in the sequential transfer group were significantly higher than those in the other two groups (P

Abstract Background Septic cardiomyopathy (SCM), a common cardiovascular comorbidity of sepsis, has emerged among the leading causes of death in patients with sepsis. SCM’s pathogenesis is strongly affected by mitochondrial metabolic dysregulation and immune infiltration disorder. However, the specific mechanisms and their intricate interactions in SCM remain unclear. This study employed bioinformatics analysis and drug discovery approaches to identify the regulatory molecules, distinct functions, and underlying interactions of mitochondrial metabolism and immune microenvironment, along with potential interventional strategies in SCM. Methods GSE79962, GSE171546, and GSE167363 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and module genes were identified using Limma and Weighted Correlation Network Analysis (WGCNA), followed by functional enrichment analysis. Machine learning algorithms, including support vector machine–recursive feature elimination (SVM–RFE), least absolute shrinkage and selection operator (LASSO) regression, and random forest, were used to screen mitochondria-related hub genes for early diagnosis of SCM. Subsequently, a nomogram was developed based on six hub genes. The immunological landscape was evaluated by single-sample gene set enrichment analysis (ssGSEA). We also explored the expression pattern of hub genes and distribution of mitochondria/inflammation-related pathways in UMAP plots of single-cell dataset. Potential drugs were explored using the Drug Signatures Database (DSigDB). In vivo and in vitro experiments were performed to validate the pathogenetic mechanism of SCM and the therapeutic efficacy of candidate drugs. Results Six hub mitochondria-related DEGs [MitoDEGs; translocase of inner mitochondrial membrane domain-containing 1 (TIMMDC1), mitochondrial ribosomal protein S31 (MRPS31), F-box only protein 7 (FBXO7), phosphatidylglycerophosphate synthase 1 (PGS1), LYR motif containing 7 (LYRM7), and mitochondrial chaperone BCS1 (BCS1L)] were identified. The diagnostic nomogram model based on the six hub genes demonstrated high reliability and validity in both the training and validation sets. The immunological microenvironment differed between SCM and control groups. The Spearman correlation analysis revealed that hub MitoDEGs were significantly associated with the infiltration of immune cells. Upregulated hub genes showed remarkably high expression in the naive/memory B cell, CD14+ monocyte, and plasma cell subgroup, evidenced by the feature plot. The distribution of mitochondria/inflammation-related pathways varied across subgroups among control and SCM individuals. Metformin was predicted to be the most promising drug with the highest combined score. Its efficacy in restoring mitochondrial function and suppressing inflammatory responses has also been validated. Conclusions This study presents a comprehensive mitochondrial metabolism and immune infiltration landscape in SCM, providing a potential novel direction for the pathogenesis and medical intervention of SCM.

ABSTRACTThe persistence of HBV covalently closed circular DNA (cccDNA) and HBV integration into the host genome in infected hepatocytes pose significant challenges to the cure of chronic HBV infection. Although CRISPR/Cas9-mediated genome editing shows promise for targeted clearance of viral genomes, a safe and efficient delivery method is currently lacking. Here, we developed a novel approach by combining light-induced heterodimerization and protein acylation to enhance the loading efficiency of Cas9 protein into extracellular vesicles (EVs). Moreover, vesicular stomatitis virus-glycoprotein (VSV-G) was incorporated onto the EVs membrane, significantly facilitating the endosomal escape of Cas9 protein and increasing its gene editing activity in recipient cells. Our results demonstrated that engineered EVs containing Cas9/gRNA and VSV-G can effectively reduce viral antigens and cccDNA levels in the HBV-replicating and infected cell models. Notably, we also confirmed the antiviral activity and high safety of the engineered EVs in the HBV-replicating mouse model generated by hydrodynamic injection and the HBV transgenic mouse model. In conclusion, engineered EVs could successfully mediate functional CRISPR/Cas9 delivery both in vitro and in vivo, leading to the clearance of episomal cccDNA and integrated viral DNA fragments, and providing a novel therapeutic approach for curing chronic HBV infection.

MUC21, also known as Epiglycanin, is a high-molecular-weight glycoprotein with transmembrane mucin properties. It consists of a tandem repeat domain, a stem domain, a transmembrane domain and a cytoplasmic tail. MUC21 is expressed is observed in normal tissues in organs like the thymus, testes, lungs, and large intestine. Research has shown that MUC21 is expressed in esophageal squamous cell carcinoma, lung adenocarcinoma, glioblastoma, thyroid cancer, melanoma, and various other malignant tumors in distinctive manner. Additionally, tumor invasion, metastasis, and poor prognosis are linked to it. Some researchers believe that MUC21 has the potential to become a new target in cancer treatment. This review aims to deliver a comprehensive overview of the glycosylation, function, and research progress of MUC21 in multiple types of cancer and infectious diseases.

Backgroud: The co-administration of Chinese patent medicine with calcium channel blockers (CCBs) is a prevalent practice in China for treating essential hypertension (EH). However, robust evidence supporting the efficacy and safety of tailored combinations of different Chinese patent medicines with CCBs, according to individual patient conditions, is still limited. This study sought to elucidate the efficacy and safety of these combinations using a systematic review and network meta-analysis.Materials and methods: Relevant studies were sourced from established databases, incorporating randomized controlled trials published up to 1 February 2023. The ROB2 tool from the Cochrane Collaborative Network was employed to independently assess and cross-verify the quality of the included literature. A network meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 and PRISMA-Network Meta-Analyses (PRISMA-NMA) guidelines. A Bayesian network meta-analysis was utilized to gauge the efficacy and safety of distinct integrations of Chinese patent medicine and CCBs. Primary outcomes were interpreted using a paired fixed-effect meta-analysis. Publication bias was appraised through Egger’s test and represented with funnel plots. All statistical analyses were executed within the R statistical framework.Results: Following rigorous selection, data extraction, and bias evaluation, 36 articles were incorporated. Tianma Gouteng Granule, when combined with CCBs, displayed superior efficacy in reducing systolic blood pressure (SBP). In terms of diastolic blood pressure (DBP) reduction, Songling Xuemaikang Capsule combined with CCBs emerged as the most effective. Regarding enhancement of antihypertensive effective rates, Qinggan Jiangya Capsule paired with CCBs demonstrated optimal results. For diminishing Traditional Chinese Medicine syndrome scores, the Qiangli Dingxuan Tablet and CCBs combination proved most beneficial. When aiming to reduce total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, Tianma Gouteng Granule and CCBs showcased superior results. In contrast, the combination of Songling Xuemaikang Capsule and CCBs was more effective in reducing LDL-C, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6).Conclusion: This study underscores variability in outcomes from combining Chinese patent medicine and CCBs for hypertension, emphasizing the importance of personalized medicinal combinations, especially Tianma Gouteng Granule and Songling Xuemaikang Capsule. The results offer robust evidence to inform clinical guidelines for essential hypertention and significantly aid clinician in seleting appropriate Chinese patent medicines for treatment.

Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear.Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment.Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA’s roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP’s main bioactives, underscoring their therapeutic potential.Conclusion: This research delineates UR-AP’s pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP’s potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies.

The presence of endotoxemia is strongly linked to the development of endothelial dysfunction and disruption of myocardial microvascular reactivity. These factors play a crucial role in the progression of endotoxemic cardiomyopathy. Sepsis-related multiorgan damage involves the participation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). However, whether DNA-PKcs contributes to endothelial dysfunction and myocardial microvascular dysfunction during endotoxemia remains unclear. Hence, we conducted experiments in mice subjected to lipopolysaccharide (LPS)-induced endotoxemic cardiomyopathy, as well as assays in primary mouse cardiac microvascular endothelial cells. Results showed that endothelial-cell-specific DNA-PKcs ablation markedly attenuated DNA damage, sustained microvessel perfusion, improved endothelial barrier function, inhibited capillary inflammation, restored endothelium-dependent vasodilation, and improved heart function under endotoxemic conditions. Furthermore, we show that upon LPS stress, DNA-PKcs recognizes a TQ motif in cofilin2 and consequently induces its phosphorylation at Thr25. Phosphorylated cofilin2 shows increased affinity for F-actin and promotes F-actin depolymerization, resulting into disruption of the endothelial barrier integrity, microvascular inflammation, and defective eNOS-dependent vasodilation. Accordingly, cofilin2-knockin mice expressing a phospho-defective (T25A) cofilin2 mutant protein showed improved endothelial integrity and myocardial microvascular function upon induction of endotoxemic cardiomyopathy. These findings highlight a novel mechanism whereby DNA-PKcs mediates cofilin2Thr25 phosphorylation and subsequent F-actin depolymerization to contribute to endotoxemia-related cardiac microvascular dysfunction.

Purpose: Magnetic resonance (MR)-guided radiotherapy enables visualization of static anatomy, capturing tumor motion, and extracting quantitative image features for treatment verification and outcome monitoring. However, magnetic fields in online MR imaging (MRI) require efforts to ensure accurate dose measurements. This study aimed to assess the dosimetric impact of a 1.5 T magnetic field in esophageal cancer radiotherapy using MR-linac, exploring treatment adaptation potential and personalized medicine benefits. Methods: A prospective cohort study enrolled 100 esophageal squamous cell carcinoma patients undergoing 4DCT and 3DCT scans before radiotherapy. The heart was contoured on 3DCT, 4DCT end expiration (EE), and 4DCT end inhalation (EI) images by the same radiation oncologist. Reference RT plans were designed on 3DCT, with adjustments for different phases generating 5 plan types per patient. Variations in dose-volume parameters for organs at risk and the target area among different plans were compared using Monaco 5.40.04. Results: Slight dose distortions at air-tissue interfaces were observed in the magnetic field's presence. Dose at air-tissue interfaces (chest wall and heart wall) was slightly higher in some patients (3.0% tissue increased by 4.3 Gy on average) compared to nonmagnetic conditions. Average clinical target volume coverage V100 dropped from 99% to 95% compared to reference plans (planEI and planEE). Dose-volume histogram variation between the original plan and reference plans was within 2.3%. Superior–inferior (SI) direction displacement was significantly larger than lateral and anterior–posterior directions ( P

Owing to their high intrinsic safety, dispersed fuel particles are an important fuel pattern for fourth-generation nuclear reactors. Due to the unique cladding layers and the random dispersion characteristics, dispersed fuel particles significantly differ from pressurized water reactors regarding operation-induced uncertainty. This study quantitatively analyzed overall uncertainty while considering a random distribution of dispersed fuel particles, material thickness, and fuel enrichment. The results demonstrated that, for all packing fractions, the uncertainty induced by the random dispersion of dispersed fuel particles was below 0.03%. For every packing fraction, the differences between the results obtained by the regular and the random distribution models increased, and then decreased, until reaching its maximum (1.297%) at 15%. Keff decreased as the radius of the UO2 kernel increased; Keff increased as the thickness of the cladding layer increased; the uncertainty of Keff was 1.003% when a random distribution of particles, material thickness, and fuel enrichment were taken into consideration; the uncertainty of the power distribution of reactor core assemblies was maximized (1.495%) at the edge of the reactor core. Quantitative analysis of uncertainty provides references for the optimization of design and safety margin analysis for reactors.

