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Lin-Feng Yan,1,* Ying-Zhi Sun,1,* Sha-Sha Zhao,1,* Yu-Chuan Hu,1,* Yu Han,1 Gang Li,2 Xin Zhang,1 Qiang Tian,1 Zhi-Cheng Liu,1 Yang Yang,1 Hai-Yan Nan,1 Ying Yu,1 Qian Sun,1 Jin Zhang,1 Ping Chen,1 Bo Hu,1 Fei Li,3 Teng-Hui Han,3 Wen Wang,1 Guang-Bin Cui1 1Department of Radiology & Functional and Molecular Imaging Key Laboratory of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710038, People’s Republic of China; 2Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710038, People’s Republic of China; 3Student Brigade, Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Wang; Guang-Bin CuiDepartment of Radiology & Functional and Molecular Imaging Laboratory of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi’an 710038, People’s Republic of ChinaTel +86-29-84778689; 86-29-84777863Email wangwen@fmmu.edu.cn; cuigbtd@fmmu.edu.cnPurpose: This study aims to incorporate informative histogram indicator analyses and advanced multimodal MRI parameters to differentiate low-grade gliomas (LGGs) from high-grade gliomas (HGGs) and to explore the features associated with patients’ survival.Patients and methods: A total of 120 patients with pathologically confirmed LGGs or HGGs receiving conventional and advanced MRI such as three-dimensional arterial spin labeling (3D-ASL), intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI), and dynamic contrast-enhanced MRI (DCE-MRI) were included. The mean and histogram indicators from advanced MRI were calculated from the entire tumor. The efficacies of a single indicator or multiple parameters were tested in distinguishing HGGs from LGGs and predicting patients’ survival. Receiver operating characteristic (ROC) curve and multivariable stepwise logistic regression were used to evaluate the diagnostic efficacies. Leave-one-out cross-validation was further used to validate the accuracy of the parameter sets in glioma grading. Log-rank test using the Kaplan–Meier curve was utilized to predict patients’ survival.Results: Overall, parameters from DCE-MRI performed better than those from 3D-ASL or IVIM-DWI in both glioma grading and survival prediction. The histogram metrics of Ve were demonstrated to have higher accuracies (the accuracies for Extended Tofts_Vemean and Extended Tofts_Vemedian were 68.33% and 71.67%, respectively, while those for the Incremental_Vemean and Incremental_Ve75th were 68.33% and 72.50%, respectively) in grading LGGs from HGGs. The combination of Tofts_Ve histogram metrics was the one with the highest accuracy (81.67%) and area under ROC curve (AUC = 0.840). On the other hand, Patlak_Ktrans95th (AUC = 0.9265) and Extended Tofts_Ve95th (AUC = 0.9154) performed better than their corresponding means (Patlak_Ktransmean: AUC = 0.9118 and Extended Tofts_Vemean: AUC = 0.9044) in predicting patients’ overall survival (OS) at 18-month follow-up.Conclusion: DCE-MRI-derived histogram features from the entire tumor were promising metrics for glioma grading and OS prediction. Combining single modal histogram features improved glioma grading.Trial registration: NCT 02622620.Keywords: multi-modal MRI, histogram features, receiver operating curve, glioma grading, survival analysis

Hyperphosphorylated tau is the major component of intracellular neurofibrillary tangles, which is positively correlated with the cognitive decline in Alzheimer's disease (AD). The upstream factors leading to tau hyperphosphorylation are still not fully understood. Endoplasmic reticulum (ER) stress has been indicated in AD pathogenesis and the increased level of binding immunoglobulin protein (Bip), an important ER associated chaperon, is increased in AD brain. Here hyperphosphorylation of tau, activation of glycogen synthase kinase-3β (GSK-3β), and elevation of Bip were induced by ventricular infusion of ER stressors, tunicamycin (TM) and thapsigargin (TG), in rats. GSK-3β was found to be responsible for tau hyperphosphorylation induced by ER stressors both in vivo and in vitro. In addition, inhibited Akt, protein tyrosine phosphatase 1B, and activated Fyn were detected in vivo. Down-regulating Bip by tranfecting its siRNA plasmid significantly revised tau hyperphosphorylation in TG treated HEK293/tau cells, but the activation of GSK-3β was still observed. By immunoprecipitation, we found that the binding levels of Bip to tau and GSK-3β were significantly increased with the elevation of Bip in TM-treated rats. Moreover, in Bip overexpressed HEK293/tau cells, the binding levels of Bip to tau (mainly phosphorylated tau) and GSK-3β were also significantly increased. However, β-catenin, another important substrate of GSK-3β, was not found bound to the increased Bip. All these data suggest an essential role of Bip in GSK-3β dependent tau hyperphosphorylation in ER stress by promoting the binding of GSK-3β to tau. [ABSTRACT FROM AUTHOR]

