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Abstract Background Postoperative delirium (POD) is a common surgical complication. However, the incidence and risk factors associated with postoperative delirium after revision total knee arthroplasty (rTKA) have not been comprehensively explored through extensive national databases. Methods Utilizing the National Inpatient Sample (NIS), the largest comprehensive U.S. hospital healthcare database, we undertook a retrospective investigation involving 127,400 patients who underwent rTKA between 2010 and 2019. We assessed various aspects, including patient demographics, hospital characteristics, pre-existing medical conditions, and perioperative complications. Results The overall incidence of postoperative delirium (POD) in patients undergoing rTKA between 2010 and 2019 was 0.97%. The highest incidence rate of 1.31% was recorded in 2013. Notably, this patient cohort demonstrated advanced age, increased burden of co-morbidities, prolonged hospital stays, increased hospitalization costs, and elevated in-hospital mortality rates (P

Abstract The outcomes of patients with sepsis are influenced by the contractile function of the right ventricle (RV), but the impact of cardiopulmonary interaction in ICU-mortality of sepsis patients remains unclear. This study aims to investigate the ICU-mortality impact of right ventricular-pulmonary artery (RV-PA) coupling in patients with sepsis. We employed echocardiography to assess patients with sepsis within the initial 24 h of their admission to the ICU. RV-PA coupling was evaluated using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio. A total of 92 subjects were enrolled, with 55 survivors and 37 non-survivors. TAPSE/PASP ratio assessed mortality with an area under the curve (AUC) of 0.766 (95% CI 0.670–0.862) and the optimal cutoff value was 0.495 mm/mmHg. We constructed a nomogram depicting the TAPSE/PASP in conjunction with IL-6 and Lac for the joint prediction of sepsis prognosis, and demonstrated the highest predictive capability (AUC = 0.878, 95% CI 0.809–0.948). In conclusion, the TAPSE/PASP ratio demonstrated prognostic value for ICU mortality in sepsis patients. The nomogram, which combines the TAPSE/PASP, IL-6, and LAC, demonstrated enhanced predictive efficacy for the prognosis of sepsis patients.

Abstract Background First generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials. Objective Given paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients. Methods We performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum’s de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death from the time of index presciption were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding. Results A total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19–90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32–90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs. 150 (30–870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.013), hypertension (6.3%-vs-25%, p = NS), sudden cardiac arrest/death (0% vs. 1.5%, p = NS) in the acalabrutinib group compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib. Conclusions There was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients.

Objective: To investigate the combined effect of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation on improving lower limb function in stroke patients. Design: Randomized controlled trial. Subjects/Patients: Subacute stroke patients. Methods: 169 post-stroke hemiplegia patients were randomly divided into 4 groups (control, transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, and transcutaneous auricular vagus nerve stimulation combined with transcranial direct current stimulation) and evaluated using the Fugl-Meyer Assessment-Lower Extremity (FMA-LL), Timed Up-and-Go (TUG) test, Modified Barthel Index (MBI), Berg Balance Scale (BBS), gait parameters, and surface electromyography (sEMG). Results: Significant improvements in FMA-LL, MBI, BBS, TUG, gait parameters, and sEMG were noted in the intervention groups compared with the control, with the transcutaneous auricular vagus nerve stimulation combined with transcranial direct current stimulation group showing the most pronounced improvements. Differences in some outcomes were also notable between the transcutaneous auricular vagus nerve stimulation and transcranial direct current stimulation groups. Conclusion: The combination of transcutaneous auricular vagus nerve stimulation and transcranial direct current stimulation effectively enhances gait, balance, and daily living activities in subacute stroke patients. These benefits are likely due to transcutaneous auricular vagus nerve stimulation activating the solitary and trigeminal nuclei and transcranial direct current stimulation stimulating the motor cortex. Wearable gait analysis systems and electromyography are valuable in clinical gait assessment for these patients.

ObjectiveThis study aims to analyze the causal relationship between autoimmune thyroiditis (AIT) and inflammatory bowel disease (IBD) using bidirectional Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms were obtained from FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. MR-Egger intercept, Cochran’s Q, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneity, and robustness, respectively.ResultsForward analysis revealed no significant association between AIT and the risk of ulcerative colitis (UC) (odds ratio [OR] 1.008, 95% confidence interval [CI] 0.986 to 1.03, p = 0.460) or Crohn’s disease (CD) (OR 0.972, 95% CI 0.935 to 1.010, p = 0.143). Reverse analysis showed that UC (OR 0.961, 95% CI 0.783 to 1.180, p = 0.707) was not associated with AIT risk, while CD (OR 2.371, 95% CI 1.526 to 3.683, p < 0.001) was linked to an increased risk of AIT. Intercept analysis and Cochran’s Q test indicated no horizontal pleiotropy or heterogeneity. Sensitivity analysis confirmed the robustness of the MR results.ConclusionThis MR analysis suggests that CD, but not UC, is a risk factor for AIT, whereas AIT is not associated with the risk of IBD. Proactive prevention and treatment of CD can help mitigate the risk of AIT.

Saccharomyces boulardii (Sb) is a probiotic yeast for the treatment of gastrointestinal disorders, including inflammatory bowel disease (IBD). Little is known about the modulatory capacity of the Sb in IBD. Here, we found that oral gavage of Sb supernatant (SbS) alleviated gut inflammation, protected the intestinal barrier, and reversed DSS-induced down-regulated activation of epidermal growth factor receptor (EGFR) in colitis. Mass spectrum analysis showed that thioredoxin (Trx) is one of the critical secreted soluble proteins participating in EGFR activation detected in SbS. Trx exerted an array of significant effects on anti-inflammatory activity, including alleviating inflammation, protecting gut barrier, suppressing apoptosis, as well as reducing oxidative stress. Mechanistically, Trx promoted EGFR ligand gene expression and transactivated EGFR in a concentration-dependent manner. EGFR kinase inhibitor could block Trx-mediated preventive effects of intestinal epithelial injury. Our data suggested that Sb-derived soluble protein Trx could serve as a potential prophylactic, as a novel postbiotic against colitis, which provides a new strategy for the precision prevention and treatment of IBD.

With the increasing demand for metal foil parts with micro-array structures in micro-electromechanical systems (MEMS), it is urgent to explore a novel array micro-forming technology with high efficiency, low cost, and high flexibility. The cavitation water jet uses the high-energy shock wave generated by the collapse of the cavitation bubble group as the loading force. It has the characteristics of large range of action, uniform pressure distribution, and can realize large-area array micro-forming processing. To verify the feasibility of cavitating water jet array micro-forming, this paper performs cavitating water jet array micro-forming on 304 stainless steel foil with a thickness of 80 μm, and analyzes the variation of cavitation bubbles collapse impact zone with target distance. The effects of target distance and impact time on the forming quality of metal foil array micro-holes were studied from the aspects of forming depth, surface roughness, and thickness thinning rate. The results show that the forming depth and uniformity of the array micro-holes located in the cavitation collapse area increase with time. However, with the increase of target distance, the forming depth increases first and then decreases. When the target distance is L = 120 mm, the forming depth reaches the maximum. The surface roughness ( Ra ) of the array micro hole is Ra = 1.54 μm. The thickness thinning rate of the micro-forming parts is between 2% and 10%, and the maximum thickness thinning rate in the die fillet area is 13.5%. This paper provides a novel processing method for manufacturing metal foil parts with micro array structure.

