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• Novel mutations (c.3543T > A, c.1850A > G, c.2536C > T) have never been reported. • c.4233_4236del may be a hotspot mutation. • CHD2 patients had varying degrees of developmental delay and intellectual disability. • A significant clustering of the mutations was found near the C-terminus of the CHD2 protein. Increasing evidence reveals critical roles for CHD2 in children with developmental and epileptic encephalopathy. The aim was to present clinical analysis results of five cases with CHD2 mutations and 157 reported cases with non-copy number variations (non-CNV) of CHD2. This study recruited pediatric epilepsy patients with CHD2 mutations and clinical data from November 2016 to October 2023 in the Linyi People's Hospital, China. Whole-exome and gene panel sequencing were employed to find mutations. The HGMD and PubMed databases were examined for documented cases that had CHD2 mutations. This study reports five cases with CHD2 mutations: c.3543T > A, c.1850A > G, c.2536C > T, c.4233_4236del, c.3782G > C. Three novel mutations (c.3543T > A, c.1850A > G, c.2536C > T) have never been reported. c.4233_4236del has been reported in three cases, indicating that this locus may be a mutation hotspot. c.3782G > C has been reported in one case. All five patients had seizures before the age of four. Three patients had varying degrees of developmental delay, and four patients had varying degrees of intellectual disability. All of them had controlled seizures after Valproic acid (VPA) monotherapy or VPA in combination with other medications. Furthermore, we reviewed 157 reported cases having non-CNV mutations of CHD2. Most mutations of these cases were de novo. Epilepsy, developmental delay, and intellectual disability were the typical clinical phenotypes. We also found a significant clustering of the mutations near the C-terminus of the CHD2 protein (P < 0.001). This study reports new CHD2 genotypes and analyzes reported CHD2 mutation cases. Given its significance in epileptic encephalopathies, research on the CHD2 gene may provide new insights into epileptogenesis. [ABSTRACT FROM AUTHOR]

Guided bone-regeneration membrane (GBRM) is commonly used in bone-repair surgery because it blocks fibroblast proliferation and provides spatial support in bone-defect spaces. However, the need for removal surgery and the lack of antibacterial properties of conventional GBRM limit its therapeutic applicability for alveolar bone defects. Here we developed a GBRM for alveolar bone-repair and -regeneration applications through double-sided electrospinning of polycaprolactone and chitosan layers on a Zn mesh surface (denoted DSZM). The DSZM showed a UTS of ∼25.6 MPa, elongation of ∼16.1%, strength-elongation product of ∼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times higher than that of commercial Bio-Gide membrane. The DSZM exhibited a corrosion rate of ∼17 µm/y and a Zn ion concentration of ∼0.23 µg/ml after 1 month of immersion in Hanks' solution. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against S. aureus and osteogenesis in a rat critical-sized maxillary defect model. Overall, the DSZM fits the requirements for alveolar bone-repair and -regeneration applications as a biodegradable GBRM material due to its spatial support, suitable degradability, cytocompatibility, and antibacterial and osteogenic capabilities. This work reports the mechanical properties, antibacterial ability and osteogenic properties of electrospun PCL-CS nanofiber on Zn mesh as biodegradable guided bone-regeneration membrane for alveolar bone-repair applications. Our findings demonstrate that the DSZM prepared by double-sided electrospinning of PCL-CS layers on Zn mesh showed a UTS of ∼25.6 MPa, elongation of ∼16.1%, strength-elongation product of ∼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times greater than that of commercial Bio-Gide® membrane. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against S. aureus and osteogenesis in a rat critical-sized maxillary defect model. [Display omitted] [ABSTRACT FROM AUTHOR]

Near-infrared-II (NIR-II) photothermal therapy is emerging as a cutting-edge modality for tumor ablation due to its good biosafety, high penetration ability and spatiotemporal controllability. Despite efforts, establishing a link between cellular metabolic regulation and photothermal performance is still promising in synergistic cancer therapy. Herein, we developed a core-shell semiconducting polymer@metal-phenolic network (SP@GFP) nanomotor by assembling diphenol-terminated cisplatin prodrug ligand (cPt-DA) and iron (III) (Fe3+) through metal coordination on SP particles in the presence of GOx and DSPE-PEG-cRGD, for NIR-II-propelled self-propulsion and synergistic cancer therapy. Remotely driving the SP@GFP nanomotor with an NIR-II laser through a thermophoresis mechanism would allow for in-depth penetration and accumulation. The synergistic photothermal effect and continuous Fe2+-mediated ROS generation of SP@GFP nanomotor could activate photothermal, chemotherapeutic effects and ferroptosis pathway for cancer cells through reshaping cellular metabolic pathways (HSP and GPX4). By combining the concepts of chemotherapeutic prodrugs, catalytic ROS generation, photothermal response and cellular metabolic regulation, the NIR-II laser-controlled core-shell SP@GFP nanomotor displayed improved outcomes for enhanced cancer therapy through synergistic oxidative stress-photothermo modulation. • A NIR-II-powered core-shell SP@GFP prodrug nanomotor was constructed through metal coordination assembly for enhanced cancer therapy; • NIR-II laser propelled the propulsion of SP@GFP nanomotor through thermophoresis mechanism for in depth penetration and accumulation. • Therapeutic outcomes were improved through synergistic modulating oxidative stress and photothermal performance. [Display omitted] [ABSTRACT FROM AUTHOR]