Persistent pain frequently precipitates the development of anxiety disorders, yet the underlying mechanisms are not fully understood. In this study, we employed a mouse model that simulates trigeminal neuralgia and observed a marked reduction in the activity of GABAergic neurons in the lateral habenula (LHb), a critical region for modulating pain and anxiety. We utilized precise optogenetic and chemogenetic techniques to modulate these neurons, which significantly alleviated behaviors associated with pain and anxiety. Our investigations revealed an inhibitory pathway from the LHb GABAergic neurons to the posterior paraventricular thalamus. Activation of this pathway primarily mitigated pain-related behaviors, with minimal effects on anxiety. Conversely, interactions between GABAergic and glutamatergic neurons within the LHb were essential in alleviating both pain and anxiety following trigeminal nerve damage. Additionally, we identified that β-sitosterol interacts directly with LHb GABAergic neurons via the estrogen receptor α, providing dual therapeutic effects for both pain and anxiety. These findings highlight the critical role of reduced GABAergic neuronal activity in the LHb in the intersection of pain and anxiety, pointing to promising therapeutic possibilities., Competing Interests: Competing interests statement:The authors declare no competing interest.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13 C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 ., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Vitamin E, an essential micronutrient with antioxidant potential, can dramatically reduce the cardiovascular risk in individuals with haptoglobin (Hp) 2-2 genotype diabetes; however, the underlying mechanism remains unclear. Objective: The objective of this study is to evaluate the effect of vitamin E supplementation on high-density lipoprotein (HDL) levels and function in individuals with diabetes stratified by Hp genotype. Methods: All relevant studies published up to May 2023 were systematically reviewed using PubMed, Cochrane Library, Web of Science, Chinese Wanfang, China Science and Technology Journal, and Chinese National Knowledge Infrastructure databases. Randomized controlled trials that evaluated the effects of vitamin E supplementation on HDL levels were included. The outcomes assessed were changes in HDL concentrations, cholesterol efflux, and HDL-associated lipid peroxides. Results: In total, 163 publications were selected. Based on inclusion and exclusion selection and quality assessment, five studies with 463 participants were included. Vitamin E supplementation did not exert any effect on HDL levels in individuals with diabetes with any Hp genotype. Three of the five studies revealed that vitamin E improved cholesterol efflux and HDL lipid peroxides in individuals with Hp2-2 diabetes but did not positively impact HDL function in Hp1 carriers. Conclusions: Although vitamin E supplementation did not significantly impact HDL levels in individuals with diabetes of any Hp genotype, it may improve HDL function in individuals with Hp2-2 diabetes. These findings indicate a pharmacogenetic interaction between vitamin E and the Hp genotype on HDL function. Moreover, vitamin E supplementation may be an effective strategy for specific individuals with diabetes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Pan-pan Zheng et al.)

Purpose: Microglia-like cells derived from stem cells (iMG) provide a plentiful cell source for studying the functions of microglia in both normal and pathological conditions. Our goal is to establish a simplified and effective method for generating iMG in a precisely defined system. Additionally, we aim to achieve functional maturation of iMG through coculture with retinal organoids., Methods: In this study, iMG were produced under precisely defined conditions. They were subjected to LPS and poly IC stimulation. Additionally, we examined distinct phenotypic and functional variances between iMG and HMC3, a commonly used human microglia cell line. To investigate how the retinal cell interaction enhances microglial properties, iMG were cocultured with retinal organoids, producing CC-iMG. We performed RNA sequencing, electrophysiological analysis, and transmission electron microscope (TEM) to examine the maturation of CC-iMG compared to iMG., Results: Our results demonstrated that iMG performed immune-responsive profiles closely resembling those of primary human microglia. Compared to HMC3, iMG expressed a higher level of typical microglial markers and exhibited enhanced phagocytic activity. The transcriptomic analysis uncovered notable alterations in the ion channel profile of CC-iMG compared to iMG. Electrophysiological examination demonstrated a heightened intensity of inward- and outward-rectifying K+ currents in CC-iMG. Furthermore, CC-iMG displayed elevated numbers of lysosomes and mitochondria, coupled with increased phagocytic activity., Conclusions: These findings contribute to advancing our understanding of human microglial biology, specifically in characterizing and elucidating the functions of CC-iMG, thereby offering an in vitro microglial model for future scientific research and potential clinical applications in cell therapy.

Background: Clostridium difficile ( C. difficile ) infection (CDI) is a rare clinical disease caused by changes in the intestinal microenvironment, which has a variety of causes and a poor prognosis, and for which there is no standardized clinical treatment., Case Summary: A patient experienced recurrent difficulty in bowel movements over the past decade. Recently, symptoms worsened within the last ten days, leading to a clinic visit due to constipation. The patient was subsequently referred to our department. Preoperatively, the patient was diagnosed with obstructed colon accompanied by gallstones. Empirical antibiotics were administered both before and after surgery to prevent infection. On the fourth day post-surgery, symptoms of CDI emerged. Stool cultures confirmed the presence of C. difficile DNA. Treatment involved a combination of vancomycin and linezolid, resulting in the patient's successful recovery upon discharge. However, the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later., Conclusion: CDI is the leading cause of nosocomial post-operative care, with limited clinical cases and poor patient prognosis, and comprehensive clinical treatment guidelines are still lacking. This infection can be triggered by a variety of factors, including intestinal hypoxia, inappropriate antibiotic use, and bile acid circulation disorders. In patients with chronic bowel disease and related etiologies, prompt preoperative attention to possible CDI and preoperative bowel preparation is critical. Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Ethnopharmacological Relevance: Metabolic-associated fatty liver disease (MAFLD) and atherosclerosis are very common disorders that frequently coexist. The therapeutic efficacy of Huanglian Wendan (HLWD) decoction, a traditional Chinese medicine (TCM) prescription, is satisfactory in treating MAFLD associated with atherosclerosis. However, the underlying mechanisms through which HLWD exerts its effects need to be elucidated. Given the complex composition of HLWD and its multiple therapeutic targets, pharmacological investigation is challenging., Aim of This Study: This study aimed to identify the effective compounds in HLWD and elucidate the mechanisms involved in its therapeutic effect on MAFLD associated with atherosclerosis., Materials and Methods: We used a systematic pharmacology method to identify effective compounds present in HLWD and determine the mechanism by which it affects MAFLD associated with atherosclerosis. The effective components of HLWD were identified through ultrahigh-performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Next, a comprehensive in silico method was used to predict potential related targets and disease targets for these compounds to establish corresponding pathways. The accuracy of our assumed systemic pharmacology results was determined by conducting follow-up experiments., Results: By conducting UHPLC-Q-Orbitrap HRMS combined with network analysis, we identified 18 potentially active components of HLWD and assessed the inflammatory regulatory mechanism by which it affects MAFLD associated with atherosclerosis on the basis of 52 key targets. We used a high-fat, high-cholesterol (HFHC)-induced mice model of MAFLD associated with atherosclerosis to confirm our results. We found that administering HLWD significantly improved the appearance of their liver and reduced their body weight, liver weight, blood lipids, hepatic damage, and hepatic pathology. HLWD also decreased atherosclerotic lesion areas, foam cells, and inflammatory cells in the aorta. HLWD showed anti-inflammatory effects, suppressed M1 polarization, and promoted M2 polarization in the liver and aorta. HLWD might also regulate peroxisome proliferator-activated receptor-γ (PPARγ)/nuclear factor kappa-B (NF-κB) signaling to influence macrophage polarization and inflammation., Conclusions: Our results showed that HLWD protected against HFHC diet-induced MAFLD associated with atherosclerosis by regulating PPARγ/NF-κB signaling, thus adjusting macrophage polarization and inflammation. Additionally, pharmacochemistry research, network pharmacology analysis, and experimental verification can be combined to form a comprehensive model used in studies on TCM., Competing Interests: Declaration of competing interest All authors declared no competing interests on this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The traditional dynamical phase transition refers to the appearance of singularities in an observable with respect to a control parameter for a late-time state or singularities in the rate function of the Loschmidt echo with respect to time. Here, we study the many-body dynamics in a continuously monitored free fermion system with conditional feedback under open boundary conditions. We surprisingly find a novel dynamical transition from a logarithmic scaling of the entanglement entropy to an area-law scaling as time evolves. The transition, which is noticeably different from the conventional dynamical phase transition, arises from the competition between the bulk dynamics and boundary skin effects. In addition, we find that while quasidisorder or disorder cannot drive a transition for the steady state, a transition occurs for the maximum entanglement entropy during the time evolution, which agrees well with the entanglement transition for the steady state of the dynamics under periodic boundary conditions.