Abstract Background & aims The individual effect of working schedule on survival in the hypertensive population has not been adequately studied. Shiftworkers are also prone to unhealthy lifestyles like pro-inflammatory diet. Therefore, we assessed the effect of shift work and its joint association with dietary inflammatory potential on mortality risk among the large US nationally representative sample of adult hypertensive population. Methods Data were from a nationally representative prospective cohort among US hypertensive population (n = 3680; weighted population, 54,192,988). The participants were linked to the 2019 public-access linked mortality archives. The working schedule were self-reported using the Occupation Questionnaire Section. Dietary inflammatory index (DII) scores were equally calculated using the 24-hour dietary recall (24 h) interviews. Multivariable Cox proportional hazards regression models were used to estimate hazard ratio and 95% confidence intervals (95%CI) for survival of hypertension individuals by work schedule and dietary inflammatory potential. The joint effect of work schedule and dietary inflammatory potential was then examined. Results Among the 3680 hypertension individuals (39.89% female [n = 1479] and 71.42% white [n = 1707]; weighted mean [SE] age, 47.35 [0.32] years), 592 individuals reported shift work status. 474 (10.76%) reported shift work status with pro-inflammatory dietary pattern (DII scores > 0). 118 (3.06%) reported shift work status with anti-inflammatory dietary pattern (DII scores

Abstract Aims Heart failure (HF) is one of the leading causes of the global burden of disability and mortality. However, the comprehensive epidemic status of HF in China is unclear. Notably, the gender‐specific survey for HF prevalence is lacking. The present study aimed to analyse the gender‐specific prevalence and temporal trend of HF in China and explore the attributable aetiology and risk factors. Methods and results The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 was used to evaluate the age‐standardized prevalence and years lived with disability of HF in China by gender. The temporal trend of HF and attributable risk factors were analysed by Joinpoint regression models from 1990 to 2019. The total age‐standardized prevalence rate of HF steadily decreased over the past two decades from 1079.4 to 1032.8 per 100 000 individuals. Since 2017, the prevalence trend of HF has significantly increased [annual percentage change (APC) of 2.72 for females and 0.61 for males, P

Hemocyanin is a critical oxygen-transporting protein exhibiting multiple physiological functions, including protein storage and transportation, osmolarity regulation, molting, and immunomodulation in arthropods and mollusks. However, the immune function of hemocyanin in Portunus trituberculatus is rarely reported. Here, we identified ten subunit genes within the hemocyanin family from the P. trituberculatus genome. These genes exhibited conserved functional domains and copper ion binding sites. Building upon prior research, we specifically focused on investigating the immune functions of PtHc1 and PtHc2. Tissue expression analysis revealed that PtHc1 and PtHc2 were prominently expressed in the hepatopancreas and hemocytes. Upon infection with Vibrio parahaemolyticus, both PtHc1 and PtHc2 demonstrated a similar expression pattern, characterized by a gradual upregulation of expression levels in the hepatopancreas. While within the hemocytes, they exhibited a trend of initial downregulation followed by subsequent upregulation in expression. In addition, Recombinant hemocyanin was able to inhibit bacterial proliferation in a dose-dependent manner, with inhibition rates of 40 % and 39 % when the recombinant proteins of PtHc1 and PtHc2 reached 0.03 mg/mL, respectively. Besides, V. parahaemolyticus challenge resulted in a significant 20–23 % increase in mortality in P. trituberculatus following knockdown of PtHc1 and PtHc2. Overall, our study sheds light on the immune-related functions of PtHc1 and PtHc2 in P. trituberculatus, revealing their potential as key players in defending against pathogenic threats like V. parahaemolyticus. These results enriched the field of innate immunity in crustacean and providing a theoretical basis for disease resistance breeding.

To describe the full-stage creep behavior of layered rock accurately, a new elastic-viscoplastic creep model is proposed based on fractional order theory in this manuscript, which consists of a Hooke elastomer, a fractional Abel dashpot, a Kelvin body, and a new non-linear visco-plastic component. The non-linear creep model can not only describe the changes in three creep stages (primary creep, steady-state creep and accelerating creep) but also reflect the influence of different bedding angles of rock. The constitutive equations of the non-linear creep model are deduced by the empirical model method and plastic theory method, respectively. The parameters of the non-linear creep model are identified using the Levenberg-Marquardt algorithm from Origin. It shows that the creep model in this paper are highly consistent with the experimental data under different load levels, creep stages and bedding angles, and the accuracy and rationality of the model are verified. Moreover, the creep constitutive equations for layered rock derived by the two methods have the same fitting effect on the same set of experimental data.

Using computers to replace pilot seats in air traffic control (ATC) simulators is an effective way to improve controller training efficiency and reduce training costs. To achieve this, we propose a deep reinforcement learning model, RoBERTa-RL (RoBERTa with Reinforcement Learning), for generating pilot repetitions. RoBERTa-RL is based on the pre-trained language model RoBERTa and is optimized through transfer learning and reinforcement learning. Transfer learning is used to address the issue of scarce data in the ATC domain, while reinforcement learning algorithms are employed to optimize the RoBERTa model and overcome the limitations in model generalization caused by transfer learning. We selected a real-world area control dataset as the target task training and testing dataset, and a tower control dataset generated based on civil aviation radio land-air communication rules as the test dataset for evaluating model generalization. In terms of the ROUGE evaluation metrics, RoBERTa-RL achieved significant results on the area control dataset with ROUGE-1, ROUGE-2, and ROUGE-L scores of 0.9962, 0.992, and 0.996, respectively. On the tower control dataset, the scores were 0.982, 0.954, and 0.982, respectively. To overcome the limitations of ROUGE in this field, we conducted a detailed evaluation of the proposed model architecture using keyword-based evaluation criteria for the generated repetition instructions. This evaluation criterion calculates various keyword-based metrics based on the segmented results of the repetition instruction text. In the keyword-based evaluation criteria, the constructed model achieved an overall accuracy of 98.8% on the area control dataset and 81.8% on the tower control dataset. In terms of generalization, RoBERTa-RL improved accuracy by 56% compared to the model before improvement and achieved a 47.5% improvement compared to various comparative models. These results indicate that employing reinforcement learning strategies to enhance deep learning algorithms can effectively mitigate the issue of poor generalization in text generation tasks, and this approach holds promise for future application in other related domains.