5-Fluorouracil has demonstrated certain efficiency in patients with colorectal cancer. However, significant side effects of use by injection are common. To address this issue defects, a reengineered 5′-deoxy-5-fluorocytidine (DFCR) based drug delivery system (POACa) is developed as a prominent tumor-selective nano-activator. Investigations demonstrate that the constructed nano-activator exhibits good biocompatibility and high therapeutic efficiency in mice with subcutaneous and orthotopic SW-480 colorectal tumors, as its activity is strictly dependent on the tumor-associated acid environment and thymidine phosphorylase. These strategies diminish the off-target toxicity and improve the specificity and sensitivity of human colorectal cancer cells to 5-Fu, obtaining potent efficiency by the combination of H 2 O 2 mediated oxidative stress, calcium overload and 5-Fu-induced chemotherapy (the combination index is 0.11). Overall, the engineered nano-activator exhibits a high therapeutic index in vitro and in vivo. In this study, we designed and prepared a pH-responsive polymer to synchronously deliver DFCR (5′-deoxy-5-fluorocytidine, a prodrug of 5-Fu), Ca2+ and H 2 O 2. The constructed nano-activator was denoted as POACa. (1) To address the problem of premature leakage of cargo by physical embedding, our research modified the inactive prodrug DFCR through chemical bonding. (2) The activation of the prepared nano-activator was strictly dependent on the tumor-associated acid environment and thymidine phosphorylase, providing the drug delivery system with inherent safety. (3) A distinctly low combination index value (0.11) of CaO 2 and DFCR indicated that POACa has a prominent tumor suppression effect by tumor calcium overload sensitized chemotherapy and H 2 O 2 mediated cytotoxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

The controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer. A cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). A total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753–1.006, P = 0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227–1.777, P < 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364–2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female. A combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone. [ABSTRACT FROM AUTHOR]

The registration-based initial public offering (IPO) system is a pivotal initiative in China's comprehensive capital market reform, but little is known about its effectiveness. Our study aims to explore the impact of the registration-based IPO reform on enterprises' environmental, social, and governance (ESG) greenwashing behaviors. Drawing on data from 2,490 enterprises listed on the Chinese growth enterprise market and the main board of the Shenzhen Stock Exchange during 2012-2022, we find that the registration-based IPO reform significantly aggravates ESG greenwashing with an effect of 0.1696. Building upon this evidence, we explore the underlying mechanism. Peer competition and retail investor sentiment play a partial mediating role and become two channels through which the registration-based IPO reform may aggravate enterprises' ESG greenwashing. Analysts' attention can alleviate the impact of registration-based IPO reform on enterprises' ESG greenwashing while management myopia intensifies it, and they both play a moderating role. Moreover, the aggravating effect of the registration-based IPO reform on ESG greenwashing is more pronounced in enterprises belonging to heavily polluting industries, in the Western region, and with low information transparency. Thus, our findings offer new insights into enterprises' ESG greenwashing behaviors in the context of the registration-based IPO reform. [ABSTRACT FROM AUTHOR]

Similarity-based prediction methods utilize degradation trend analysis based on degradation indicators (DIs). These methods are gaining prominence in industrial predictive maintenance because they effectively address prognostics for machines with unknown failure mechanisms. However, current studies often neglect the discrepancies in degradation trends when constructing DIs from multi-sensor data and lack automatic normalization of operating regimes during feature fusion. In this study, a feature fusion methodology based on a signal-to-noise ratio metric that leverages slow feature analysis (SFA) is proposed. This customized metric utilizes SFA to quantify degradation trend discrepancies of constructed DIs, while automatically filtering out the effects of multiple operating regimes during feature fusion. The effectiveness and superiority of the proposed method are demonstrated using publicly available aero-engine and rolling bearing datasets. • An improved version of the signal-to-noise ratio for feature fusion of similarity-based prognostics. • Discrepancy information of prognostics variables is characterized through differential analysis. • Slow feature analysis is utilized to normalize multiple operating regimes automatically. [ABSTRACT FROM AUTHOR]

Accurate differentiation between benign and malignant cystic renal masses (CRMs) is challenging in clinical practice. This study aimed to develop MRI-based machine learning models for differentiating between benign and malignant CRMs and compare the best-performing model with the Bosniak classification, version 2019 (BC, version 2019). Between 2009 and 2021, consecutive surgery-proven CRM patients with renal MRI were enrolled in this multicenter study. Models were constructed to differentiate between benign and malignant CRMs using logistic regression (LR), random forest (RF), and support vector machine (SVM) algorithms, respectively. Meanwhile, two radiologists classified CRMs into I–IV categories according to the BC, version 2019 in consensus in the test set. A subgroup analysis was conducted to investigate the performance of the best-performing model in complicated CRMs (II-IV lesions in the test set). The performances of models and BC, version 2019 were evaluated using the area under the receiver operating characteristic curve (AUC). Performance was statistically compared between the best-performing model and the BC, version 2019. 278 and 48 patients were assigned to the training and test sets, respectively. In the test set, the AUC and accuracy of the LR model, the RF model, the SVM model, and the BC, version 2019 were 0.884 and 75.0%, 0.907 and 83.3%, 0.814 and 72.9%, and 0.893 and 81.2%, respectively. Neither the AUC nor the accuracy of the RF model that performed best were significantly different from the BC, version 2019 (P = 0.780, P = 0.065). The RF model achieved an AUC and accuracy of 0.880 and 81.0% in complicated CRMs. The MRI-based RF model can accurately differentiate between benign and malignant CRMs with comparable performance to the BC, version 2019, and has good performance in complicated CRMs, which may facilitate treatment decision-making and is less affected by interobserver disagreements. [ABSTRACT FROM AUTHOR]