ObjectiveWhether the role of post-traumatic stress disorder (PTSD) on type 2 diabetes (T2D) is mediated by obesity or other mediating factors is controversial. This study was designed to assess the impact of PTSD on genetic susceptibility to T2D and mediating factors.MethodsThe datasets for PTSD, T2D, obesity, hypertension, hyperlipidemia, smoking status, and alcohol consumption were obtained from genome-wide association studies. Mendelian randomization (MR) was used to assess exposure-outcome causality, and inverse variance weighted was used as the primary tool for MR analysis. MR-Egger intercept, Cochran’s Q, and leave-one-out sensitivity analysis were employed to assess horizontal pleiotropy, heterogeneity, and robustness, respectively.ResultsThe MR analysis showed that PTSD was associated with increased genetic susceptibility to T2D (OR, 1.036; 95% CI, 1.008-1.064; p = 0.011), obesity (OR, 1.033; 95% CI, 1.016-1.050; p < 0.001), and hypertension (OR, 1.002; 95% CI, 1.000-1.003; p = 0.015), but not not with genetic susceptibility to hyperlipidemia, alcohol consumption, and smoking status (p ≥ 0.05). Mediated effect analysis showed that PTSD increased genetic susceptibility to T2D by increasing genetic susceptibility to obesity and hypertension, with obesity accounting for 9.51% and hypertension accounting for 2.09%. MR-Egger intercept showed no horizontal pleiotropy (p ≥ 0.05). Cochran’s Q showed no heterogeneity (p ≥ 0.05). Leave-one-out sensitivity analysis showed that the results were robust.ConclusionThis MR analysis suggests that PTSD increases the risk of T2D and that this effect is partially mediated by obesity and hypertension. Active prevention and treatment of PTSD can help reduce the risk of T2D.

BackgroundIn recent years, septic shock remains a common fatal disease in the intensive care unit (ICU). After sufficient fluid resuscitation, some patients still experience tachycardia, which may lead to adverse effects on cardiac function. However, the use of β-blockers in the treatment of septic shock remains controversial. Thus, the purpose of this study is to evaluate the efficacy of β-blockers in the treatment of patients with septic shock and explore the most appropriate patient subgroups for this treatment.MethodsThis retrospective observational study enrolled septic shock patients from the Medical Information Mart for Intensive Care (MIMIC)-IV and used propensity score matching (PSM) to balance some baseline differences between patients with and without β-blockers treatment. The primary outcome was the 28-day mortality. Length of stay (LOS) in the ICU and hospital, and the degree of support for organs such as circulatory, respiratory and renal systems were also assessed. Subgroup analysis and multivariate logistic regression were performed to determine the relationship between β-blockers therapy and 28-day mortality in different patient groups.ResultsA total of 4,860 septic shock patients were enrolled in this study and 619 pairs were finally matched after PSM. Our analysis revealed that β-blocker therapy was associated with a significant improvement in 28-day mortality (21.5% vs. 27.1%; P = 0.020) and led to a prolonged LOS in both the ICU and hospital. Subgroup analysis indicated that there was an interaction between cardiovascular diseases and β-blocker therapy in patients with septic shock. Patients with pre-existing heart disease or atrial arrhythmias were more likely to derive benefits from β-blocker treatment.ConclusionWe found β-blockers therapy was effective to improve 28-day mortality in patients with septic shock. Patients in the subgroup with cardiovascular diseases were more likely to benefit from β-blockers in mortality.

Abstract Background Dysregulation of cholesterol metabolism is associated with the metastasis of triple-negative breast cancer (TNBC). Apolipoprotein A1 (ApoA1) is widely recognized for its pivotal role in regulating cholesterol efflux and maintaining cellular cholesterol homeostasis. However, further exploration is needed to determine whether it inhibits TNBC metastasis by affecting cholesterol metabolism. Additionally, it is necessary to investigate whether ApoA1-based oncolytic virus therapy can be used to treat TNBC. Methods In vitro experiments and mouse breast cancer models were utilized to evaluate the molecular mechanism of ApoA1 in regulating cholesterol efflux and inhibiting breast cancer progression and metastasis. The gene encoding ApoA1 was inserted into the adenovirus genome to construct a recombinant adenovirus (ADV-ApoA1). Subsequently, the efficacy of ADV-ApoA1 in inhibiting the growth and metastasis of TNBC was evaluated in several mouse models, including orthotopic breast cancer, spontaneous breast cancer, and human xenografts. In addition, a comprehensive safety assessment of Syrian hamsters and rhesus monkeys injected with oncolytic adenovirus was conducted. Results This study found that dysregulation of cholesterol homeostasis is critical for the progression and metastasis of TNBC. In a mouse orthotopic model of TNBC, a high-cholesterol diet promoted lung and liver metastasis, which was associated with keratin 14 (KRT14), a protein responsible for TNBC metastasis. Furthermore, studies have shown that ApoA1, a cholesterol reverse transporter, inhibits TNBC metastasis by regulating the cholesterol/IKBKB/FOXO3a/KRT14 axis. Moreover, ADV-ApoA1 was found to promote cholesterol efflux, inhibit tumor growth, reduce lung metastasis, and prolonged the survival of mice with TNBC. Importantly, high doses of ADV-ApoA1 administered intravenously and subcutaneously were well tolerated in rhesus monkeys and Syrian hamsters. Conclusions This study provides a promising oncolytic virus treatment strategy for TNBC based on targeting dysregulated cholesterol metabolism. It also establishes a basis for subsequent clinical trials of ADV-ApoA1 in the treatment of TNBC.

Metal anodes (e.g., Li and Zn) are promising candidates for high-energy and high-power rechargeable batteries. However, the commercialization of metal anodes is hampered by irregular dendrite growth, which severely deteriorates the safety and cyclability of metal anodes. Optimizing the electrolyte by nanostructured additives to regulate the metal deposition shows great potential since the electrochemically nonreactive feature endows the regulation function with good sustainability. In this manuscript, the fundamental dendrite formation models and key parameters for stabilizing metal anode are first discussed. The progress and functional mechanism of nanostructured additives for regulating the metal deposition are summarized in terms of regulatory model, i.e., deposition-, adsorption- and dispersion-type. Finally, we also provide a detailed concluding outlook, pointing out the future trend of selecting new nanostructured additive candidates and elucidating synergistic effects and underlying mechanisms with the key attention being given to the assessments of practicality.

Introduction: Common postoperative complications of total knee arthroplasty (TKA) include blood transfusion. Although risk factors and incidence of blood transfusion have been studied through national databases, the relative impact of each risk factor needs to be synthesized over a longer time period into a new model need to be revised. Material and methods: Patient data were extracted from the National Inpatient Sample (NIS), which is the largest hospital care database in the US, and analyse patient data retrospectively from 2010 through 2019. The final data included the patients undergoing TKA. The final analysis assessed the demographics of patients, type of insurance, type of hospital, length of stay (LOS), preoperative comorbidities, total charge, inpatient mortality, medical-surgical postoperative complications. Results: After extracting data from the NIS database, a total of 1,250,533 patients with TKA were included in the analysis, and the rate of transfusion was 6.60 %. TKA patients who receive blood transfusion had longer LOS (from 2-3 days to 3–4 days), more preoperative comorbidities, higher inpatient mortality rate, and increased total charge (P < 0.001). Moreover, postoperative complications associated with inpatients included sepsis, acute myocardial infarction and shock. Elective admission and private insurance were also regarded as protective factors. Conclusion: Blood transfusion could bring postoperative complications to patients, which were also linked to health costs and risks. It was also a common preoperative comorbidities for older patients who underwent TKA. Through better blood management strategies, we could reduce patient transfusion rates and improve clinical outcomes.Level of Evidence: Diagnostic Level Ⅲ.

ObjectiveThe relationship between diabetes mellitus (DM) and autism spectrum disorder (ASD) remains controversial. This study aimed to analyze the causal relationship between different types of DM and ASD by bidirectional Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms for type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and ASD were obtained from genome-wide association studies. Subsequently, inverse variance weighted, MR-Egger, and weighted median were used to test the exposure-outcome causality. Finally, MR-Egger’s intercept, Cochran’s Q, and leave-one-out method were used to assess horizontal pleiotropy, heterogeneity, and sensitivity of the results, respectively.ResultsThe positive analysis showed that T2DM was associated with an increased risk of ASD, whereas neither T1DM nor GDM was associated with the risk of ASD. The reverse analysis showed that ASD was associated with an increased risk of T2DM, while it was not associated with the risk of either T1DM or GDM. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05) for these results. Cochran’s Q showed no heterogeneity expect for the results of T1DM on the risk of ASD, and leave-one-out sensitivity analysis showed these results were robust.ConclusionThis MR analysis suggests that T2DM and ASD are reciprocal risk factors and that they may create an intergenerational risk cycling in female patients. Aggressive prevention and treatment of T2DM and ASD help to break the trap of this risk cycling. Additionally, this study does not support a causal relationship between T1DM and ASD, as well as GDM and ASD. And more studies are needed in the future to continue to explore the interactions and underlying mechanisms between different types of DM and ASD.