Background: The results of existing lower extremity robotics studies are conflicting, and few relevant clinical trials have examined short-term efficacy. In addition, most of the outcome indicators in existing studies are scales, which are not objective enough. We used the combination of objective instrument measurement and scale to explore the short-term efficacy of the lower limb A3 robot, to provide a clinical reference., Aim: To investigate the improvement of lower limb walking ability and balance in stroke treated by A3 lower limb robot., Methods: Sixty stroke patients were recruited prospectively in a hospital and randomized into the A3 group and the control group. They received 30 min of A3 robotics training and 30 min of floor walking training in addition to 30 min of regular rehabilitation training. The training was performed five times a week, once a day, for 2 wk. The t -test or non-parametric test was used to compare the three-dimensional gait parameters and balance between the two groups before and after treatment., Results: The scores of basic activities of daily living, Stroke-Specific Quality of Life Scale, FM balance meter, Fugl-Meyer Assessment scores, Rivermead Mobility Index, Stride speed, Stride length, and Time Up and Go test in the two groups were significantly better than before treatment (19.29 ± 12.15 vs 3.52 ± 4.34; 22.57 ± 17.99 vs 4.07 ± 2.51; 1.21 ± 0.83 vs 0.18 ± 0.40; 3.50 ± 3.80 vs 0.96 ± 2.08; 2.07 ± 1.21 vs 0.41 ± 0.57; 0.89 ± 0.63 vs 0.11 ± 0.32; 12.38 ± 9.00 vs 2.80 ± 3.43; 18.84 ± 11.24 vs 3.80 ± 10.83; 45.12 ± 69.41 vs 8.41 ± 10.20; 29.45 ± 16.62 vs 8.68 ± 10.74; P < 0.05). All outcome indicators were significantly better in the A3 group than in the control group, except the area of the balance parameter., Conclusion: For the short-term treatment of patients with subacute stroke, the addition of A3 robotic walking training to conventional physiotherapy appears to be more effective than the addition of ground-based walking training., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size., Methods: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy., Results: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%., Conclusions: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 )., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the intra- and inter-observer consistency of the Visually Accessible Rembrandt Images (VASARI) feature set before and after dichotomization, and the association between dichotomous VASARI features and the overall survival (OS) in glioblastoma (GBM) patients., Methods: This retrospective study included 351 patients with pathologically confirmed IDH1 wild-type GBM between January 2016 and June 2022. Firstly, VASARI features were assessed by four radiologists with varying levels of experience before and after dichotomization. Cohen's kappa coefficient (κ) was calculated to measure the intra- and inter-observer consistency. Then, after adjustment for confounders using propensity score matching, Kaplan-Meier curves were used to compare OS differences for each dichotomous VASARI feature. Next, patients were randomly stratified into a training set (n = 211) and a test set (n = 140) in a 3:2 ratio. Based on the training set, Cox proportional hazards regression analysis was adopted to develop combined and clinical models to predict OS, and the performance of the models was evaluated with the test set., Results: Eleven VASARI features with κ value of 0.61-0.8 demonstrated almost perfect agreement after dichotomization, with the range of κ values across all readers being 0.874-1.000. Seven VASARI features were correlated with GBM patient OS. For OS prediction, the combined model outperformed the clinical model in both training set (C-index, 0.762 vs. 0.723) and test set (C-index, 0.812 vs. 0.702)., Conclusion: The dichotomous VASARI features exhibited excellent inter- and intra-observer consistency. The combined model outperformed the clinical model for OS prediction., (© 2024. The Author(s).)

Background: The prevalence of hypertension still increases with the very rapidly increasing longevity in some countries, such as China. The control rate remains low., Objectives: This randomized, double-blind, phase 3 study assessed the efficacy and safety of sacubitril/allisartan, compared with olmesartan in Chinese patients with mild-to-moderate hypertension., Methods: Eligible patients aged 18 to 75 years (n = 1,197) with mild-to-moderate hypertension were randomized to receive sacubitril/allisartan 240 mg (n = 399), sacubitril/allisartan 480 mg (n = 399), or olmesartan 20 mg (n = 399) once daily for 12 weeks. Patients who completed the 12-week treatment then received another 12-week extended treatment (n = 1,084) and 28-week prolonged treatment (n = 189). The primary end point was a reduction in clinic mean sitting systolic blood pressure (msSBP) from baseline at 12 weeks., Results: Sacubitril/allisartan 240 mg/d provided a greater reduction in msSBP than olmesartan at 12 weeks (between-group difference: -1.9 mm Hg [95% CI: -4.2 to 0.4 mm Hg]; P  = 0.0007, for noninferiority). Sacubitril/allisartan 480 mg/d provided a significantly greater reduction in msSBP than olmesartan at 12 weeks (between-treatment difference: -5.0 mm Hg [95% CI: -7.3 to -2.8 mm Hg]; P  < 0.001, for superiority). Greater reductions in 24-hour, and daytime and nighttime systolic and diastolic blood pressure were also observed with both doses of sacubitril/allisartan compared with olmesartan ( P  ≤ 0.001 for 480 mg/d). The blood pressure reductions tended to be dose-dependent for sacubitril/allisartan. Sacubitril/allisartan was well tolerated, and no cases of angioedema or death were reported., Conclusions: Sacubitril/allisartan is effective for the treatment of hypertension and well tolerated in Chinese patients., Competing Interests: The study was funded by Salubris Pharma (Shenzhen, Guangdong Province, China). The study investigators were also financially supported by National Natural Science Foundation of China (grants 82070432, 82070435, 82270469, and 82370426); Ministry of Science and Technology (grants 2018YFC1704902 and 2022YFC3601302); Shanghai Municipal Commissions of Science and Technology (grant 19DZ2340200) and Health (a special grant for “leading academics”); the Three-year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System (GWV-10.1-XK05) Big Data and Artificial Intelligence Application; the Clinical Research Program, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (grant 2018CR010); and the Shenzhen Science and Technology Program (grant KQTD20200820151701004). Prof Wang has received lecture and consulting fees from Novartis, Omron, Servier, and Viatris. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO 2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.