The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters. This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM. A total of 758 patients with HCM (67% male; age 49 ± 14 years) who were admitted between 2010 and 2017 from 4 medical centers were included. The ML model was built on the internal discovery cohort (533 patients with HCM, admitted to Fuwai Hospital, Beijing, China) by using the light gradient-boosting machine and internally evaluated using cross-validation. The external test cohort consisted of 225 patients with HCM from 3 medical centers. A total of 14 CMR imaging features (strain and late gadolinium enhancement [LGE]) and 23 clinical variables were evaluated and used to inform the ML model. MACEs included a composite of arrhythmic events, SCD, heart failure, and atrial fibrillation–related stroke. MACEs occurred in 191 (25%) patients over a median follow-up period of 109.0 months (Q1-Q3: 73.0-118.8 months). Our ML model achieved areas under the curve (AUCs) of 0.830 and 0.812 (internally and externally, respectively). The model outperformed the classic HCM Risk-SCD model, with significant improvement (P < 0.001) of 22.7% in the AUC. Using the cubic spline analysis, the study showed that the extent of LGE and the impairment of global radial strain (GRS) and global circumferential strain (GCS) were nonlinearly correlated with MACEs: an elevated risk of adverse cardiovascular events was observed when these parameters reached the high enough second tertiles (11.6% for LGE, 25.8% for GRS, −17.3% for GCS). ML-empowered risk stratification using CMR and clinical features enabled accurate MACE prediction beyond the classic HCM Risk-SCD model. In addition, the nonlinear correlation between CMR features (LGE and left ventricular pressure gradient) and MACEs uncovered in this study provides valuable insights for the clinical assessment and management of HCM. [Display omitted] [ABSTRACT FROM AUTHOR]

The tricuspid valve is known as "the forgotten valve". Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease. TR is often late in the course of the disease when it becomes symptomatic, often being a marker of late-stage chronic heart failure with a poor prognosis and high mortality rate at long-term follow-up. Despite the clear correlation between TR and mortality, most TR patients are under-treated. Neither pharmacologic nor surgical treatment demonstrates a significant survival benefit. Isolated tricuspid valve surgery has the highest mortality rate of all valve surgeries. Therefore, there is an urgent clinical need for minimally invasive therapies to meet the needs of patients with TR. In recent years, a variety of transcatheter tricuspid valve interventions representing less invasive alternatives to surgery have shown promising results, which bring hope to patients with severe TR. The purpose of this review is to provide a complete and updated overview on current transcatheter tricuspid valve interventions and clinical evidence. CAVI, caval valve implantation; TTVR, transcatheter tricuspid valve replacement; MIA, minimally invasive annuloplasty; PASTA, pledget-assisted suture tricuspid annuloplasty; TRAIPTA, transatrial intrapericardial tricuspid annuloplasty. [Display omitted] • Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease. • Neither pharmacologic nor surgical treatment significantly improves survival in TR patients. • Transcatheter tricuspid valve interventions have emerged as a promising alternative for open heart surgery. • Many transcatheter tricuspid valve intervention devices have shown excellent clinical results. • Tricuspid valve is no longer "the forgotten valve". [ABSTRACT FROM AUTHOR]

Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, −1.42 [-2.68, −0.17] mmHg), total cholesterol (TC, −0.18 [-0.30, −0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, −0.16 [-0.27, −0.05] mmol/L). Milk protein supplementation decreased SBP (−2.30 [-3.45, −1.15] mmHg) and total cholesterol (−0.27 [-0.51, −0.03] mmol/L). Whey supplementation decreased SBP (−2.20 [-3.89, −0.51] mmHg), diastolic blood pressure (DBP, −1.07 [-1.98, −0.16] mmHg), triglycerides (−0.10 [-0.17, −0.03] mmol/L), TC (−0.18 [-0.35, −0.01] mmol/L), LDL-C (−0.09 [-0.16, −0.01] mmol/L) and fasting blood insulin (FBI, −2.02 [-3.75, −0.29] pmol/L). Casein supplementation decreased SBP (−4.10 [-8.05, −0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (−2.69 [-3.50, −1.87] mmHg) and DBP (−1.34 [-2.09, −0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (−1.40 [-2.22, −0.59] mmHg), DBP (−2.59 [-3.20, −1.98] mmHg), triglycerides (−0.09 [-0.15, −0.02] mmol/L), TC (−0.14 [-0.22, −0.05] mmol/L), LDL-C (−0.12 [-0.16, −0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders. [ABSTRACT FROM AUTHOR]