Importance: Abnormal blood pressure pattern is an independent risk factor for vascular events. Blood pressure variability can predict cardiovascular and cerebrovascular disease outcomes and is closely associated with the risk of cognitive impairment. However, the relationship between blood pressure variability and cerebral small vessel disease neuroimaging markers remains unclear. This study aimed to evaluate the relationship between blood pressure variability and cerebral small vessel disease neuroimaging markers. Data sources: We searched multiple databases, including Embase, Web of Science, PubMed, Cochrane Library, UpToDate, and World of Science, from their inception until November 27, 2023.Main Outcomes and Measures: A meta-analysis of 19 observational studies involving 14519 participants was performed. Findings: ①Systolic blood pressure variability was correlated with the cerebral small vessel disease total burden, white matter hyperintensities and lacunar infarction; ② Diastolic blood pressure variability was correlated with the cerebral small vessel disease total burden, white matter hyperintensities and cerebral microbleeds; ③ Non-dipping patterns were correlated with white matter hyperintensities and lacunar infarction. ④ Reverse-dipping patterns were significantly correlated with white matter hyperintensities and cerebral microbleeds. Conclusions: and Relevance: Blood pressure variability correlates with neuroimaging markers of cerebral small vessel disease and its burden. Hence, early monitoring and intervention of blood pressure variability may be essential for the early diagnosis, prevention and treatment of cerebral small vessel disease.

ObjectiveThe effect of mental disorders (MD) on cardiovascular disease (CVD) remains controversial, and this study aims to analyze the causal relationship between eight MD and CVD by Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms of attention-deficit/hyperactivity disorder (ADHD), anorexia nervosa (AN), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), depression, obsessive-compulsive disorder (OCD), schizophrenia (SCZ), and CVD were obtained from UK Biobank and FinnGen. Exposure-outcome causality was tested using inverse variance weighted (IVW), MR-Egger, and weighted median. Horizontal pleiotropy and heterogeneity were assessed by MR-Egger intercept and Cochran's Q, respectively, while stability of results was assessed by leave-one-out sensitivity analysis.ResultsMR analysis showed that ANX (IVW [odds ratio (OR) 1.11, 95% confidence intervals (CI) 1.07–1.15, p 0.05). Intercept analysis showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity except for BD (p = 0.035). Sensitivity analysis suggested that these results were robust.ConclusionsANX, ASD, and depression are associated with an increased risk of CVD, whereas AN, ADHD, BD, OCD, and SCZ are not causally associated with CVD. Active prevention and treatment of ANX, ASD, and depression may help reduce the risk of CVD.

IntroductionExport quality improvement is a crucial path for a country or region to climb up the advanced division of labor in the global value chain. For developing countries that have long been at the lower end of the global value chain division of labor, the dominance of agricultural trade is often controlled by international retailers, leading to higher costs of agricultural trade and hindering the upgrading of the quality of agricultural exports. As a traditional agricultural exporting country, China still needs a competitive advantage despite the large scale of its agricultural exports. Currently, e-commerce can provide buyers and sellers with comprehensive transaction information and technical support, allowing them to realize rational allocation of resources and export upgrading. Therefore, studying how e-commerce can promote the quality upgrade of agricultural exports is crucial for China to build a trade power.MethodsThis paper clarifies the mechanism of e-commerce’s theoretical impact on the quality of agricultural exports and then empirically tests it using a high-dimensional fixed-effects model with Chinese customs data from 2000 to 2020 as a sample.ResultsThe results show that e-commerce significantly promotes the quality of agricultural exports in all regions of China, and this conclusion still holds after various robustness tests; the heterogeneity test shows that e-commerce fosters the quality of agricultural exports in eastern China, densely populated regions, and economically underdeveloped regions, especially in the case of heterogeneous products; the mechanism analysis confirms that e-commerce promotes the quality of agricultural exports mainly through the optimization of the agricultural industry chain and supply chain, and the enhancement of the level of servicing. Mechanism analysis confirms that e-commerce improves agricultural export quality mainly through optimizing the agricultural industry chain and supply chain, improving the level of servitization, and docking the demand information of the consumer market, etc. Expanded analysis shows that constructing cross-border e-commerce platforms also significantly improves the quality of micro enterprises’ agricultural exports. This paper enriches the research on e-commerce and agricultural trade.DiscussionThis paper provides an essential reference for constructing a robust agricultural trade country and developing high-quality agriculture. Despite encompassing data up to 2020, in the context of today’s global economic volatility directly affecting agricultural trade, future investigations will broaden the scope to delve deeper into how e-commerce can help countries cope with global economic uncertainty.

ABSTRACTAcetyl-CoA carboxylases (ACCs) convert acetyl-CoA to malonyl-CoA, a key step in fatty acid biosynthesis and autotrophic carbon fixation pathways. Three functionally distinct components, biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT), are either separated or partially fused in different combinations, forming heteromeric ACCs. However, an ACC with fused BC-BCCP and separate CT has not been identified, leaving its catalytic mechanism unclear. Here, we identify two BC isoforms (BC1 and BC2) from Chloroflexus aurantiacus, a filamentous anoxygenic phototroph that employs 3-hydroxypropionate (3-HP) bi-cycle rather than Calvin cycle for autotrophic carbon fixation. We reveal that BC1 possesses fused BC and BCCP domains, where BCCP could be biotinylated by E. coli or C. aurantiacus BirA on Lys553 residue. Crystal structures of BC1 and BC2 at 3.2 Å and 3.0 Å resolutions, respectively, further reveal a tetramer of two BC1-BC homodimers, and a BC2 homodimer, all exhibiting similar BC architectures. The two BC1-BC homodimers are connected by an eight-stranded β-barrel of the partially resolved BCCP domain. Disruption of β-barrel results in dissociation of the tetramer into dimers in solution and decreased biotin carboxylase activity. Biotinylation of the BCCP domain further promotes BC1 and CTβ-CTα interactions to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-HP via co-expression with a recombinant malonyl-CoA reductase in E. coli cells. This study revealed a heteromeric ACC that evolves fused BC-BCCP but separate CTα and CTβ to complete ACC activity.IMPORTANCEAcetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in fatty acid biosynthesis and autotrophic carbon fixation pathways across a wide range of organisms, making them attractive targets for drug discovery against various infections and diseases. Although structural studies on homomeric ACCs, which consist of a single protein with three subunits, have revealed the “swing domain model” where the biotin carboxyl carrier protein (BCCP) domain translocates between biotin carboxylase (BC) and carboxyltransferase (CT) active sites to facilitate the reaction, our understanding of the subunit composition and catalytic mechanism in heteromeric ACCs remains limited. Here, we identify a novel ACC from an ancient anoxygenic photosynthetic bacterium Chloroflexus aurantiacus, it evolves fused BC and BCCP domain, but separate CT components to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-hydroxypropionate (3-HP) via co-expression with recombinant malonyl-CoA reductase in E. coli cells. These findings expand the diversity and molecular evolution of heteromeric ACCs and provide a structural basis for potential applications in 3-HP biosynthesis.

ObjectiveThe impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran’s Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis.ResultsMR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962–0.989; p 0.05). Cochran’s Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust.ConclusionCHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.

ObjectiveTo evaluate intracerebral hemorrhage (ICH) risk in patients with ischemic stroke (IS) and cerebral microbleeds (CMBs) undergoing anticoagulation therapy for non-valvular atrial fibrillation (AF).MethodsWe conducted a comprehensive search across multiple databases, including Embase, PubMed, Cochrane, UpToDate, Scopus, WOS, and SinoMed. The search covered observational literature published from each database inception until February 1, 2023. We analyzed the prevalence of CMBs during the follow-up period, compared future ICH risk between patients with and without baseline CMBs (CMBs presence/absence, ≧5 CMBs), and examined factors influencing ICH occurrence in patients with CMBs. Also studied recurrent stroke during anticoagulation therapy, the risk of future ICH when white matter hyperintensity (WMH) and CMBs coexist, and the effects of anticoagulants vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on future ICH.ResultsWe included 7 articles involving 5,134 participants. The incidence of CMBs was 24%; baseline CMBs were associated with an increased ICH risk compared to patients without CMBs. ICH—risk was more significant in patients with baseline ≥5 CMBs. After anticoagulant therapy, ICH risk was higher than that of recurrent IS. The risk of future ICH was significantly increased with anticoagulant VKAs compared with NOAC.ConclusionAnticoagulant therapy for ischemic stroke patients with non-valvular AF and CMBs increases future ICH risk. Discontinuing anticoagulation due to ICH risk should be avoided. NOACs are safe and effective for patients with CMBs and IS.