Background: Hepatocellular carcinoma (HCC) is a serious complication of hepatic vena cava Budd-Chiari syndrome (HVC-BCS) that significantly reduces the survival time of patients. Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system., Methods: The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed. Kaplan-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups. Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical, tumor, and etiological characteristics on the total survival time of patients, and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model. The prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance index., Results: Multivariate analysis showed that serum albumin level < 34 g/L [hazard ratio (HR) = 4.207, 95% confidence interval (CI): 1.816-8.932, P = 0.001], maximum tumor diameter > 7 cm (HR = 8.623, 95% CI: 3.771-19.715, P < 0.001), and inferior vena cava stenosis (HR = 3.612, 95% CI: 1.646-7.928, P = 0.001) were independent predictors of survival. A prognostic scoring system was developed according to the above-mentioned independent predictors, and patients were classified into grades A, B, C and D. Significant differences in survival were found among the four groups., Conclusions: This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC, which is helpful for clinical evaluation of patient prognosis., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Renal cell carcinoma (RCC) is considered a "metabolic disease" characterized by elevated glycolysis in patients with advanced RCC. Tyrosine kinase inhibitor (TKI) therapy is currently an important treatment option for advanced RCC, but drug resistance may develop in some patients. Combining TKI with targeted metabolic therapy may provide a more effective approach for patients with advanced RCC. An analysis of 14 RCC patients (including three needle biopsy samples with TKI resistance) revealed by sing-cell RNA sequencing (scRNA-seq) that glycolysis played a crucial role in poor prognosis and drug resistance in RCC. TCGA-KIRC and glycolysis gene set analysis identified DEPDC1 as a target associated with malignant progression and drug resistance in KIRC. Subsequent experiments demonstrated that DEPDC1 promoted malignant progression and glycolysis of RCC, and knockdown DEPDC1 could reverse TKI resistance in RCC cell lines. Bulk RNA sequencing (RNA-seq) and non-targeted metabolomics sequencing suggested that DEPDC1 may regulate RCC glycolysis via AKT/mTOR/HIF1α pathway, a finding supported by protein-level analysis. Clinical tissue samples from 98 RCC patients demonstrated that DEPDC1 was associated with poor prognosis and predicted RCC metastasis. In conclusion, this multi-omics analysis suggests that DEPDC1 could serve as a novel target for TKI combined with targeted metabolic therapy in advanced RCC patients with TKI resistance., (© 2024. The Author(s).)