This study discovered non-monotonic variations in river flows for seven rivers originating from the Tibetan Plateau at warming levels of 1.5 °C, 2.0 °C, and 3.0 °C, which then resulted in different consequences for riparian countries

It is vital to employ efficient methods to calculate and determine the threshold of river ecological flow. These methods help to get the river ecological status control countermeasures in the plain river networks and construct a flawless long-term mechanism of ecological flow control (water level). According to the river's current environment and the actual circumstances surrounding its operation and administration, the upper, middle, and lower reaches make up the three sections of the Zong-Liutang River in the Plain of Northern Jiangsu. Furthermore, the ecological water level governing factor for each reach was analyzed and studied. The ecological water level threshold in the upper and lower reaches of the Zong-Liutang River adopted the specified values of Jiangsu Provincial Department of water resources. The threshold of the middle reach was thoroughly analyzed by using the determination method with multi-criteria, which consisted of the hydrological and hydraulic methods (including yearly minimum water level with a 90% assured rate method; wetted perimeter method; minimum monthly average water level method), aquatic living conditions method, and river landscape entertainment factor method. Taking into account the hydrological and hydrodynamic characteristics, observed hydrological data conditions of rivers, and the actual operation rules of rivers and water projects regulations in the Northern Jiangsu plain. Through comparing and contrasting actual operation and management plans, the target values of the ecological water level for the river's upper, middle, and lower reaches were 17.4 m, 8.96 m, and 7.5 m, respectively. Based on the river's ecological water level's control value, which was found through a thorough analysis, and the river's real operation and management conditions, specific measures to protect the river's ecological water level were suggested. These included developing a perfect and workable ecological flow control method, speeding up the development of an ecological water level goal assurance early warning system, and an ecological flow and inlet system.

Objectives: This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50–85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60 ​mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Results: Of the 448 randomized patients, 409 (LY06006, n ​= ​311; placebo, n ​= ​98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P ​

Z-scheme heterojunction Bi2WO6/g-C3N4 was obtained by a novel hydrothermal process; its photocatalysis–persulfate (PDS) activation for tetracycline (TC) removal was explored under solar light (SL). The structure and photoelectrochemistry behavior of fabricated samples were well characterized by FT-IR, XRD, XPS, SEM-EDS, UV-vis DRS, Mott-Schottky, PL, photocurrent response, EIS and BET. The critical experimental factors in TC decomposition were investigated, including the Bi2WO6 doping ratio, catalyst dosage, TC concentration, PDS dose, pH, co-existing ion and humic acid (HA). The optimum test conditions were as follows: 0.4 g/L Bi2WO6/g-C3N4 (BC-3), 20 mg/L TC, 20 mg/L PDS and pH = 6.49, and the maximum removal efficiency of TC was 98.0% in 60 min. The decomposition rate in BC-3/SL/PDS system (0.0446 min−1) was 3.05 times higher than that of the g-C3N4/SL/PDS system (0.0146 min−1), which might be caused by the high-efficiency electron transfer inside the Z-scheme Bi2WO6/g-C3N4 heterojunction. Furthermore, the photogenerated hole (h+), superoxide (O2•−), sulfate radical (SO4•−) and singlet oxygen (1O2) were confirmed as the key oxidation factors in the BC-3/SL/PDS system for TC degradation by a free radical quenching experiment. Particularly, BC-3 possessed a wide application potential in actual antibiotic wastewater treatment for its superior catalytic performance that emerged in the experiment of co-existing components.

Experiments and simulations have been carried out to study the colliding process by two lasers irradiating a gold half-hohlraum. Via analyzing the evolutionary x-ray images, radiation fluxes and self-emission spectrum of tracers, influence on the x-ray conversion efficiency and the local plasma temperature $T_{e,i}$ from two gold-plasma plumes have been investigated deeply, which is similar as the configuration in Inertial Confinement Fusion (ICF). Experimental results confirm a region with high electron and ion temperatures $T_{e,i}$ are induced, satisfying the strong collision condition of $\lambda_{i} \lt \Delta{L}$ , where λ _i and $\Delta{L}$ are respectively the ion mean-free path and the gradient length of T _e . It leads to almost $30\%$ increasing of M-band component compared to that from a single laser-irradiation case. Meanwhile ion temperature in this region increases more rapidly than electrons, reaching about $T_i\approx(16\pm4)$ keV ( $T_e\approx(2\pm 0.2)$ keV). Thus, our studies provide the experimental evidence of quantitative x-ray enhancement and a non-equilibrium evolution simultaneously due to the plasma collision for the first time. Besides, two-dimensional simulation results reveal that this process can not be precisely described by the traditional shock-heating model by dissipating the shock energy only to ions. But by distributing the viscous heating between both electrons and ions as theoretically discussed by Miller (2020 Comput. Fluids 210 104672), numerical results can match experiments better. This discovery will be of great importance to improve the precision of prediction for ICF.

For service robots， security reconnaissance vehicles， etc. their mobile range is large and working space is complex. The drive system is vulnerable to impact， blocking or overload due to external impact， thereby resulting in tooth fractures and large bending of support shafts. The application of micro servo drive system is greatly limited. Aiming at this problem， a clutch structure is proposed to protect miniature reducer in this study. Using the finite element method， basic parameters of the spring and the protection threshold of the clutch structure is designed. Then， the threshold is captured and verified through the clutch performance test rig. Experimental results show that the miniature reducer can realize the clutch function accurately under the overload condition， and the measured clutch protection threshold is in good agreement with the design threshold. The clutch structure can limit the maximum threshold of the gear load， enable the gears of the miniature reducer to work within the design load range and improve the working reliability of the miniature reducer.