Background: Flooding has become more frequent and intensive due to climate change, particularly in Asian countries. However, evidence on the long-term health effects of floods from large-scale studies on the vulnerable aged population in China is insufficient. This study analyzed the long-term effects of exposure to flood on electrocardiographic (ECG) abnormalities, a commonly used indicator of cardiovascular disease (CVD) screening, in middle-aged and elderly people. Method: We evaluated the Chinese National Stroke Screening Survey data of 80,711 follow-up records from 38,375 participants aged > 40 years with two or more visits between 2013 and 2018 in this longitudinal study. Flood exposure was assessed as the presence of a satellite-detected flooded area within 500 m of the residence within 5 years before the survey date. The association between ECG abnormalities and flood exposure was analyzed using a random effects model with multiple adjustments. As age is an important CVD risk factor, a varying-coefficient function was derived to estimate the nonlinear modifying effect of age on the association between ECG abnormalities and flood exposure. The strata-specific associations between ECG abnormalities and flood exposure were applied to characterize vulnerability to flood. Results: The fully adjusted model suggested that flood exposure was associated with an increased risk for ECG abnormalities among the middle-aged and elderly population (odds ratio [OR] 1.74, 95 % confidence interval [CI] 1.49, 2.03). The ORs of flood exposure for ECG suggesting atrial fibrillation, ST depression, and left ventricular hypertrophy were 1.85 (95 % CI 1.16, 2.94), 6.92 (95 % CI 5.23, 9.16), and 1.55 (95 % CI 0.66, 3.65), respectively. These associations were generally robust in various subpopulations, while a sublinear curve for the negative modifying effect of age was observed on the population vulnerability to flood. Conclusion: Flood exposure was associated with an increased long-term risk for an ECG abnormality. The need for effective measures to mitigate vulnerability to flood is not negligible in China.

Abstract Objective This study aims to characterize the current status of the nephrology workforce in China and evaluate its optimal capacity based on real-world patient mobility data. Methods Data on nephrologists in China were collected from two prominent online healthcare platforms using web crawlers and natural language processing techniques. Hospitalization records of patients with chronic kidney disease (CKD) from January 2014 to December 2018 were extracted from a national administrative database in China. City-level paths of patient mobility were identified. Effects of nephrology workforce on patient mobility were analyzed using multivariate Poisson regression models. Results Altogether 9.13 nephrologists per million population (pmp) were in practice, with substantial city-level variations ranging from 0.16 to 88.79. The ratio of nephrologists to the estimated CKD population was 84.57 pmp. Among 6 415 559 hospitalizations of patients with CKD, 21.3% were cross-city hospitalizations and 7441 city-level paths of patient mobility with more than five hospitalizations were identified. After making adjustment for healthcare capacity, healthcare insurance, economic status, and travel characteristics, the Poisson regression models revealed that the number of nephrologists in both the source city (incidence rate ratio [IRR] 0.99, per 1 pmp increase) and destination city (IRR 1.07, per 1 pmp increase) were independently associated with patient mobility. An IRR plateau was observed when the number of nephrologists exceeded 12 pmp in the source city, while a rapidly increasing IRR was observed beyond 20 pmp in the destination city. Conclusions The nephrology workforce in China exhibits significant geographic variations. Based on local healthcare needs, an optimal range of 12–20 nephrologists pmp is suggested.

Abstract The codependency of cholesterol metabolism sustains the malignant progression of glioblastoma (GBM) and effective therapeutics remain scarce. In orthotopic GBM models in male mice, we identify that codependent cholesterol metabolism in tumors induces phagocytic dysfunction in monocyte-derived tumor-associated macrophages (TAMs), resulting in disease progression. Manipulating cholesterol efflux with apolipoprotein A1 (ApoA1), a cholesterol reverse transporter, restores TAM phagocytosis and reactivates TAM-T cell antitumor immunity. Cholesterol metabolomics analysis of in vivo-sorted TAMs further reveals that ApoA1 mediates lipid-related metabolic remodeling and lowers 7-ketocholesterol levels, which directly inhibits tumor necrosis factor signaling in TAMs through mitochondrial translation inhibition. An ApoA1-armed oncolytic adenovirus is also developed, which restores antitumor immunity and elicits long-term tumor-specific immune surveillance. Our findings provide insight into the mechanisms by which cholesterol metabolism impairs antitumor immunity in GBM and offer an immunometabolic approach to target cholesterol disturbances in GBM.

ABSTRACTAqueous zinc-based devices (AZDs) are considered as a promising candidate for next-generation energy storage due to high safety, economic benefit, and environmental benignity. However, the wide-spread application of AZD cathodes still faces challenges such as inferior energy density and cycling life. This manuscript focuses on the key design parameters for AZD cathodes and highlights the diverse functions of well-designed carbon architectures in AZD cathodes. The emerging opportunities are also presented to guide future endeavors towards high-performance AZD cathodes.

ObjectiveThe influence of vitamin D on autoimmune thyroid disease (AITD) remains a subject of ongoing debate. This study employs Mendelian randomization (MR) to investigate the causal correlations of serum 25-hydroxyvitamin D (25[OH]D) levels with autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves disease (GD).MethodsData on single nucleotide polymorphisms related to serum 25(OH)D levels, AIT, AIH, and GD were sourced from UK Biobank and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were employed to test the exposure-outcome causal relationship. Assessments of horizontal pleiotropy, heterogeneity, and stability were performed using the MR-Egger intercept, Cochran’s Q test, and leave-one-out sensitivity analysis, respectively.ResultsThe results of MR analysis showed increased serum 25(OH)D levels was associated with a reduced risk of AIT (OR 0.499, 95% CI 0.289 to 0.860, p = 0.012) but not causal associated with AIH (OR 0.935, 95% CI 0.695 to 1.256, p = 0.654) and GD (OR 0.813, 95% CI 0.635 to 1.040, p = 0.100). Intercept analysis showed no horizontal pleiotropy (p > 0.05), and Cochran’s Q test showed no heterogeneity (p > 0.05). Sensitivity analysis suggested that these results were robust.ConclusionAn increased serum 25(OH)D level is associated with AIT risk reduction but unrelated to AIH and GD. This finding suggests that vitamin D supplementation can be valuable for preventing and treating AIT.

The use of strong intermolecular interaction force to promote the formation of ion transport channels is one of the common methods to increase the conductivity of AEMs. In this work, a series of poly(acenaphthylenyl aryl piperidinium) membranes and ionomer were prepared by ultra-strong acid-catalyzed polymerization. The π-π self-assembly of acenaphthylene monomer promoted the aggregation of piperidinium cation and the formation of efficient ion transport channel, which was confirmed by well aggregated transmission electron micrographs of the ion clusters. Therefore, the prepared membrane had desirable conductivity (173.38 mS cm−1 at 80 °C). Meanwhile, the membrane exhibited excellent alkaline stability (99 % retention of conductivity in 3 M NaOH solution immersed at 80 °C for 1000 h), acceptable dimensional stability (swelling rate < 27.78 % at 80 °C), and high mechanical properties (tensile strength >33.9 MPa). The H2/O2 fuel cell assembled based on the prepared QPANTP-20 membrane and ionomer exhibited peak power density of 266 mW cm−2 at 80 °C.

ABSTRACTThe epidemic of coronavirus disease-19 (COVID-19) has grown to be a global health threat. Gastrointestinal symptoms are thought to be common clinical manifestations apart from a series of originally found respiratory symptoms. The human gut harbors trillions of microorganisms that are indispensable for complex physiological processes and homeostasis. Growing evidence demonstrate that gut microbiota alteration is associated with COVID-19 progress and severity, and post-COVID-19 syndrome, characterized by decrease of anti-inflammatory bacteria like Bifidobacterium and Faecalibacterium and enrichment of inflammation-associated microbiota including Streptococcus and Actinomyces. Therapeutic strategies such as diet, probiotics/prebiotics, herb, and fecal microbiota transplantation have shown positive effects on relieving clinical symptoms. In this article, we provide and summarize the recent evidence about the gut microbiota and their metabolites alterations during and after COVID-19 infection and focus on potential therapeutic strategies targeting gut microbiota. Understanding the connections between intestinal microbiota and COVID-19 would provide new insights into COVID-19 management in the future.