Neoadjuvant tyrosine kinase inhibitor (TKI) therapy is an important treatment option for advanced renal cell carcinoma (RCC). Many RCC patients may fail to respond or be resistant to TKI therapy. We aimed to explore the key mechanisms of neoadjuvant therapy résistance. We obtained tumor samples from matched pre-treatment biopsy and post-treatment surgical samples and performed single-cell RNA sequencing. Sunitinib-resistant ccRCC cell lines were established. Ferroptosis was detected by ferrous ion and lipid peroxidation levels. Tumor growth and resistance to Sunitinib was validated in vitro and vivo. Immunohistochemistry was used to validate the levels key genes and lipid peroxidation. Multi-center cohorts were included, including TCGA, ICGC, Checkmate-025 and IMmotion151 clinical trial. Survival analysis was performed to identify the associated clinical and genomic variables. Intratumoral heterogeneity was first described in the whole neoadjuvant management. The signature of endothelial cells was correlated with drug sensitivity and progression-free survival. Ferroptosis was shown to be the key biological program in malignant cell resistance. We observed tissue lipid peroxidation was negatively correlated with IL6 and tumor response. TKI-resistant cell line was established. SLC7A11 knockdown promoted cell growth and lipid peroxidation, increased the ferroptosis level, and suppressed the growth of tumor xenografts significantly (P < 0.01). IL6 could reverse the ferroptosis and malignant behavior caused by SLC7A11 (-) via JAK2/STAT3 pathway, which was rescued by the ferroptosis inducer Erastin. Our data indicate that ferroptosis is a novel strategy for advanced RCC treatment, which activated by IL6, providing a new idea for resistance to TKIs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Nitrate reduction in bio-electrochemical systems (BESs) has attracted wide attention due to its low sludge yields and cost-efficiency advantages. However, the high resistance of traditional electrodes is considered to limit the denitrification performance of BESs. Herein, a new graphene/polypyrrole (rGO/PPy) modified electrode is fabricated via one-step electrodeposition and used as cathode in BES for improving nitrate removal from wastewater. The formation and morphological results support the successful formation of rGO/PPy nanohybrids and confirm the part covalent bonding of Py into GO honeycomb lattices to form a three-dimensional cross-linked spatial structure. The electrochemical tests indicate that the rGO/PPy electrode outperforms the unmodified electrode due to the 3.9-fold increase in electrochemical active surface area and 6.9-fold decrease in the charge transfer resistance (R ct ). Batch denitrification activity tests demonstrate that the BES equipped with modified rGO/PPy biocathode could not only achieve the full denitrification efficiency of 100% with energy recovery (15.9 × 10 -2  ± 0.14 A/m 2 ), but also favor microbial attach and growth with improved biocompatible surface. This work provides a feasible electrochemical route to fabricate and design a high-performance bioelectrode to enhance denitrification in BESs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the realm of animal phenotyping, manual measurements are frequently utilised. While machine-generated data show potential for enhancing high-throughput breeding, additional research and validation are imperative before incorporating them into genetic evaluation processes. This research presents a method for managing meat sheep and collecting data, utilising the Sheep Data Recorder system for data input and the Sheep Body Size Collector system for image capture. The study aimed to investigate the genetic parameter changes of growth traits in Ujumqin sheep by comparing machine-generated measurements with manual measurements. The dataset consisted of 552 data points from the offspring of 75 breeding rams and 399 breeding ewes. Six distinct random regression models were assessed to pinpoint the most suitable model for estimating genetic parameters linked to growth traits. These models were distinguished based on the inclusion or exclusion of maternal genetic effects, maternal permanent environmental effects, and covariance between maternal and direct genetic effects. Fixed factors such as individual age, individual sex, and ewe age were taken into account in the analysis. The genetic parameters for the yearling growth traits of Ujumqin sheep were calculated using ASReml software. The Akaike information criterion, the Bayesian information criterion, and fivefold cross-validation were employed to identify the optimal model. Research findings indicate that the most accurate models for manually measured data revealed heritability estimates of 0.12 ± 0.15 for BW, 0.05 ± 0.07 for body slanting length, 0.03 ± 0.07 for withers height, 0.15 ± 0.12 for hip height, 0.11 ± 0.11 for chest depth, 0.13 ± 0.13 for shoulder width, and 0.53 ± 0.15 for chest circumference. The optimal models for machine-predicted data showed heritability estimates of 0.1 ± 0.09 for body slanting length, 0.14 ± 0.12 for withers height, 0.55 ± 0.15 for hip height, 0.34 ± 0.15 for chest depth, 0.26 ± 0.15 for shoulder width, and 0.47 ± 0.16 for chest circumference. In manually measured data, genetic correlations ranged from 0.35 to 0.99, while phenotypic correlations ranged from 0.07 to 0.90. In machine data, genetic correlations ranged from -0.05 to 0.99, while phenotypic correlations ranged from 0.03 to 0.84. The results suggest that machine-based estimations may lead to an overestimation of heritability, but this discrepancy does not impact the selection of breeding models., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tertiary lymphoid structures (TLSs) serve as organized lymphoid aggregates that influence immune responses within the tumor microenvironment. This study aims to investigate the characteristics and clinical significance of TLSs and tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC)., Methods: TLSs and TILs were analyzed comprehensively in 754 ccRCC patients from 6 academic centers and 532 patients from The Cancer Genome Atlas. Integrated analysis was performed based on single-cell RNA-sequencing datasets from 21 ccRCC patients to investigate TLS heterogeneity in ccRCC. Immunohistochemistry and multiplex immunofluorescence were applied. Cox regression and Kaplan-Meier analyses were used to reveal the prognostic significance., Results: The study demonstrated the existence of TLSs and TILs heterogeneities in the ccRCC microenvironment. TLSs were identified in 16% of the tumor tissues in 113 patients. High density (>0.6/mm 2 ) and maturation of TLSs predicted good overall survival (OS) (p<0.01) in ccRCC patients. However, high infiltration (>151) of scattered TILs was an independent risk factor of poor ccRCC prognosis (HR=14.818, p<0.001). The presence of TLSs was correlated with improved progression-free survival (p=0.002) and responsiveness to therapy (p<0.001). Interestingly, the combination of age and TLSs abundance had an impact on OS (p<0.001). Higher senescence scores were detected in individuals with immature TLSs (p=0.003)., Conclusions: The study revealed the contradictory features of intratumoral TLSs and TILs in the ccRCC microenvironment and their impact on clinical prognosis, suggesting that abundant and mature intratumoral TLSs were associated with decreased risks of postoperative ccRCC relapse and death as well as favorable therapeutic response. Distinct spatial distributions of immune infiltration could reflect effective antitumor or protumor immunity in ccRCC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the 'floristic geo-lithology hypothesis', which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions., (© 2024. The Author(s).)

Objective: To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value. Methods: This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group ( n =38) and the survival group ( n =133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model's differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results: Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors ( P <0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P -values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions: The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