Purpose: The goal of this study was to examine the role of sodium butyrate in preserving the intestinal mucosal barrier and reducing hyperuricemia (HUA). Methods: First, we established a mouse model of HUA via intraperitoneal injection of potassium oxonate together with a yeast-rich diet to detect the levels of serum uric acid (UA) and fecal short-chain fatty acids (SCFAs). Then, in vitro, different concentrations of UA and sodium butyrate (NaB) were used to treat LS174T and Caco2 cells. The effects of UA and NaB on the gut barrier were determined based on the expression levels of MUC2, ZO-1, and Occludin.Finally, C57BL/6 mice were used to model HUA, and these mice were administered 200 mg·kg−1·d−1 NaB by gavage to counter the HUA. The effect of NaB on HUA in the intestinal tract was elucidated by determining serum UA levels, inflammatory parameters, epithelial barrier integrity, and via histological analysis. Results: The data showed that the content of fecal SCFAs in HUA mice decreased. Additionally, in LS174T and Caco2 cells, NaB reversed the decrease of ZO-1, Occludin, and MUC2 protein expression caused by high UA levels. Furthermore, NaB decreased serum UA of HUA mice, and reversed both the decreased expression of MUC2, ZO-1, Occludin, and ABCG2 proteins and the increased level of inflammatory factors in the intestinal tissues of these mice. Conclusion: The HUA mouse model showed intestinal barrier damage. NaB protected the intestinal barrier of HUA mice and reduced the serum UA level.

Vibrio parahaemolyticus is one of the main pathogenic bacteria of Portunus trituberculatus and causes mass mortality of P. trituberculatus in aquaculture. In addition, low-salinity stimulation makes P. trituberculatus more susceptible to V. parahaemolyticus infections. In order to elucidate the molecular mechanism of resistance to V. parahaemolyticus in P. trituberculatus, comparative transcriptomic analysis of blood cells stimulated by low salinity and V. parahaemolyticus was carried out in this study. Transcriptome sequencing of low-salinity stress and pathogen infection at different time points was completed using Illumina sequencing technology. A total of 5827, 6432, 5362 and 1784 differentially expressed genes (DEGs) involved in pathways related to ion transport and immunoregulation were found under low-salinity stress at 12, 24, 48 and 72 h compared with the control at 0 h. In contrast, 4854, 4814, 5535 and 6051 DEGs, which were significantly enriched in Toll and IMD signaling pathways, were found at 12, 24, 48 and 72 h compared with the control at 0 h under V. parahaemolyticus infection. Among them, 952 DEGs were shared in the two treatment groups, which were mainly involved in apoptosis and Hippo signaling pathway. Cluster analysis screened 103 genes that were differentially expressed in two factors that were negatively correlated, including immunoglobulin, leukocyte receptor cluster family, scavenger receptor, macroglobulin and other innate-immune-related genes. These results provide data support for the analysis of the mechanisms of immunity to V. parahaemolyticus under low-salinity stress in P. trituberculatus and help to elucidate the molecular mechanisms by which environmental factors affect immunity.

Tyrosine kinase inhibitors (TKIs) are a novel category of antitumor agents with remarkable efficacy in extending patient survival. However, clinical use of TKIs has been hindered by the major adverse effect of atrial fibrillation (AF). Recent studies have revealed that TKIs induce metabolic alterations and remodeling in cardiomyocytes, thus perturbing energy metabolism. Specifically, mitochondrial dysfunction and shifts in cardiac substrate utilization have been implicated in the mechanisms underlying TKI-induced AF. In light of these findings, this article reviews the energy metabolism-associated pathways involved in TKI-induced AF, identifies precise therapeutic targets for managing this condition, and discusses evidence that may contribute to the development of novel TKIs without cardiac adverse effects.

In order to attain phosphor ceramics with a high Color-Rendering Index (CRI), samples with the composition of Y0.997−xRexCe0.003)3(Al0.9748 Mn2+0.024Cr3+0.0012)5O12(Rex = 0, Gd0.333, Gd0.666, Gd0.997, Tb0.333, Tb0.666, Tb0.997 and Lu0.997 were prepared by solid-state reaction and vacuum sintering, and exhibited potential for high-quality, solid-state lighting. Doping with Cr3+ and Mn2+ effectively enhanced the red component of Ce3+ spectra through the intense energy transfer from Ce3+ ions to Mn2+/Cr3+ ions. The crystal field splitting of [GdO8] and [TbO8] was more extensive than that of [YO8], causing a massive redshift in the Ce3+ emission peaks from 542 to 561 and 595 nm, while [LuO8] had an opposite effect and caused a blueshift with a peak position at 512 nm. White LED devices incorporating Ce/Mn/Cr: (Gd0.333Y0.664)3Al5O12 phosphor ceramic exhibited a high CRI of 83.97, highlighting the potential for enhancing the red-light component of white LED lighting.

Microbes communicate with each other by Quorum sensing (QS) languages. Here the authors construct a QS database and the QS communication network to decipher intricate QSbased communications and form one of the key knowledge maps for human gut microbiota.

As a kind of clean and renewable geothermal resource, dry hot rock (HDR) contains a huge potential for geothermal energy, which is of great development prospect and research value. To provide cases for the theoretical study on the generation and the analysis of occurrence conditions of dry-hot geothermal resources, and contribute the experience of Guangxi to the systematic summary of the genesis and occurrence models of HDR, this article selects Qinzhou and Hepu basins, which contain rich geothermal resources, as the research objects, using regional geological survey, thermophysical determination, radioactive element measurement, geothermal geochemistry, geophysical exploration and other comprehensive research methods, systematically summary the heat source mechanism, migration and heat accumulation model of two potential dry heat geothermal resource regions. Under the constraint of limited geological, geothermal well, thermophysical property, and magnetotelluric sounding(MT)data, establish an organic and unified geology-geophysics model of density, magnetism, electrical property parameters, and basic geological knowledge, an occurrence model of dry hot geothermal resources. The results suggest that under the restriction of the generation and evolution of the earth′s internal heat, Qinzhou Basin is classified as an active tectonic belt - sedimentary basin type of HDR resources area, which regards crust-mantle upwelling material as the main heat source; Hepu Basin is classified as the modern volcano-sedimentary basin type of HDR resources area, which regards local molten layer as the main heat source with the "low speed and high resistance" and secondary mantle branch / hot spot as the supply heat source. The research results provide a theoretical basis for the exploration of dry-hot geothermal resources and have demonstrative significance for the comparative study and fine evaluation of dry-hot geothermal resource potential areas in Guangxi.