Abstract Association between calcium intake and premature mortality in the general population has been well studied, but little is known about the association among specific populations. The authors aim to evaluate the association among people with hypertension and to provide a proper reference range of dietary calcium intake. This prospective cohort study included 8534 US adults with hypertension from National Health and Nutrition Examination Survey cycles 2003–2014. Dietary calcium intakes were self‐reported and mortality status was ascertained by National Death Index records. During a median follow‐up of 5.9 years, 1357 death occurred. Compared with participants of dietary calcium intake in quintile 1, participants in quintiles 2 and 4 had a 27% (HR: 0.73, 95% CI: 0.60–0.89) and a 29% lower risk (HR: 0.71, 95% CI: 0.57–0.88) of all‐cause mortality respectively. The authors also observed a 34% lower risk (HR: 0.66, 95% CI: 0.45–0.97) of CVD death among participants in quintile 3 and a 37% lower risk (HR: 0.63, 95% CI: 0.40–0.99) of cancer‐related death in participants in quintile 4 respectively. Restricted cubic spline (RCS) regression revealed a consistent protective effect of dietary calcium in participants with a daily intake of over 1000 mg, but a daily intake over 1200 mg fails to show further protective effect. Our findings suggest that elevated dietary calcium was associated with lower mortality risk from all‐causes, cardiovascular disease (CVD) and cancer, and supplying sufficient dietary calcium intake, between 1000 and 1200 mg per day, in people with hypertension may be considered cost‐effective to decrease risk of premature death.

Abstract Background Hypertension affects 31.1% of adults worldwide, with higher prevalence of great than 60% in elderly. Advanced hypertension stage was associated with the higher risk of mortality. However, little is known about the age-specific association of stage of hypertension at diagnosis on cardiovascular mortality or all-cause mortality. Therefore, we aim to explore this age-specific association among the hypertensive elderly through stratified and interaction analyses. Methods This cohort study included 125,978 elderly hypertensive patients aged 60+ years from Shanghai of China. Cox regression was used to estimate the independent and joint effect of hypertension stage and age at diagnosis on cardiovascular and all-cause mortality. Interactions were evaluated both additively and multiplicatively. Multiplicative interaction was examined by the Wald test of the interaction term. Additive interaction was assessed by relative excess risk due to interaction (RERI). All analyses were performed stratified by sex. Results 28,250 patients died during the follow-up up to 8.85 years, and 13,164 died of cardiovascular events. Older age and advanced hypertension stage were risk factors of cardiovascular mortality and all-cause mortality. Besides, smoking, rarely exercise, BMI

Abstract Background Epithelium-mesenchymal interactions are involved in odontogenic processes. Previous studies have focused on the intracellular signalling regulatory network in tooth development, but the functions of extracellular regulatory molecules have remained unclear. This study aims to explore the gene profile of extracellular proteoglycans and their glycosaminoglycan chains potentially involved in dental epithelium-mesenchymal interactions using high-throughput sequencing to provide new understanding of early odontogenesis. Results Whole transcriptome profiles of the mouse dental epithelium and mesenchyme were investigated by RNA sequencing (RNA-seq). A total of 1,281 and 1,582 differentially expressed genes were identified between the dental epithelium and mesenchyme at E11.5 and E13.5, respectively. Enrichment analysis showed that extracellular regions and ECM-receptor interactions were significantly enriched at both E11.5 and E13.5. Polymerase chain reaction analysis confirmed that the extracellular proteoglycan family exhibited distinct changes during epithelium-mesenchymal interactions. Most proteoglycans showed higher transcript levels in the dental mesenchyme, whereas only a few were upregulated in the epithelium at both stages. In addition, 9 proteoglycans showed dynamic expression changes between these two tissue compartments. Gpc4, Sdc2, Spock2, Dcn and Lum were expressed at higher levels in the dental epithelium at E11.5, whereas their expression was significantly higher in the dental mesenchyme at E13.5, which coincides with the odontogenic potential shift. Moreover, the glycosaminoglycan biosynthetic enzymes Ext1, Hs3st1/5, Hs6st2/3, Ndst3 and Sulf1 also exhibited early upregulation in the epithelium but showed markedly higher expression in the mesenchyme after the odontogenic potential shift. Conclusion This study reveals the dynamic expression profile of extracellular proteoglycans and their biosynthetic enzymes during the dental epithelium–mesenchymal interaction. This study offers new insight into the roles of extracellular proteoglycans and their distinct sulfation underlying early odontogenesis.

Dye/salt separation has gained increasing attention in recent years, prompting the quest to find cost-effective and environmentally friendly raw materials for synthesizing high performance nanofiltration (NF) membrane for effective dye/salt separation. Herein, a high-performance loose-structured NF membrane was fabricated via a simple vacuum filtration method using a green nanomaterial, 2,2,6,6-tetramethylpiperidine-1-oxide radical (TEMPO)-oxidized cellulose nanofiber (TOCNF), by sequentially filtrating larger-sized and finer-sized TOCNFs on a microporous substrate, followed by crosslinking with trimesoyl chloride. The resulting TCM membrane possessed a separating layer composed entirely of pure TOCNF, eliminating the need for other polymer or nanomaterial additives. TCM membranes exhibit high performance and effective dye/salt selectivity. Scanning Electron Microscope (SEM) analysis shows that the TCM membrane with the Fine-TOCNF layer has a tight layered structure. Further characterizations via Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the presence of functional groups and chemical bonds of the crosslinked membrane. Notably, the optimized TCM-5 membrane exhibits a rejection rate of over 99% for various dyes (Congo red and orange yellow) and 14.2% for NaCl, showcasing a potential candidate for efficient dye wastewater treatment.

(1) Background: This study evaluates the effectiveness of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in improving gait in post-stroke hemiplegic patients, using wearable sensor technology for objective gait analysis. (2) Methods: A total of 72 stroke patients were randomized into control, sham stimulation, and LF-rTMS groups, with all receiving standard medical treatment. The LF-rTMS group underwent stimulation on the unaffected hemisphere for 6 weeks. Key metrics including the Fugl-Meyer Assessment Lower Extremity (FMA-LE), Berg Balance Scale (BBS), Modified Barthel Index (MBI), and gait parameters were measured before and after treatment. (3) Results: The LF-rTMS group showed significant improvements in the FMA-LE, BBS, MBI, and various gait parameters compared to the control and sham groups (p < 0.05). Specifically, the FMA-LE scores improved by an average of 5 points (from 15 ± 3 to 20 ± 2), the BBS scores increased by 8 points (from 35 ± 5 to 43 ± 4), the MBI scores rose by 10 points (from 50 ± 8 to 60 ± 7), and notable enhancements in gait parameters were observed: the gait cycle time was reduced from 2.05 ± 0.51 s to 1.02 ± 0.11 s, the stride length increased from 0.56 ± 0.04 m to 0.97 ± 0.08 m, and the walking speed improved from 35.95 ± 7.14 cm/s to 75.03 ± 11.36 cm/s (all p < 0.001). No adverse events were reported. The control and sham groups exhibited improvements but were not as significant. (4) Conclusions: LF-rTMS on the unaffected hemisphere significantly enhances lower-limb function, balance, and daily living activities in subacute stroke patients, with the gait parameters showing a notable improvement. Wearable sensor technology proves effective in providing detailed, objective gait analysis, offering valuable insights for clinical applications in stroke rehabilitation.