Left bundle branch block (LBBB) represents a frequently encountered conduction system disorder. Despite its widespread occurrence, a continual dilemma persists regarding its intricate association with underlying cardiomyopathy and its pivotal role in the initiation of dilated cardiomyopathy. The pathologic alterations linked to LBBB-induced cardiomyopathy (LBBB-CM) have remained elusive. This study sought to investigate the chronologic dynamics of LBBB to left ventricular dysfunction and the pathologic mechanism of LBBB-CM. LBBB model was established through main left bundle branch trunk ablation in 14 canines. All LBBB dogs underwent transesophageal echocardiography and electrocardiography before ablation and at 1 month, 3 months, 6 months, and 12 months after LBBB induction. Single-photon emission computed tomography imaging was performed at 12 months. We then harvested the heart from all LBBB dogs and 14 healthy adult dogs as normal controls for anatomic observation, Purkinje fiber staining, histologic staining, and connexin43 protein expression quantitation. LBBB induction caused significant fibrotic changes in the endocardium and mid-myocardium. Purkinje fibers exhibited fatty degeneration, vacuolization, and fibrosis along with downregulated connexin43 protein expression. During a 12-month follow-up, left ventricular dysfunction progressively worsened, peaking at the end of the observation period. The association between myocardial dysfunction, hypoperfusion, and fibrosis was observed in the LBBB-afflicted canines. LBBB may lead to profound myocardial injury beyond its conduction impairment effects. The temporal progression of left ventricular dysfunction and the pathologic alterations observed shed light on the complex relationship between LBBB and cardiomyopathy. These findings offer insights into potential mechanisms and clinical implications of LBBB-CM. [Display omitted] [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is restricted due to its severe cardiotoxicity. There is still a lack of viable and effective drugs to prevent or treat DOX-induced cardiotoxicity(DIC). Vericiguat is widely used to treat heart failure with reduced ejection fraction. However, it is not clear whether vericiguat can improve DIC. In the present study, we constructed a DIC model using mice and neonatal rat cardiomyocytes and found that vericiguat ameliorated DOX-induced cardiac insufficiency in mice, restored DOX-induced mitochondrial dysfunction in neonatal rat cardiomyocytes, and inhibited the expression of inflammatory factors. Further studies showed that vericiguat improved mitochondrial dysfunction and reduced mtDNA leakage into the cytoplasm by up-regulating PRKG1, which activated PINK1 and then inhibited the STING/IRF3 pathway to alleviate DIC. These findings demonstrate for the first time that vericiguat has therapeutic potential for the treatment of DIC. The model illustrated that DOX inhibited PRKG1, PINK1 and PARKIN expression in the heart and activated STING/INF3 signaling pathway, leading to myocardial inflammation and cardiac dysfunction. Vericiguat alleviated myocardial inflammation and cardiac dysfunction by activating PRKG1, promoting PINK1 and PARKIN expression, inhibiting STING/INF3 signaling pathway, and improving mitochondrial function [Display omitted]. [ABSTRACT FROM AUTHOR]

To investigate the predictors of Gleason Grading Group (GGG) upgrading in low-risk prostate cancer (Gleason score = 3 + 3) from transperineal biopsy after radical prostatectomy (RP). The clinical data of 160 patients who underwent transperineal biopsy and RP from January 2017 to December 2022 were retrospectively analyzed. First, univariate and multivariate logistic regression analysis were used to obtain independent predictors of postoperative GGG upgrading. Then receiver operating characteristic curve was used to evaluate the diagnostic efficacy of predictors. Finally, Linear-by-Linear Association test was used to analyze the risk trends of patients in different predictor groups in the postoperative GGG. In this study, there were 81 cases (50.6%) in the GGG concordance group and 79 cases (49.4%) in the GGG upgrading group. Univariate analysis showed age, free/total prostate-specific antigen (f/tPSA), proportion of positive biopsies, positive target of magnetic-resonance imaging (MRI) and positive target of contrast-enhanced ultrasound had significant effects on GGG upgrading (all P <.05). In multivariate logistic regression analysis, age (odds ratio [OR] = 1.066, 95%CI = 1.007-1.127, P =.027), f/tPSA (OR = 0.001, 95%CI = 0-0.146, P =.001) and positive target of MRI (OR = 3.005, 95%CI = 1.353-76.674, P =.007) were independent predictors. The prediction model (area under curve = 0.751 P <.001) had higher predictive efficacy than all independent predictors. The proportion of patients in exposed group of different GGG increased with the level of GGG, but decreased in nonexposed group, and the linear trend was significantly different (all P <.001). Age, f/tPSA, and positive target of MRI were independent predictors of postoperative GGG upgrading. The predictive model constructed had the best diagnostic efficacy. [ABSTRACT FROM AUTHOR]