Abstract The electrocatalysts are widely applied in lithium–sulfur (Li–S) batteries to selectively accelerate the redox kinetics behavior of Li2S, in which bifunctional active sites are established, thereby improving the electrochemical performance of the battery. Considering that the Li–S battery is a complex closed “black box” system, the internal redox reaction routes and active sites cannot be directly observed and monitored especially due to the distribution of potential active‐site structures and their dynamic reconstruction. Empirical evidence demonstrates that traditional electrochemical test methods and theoretical calculations only probe the net result of multi‐factors on an average and whole scale. Herein, based on the amorphous TiO2‐x@Ni selective bifunctional model catalyst, these limitations are overcome by developing a system that couples the light field and in situ irradiated X‐ray photoelectron spectroscopy to synergistically convert the “black box” battery into a “see‐through” battery for direct observation of the charge transportation, thus revealing that amorphous TiO2‐x and Ni nanoparticle as the oxidation and reduction sites selectively promote the decomposition and nucleation of Li2S, respectively. This work provides a universal method to achieve a deeper mechanistic understanding of bidirectional sulfur electrochemistry.

Abstract The identity of charge transfer process at the heterogeneous interface plays an important role in improving the stability, activity, and selectivity of heterojunction catalysts. And, in situ irradiation X‐ray photoelectron spectroscopy (XPS) coupled with UV light optical fiber measurement setup is developed to monitor and observe the photoelectron transfer process between heterojunction. However, the in‐depth relationship of binding energy and irradiation light wavelength is missing based on the fact that the incident light is formed by coupling light with different wavelengths. Furthermore, a quantitative understanding of the charge transfer numbers and binding energy remains elusive. Herein, based on the g‐C3N4/SnO2 model catalyst, a wavelength‐dependent Boltzmann function to describe the changes of binding energy and wavelength through utilizing a continuously adjustable monochromatic light irradiation XPS technique is established. Using this method, this study further reveals that the electrons transfer number can be readily calculated forming an asymptotic model. This methodology provides a blueprint for deep understanding of the charge‐transfer rules in heterojunction and facilitates the future development of highly active advanced catalysts.

Objectives. Management of chronic coronary syndrome (CCS) encompasses a broad spectrum of practices, posing considerable complexity and variability. While guidelines have been established to augment the management quality of CCS, notable disparities persist across their recommendations. This study strives to scrutinize, compare, and reconcile these guideline recommendations pertaining to the diagnosis, treatment, and management of CCS patients. Our goal is to align these recommendations with contemporary clinical practices, thus laying a robust foundation for their pragmatic application in clinical settings. Methods. A comprehensive systematic search was conducted across multiple databases, including PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, Chinese Biomedical Literature Service System, Chinese Science and Technology Periodical Database, and Chinese Biological Medicine Database. The timeframe for this search spanned from their inception up to May 30, 2022, aiming to collate all published guidelines relevant to CCS. Subsequently, two independent reviewers undertook the task of appraising the quality of these guidelines by utilizing the Appraisal of Guidelines for Research and Evaluation II instrument. Results. The search yielded a total of 10,699 citations. Following a thorough evaluation, fourteen clinical practice guidelines and four consensus statements, each offering specific recommendations for CCS, were selected. The quality of these guidelines showcased a broad spectrum of variation. The domain of “presentation clarity” received the highest accolades, while “applicability” languished at the lower end of the scoring spectrum. On average, the guidelines attained a quality score denoting sufficiency. Furthermore, recommendations across different guidelines for the diagnosis, treatment, and management of CCS displayed a striking level of divergence. Conclusion. The landscape of published CCS guidelines is marked by extensive variations in scope, quality, and recommendations. Hence, there is a compelling need for collaborative efforts amongst multidisciplinary professionals to forge comprehensive, higher-quality evidence-based guidelines; such a concerted approach is paramount to enhance treatment efficacy and health outcomes for patients grappling with CCS.

During the laying of long-distance pipelines, pipe butt is always one of the construction difficulties faced by the field technicians, and accurately drawing the cutting trajectory is the key to improve the quality and efficiency of pipe butt.Therefore, a pipe butt model was established based on 9 basic variables according to the field condition of pipe connection.Then, the equations for the cutting trajectories of two pipes in a local spatial coordinate system were obtained through the calculation with the spatial analytic geometry method, and the coordinate transformation matrix between the two coordinate systems was also provided. Thereby, the cutting quantity of the pipe to be connected was calculated automatically by programming according to the calculation process, and measurement tests were performed for the relative position and cutting quantity of the pipe. The results show that no gap or overlay appears at the connection between the upstream and transition pipes in the butt model, and the starting and ending points of cutting trajectory drawn are coincided perfectly, which further verify the feasibility of the calculation method for cutting quantity of the butt pipe and could provide technical support for the onsite pipe butt and cutting.

Abstract Background Accumulating evidence suggests a strong association between polycystic ovary syndrome (PCOS) and ovarian cancer (OC), but the potential molecular mechanism remains unclear. In this study, we identified previously unrecognized genes that are significantly correlated with PCOS and OC via bioinformatics. Materials and methods Multiple bioinformatic analyses, such as differential expression analysis, univariate Cox analysis, functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis, and immune infiltration analysis, were utilized. We further evaluated the effect of OGN on FSHR expression via immunofluorescence. Results TCGA-OC, GSE140082 (for OC) and GSE34526 (for PCOS) datasets were downloaded. Twelve genes, including RNF144B, LPAR3, CRISPLD2, JCHAIN, OR7E14P, IL27RA, PTPRD, STAT1, NR4A1, OGN, GALNT6 and CXCL11, were identified as signature genes. Drug sensitivity analysis showed that OGN might represent a hub gene in the progression of PCOS and OC. Experimental analysis found that OGN could increase FSHR expression, indicating that OGN could regulate the hormonal response in PCOS and OC. Furthermore, correlation analysis indicated that OGN function might be closely related to m6A and ferroptosis. Conclusions Our study identified a 12-gene signature that might be involved in the prognostic significance of OC. Furthermore, the hub gene OGN represent a significant gene involved in OC and PCOS progression by regulating the hormonal response.