Composite solid-state electrolytes are viewed as promising materials for solid-state lithium-ion batteries due to their combined advantages of inorganic solid-state electrolytes and solid-state polymer electrolytes. In this study, the solid electrolytes Li6.7−xLa3Zr1.7−xSb0.3NbxO12 (LLZSNO) with Sb and Nb co-doping were prepared by a high-temperature solid-phase method. Results indicate that Sb/Nb co-doping causes lattice deformation in LLZO and increases the lithium vacancy concentration and conductivity of LLZO. Then, with the co-doped LLZSNO as an inorganic filler, a composite solid electrolyte of polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) was prepared with a casting method. The obtained composite solid electrolyte exhibits a high ionic conductivity of 1.76 × 10−4 S/cm at room temperature, a wide electrochemical stable window of 5.2 V, and a lithium-ion transfer number of 0.32. The Li|LiFePO4 coin battery with the composite solid electrolyte shows a high specific capacity of 161.2 mAh/g and a Coulombic efficiency close to 100% at 1 C. In addition, the symmetrical lithium battery Li|Li with the composite electrolyte could cycle stably for about 1500 h without failure at room temperature.

The rapid development of the photovoltaic industry has also brought some economic losses and environmental problems due to the waste generated during silicon ingot cutting. This study introduces an effective and facile method to reutilize silicon-cutting waste by constructing a multilayer Si@SiO2@C composite for Li-ion batteries via two-step annealing. The double-layer structure of the resultant composite alleviates the severe volume changes of silicon effectively, and the surrounding slightly graphitic carbon, known for its high conductivity and mechanical strength, tightly envelops the silicon nanoflakes, facilitates ion and electron transport and maintains electrode structural integrity throughout repeated charge/discharge cycles. With an optimization of the carbon content, the initial coulombic efficiency (ICE) was improved from 53% to 84%. The refined Si@SiO2@C anode exhibits outstanding cycling stability (711.4 mAh g−1 after 500 cycles) and rate performance (973.5 mAh g−1 at 2 C). This research presents a direct and cost-efficient strategy for transforming photovoltaic silicon-cutting waste into high-energy-density lithium-ion battery (LIB) anode materials.

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) emerges as a promising neuromodulatory technique. However, taVNS uses left ear stimulation in stroke survivors with either left or right hemiparesis. Understanding its influence on the cortical responses is pivotal for optimizing post-stroke rehabilitation protocols.ObjectiveThe primary objective of this study was to elucidate the influence of taVNS on cortical responses in stroke patients presenting with either left or right hemiparesis and to discern its potential ramifications for upper limb rehabilitative processes.MethodsWe employed functional near-infrared spectroscopy (fNIRS) to ascertain patterns of cerebral activation in stroke patients as they engaged in a “block transfer” task. Additionally, the Lateralization Index (LI) was utilized to quantify the lateralization dynamics of cerebral functions.ResultsIn patients exhibiting left-side hemiplegia, there was a notable increase in activation within the pre-motor and supplementary motor cortex (PMC-SMC) of the unaffected hemisphere as well as in the left Broca area. Conversely, those with right-side hemiplegia displayed heightened activation in the affected primary somatosensory cortex (PSC) region following treatment.Significantly, taVNS markedly amplified cerebral activation, with a pronounced impact on the left motor cortical network across both cohorts. Intriguingly, the LI showcased consistency, suggesting a harmonized enhancement across both compromised and uncompromised cerebral regions.ConclusionTaVNS can significantly bolster the activation within compromised cerebral territories, particularly within the left motor cortical domain, without destabilizing cerebral lateralization. TaVNS could play a pivotal role in enhancing upper limb functional restoration post-stroke through precise neuromodulatory and neuroplastic interventions.

Abstract Developing novel solid electrolytes with high performance is of great significance for the practical application of lithium metal batteries. Among all the developed solid electrolytes, composite polymer electrolytes (CPEs) have been deemed one of the most viable candidates because of their comprehensive performance. Nevertheless, the random distribution of inorganic filler nanoparticles may cause discontinuities in ion transport and low mechanical strength. Therefore, the introduction of a filler network with fast ion conduction is an effective strategy to provide continuous ion transport and mechanical support. The mechanically reinforced filler network enhances the mechanical strength of the CPE, providing opportunities to reduce the thickness of CPE. In this review, the progress of mechanically reinforced filler structures in CPE is summarized, along with the introduction of mechanically reinforced filler networks with random and ordered structures and electrode‐integrated CPE with mechanically reinforced filler networks. Finally, challenges and possible future research directions for mechanically reinforced filler network CPE are presented.

This review provides an in-depth exploration of the mechanisms and applications of transcutaneous auricular vagus nerve stimulation (taVNS) in treating disorders of consciousness (DOC). Beginning with an exploration of the vagus nerve’s role in modulating brain function and consciousness, we then delve into the neuroprotective potential of taVNS demonstrated in animal models. The subsequent sections assess the therapeutic impact of taVNS on human DOC, discussing the safety, tolerability, and various factors influencing the treatment response. Finally, the review identifies the current challenges in taVNS research and outlines future directions, emphasizing the need for large-scale trials, optimization of treatment parameters, and comprehensive investigation of taVNS’s long-term effects and underlying mechanisms. This comprehensive overview positions taVNS as a promising and safe modality for DOC treatment, with a focus on understanding its intricate neurophysiological influence and optimizing its application in clinical settings.

Background: Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis. Cuproptosis is a novel type of cell death, which differs from previously reported types of cell death such as apoptosis, autophagy, proptosis, ferroptosis, necroptosis, etc. Long non-coding RNAs (lncRNAs) play multiple roles in HCC. Methods: We downloaded information from The Cancer Genome Atlas (TCGA) database, and obtained cuproptosis-related genes from published studies. The cuproptosis-related lncRNAs were obtained by correlation analysis, and subsequently used to construct a prognostic cuproptosis-related lncRNA signature. Analyses of overall survival (OS), progression-free survival (PFS), receiver operating characteristic (ROC) curve with the area under the curve (AUC) values and the index of concordance (c-index) curve were used to evaluate the signature. The tumor microenvironment (TME) was analyzed by ESTIMATE algorithm. The immune cell data was downloaded from the Tumor Immune Estimation Resource (TIMER) 2.0 database. Immune-related pathways were analyzed by single-sample gene set enrichment analysis (ssGSEA) algorithm. Immunophenoscore (IPS) scores from The Cancer Immunome (TCIA) database were used to evaluate immunotherapy response. The “pRRophetic” was employed to screen drugs for high-risk patients. The candidate lncRNA expression levels were detected by Real Time Quantitative PCR. Results: We constructed a cuproptosis-related lncRNA signature containing seven lncRNAs: AC125437.1, PCED1B-AS1, PICSAR, AP001372.2, AC027097.1, LINC00479, and SLC6A1-AS1. This signature had excellent accuracy, and was independent of the stratification of clinicopathological features. Further study showed that high-risk tumors under this signature had higher TMB, fewer TME components and higher tumor purity. The tumors with high risk were not enriched in immune cell infiltration or immune process pathways, and high-risk patients had a poor response to immunotherapy. Moreover, 29 drugs such as sorafenib, dasatinib and paclitaxel were screened for high-risk HCC patients to improve their prognosis. The expression levels of the candidate lncRNAs in HCC tissue were significantly increased (except PCED1B-AS1). Conclusions: Our prognostic cuproptosis-related lncRNA signature was accurate and effective for predicting the prognosis of HCC. The immunotherapy was unsuitable for high-risk HCC patients with this signature.

Abstract Solid‐state electrolytes (SSEs) are recognized as attractive candidates to realize safe and high‐energy‐density lithium metal batteries (LMBs). However, the practical application of SSEs still faces challenges such as insufficient room‐temperature ionic conductivity, unsatisfactory mechanical properties, and large internal resistance. Extensive research efforts have been made to explore new electrochemistry and technologies to address those challenges. Among them, the construction of order‐structured SSEs has emerged as a promising strategy. The anisotropic behavior induced by the orientation offers SSEs with desired properties targeting specific functions, and therefore the rational design of the order‐structured SSE provides an alternative solution to achieve an ideal SSE. This review discusses the structure‐property correlation of SSEs, and then summarizes the design strategies to construct order‐structured SSEs. Finally, the current challenges and possible future research directions for order‐structured SSEs for scalable high‐energy‐density LMBs are presented.