Background: The overproliferation of fibroblast-like synoviocytes (FLS) contributes to synovial hyperplasia, a pivotal pathological feature of rheumatoid arthritis (RA). Shikonin (SKN), the active compound from Lithospermum erythrorhizon, exerts anti-RA effects by diverse means. However, further research is needed to confirm SKN's in vitro and in vivo anti-proliferative functions and reveal the underlying specific molecular mechanisms., Purpose: This study revealed SKN's anti-proliferative effects by inducing both apoptosis and autophagic cell death in RA FLS and adjuvant-induced arthritis (AIA) rat synovium, with involvement of regulating the AMPK/mTOR/ULK-1 pathway., Methods: SKN's influences on RA FLS were assessed for proliferation, apoptosis, and autophagy with immunofluorescence staining (Ki67, LC3B, P62), EdU incorporation assay, staining assays of Hoechst, Annexin V-FITC/PI, and JC-1, transmission electron microscopy, mCherry-GFP-LC3B puncta assay, and western blot. In AIA rats, SKN's anti-arthritic effects were assessed, and its impacts on synovial proliferation, apoptosis, and autophagy were studied using Ki67 immunohistochemistry, TUNEL, and western blot. The involvement of AMPK/mTOR/ULK-1 pathway was examined via western blot., Results: SKN suppressed RA FLS proliferation with reduced cell viability and decreased Ki67-positive and EdU-positive cells. SKN promoted RA FLS apoptosis, as evidenced by apoptotic nuclear fragmentation, increased Annexin V-FITC/PI-stained cells, reduced mitochondrial potential, elevated Bax/Bcl-2 ratio, and increased cleaved-caspase 3 and cleaved-PARP protein levels. SKN also enhanced RA FLS autophagy, featuring increased LC3B, reduced P62, autophagosome formation, and activated autophagic flux. Autophagy inhibition by 3-MA attenuated SKN's anti-proliferative roles, implying that SKN-induced autophagy contributes to cell death. In vivo, SKN mitigated the severity of rat AIA while also reducing Ki67 expression, inducing apoptosis, and enhancing autophagy within AIA rat synovium. Mechanistically, SKN modulated the AMPK/mTOR/ULK-1 pathway in RA FLS and AIA rat synovium, as shown by elevated P-AMPK and P-ULK-1 expression and decreased P-mTOR expression. This regulation was supported by the reversal of SKN's in vitro and in vivo effects upon co-administration with the AMPK inhibitor compound C., Conclusion: SKN exerted in vitro and in vivo anti-proliferative properties by inducing apoptosis and autophagic cell death via modulating the AMPK/mTOR/ULK-1 pathway. Our study revealed novel molecular mechanisms underlying SKN's anti-RA effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The pursuit of high energy densities propels the design of next-generation nickel-based layered oxide cathodes. The utilization of low-cobalt, ultrahigh-nickel layered oxide cathodes, and the extension of operating voltages promise enhanced energy density. However, stability and safety face challenges associated with nickel content, including structural degradation, lattice oxygen evolution, and thermal instability. In this study, a promising strategy of Al and Nb dual-bulk-doping is presented in high-Ni cathode materials of LiNi 0.96 Co 0.04 O 2 (NC) to stabilize the bulk structure, suppress oxygen release, and attain superior electrochemical performance at high voltages. The introduction of Al and Nb effectively raises the migration energy of Ni 2+ into Li sites and stabilizes lattice oxygen through strengthened Al─O and Nb─O bonds. Furthermore, the substitution of high-valence Nb ions reduces the charge depletion of lattice oxygen and induces an ordered microstructure. The Al and Nb dual-bulk-doping strategy mitigates strain and stress associated with the H2↔H3 phase transition, reducing the generation and propagation of microcracks. The resulting Li(Ni 0.96 Co 0.04 ) 0.985 Al 0.01 Nb 0.005 O 2 (NCAN) cathode exhibits superior cycling stability, with a capacity retention of 77.8% after 300 cycles, even when operating at a high-voltage of 4.4 V, outperforming the NC (48.5%). This work provides a promising perspective for developing high-voltage and high-Ni cathode materials., (© 2024 Wiley‐VCH GmbH.)

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown., Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk., Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu., Exposures: H pylori treatment and nutrition supplementation., Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk., Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation., Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.

Background: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment., Results: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients., Conclusion: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested., (© 2024. The Author(s).)

Serving as neuromorphic hardware accelerators, memristors play a crucial role in large-scale neuromorphic computing. Herein, two-terminal memristors utilizing amorphous indium-gallium-zinc oxide (a-IGZO) are fabricated through room-temperature sputtering. The electrical characteristics of these memristors are effectively modulated by varying the oxygen flow during the deposition process. The optimized a-IGZO memristor, fabricated under 3 sccm oxygen flow, presents a 5 × 10 3 ratio between its high- and low-resistance states, which can be maintained over 1 × 10 4 s with minimal degradation. Meanwhile, desirable properties such as electroforming-free and self-compliance, crucial for low-energy consumption, are also obtained in the a-IGZO memristor. Moreover, analog conductance switching is observed, demonstrating an interface-type behavior, as evidenced by its device-size-dependent performance. The coexistence of negative differential resistance with analog switching is attributed to the migration of oxygen vacancies and the trapping/detrapping of charges. Furthermore, the device demonstrates optical storage capabilities by exploiting the optical properties of a-IGZO, which can stably operate for up to 50 sweep cycles. Various synaptic functions have been demonstrated, including paired-pulse facilitation and spike-timing-dependent plasticity. These functionalities contribute to a simulated recognition accuracy of 90% for handwritten digits. Importantly, a one-selector one-memristor (1S1M) architecture is successfully constructed at room temperature by integrating a-IGZO memristor on a TaO x -based selector. This architecture exhibits a 10 7 on/off ratio, demonstrating its potential to suppress sneak currents among adjacent units in a memristor crossbar.

Purpose: To study the stability of physicochemical properties and sterilizing effect about two commercially available hypochlorous acid (HClO) products under simulated clinical conditions, and to evaluate the compatibility of HClO on soft and hard tissues and cells in oral cavity., Methods: Samples of HClO solution with different production processes were prepared, to detect the changes of physicochemical indexes of each sample over time under simulated clinical conditions (shielded from light at 20-25 ℃, open the cover for 5 minutes every day), including free available chlorine, oxidation-reduction potential and pH. Through suspension quantitative germicidal test, the antibiosis-concentration curve of HClO solution was made, so as to calibrate the change of antibacterial ability of disinfectant with the decrease of available chlorine content during storage. Pulp, tongue and dentine were immersed in PBS, 100 ppm HClO, 200 ppm HClO and 3% NaClO. The influence on soft and hard tissues was evaluated by weighing method and microhardness test. The toxic effects of HClO, NaClO and their 10-fold diluent on human gingival fibroblasts were determined by CCK-8 cytotoxicity assay. GraphPad PRIS 8.0 software was used to analyze the data., Results: Under simulated conditions, the free available chlorine (FAC) of HClO solution decayed with time, and the attenuation degree was less than 20 ppm within 1 month. The bactericidal effect of each HClO sample was still higher than 5log after concentration decay. There was no obvious dissolution and destruction to soft and hard tissues for HClO(P＞0.05). The cell viability of HClO to human gingival fibroblast cells (HGFC) was greater than 80%, which was much higher than 3% NaClO (P＜0.001)., Conclusions: The bactericidal effect and stability of HClO solution can meet clinical needs, which has low cytotoxicity and good histocompatibility. It is expected to become a safe and efficient disinfection product in the field of living pulp preservation and dental pulp regeneration.