In recent years, with the continuous development of spacecraft, the demand for experimental and analytical simulation of space debris impact is increasing. Therefore, the simulation of space debris technology such as laser-driven flyer (LDF) is becoming increasingly strategic. However, in traditional LDF experiments, the experimental environment is difficult to control and the number of experiments is constrained by cost, resulting in only a small amount of valid data available. This makes it difficult to evaluate the sample damage. In this paper, thus, a method of LDF digital twinning with two phases and its experimental equipment is proposed. During the experimental phase, it provides a standardized experimental environment, while its experimental equipment facilitates automated, remote experiments and virtual training. In the evaluation phase, it is possible to use neural networks to enrich a small amount of experimental data into high-throughput data containing physical damage parameters, and finite element simulation to obtain microscopic damage processes and related data. Both methods have been validated by additional experiments, and the average error rate is 8.13% for the neural network and 3.1% for the simulation, using the fragmentation zone diameter as the predicted object. Again, both of these are much smaller than the 10% error rate, which is defined by the analysis of the experimental data. In addition, this paper proposes a full-cycle experimental path that is more compact, saves experimental costs, and reduces experimental cycle time compared with the traditional experimental path.

Abstract Background Guillain–Barre syndrome (GBS) is a rare neurological complication of brucellosis, and neurobrucellosis is the most common, but they have many similarities in clinical manifestations. Many clinicians are accustomed to merely explaining the manifestations of nervous system involvement with neurobrucellosis, but they ignore the possibility of GBS, and this leads to misdiagnosis, untimely treatment, and serious consequences. Case presentation A 55-year-old male patient was admitted to The First Affiliated Hospital of Harbin Medical University for intermittent fever, fatigue, and waist pain more than three months. Brucellosis was diagnosed from the blood test. Although anti-brucella treatment was given at the time of diagnosis, the disease continued to progress. At the time of the cerebrospinal fluid systematic physical examination and the neuroelectrophysiological test, acute motor sensory axonal neuropathy was diagnosed. The patient was given immediately administered immunoglobulin therapy. After three months of systemic treatment, the patient's muscle strength of the distal limbs gradually recovered. The numbness of the limbs eased slowly, and urination function and respiratory function returned to normal. He could sit by himself. Conclusions The possibility of GBS should be closely monitored for when a brucellosis patient shows typical clinical manifestations of progressive muscle weakness, protein-cell separation of the cerebral spinal fluid, and typical demyelinating sensorimotor polyneuropathy.

Lu3Al5O12:Ce3+ phosphor ceramics were fabricated by vacuum sintering. On this basis, a bi-layer composite phosphor was prepared by low-temperature sintering to cover the phosphor ceramics with a layer of SrAlSiN3:Eu2+-phosphor-in-glass (PiG). The optical, thermal, and colorimetric properties of LuAG:Ce3+ phosphor ceramics, SrAlSiN3:Eu2+ phosphors and SrAlSiN3:Eu2+-PiG were studied individually. Combining the bi-layer composite phosphors with the blue LED chip, it is found that the spectrum can be adjusted by varying the doping concentration of SrAlSiN3:Eu2+-PiG and the thickness of Lu3Al5O12:Ce3+ phosphor ceramics. The maximal color rendering index value of the white LED is 86, and the R9 is 61. Under the excitation of a laser diode, the maximum phosphor conversion efficacy of the bi-layer composite phosphors is 120 lm/W, the Ra is 83, and the correlated color temperature is 4534 K. These results show that the bi-layer composite phosphor ceramic is a candidate material to achieve high color rendering index for high brightness lighting.

Abstract Background Liquid–liquid phase separation (LLPS) within the nucleus is directly linked to driving gene expression through transcriptional complexes. Histone lysine methyltransferase 2D (KMT2D) is widely present in many cancers. It is known to epigenetically stimulate the expression of genes associated with tumorigenesis and metastasis. Our analyses show that KMT2D possesses two distinct low-complexity domains (LCDs) capable of driving the assembly of membrane-less condensates. The dependence of the mechanisms underlying monomethylation of H3K4 on the LLPS microenvironment derived from KMT2D LCDs is unclear in tumor. Methods KMT2D LCD-depletion cells were used to investigate tumor cell proliferation, apoptosis, and migration. We identified some core proteins, including WDR5, RBBP5, and ASH2L, which are involved in the KMT2D-associated catalytic complex in KMT2D LCD-deficient cells to further elucidate the mechanism that decreases monomethylation of H3K4. We also evaluated the viability of KMT2D LCD-deficient cells in vivo. Finally, using 1,6-hexanediol (HD), an inhibitor of LLPS, we determined cell activities associated with KMT2D function in wild-type PANC-1 cells. Results Without the LLPS microenvironment in KMT2D LCD-deficient cells or wild-type PANC-1 cells treated with HD, the WDR5 protein was significantly less stable and the protein–protein interactions between the components of the KMT2D–enzyme complex were attenuated, impairing the formation of the complex. Moreover, with the decrease in H3K4me1 level at enhancers, transcription factors such as LIFR and KLF4 were markedly downregulated, effectively inhibiting tumor progression. In xenograft tumor models, PANC-1 cells lacking the KMT2D LCDs showed effectively suppressed tumor growth compared to normal cells. Conclusions Our data indicate that the two low-complexity domains of the KMT2D protein could form a stable LLPS microenvironment, promoting the KMT2D catalysis of H3K4 monomethylation through stabilization of the WDR5 protein and KMT2D–enzyme complex. Therefore, finding ways to regulate the LLPS microenvironment will be benefitial for new cancer treatment strategies.