Corilagin, a polyphenolic tannic acid compound, showed significant anti-inflammatory activity in atherosclerotic mice. The present study aimed to evaluate the effect and mechanism of corilagin in atherosclerosis by in vivo, in vitro and in molecular docking strategies analysis. An atherosclerotic model was established by feeding ApoE−/− mice a high-fat diet. Murine RAW264.7 macrophages were cultured and induced with lipopolysaccharide (LPS). Treatment with corilagin had a marked inhibitory effect on the plaque area and lipid accumulation in atherosclerotic mice. Corilagin decreased the expression of iNOS and promoted the expression of CD206 in aortic plaque, as well as inhibited the production of proinflammatory factors in HFD-fed ApoE−/− mice and LPS-induced RAW264.6 cell. Corilagin also obviously inhibited the expression of TLR4, reduced the phosphorylation of the JNK, the protein expressions of p38 and NF-κB pathway. In addition, corilagin markedly diminished the nuclear translocation of NF-κBp65. Similarly, molecular docking study suggested that hydrogen bonds were detected between the corilagin and the five proteins (TLR4, Myd88, p65, P38, and JNK) with a significant “CDOCKER energy”. These results showed that the antiatherosclerotic effect of corilagin against M1 macrophage polarization and inflammation via suppression the activation of TLR4-NFκB/MAPK signaling pathway. Therefore, corilagin could be a promising lead compound to develop drugs for the treatment of atherosclerosis.

BackgroundSelecting features related to postoperative infection following cardiac surgery was highly valuable for effective intervention. We used machine learning methods to identify critical perioperative infection-related variables after mitral valve surgery and construct a prediction model.MethodsParticipants comprised 1223 patients who underwent cardiac valvular surgery at eight large centers in China. The ninety-one demographic and perioperative parameters were collected. Random forest (RF) and least absolute shrinkage and selection operator (LASSO) techniques were used to identify postoperative infection-related variables; the Venn diagram determined overlapping variables. The following ML methods: random forest (RF), extreme gradient boosting (XGBoost), Support Vector Machine (SVM), Gradient Boosting Decision Tree (GBDT), AdaBoost, Naive Bayesian (NB), Logistic Regression (LogicR), Neural Networks (nnet) and artificial neural network (ANN) were developed to construct the models. We constructed receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) was calculated to evaluate model performance.ResultsWe identified 47 and 35 variables with RF and LASSO, respectively. Twenty-one overlapping variables were finally selected for model construction: age, weight, hospital stay, total red blood cell (RBC) and total fresh frozen plasma (FFP) transfusions, New York Heart Association (NYHA) class, preoperative creatinine, left ventricular ejection fraction (LVEF), RBC count, platelet (PLT) count, prothrombin time, intraoperative autologous blood, total output, total input, aortic cross-clamp (ACC) time, postoperative white blood cell (WBC) count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), PLT count, hemoglobin (Hb), and LVEF. The prediction models for infection after mitral valve surgery were established based on these variables, and they all showed excellent discrimination performance in the test set (AUC > 0.79).ConclusionsKey features selected by machine learning methods can accurately predict infection after mitral valve surgery, guiding physicians in taking appropriate preventive measures and diminishing the infection risk.

The Carboniferous Yanghugou Formation in the western margin of the Ordos Basin exhibits significant potential for oil and gas exploration. However, due to the influence of complex tectonic activities, there are substantial variations in stratigraphic thickness and depositional environments across the formation. The lack of a systematic source–sink comparative study has resulted in an unclear understanding of sediment sources and paleogeographic patterns, impacting the exploration for hydrocarbon accumulations. We conducted a comprehensive study of the source–sink system characteristics and paleogeography in the research area through field outcrop observations and drilling core sampling. By utilizing detrital zircon U–Pb geochronology and geochemistry, paleocurrent directions, lithofacies types, and sedimentary features, we delve into the understanding of the source–sink systems. Four major source–sink regions in the research area were identified: the Alxa, Yinshan, Alxa–Yinshan mixed and Qilian source–sink regions. The Alxa source–sink region formed a transitional delta-barrier-island sedimentary system. The northern part of the Yinshan source–sink region developed a transitional tidal-controlled delta-tidal-flat sedimentary system, while the southern deep-water area developed a shallow marine to semi-deep marine shelf sedimentary systems. The sediments of Alxa–Yinshan mixed source–sink region were deposited in a transitional tidal-controlled delta-tidal-flat barrier-island system. The Qilian source–sink region is characterized by small tidal-controlled delta-barrier-island system. From the analysis of the source–sink systems, it is inferred that the Alxa Block and the North China Craton had already merged before deposition of the late Carboniferous Yanghugou Formation. The delta sand bodies in the Alxa–Yinshan mixed source–sink region have the highest compositional and structural maturity, the best reservoir performance, and the great exploration potential.

Geographical indications (GIs) mitigate information asymmetry in agri-food transactions by providing consumers with origin and quality information. This paper explores the impact of GIs on rural development in China by examining agricultural output and farmers’ income. Utilizing a large county-level dataset and comprehensive official GI information, this study estimates the impact of GIs on agricultural output and rural income using panel-fixed-effects models. The results reveal that GIs significantly boost agricultural added value and rural per capita disposable income. A series of methods, including difference-in-differences, propensity score matching with difference-in-differences, and double machine learning combined with difference-in-differences using random forests verify the robustness of the results. Moreover, by categorizing GIs based on product types, the analysis reveals heterogeneous effects of different GI categories on agricultural growth and income gains for farmers. The research findings in this paper offer valuable insights to inform policymaking aimed at advancing rural development, raising farmers’ incomes, and promoting sustainable agri-food supply chains.

This study explores the sedimentary environment and tectonic implications of the Upper Carboniferous Yanghugou Formation on the western margin of the Ordos Basin through the analysis of major elements, trace elements, and rare earth elements in 23 mudstone samples. The results indicate moderate chemical weathering conditions, as reflected in the Chemical Alteration Index (CIA) and Component Variability Index (ICV) values. Warm and humid paleoclimatic conditions are suggested by Rb/Sr, Sr/Cu, spore, and pollen fossil samples. The paleosalinity of the water is identified as a transitional phase of a brackish water environment based on Sr/Ba and Th/U ratios. Additionally, V/(V + Ni) and δU values imply a transitional phase of a weak oxidation–reduction environment for the water. In accordance with the La-Th-Sc, Th-Sc-Zr, Th-Co-Zr, (La/Yb)-∑REE, and (La/Th)-Hf discrimination diagrams, it is inferred that the study area is part of a continental marginal tectonic setting. The sediments are primarily derived from an upper-crust felsic source area. The sedimentary period of the Yanghugou Formation in the western margin of the basin is considered a marginal rift basin characterized by north–south compression and western rift extension. This setting is influenced by the active continental margin of the Alxa block and the passive continental margin of the Qilian–north Qinling orogenic belt.

Broiler weighing is essential in the broiler farming industry. Camera-based systems can economically weigh various broiler types without expensive platforms. However, existing computer vision methods for weight estimation are less mature, as they focus on young broilers. In effect, the estimation error increases with the age of the broiler. To tackle this, this paper presents a novel framework. First, it employs Mask R-CNN for instance segmentation of depth images captured by 3D cameras. Next, once the images of either a single broiler or multiple broilers are segmented, the extended artificial features and the learned features extracted by Customized Resnet50 (C-Resnet50) are fused by a feature fusion module. Finally, the fused features are adopted to estimate the body weight of each broiler employing gradient boosting decision tree (GBDT). By integrating diverse features with GBTD, the proposed framework can effectively obtain the broiler instance among many depth images of multiple broilers in the visual field despite the complex background. Experimental results show that this framework significantly boosts accuracy and robustness. With an MAE of 0.093 kg and an R2 of 0.707 in a test set of 240 63-day-old bantam chicken images, it outperforms other methods.

Abstract Screen channel liquid acquisition devices (LADs) are among the most promising technologies for separating liquid and vapor phases in propellant storage tanks under microgravity conditions and thus ensuring vapor-free propellant supply to spacecraft engines. However, the prediction of the critical flow rate of a screen channel LAD relies on the full understanding of the three dimensional distribution of injection velocity. In this study, the flow characteristics at the entrance region of the LAD were investigated via particle image velocimetry (PIV) technique and numerical simulations under various working conditions. The experimental results illustrated that the velocity component normal to the porous woven mesh is non-uniform in both streamwise and spanwise directions of channel flow and that this phenomenon has a significant influence on the critical flow rate. Hence, a model that accounts for the three-dimensional flow field was proposed to predict the critical flow rate. The average error in the critical flow rate, which was determined by comparing the proposed model’s predictions and the experimental results, was less than 8.4%.