Objective: To provide a reference for future policy and measure formulation by conducting a detailed analysis of the burden of vision loss due to cataract by year, age, and gender in China from 1990 to 2019., Methods: Data on the prevalence and disability-adjusted life-years (DALYs) due to cataract in China and neighboring and other G20 countries were extracted from the 2019 Global Burden of Disease (GBD) study to observe the changing trends of vision loss., Results: The number and rate of all-age prevalence and DALYs for cataract in China increased significantly from 1990 to 2019. The age-standardized DALYs rate witnessed a slowly declining trend by 10.16%. And the age-standardized prevalence increased by 14.35% over the 30-year period. Higher prevalence and DALYs were observed in female population from 1990 through 2019, with little improvement over the decades(all p < 0.001). The disease burden of cataract is higher in middle-aged and elderly people. Blindness accounted for the largest proportion of vision impairment burden caused by cataract in China. The age-standardized prevalence and DALY rate of cataract in China were lower than those in India and Pakistan, but higher than those in Russia, South Korea, North Korea, Singapore, and Japan., Conclusions: In the past 30 years, although the age-standardized DALYs rate has decreased slightly in China, the all-age prevalence and DALYs have both increased. This study highlights the importance of reducing cataract burden by providing timely and easily accessible quality care, especially in females and the elderly population., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: Accumulated evidence has shown that microRNAs (miRNAs) are closely related to the pathogenesis and progression of senile cataracts. Here we investigate the effect of miR-29a-3p in cataractogenesis and determined the potential molecular mechanism involved., Methods: In this study, we constructed a selenite cataract model in rats and obtained the miRNAs related to cataracts by whole transcriptome sequencing. To investigate the effect and mechanism of miR-29a-3p on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, luciferase reporter assay, Edu assay, and western blot analysis., Result: Sequencing data showed downregulation of miR-29a-3p in rats with selenite cataracts. Down-regulation of miR-29a-3p could promote lens epithelial cells (SRA01/04) proliferation and inhibit cell apoptosis, and miR-29a-3p silence could inhibit the development of cataracts. Additionally, CAND1 was a direct target gene for miR-29a-3p., Conclusion: These data demonstrate that miR-29a-3p inhibits apoptosis of lens epithelial cells by regulating CAND1, which may be a potential target for senile cataracts.

Introduction: Repeated exposure to cocaine induces microglial activation. Cocaine exposure also induces a release of high mobility group box-1 (HMGB1) from neurons into the extracellular space in the nucleus accumbens (NAc). HMGB1 is an important late inflammatory mediator of microglial activation. However, whether the secretion of HMGB1 acts on microglia or contributes to cocaine addiction is largely unknown., Methods: Rats were trained by intraperitoneal cocaine administration and cocaine-induced conditioned place preference (CPP). Expression of HMGB1 was regulated by viral vectors. Activation of microglia was inhibited by minocycline. Interaction of HMGB1 and the receptor for advanced glycation end products (RAGE) was disrupted by peptide., Results: Cocaine injection facilitated HMGB1 signaling, together with the delayed activation of microglia concurrently in the NAc. Furthermore, the inhibition of HMGB1 or microglia activation attenuated cocaine-induced CPP. Box A, a specific antagonist to interrupt the interaction of HMGB1 and RAGE, abolished the expression of cocaine reward memory. Meanwhile, the inhibition of HMGB1-RAGE interaction suppressed cocaine-induced microglial activation, as well as the consolidation of cocaine-induced memory., Conclusion: All above results suggest that the neural HMGB1 induces activation of microglia through RAGE, which contributes to the consolidation of cocaine reward memory. These findings offer HMGB1-RAGE axis as a new target for the treatment of drug addiction., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD)., Methods: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022., Results: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05)., Conclusion: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Human gene editing technology is a hot spot and focus in the development of biotechnology, but it has also caused controversies over technical risks, genetic biosecurity, ethical dignity of human society and the legality of application, causing people to worry about the application of this technology. Gene editing for reproductive purposes is generally prohibited internationally, and countries have established legal regulatory systems to regulate the application of gene editing technology according to their own conditions. China shall establish a security risk access system for gene editing technology, ensure national biosecurity, establish and improve the system of ethical norms for scientific research, improve the construction of legislative standardization, and provide legal guarantees for the research and application of gene editing technology.

A Gram-positive, acid-fast, aerobic, rapidly growing and non-motile strain was isolated from lead-zinc mine tailing sampled in Lanping, Yunnan province, Southwest China. 16S rRNA gene sequence analysis showed that the most closely related species of strain KC 300 T was Mycolicibacterium litorale CGMCC 4.5724 T (98.47 %). Additionally, phylogenomic and specific conserved signature indel analysis revealed that strain KC 300 T should be a member of genus Mycolicibacterium , and Mycobacterium palauense CECT 8779 T and Mycobacterium grossiae DSM 104744 T should also members of genus Mycolicibacterium . The genome size of strain KC 300 T was 6.2 Mb with an in silico DNA G+C content of 69.2 mol%. Chemotaxonomic characteristics of strain KC 300 T were also consistent with the genus Mycolicibacterium . The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values, as well as phenotypic, physiological and biochemical characteristics, support that strain KC 300 T represents a new species within the genus Mycolicibacterium , for which the name Mycolicibacterium arseniciresistens sp. nov. is proposed, with the type strain KC 300 T (=CGMCC 1.19494 T =JCM 35915 T ). In addition, we reclassified Mycobacterium palauense and Mycobacterium grossiae as Mycolicibacterium palauense comb. nov. and Mycolicibacterium grossiae comb. nov., respectively.

Mode-locking in laser cavities has attracted great interest due to its wide range of applications in generating optical frequency combs and ultra-short pulse trains. Here, a mode-locked fiber laser with a distributed selectable wavelength feedback is proposed based on radio frequency maneuverability. The laser is capable of generating transform-limited pulses with a selectable wavelength and repetition rates by interrogating different reflectors through active modulation. Intriguing laser pulses were realized, which can have >930 times width compression ratio compared with the modulation signal and can be selectively locked to reflectors separated in centimeter scale.