ObjectiveThe objective of this study was to analyze the quantitative association between advanced glycation end products (AGEs) and adjusted FRAX by rheumatoid arthritis (FRAX-RA) in postmenopausal type 2 diabetic (T2D) patients. The optimal cutoff value of AGEs was also explored, which was aimed at demonstrating the potential value of AGEs on evaluating osteoporotic fracture risk in postmenopausal T2D patients.MethodsWe conducted a cross-sectional study including 366 postmenopausal participants (180 T2D patients [DM group] and 186 non-T2D individuals [NDM group]). All the subjects in each group were divided into three subgroups according to BMD. Physical examination, dual-energy x-ray absorptiometry (DXA), and serum indicators (including serum AGEs, glycemic parameters, bone turnover markers and inflammation factors) were examined. The relationship between FRAX-RA, serum laboratory variables, and AGEs were explored. The optimal cutoff value of AGEs to predict the risk of osteoporotic fracture was also investigated.ResultsAdjusting the FRAX values with rheumatoid arthritis (RA) of T2D patients reached a significantly increased MOF-RA and an increasing trend of HF-RA. AGEs level was higher in the DM group compared to the NDMs, and was positively correlated with MOF-RA (r=0.682, P

Vibrio parahaemolyticus is a common pathogen of marine crustaceans and is responsible for large losses in aquaculture. Salinity is an important environmental factor, and abrupt changes in salinity can affect the immunity of crustaceans. In this study, we carried out a transcriptomic analysis under pathogenic infection and low salt stress, and conducted a comparative analysis of the differentially expressed genes (DEGs) after stimulation by the two factors. Illumina sequencing technology was used for the transcriptome sequencing of 27 hepatopancreas samples, and 178.77 G sequencing data and an average of 44,142,119 clean reads per sample were obtained. A total of 3,047 and 3,710 DEGs were found after V. parahaemolyticus infection and low salt stress, which included a number of innate immunity genes, such as Toll-like receptor (TLR), anti-lipopolysaccharide factor (ALF), lectin, and hemocyanin. In addition, 2,016 common DEGs were found, accounting for 42.52% of the total DEGs. Among these, 169 DEGs were up-regulated after pathogenic infection and down-regulated after low salt stress, and were mainly enriched in starch and sucrose metabolism, nitrogen metabolism, amino sugar and nucleotide sugar processes, and other pathways. Collectively, these results provide data support for the analysis of the immune mechanism of crabs against V. parahaemolyticus and will also help to clarify the molecular mechanism by which salinity affects immunity.

Abstract Background Green tea has been one of the most popular beverages in China since ancient times. Mixed results concerning the effect of green tea consumption on the incidence of hypertension have been published over the past decades. However, no previous studies have focused on longevous individuals in China and the sex differences in the association between habitual green tea intake and hypertension. Methods The data extracted from the database of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2018 were used for a secondary analysis. Logistic regression models were employed to examine the odds ratio (OR) of daily green tea consumption on the incidence of hypertension by sex. Results A total of 9277 individuals were included in the analysis (39.8% were men). The included individuals had a mean age of 80.9 and 84.8 years for those who drank green tea daily and those who had never, respectively (p

Abstract Purpose/objective(s) The purpose of the study was to assess the uterus motions and bladder volume changes of fractional movements in cervical sites throughout the external beam radiotherapy (EBRT) treatment. Materials/methods A prospective online MR imaging tracking study was conducted in EBRT 43 patients with at least 4 scans during each treatment (before: ultrasound scan, MRI scan, CBCT scan, after: MRI scan) were included. In order to improve the treatment repeatability, each patient was instructed to empty the bladder and drink 500 ml water 1 h before CT simulation and each treatment. If the ultrasound scan result reached the CT simulation volume of bladder, the treatment began. Bladder was outlined on the T2 weighted axial sequence and CBCT image by the two observers to avoid the influence of contouring. The data of bladder volume and scanning time were accurately recorded. The bladder volumes, filling rates and uterus motion were retrospectively analyzed by MIM software. Results Inter-fraction variation of the bladder volume was significant (p

Abstract Skeletal interoception regulates bone homeostasis through the prostaglandin E2 (PGE2) concentration in bone. Vertebral endplates undergo ossification and become highly porous during intervertebral disc degeneration and aging. We found that the PGE2 concentration was elevated in porous endplates to generate spinal pain. Importantly, treatment with a high-dose cyclooxygenase 2 inhibitor (celecoxib, 80 mg·kg−1 per day) decreased the prostaglandin E2 concentration and attenuated spinal pain in mice with lumbar spine instability. However, this treatment impaired bone formation in porous endplates, and spinal pain recurred after discontinuing the treatment. Interestingly, low-dose celecoxib (20 mg·kg−1 per day, which is equivalent to one-quarter of the clinical maximum dosage) induced a latent inhibition of spinal pain at 3 weeks post-treatment, which persisted even after discontinuing treatment. Furthermore, when the prostaglandin E2 concentration was maintained at the physiological level with low-dose celecoxib, endplate porosity was reduced significantly, which was associated with decreased sensory nerve innervation and spinal pain. These findings suggest that low-dose celecoxib may help to maintain skeletal interoception and decrease vertebral endplate porosity, thereby reducing sensory innervation and spinal pain in mice.

Land-use/land-cover mapping in coastal areas is a foundational yet significant pixel-wise classification work. Fully supervised semantic segmentation models have recently achieved tremendous success on this topic, but the limited annotation data will give rise to severe performance degradation. Besides, the ground categories in coastal areas characterized by great diversities may further exacerbate the adverse effects. In this paper, we propose a novel semi-supervised semantic segmentation framework based on pseudo supervision to address these issues. We first focus on the feature representation and impose perturbation to enforce consistency constraints. Unlike the naive distance measurement used in traditional consistency training, the predictions formalized with one-hot encoding from the auxiliary segmentation network are leveraged as the online pseudo supervisions. It possesses a lightweight structure and is easily generalized to multi-level architecture for exploring preferable behavior on lower-scale objects. In addition, we introduce a plain pseudo-labeling scheme to further improve the segmentation results. Its used offline pseudo supervisions are sampled from the first-stage predictions via adopting a class-wise soft version to confidence thresholds. We measure the proposed framework on two typical coastal datasets and compare it with other state-of-the-art methods. The experimental results demonstrate its excellent and competitive performance on land-use/land-cover mapping within semi-supervised scenarios.