To investigate the effectiveness of combining split diffusion tensor imaging (DTI) measurements with split renal parenchymal volume (RPV) for assessing split renal functional impairment in patients with lupus nephritis (LN). Seventy-four participants [48 LN patients and 26 healthy volunteers (HV)] were included in the study. All participant underwent conventional MR and DTI (b = 0, 400, and 600 s/mm2) examinations using a 3.0 T MRI scanner to determine the split renal DTI measurements and split RPV. In LN patients, renography glomerular filtration rate (rGFR) was measured using 99mTc-DTPA scintigraphy based on Gates' method, serving as the reference standard to categorize all split kidneys of LN patients into LN with mild impairment (LN m , n = 65 kidneys) and LN with moderate to severe (LN ms , n = 31 kidneys) groups according to the threshold of 30 ml/min in spilt rGFR. All statistical analyses were performed using SPSS 25.0 and MedCalc 20.0 software packages. Only split medullary fractional anisotropy (FA) and the product of split medullary FA and RPV could distinguish pairwise subgroups among the HV and each LN subgroup (all p < 0.05). ROC curve analysis demonstrated that split medullary FA (AUC = 0.866) significantly outperformed other parameters in differentiating HV from LN m groups, while the product of split medullary FA and split RPV was superior in distinguishing LN m and LN ms groups (AUC = 0.793) than other parameters. The combination of split medullary FA and split RPV showed best correlation with split rGFR (r = 0.534, p < 0.001). Split medullary FA, and its combination with split RPV, are valuable biomarkers for detecting early functional changes in renal alterations and predicting disease progression in patients with LN. [ABSTRACT FROM AUTHOR]

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A–C (1 – 3), with distinctive C–C and C–O–C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF. A novel bicyclic peptide derived from Glycyrrhiza uralensis preserves cardiac mitochondrial homeostasis by replenishing iron levels in cardiomyocytes. [Display omitted] [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field. [ABSTRACT FROM AUTHOR]

In July 2021, a heavy rainstorm was sweeping across Henan Province, causing geological disasters such as floods, mudslides, and landslides, which seriously threatened the safety of human life and property. Precipitable water vapor (PWV) is related to the occurrence and scale of rainfall. Here, based on Global Navigation Satellite System (GNSS) observations, in-situ meteorological files (GMET), ephemeris products, ERA5 data, and weather station data, the relationship between PWV and rainstorm from July 1st to 30th was studied. The results show that GMET and ERA5 in July 2021 have high consistency in some stations, with a root mean square error (RMSE) for temperature below 1.6 °C, for pressure below 0.5 hPa, and for relative humidity below 9 %. During the week before the heavy rainstorm, the temperature dropped remarkably and the temperature difference decreased, while the relative humidity increased and the relative humidity difference decreased. Compared with ERA5 PWV, the RMSE of GNSS PWV retrieved using real-time ephemeris is 3.238 mm. Different from the normal rainfall, we found that the PWV variation during the Henan rainstorm experienced a unique "accumulation" period. We also observed a clear correlation between PWV and the rainstorm, both temporally and spatially. In addition, the PWV in the severely damaged area was 20 mm higher than the average value of the past decade. Ten days after the rainstorm, the surface of this area had subsided by 1.5–3 mm. Finally, we found that the topography of Henan, the low vortex, the north-biased subtropical high, and the double typhoons all played a role in the successful transport and deposition of water vapor. [ABSTRACT FROM AUTHOR]

Mechanical engineering drawings (MEDs) accompany a product lifecycle from conceptional design to final production. The digitisation of MEDs has become increasingly important due to demands for data authenticity, intellectual property protection, efficient data storage and communication, and compliance with data integrity and security regulations. Unlike CAD-based engineering design software, legacy MEDs are often manually drawn or contain manually labeled specifications on blueprints. A notable gap exists in the automated process pipeline of modern Computer-Aided Tolerance (CAT) software, particularly in integrating Geometrical Tolerance Specification Callouts (GTSC) on MEDs. This study proposes an integrated model based on digital image processing and deep learning, which combines character (symbol, text and number) localization, segmentation, and recognition to intelligently identify and read GTSCs on MEDs. The focus of this work is on image filtering, GTSC block localization and tilt correction, multiple lines and character segmentation, and semantic recognition. Experiment results demonstrate that this innovative technique effectively automates the labor-intensive process of reading and registering GTSC with a precision performance that meets industry benchmarks. [ABSTRACT FROM AUTHOR]

Ageing and aberrant biomechanical stimulation are two major risk factors for osteoarthritis (OA). One of the main characteristics of aged cartilage is cellular senescence. One of the main characteristics of osteoarthritic joints is cartilage degeneration. The cells in the temporomandibular joint (TMJ) cartilage are zonally arranged. The deep zone cells are differentiated from the superficial zone cells (SZCs). The purpose of the present study was to investigate whether degenerative shear stress (SS) stimulates the senescence programme in TMJ SZCs, and to determine which miRNA is involved in this process. SZCs were isolated from the TMJ condyles of 3-week-old rats and treated with continuous passaging or SS. RNA sequencing was conducted to identify miRNA(s) that overlap with those involved in the replication senescence process and the SS-induced degeneration programme. Unilateral anterior crossbite (UAC), which is TMJ-OA inducible, was applied to 2-month-old and 12-month-old mice for 3 weeks. The effect of TMJ local injection of agomiR-708–5p was evaluated histologically. Both replication and SS treatment induced SZC senescence. miR-708–5p was identified. Knocking down miR-708–5p in SS-treated SZCs led to more severe senescence by alleviating the inhibitory impact of miR-708–5p on the TLR4/NF-κB pathway. miR-708–5p expression in mouse TMJ cartilage decreased with age. UAC induced more severe osteoarthritic cartilage lesions in 12-month-old mice than in 2-month-old mice. Injection of agomiR-708–5p suppressed UAC-induced osteoarthritic cartilage lesions. Age-related miR-708–5p deficiency is involved in the mechanically stimulated OA process. Intra-articular administration of agomiR-708–5p is a promising new strategy for OA treatment. [ABSTRACT FROM AUTHOR]