In order to revise the problem of inferior hand-feeling of cashmere textile anti-filling finished with “addition” or “subtraction-addition” technology and indicate the effects of graphene distributed state in the surface on antistatic properties of cashmere fibers, A couple of flexible hydrophilic cationic polyurethanes used as a dispersion medium for graphene purposefully are designed and prepared. In addition, the state of polymer coating and graphene on the fiber is effectively controlled by foam micro-coating technology. The admirable pilling resistance, static resistance, and hand-feeling of cashmere textile attributed to two-layer polyurethane membranes realized through “bottom coating (BC)” and “surface coating (SC)” are definite and reliable. The results show that the cashmere textile obtained 1.0% (o.m.f. on mass of fabric) weight gain rate (WGR) under the foam bottom coating process, correspondingly, obtained 3–4% (o.m.f.) weight gain rate (WGR) under traditional dipping process, the pilling resistance grade of cashmere textile is improved to Grade 4–5 from Grade 1–2. The semi-embed state of graphene in the “surface coating” resin film on cashmere surface results in the decrease of static voltage half-life from 180 s to about 2 s. Clearly, the foam microcoating technology scheme of “BC+ SC@graphene” has achieved good expected results.

Tumor immune microenvironment (TIME), a tumor-derived immune component, is proven to be closely related to the development, metastasis, and recurrence of tumors. Gut microbiota and its fermented-metabolites short-chain fatty acids (SCFAs) play a critical role in maintaining the immune homeostasis of gastrointestinal tumors. Consisting mainly of acetate, propionate, and butyrate, SCFAs can interact with G protein-coupled receptors 43 of T helper 1 cell or restrain histone deacetylases (HDACs) of cytotoxic T lymphocytes to exert immunotherapy effects. Studies have shed light on SCFAs can mediate the differentiation and function of regulatory T cells, as well as cytokine production in TIME. Additionally, SCFAs can alter epigenetic modification of CD8+ T cells by inhibiting HDACs to participate in the immune response process. In gastrointestinal tumors, the abundance of SCFAs and their producing bacteria is significantly reduced. Direct supplementation of dietary fiber and probiotics, or fecal microbiota transplantation to change the structure of gut microbiota can both increase the level of SCFAs and inhibit tumor development. The mechanism by which SCFAs modulate the progression of gastrointestinal tumors has been elucidated in this review, aiming to provide prospects for the development of novel immunotherapeutic strategies.

Summary: Background: Immune-enhancing thymosin alpha 1 (Tα1) therapy may reduce infected pancreatic necrosis (IPN) in acute necrotising pancreatitis (ANP). However, the efficacy might be impacted by lymphocyte count due to the pharmacological action of Tα1. In this post-hoc analysis, we tested the hypothesis that pre-treatment absolute lymphocyte count (ALC) determines whether patients with ANP benefit from Tα1 therapy. Methods: A post-hoc analysis of data from a multicentre, double-blind, randomised, placebo-controlled trial testing the efficacy of Tα1 therapy in patients with predicted severe ANP was performed. Patients from 16 hospitals of China were randomised to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the frst 7 days and 1.6 mg once a day for the following 7 days or a matching placebo during the same period. Patients who discontinued the Tα1 regimen prematurely were excluded. Three subgroup analyses were conducted using the baseline ALC (at randomisation), and the group allocation was maintained as intention-to-treat. The primary outcome was the incidence of IPN 90 days after randomisation. The fitted logistic regression model was applied to identify the range of baseline ALC where Tα1 therapy could exert a maximum effect. The original trial is registered with ClinicalTrials.gov, NCT02473406. Findings: Between March 18, 2017, and December 10, 2020, a total of 508 patients were randomised in the original trial, and 502 were involved in this analysis, with 248 in the Tα1 group and 254 in the placebo group. Across the three subgroups, there was a uniform trend toward more significant treatment effects in patients with higher baseline ALC. Within the subgroup of patients with baseline ALC≥0.8 × 10ˆ9/L (n = 290), the Tα1 therapy significantly reduced the risk of IPN (covariate adjusted risk difference, −0.12; 95% CI, −0.21,-0.02; p = 0.015). Patients with baseline ALC between 0.79 and 2.00 × 10ˆ9/L benefited most from the Tα1 therapy in reducing IPN (n = 263). Interpretation: This post-hoc analysis found that the efficacy of immune-enhancing Tα1 therapy on the incidence of IPN may be associated with pretreatment lymphocyte count in patients with acute necrotising pancreatitis. Funding: National Natural Science Foundation of China.

Ammonia, as one of the primary water pollutants in aquaculture, has been shown to induce a wide range of ecotoxicological effects on aquatic animals. In order to investigate the antioxidant and innate immune responses in crustaceans disrupted by ammonia, red swamp crayfish (Procambarus clarkii) were exposed to 0, 15, 30, and 50 mg/L total ammonia nitrogen for 30 d, the alterations of antioxidant responses as well as innate immunity were studied. The results showed that the severity of hepatopancreatic injury were aggravated by the increasing ammonia levels, which were mainly characterized by tubule lumen dilatation and vacuolization. The swollen mitochondria and disappeared mitochondria ridges suggested that oxidative stress induced by ammonia targets the mitochondria. Concurrently, enhanced MDA levels, and decreased GSH levels as well as the decreased transcription and activity of antioxidant enzymes, including SOD, CAT, and GPx were noticed, which suggested that high concentrations of ammonia exposure induce oxidative stress in P. clarkii. Furthermore, a significant decrease of the hemolymph ACP, AKP, and PO along with the significant downregulation of immune-related genes (ppo, hsp70, hsp90, alf1, ctl) jointly indicated that ammonia stress inhibited the innate immune function. Our findings demonstrated that sub-chronic ammonia stress induced hepatopancreatic injury and exert suppressive effects on the antioxidant capacity as well as innate immunity of P. clarkii. Our results provide a fundamental basis for the deleterious effects of ammonia stress on aquatic crustaceans.

Introduction: The pathological progression of non-alcoholic fatty liver disease (NAFLD) is driven by multiple factors, and non-alcoholic steatohepatitis (NASH) represents its progressive form. In our previous studies, we found that bicyclol had beneficial effects on NAFLD/ NASH. Here we aim to investigate the underlying molecular mechanisms of the bicyclol effect on NAFLD/NASH induced by high-fat diet (HFD) feeding.Methods: A mice model of NAFLD/NASH induced by HFD-feeding for 8 weeks was used. As a pretreatment, bicyclol (200 mg/kg) was given to mice by oral gavage twice daily. Hematoxylin and eosin (H&E) stains were processed to evaluate hepatic steatosis, and hepatic fibrous hyperplasia was assessed by Masson staining. Biochemistry analyses were used to measure serum aminotransferase, serum lipids, and lipids in liver tissues. Proteomics and bioinformatics analyses were performed to identify the signaling pathways and target proteins. Data are available via Proteome X change with identifier PXD040233. The real-time RT-PCR and Western blot analyses were performed to verify the proteomics data.Results: Bicyclol had a markedly protective effect against NAFLD/NASH by suppressing the increase of serum aminotransferase, hepatic lipid accumulation and alleviating histopathological changes in liver tissues. Proteomics analyses showed that bicyclol remarkably restored major pathways related to immunological responses and metabolic processes altered by HFD feeding. Consistent with our previous results, bicyclol significantly inhibited inflammation and oxidative stress pathway related indexes (SAA1, GSTM1 and GSTA1). Furthermore, the beneficial effects of bicyclol were closely associated with the signaling pathways of bile acid metabolism (NPC1, SLCOLA4 and UGT1A1), cytochrome P450-mediated metabolism (CYP2C54, CYP3A11 and CYP3A25), biological processes such as metal ion metabolism (Ceruloplasmin and Metallothionein-1), angiogenesis (ALDH1A1) and immunological responses (IFI204 and IFIT3).Discussion: These findings suggested that bicyclol is a potential preventive agent for NAFLD/NASH by targeting multiple mechanisms in future clinical investigations.