Intercellular adhesion molecule 1 (ICAM-1) plays prominent roles in mediating cell-cell adhesion which also facilitates B cell activation and differentiation with the help from CD4 + T cells. Here, we have reported a unique phenomenon that increased ICAM-1 on purified human CD4 + T cells upon anti-CD3/CD28 stimulation enhanced CD4 + T-B cell adhesion whereas induced less B cell differentiation and IgG production. This was largely due to increased PD-1 expression on CD19 hi B cells after coculturing with hyperactivated CD4 + T cells. Consequently, ICAM-1 blockade during CD4 + T cell-B cell coculture promoted IgG production with the activation of ERK1/2 and Blimp-1/IRF4 upregulation. Consistently, CD4 + T cells from moderate-to-severe SLE patients with high ICAM-1 expression mediated less IgG production after T-B coculture. Therefore, ICAM-1-mediated human CD4 + T-B cell adhesion provides dual roles on B cell differentiation and IgG production partially depending on expression levels of PD-1 on B cells, supporting cell adhesion and subsequent PD-1 induction as an alternative intrinsic checkpoint for B cell differentiation., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: A sight-threatening, cataract is a common degenerative disease of the ocular lens. This study aimed to explore the regulatory mechanism of age-related cataract (ARC) formation and progression., Methods: Cataracts in Sprague Dawley rats were induced by adopting the method that injected selenite subcutaneously in the nape. We performed high-throughput RNA sequencing technology to identify the mRNA and microRNA(miRNA) expression profiles of the capsular membrane of the lens from Na 2 SeO 3 -induced and saline-injected Sprague Dawley rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of mRNAs in cataracts by DAVID and Metascape. The protein-protein interaction(PPI) network of differentially expressed mRNA(DEmRNAs) was built via the STRING. Target miRNAs of hub genes were predicted by miRBD and TargetScan. Furthermore, differentially expressed miRNA(DEmiRNAs) were selected as hub genes' targets, validated by quantitative real-time polymerase chain reaction(qRT-PCR), and a DEmiRNA-DEmRNA regulatory network was constructed via Cytoscape., Result: In total, 329 DEmRNAs including 40 upregulated and 289 downregulated genes were identified. Forty seven DEmiRNAs including 29 upregulated and 18 downregulated miRNAs were detected. The DEmRNAs are involved in lens development, visual perception, and aging-related biological processes. A protein-protein interaction network including 274 node genes was constructed to explore the interactions of DEmRNAs. Furthermore, a DEmiRNA-DEmRNA regulatory network related to cataracts was constructed, including 8 hub DEmRNAs, and 8 key DEmiRNAs which were confirmed by qRT-PCR analysis., Conclusion: We identified several differentially expressed genes and established a miRNA-mRNA-regulated network in a Na 2 SeO 3 -induced Sprague Dawley rat cataract model. These results may provide novel insights into the clinical treatment of cataracts, and the hub DEmRNAs and key DEmiRNAs could be potential therapeutic targets for ARC., (© 2023. The Author(s).)

Owing to the high energy density, ultrahigh-nickel (Ni > 0.9) layered oxides are used as promising cathode materials for next-generation Li-ion batteries. Unfortunately, the serious pulverization and rapid capacity fading during cycling limit the commercial viability of an ultrahigh-nickel oxide cathode. Herein, the introduction of Ga into LiNi 0.96 Co 0.04 O 2 brings a radially aligned microstructural change of oxide microspheres during the lithiation of the Ni 0.96 Co 0.04 (OH) 2 precursor. As expected, such radially aligned needle-like primary grains on microspheres have a positive influence to reduce the anisotropic volume change and suppress the formation of microcracks of Ga-induced Li(Ni 0.96 Co 0.04 ) 0.99 Ga 0.01 O 2 during cycling. Specifically, compared with irregular primary grains of LiNi 0.96 Co 0.04 O 2 , Ga-induced oxide presents a high initial discharge capacity of 227.9 mA h g -1 at 0.1C rate between 2.8 and 4.3 V. Especially, Ga-induced oxide delivers higher initial discharge capacities of 233.9 and 240.3 mA h g -1 with higher cutoff charge voltages of 4.4 and 4.5 V at 0.1C, respectively. Furthermore, a good capacity retention of 74.1% at 1 C rate is obtained after 300 cycles, which is almost 85% higher than that of the pristine sample, mainly due to the generation of microcracks of oxide microspheres during the long-term cycle. Therefore, the introduction of Ga into LiNi 0.96 Co 0.04 O 2 is a feasible approach for improving the microstructure and cycling stability of the ultrahigh-Ni layered oxides.

Objective: To compare the posterior cruciate ligament(PCL) index with six different measurement methods, and analyze and verify its clinical diagnostic value in anterior cruciate ligament (ACL) injury., Methods: The Magnetic resonance imaging (MRI) data of 225 knee joints in our hospital from May 2018 to March 2022 were retrospectively analyzed, aged from 18 to 60 years old, with a median of 32 years old. On the sagittal MRI images of 114 patients with ACL injury and 111 patients with intact ACL, Measure the straight-line distance (A) between the femoral attachment point and the tibial attachment point of the PCL on the MRI sagittal image and the maximum vertical distance (B) between the straight line and the arcuate mark point of the PCL on the sagittal image, calculate the PCL index and evaluate the diagnostic value of the PCL index for ACL injury., Results: The PCL index of the ACL normal group and the ACL injury group were statistically described. There was no significant difference in PCL index 1, 2, 3 and 6 between the two groups( P >0.05). The difference of PCL index 4 and 5 between the two groups was statistically significant ( P <0.001). This study only found that the PCL index 2, 6 in the ACL normal group had a negative correlation with the patient's age (correlation coefficient=-0.213, -0.819; P <0.05), and the PCL index 5 in the ACL injury group was significantly correlated with the patient's body mass index(BMI)had a negative correlation (correlation coefficient=-0.277, P <0.05)., Conclusion: The change of PCL index is helpful for the diagnosis of ACL injury, PCL index 4 and 5 can be used as effective reference indexes for diagnosing ACL injury in clinic.