A new diarylpropane (1) along with seventeen known compounds (2 – 18), were extracted from the entire plant of Dianella ensifolia. The compounds 1 – 3 were identified as a distinctive group of diarylpropanes. Their structures were determined through comprehensive spectral analysis. An anti-inflammatory activity assay revealed that compound 7 demonstrated significant inhibitory effects on NO generation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, with an IC 50 value of 9.93 μg/mL. Further in-depth mechanistic studies indicated that compound 7 suppresses LPS-induced NO production by inhibiting the activation of NF-κB, which subsequently led to a decrease in the expression of nitric oxide synthase enzymes (iNOS). [Display omitted] • A new diarylpropane was isolated from Dianella ensifolia. • Compound 7 showed effective anti-inflammatory activity. • Compound 7 inhibited the activation of NF- κ B. [ABSTRACT FROM AUTHOR]

Companies need to consider corporate social responsibility (CSR) as they seek to achieve digital transformation. However, scholars know little about whether CSR can "feed" digital transformation. We argue that engaging in CSR can improve a firm's resource base in terms of human, financial, and technological resources, thereby contributing to the development of digital transformation. Using data from A-share listed companies from 2011 to 2020, we test our hypothesis and find that CSR facilitates digital transformation of firms and that the effect is persistent. Mechanism tests show that CSR promotes digital transformation only by improving firms' human and technological resources. In addition, the facilitating role of CSR is more pronounced in non-state-owned enterprises and small and medium-sized enterprises. This study enriches the literature on the relationship between CSR and digital transformation. [ABSTRACT FROM AUTHOR]

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O 2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. Genetically engineered bacteria produce melanin granules in vivo , exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O 2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • ∼50° post-Eocene clockwise rotation occurred in Mangkang of the eastern Qiangtang. • Discordant rotations in Gonjo-Mangkang imply oroclinal bending after Late Eocene. • Extensive Eocene crustal shortening occurred between Eurasian and eastern Qiangtang. The extrusion and clockwise rotation of the southeastern Tibetan Plateau around the Eastern Himalaya Syntaxis has been playing an important role in accommodating the Tibetan Plateau lithosphere shortening. Establishing the extrusion and rotation processes has great significance in understanding the still hotly debated deformation of the Tibetan Plateau. Here we conduct a new paleomagnetic study of the Upper Eocene (∼33.4–36.4 Ma) volcanogenic rocks from Mangkang (29.7°N, 98.6°E), which is located in the eastern Qiangtang Terrane that bent around the Eastern Himalaya Syntaxis. A total of 184 characteristic remnant magnetizations of 20 sites were identified and have a tilt-corrected site-mean direction of Ds = 62.2 ± 5.5°, Is = 47.6 ± 5.7°, K = 46.7, A 95 = 4.8°. The statistical properties of the obtained paleomagnetic directions can be straightforwardly explained by paleosecular variation, together with a positive fold test, yielding likely Late Eocene primary magnetizations. Integrated with other available paleomagnetic results and geological evidence in the adjacent areas, we speculate that there existed a ∼ 50° clockwise rotation of the Mangkang area with respect to the Eurasian Plate after the Late Eocene, due to the oroclinal bending around the Eastern Himalaya Syntaxis. The paleolatitudes estimated from paleomagnetic results indicate that the area between Eurasian and eastern Qiangtang has experienced significant latitudinal crustal shortening during the Eocene, which is consistent with geological evidence. [ABSTRACT FROM AUTHOR]

Pericoronary adipose tissue (PCAT) CT attenuation of right coronary artery (RCA) and non-alcoholic fatty liver disease (NAFLD) have prognostic value for major adverse cardiovascular events (MACE) in patients with coronary artery disease. However, the superior prognostic value between RCA PCAT CT attenuation and NAFLD remains unclear in patients with acute chest pain. This study is to evaluate the prognostic value of NAFLD for MACE, and further assess the incremental prognostic value of NAFLD over PCAT CT attenuation. Between January 2011 and December 2021, all consecutive emergency patients with acute chest pain referred for coronary CT angiography (CCTA) were retrospectively enrolled. MACE included unstable angina requiring hospitalization, coronary revascularization, non-fatal myocardial infarction, and all-cause death. Patients' baseline and CCTA characteristics, RCA PCAT CT attenuation, and the presence of NAFLD were used to evaluate risk factors of MACE using multivariable Cox regression analysis. The prognostic value of NAFLD compared to RCA PCAT CT attenuation was analyzed. A total of 514 patients were enrolled (mean age, 58.36 ± 13.05 years; 310 men). During a median follow-up of 31 months, 60 patients (11.67%) experienced MACE. NAFLD (HR = 2.599, 95% CI: 1.207, 5.598, P = 0.015) and RCA PCAT CT attenuation (HR = 1.026, 95% CI: 1.001, 1.051, P = 0.038) were independent predictors of MACE. The global Chi-square analysis showed that NAFLD improved the risk of MACE more than that using clinical risk factors and CCTA metrics (59.51 vs 54.44, P = 0.024) or combined with RCA PCAT CT attenuation (63.75 vs 59.51, P = 0.040). NAFLD and RCA PCAT CT attenuation were predictors of MACE. NAFLD had an incremental prognostic value beyond RCA PCAT CT attenuation for MACE in patients with acute chest pain. Adding CT-FFR into the risk prediction of patients with acute chest pain is worth considering. [ABSTRACT FROM AUTHOR]

• It is vital to know the incidence and epidemic trend of tuberculosis to track the success of tuberculosis control programs and determine the remaining challenges. • Using the age cohort model and gender subgroup analysis, we estimated the net drift (overall annual percentage change), local drift (age annual percentage change), longitudinal age curve (expected age ratio) and cycle and cohort effect (relative risk of cycle and birth cohort) of the incidence of tuberculosis during 1990–2019. • ·The incidence of tuberculosis has decreased worldwide, but adverse period and cohort effects have been found in many countries, which raises the question of whether medical care for tuberculosis patients of all age groups is adequate. • In addition, the study found that there are sex differences in the incidence of tuberculosis. Tuberculosis (TB) represents a significant global health concern, being the leading cause of mortality from a single infectious agent worldwide. The investigation of TB incidence and epidemiological trends is critical for evaluating the effectiveness of control strategies and identifying ongoing challenges. This study presents the trend in TB incidence across 204 countries and regions over a 30-year period. The study utilises data sourced from the Global Burden of Disease (GBD) database. The age cohort model and gender subgroup analysis were employed to estimate the net drift (overall annual percentage change), local drift (age annual percentage change), longitudinal age curve (expected age ratio), and cycle and cohort effect (relative risk of cycle and birth cohort) of TB incidence from 1990 to 2019. This approach facilitates the examination and differentiation of age, period, and cohort effects in TB incidence trends, potentially identifying disparities in TB prevention across different countries. Over the past three decades, a general downward trend in TB incidence has been observed in most countries. However, in 15 of the 204 countries, the overall incidence rate is still on the rise (net drift ≥0.0 %) or stagnant decline (≥–0.5 %). From 1990 to 2019, the net drift of tuberculosis mortality ranged from –2.2 % [95 % confidence interval (CI): –2.33, –2.05] in high Socio-demographic Index (SDI) countries to –1.7 % [95 % CI: –1.81, –1.62] in low SDI countries. In some below-average SDI countries,men in the birth cohort are at a disadvantage and at risk of deterioration, necessitating comprehensive TB prevention and treatment. While the global incidence of TB has declined, adverse period and cohort effects have been identified in numerous countries, raising questions about the adequacy of TB healthcare provision across all age groups. Furthermore, this study reveals gender disparities in TB incidence. [ABSTRACT FROM AUTHOR]

Bacterial infection hampers wound repair by impeding the healing process. Concurrently, inflammation at the wound site triggers the production of reactive oxygen species (ROS), causing oxidative stress and damage to proteins and cells. This can lead to chronic wounds, posing severe risks. Therefore, eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing. Nanozymes, possessing enzyme-like catalytic activity, can convert endogenous substances into highly toxic substances, such as ROS, to combat bacteria and biofilms without inducing drug resistance. However, the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy. Thus, developing nanozymes with multiple enzymatic activities is essential. Herein, we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles (Ru-PC NPs) with diverse enzymatic activities to aid wound healing and combat bacterial infections. Under acidic conditions, due to their glutathione (GSH) depletion and peroxidase (POD)-like activity, Ru-PC NPs combined with H 2 O 2 exhibit excellent antibacterial effects. However, in a neutral environment, the Ru-PC NPs, with catalase (CAT) activity, decompose H 2 O 2 to O 2 , alleviating hypoxia and ensuring a sufficient oxygen supply. Furthermore, Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase (SOD) enzyme activity, effectively scavenging excess ROS and reactive nitrogen species (RNS) in a neutral environment. This maintains the balance of the antioxidant system and prevents inflammation. Ru-PC NPs also promote the polarization of macrophages from M1 to M2, facilitating wound healing. More importantly, Ru-PC NPs show good biosafety with negligible toxicity. In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing. The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing. Ru-PC NPs, a novel nanozyme with quadruple enzymatic activity, effectively treats infected wounds. They demonstrate strong antimicrobial effects, antioxidant capacity, and anti-inflammatory properties, promoting M2 macrophage conversion for enhanced healing. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A sample dataset of 41 inkjet printers is established in complex printing conditions. • An analysis of varying nozzle patterns is conducted in draft printing mode. • Paired two-sample Wilcoxon test using features acquired from microscopy images. • Algorithm performance is assessed using the mean value of accuracy. A novel technique is introduced to predict the printer model used to produce a given document. Samples containing only a few letters printed under varying conditions (i.e., different printing modes, letter types, fonts) were collected to establish a dataset of 41 inkjet printer models from common manufacturers, such as HP, Canon, and Epson. Morphological features were analyzed by extraction of image features using several algorithms in a series of microscopic images and a Wilcoxon test was used to measure the significance of variations between printed samples. Significant differences between various printing conditions might post potential challenge to questioned document examination. Discriminant analysis and the k-nearest neighbor (KNN) algorithm were also employed for source printer prediction under varying printing condition on 30% images with the rest images as training dataset. The results of a validation experiment demonstrated that while quadratic discriminant analysis (QDA) achieved an accuracy of 96.3%, a combination of KNN and QDA reached 98.6%. As such, this technique could aid in the forensic examination of printed documents. [ABSTRACT FROM AUTHOR]

We report a case of ST segment elevation in left precordial leads with a convex shape caused by a rare etiology. By carefully analyzing the electrocardiogram (leads I, II, V3 to V9) of a patient with convex ST segment elevation in the left-sided chest leads, relevant etiological clues were derived. The findings were further supported by cardiac ultrasound and cardiac magnetic resonance imaging, ruling out other common causes. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) was postulated as the underlying cause, and potential mechanisms were discussed. The diagnosis was further confirmed through a follow-up period of over three years. [ABSTRACT FROM AUTHOR]

In the realm of autoimmune and inflammatory diseases, the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) signaling pathway has been thoroughly investigated and established. Despite this, the clinical approval of drugs targeting the cGAS-STING pathway has been limited. The Total glucosides of paeony (TGP) is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis (RA), emerged as a subject of our study. We found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway, triggered by various cGAS-STING agonists, in mouse bone marrow-derived macrophages (BMDMs) and Tohoku Hospital Pediatrics-1 (THP-1) cells. This inhibition was noted alongside the suppression of interferon regulatory factor 3 (IRF3) phosphorylation and the expression of interferon-beta (IFN-β), C-X-C motif chemokine ligand 10 (CXCL10), and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The mechanism of action appeared to involve the TGP's attenuation of the STING-IRF3 interaction, without affecting STING oligomerization, thereby inhibiting the activation of downstream signaling pathways. In vivo , the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid (DMXAA) and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN). Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway, offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway. [ABSTRACT FROM AUTHOR]

Underwater target information is submerged in background scattered light due to the scattering effect of suspended particles in turbid water. In order to improve the quality of target imaging in turbid water, this paper proposes a method for achieving clear underwater target imaging using the second Lorentz depolarization index based on a dual division of focal plane Mueller matrix imaging system. This method can directly quantify the attenuation of light in water, and then solve a clear image of the target. Experimental results on underwater targets of different materials (plastic, paper, metal) show that the method proposed can effectively remove background scattering light while enhancing image contrast, ultimately improving the imaging quality of targets in turbid water. [ABSTRACT FROM AUTHOR]

The presented work concerns with some novel solutions of the (2+1)-dimensional Boussinesq equation (BE), which acts as an important model for shallow water wave. Some resonant soliton solutions such as the X -shape soliton (XSS) and Y -shape soliton (YSS) solutions are developed via imposing the resonant conditions on the N -soliton solutions (N -SSs) that developed by the Hirota bilinear approach(HBA). Based on the XSS and YSS solutions, the novel hybrid interactions including the interaction between the 1-soliton and the YSS, the interaction between two YSS solutions are extracted. In addition, the complex N -SSs are also explored and discussed. Finally, the travelling wave solutions including the bright solitary and kinky solitary wave solutions are studied by employing the Bernoulli sub-equation function method (BSEFM). The graphs of the attained solutions are drawn to show the physical properties. The findings of this study are expected to help us apprehend the dynamics of the (2+1)-dimensional BE better. [ABSTRACT FROM AUTHOR]

Static air-gap eccentricity (SAGE) is a common fault in generators. Current researches primarily focus on the parallel SAGE types, while the inclined static air-gap eccentricity (ISAGE) has been rarely investigated. This paper proposes an improved air-gap eccentricity model and presents a study on the electromagnetic-mechanical properties in synchronous generators under typical ISAGE running conditions. Such electromagnetic-mechanical properties include not only the magnetic flux density (MFD) variations, but also the mechanical responses of the electromagnetic torque (EMT) and rotor unbalanced magnetic pulls (UMP). The typical ISAGE factors include: 1) a varied rotor inclined angle θ , and 2) different values of axial inclined distance z (indicates the offset combination case of the two rotor ends). This work is based on the MFD analysis calculation. Theoretical analysis, finite element analysis, and experimental study are carried out, respectively, by taking a 5 kVA two-pole prototype generator as the study object. It is shown that the electromagnetic-mechanical properties of the generator will change when the inclined eccentricity occurs. The EMT, and the rotor UMP as well as the vibrations will increase as the rotor inclined θ and z increase. Specifically, the 2nd harmonic has the most significant variation. [ABSTRACT FROM AUTHOR]

A novel direct instantaneous torque control (DITC) strategy based on optimized conduction angle is proposed with the aim of reducing the torque ripple of permanent magnet-assisted switched reluctance motor (PMa-SRM) during the two-phase exchange (TpE) region in this paper. Firstly, according to the inductance characteristics, the TpE region is subdivided into TpE I and TpE II region where the turn-off angle is acted as the region separation point, and the corresponding torque hysteresis strategies are formulated in different regions. Secondly, K-fold extreme learning machine (ELM) method is used to optimize the turn-on angle in order that the current of incoming phase can quickly increase to maintain torque balance. In order to make full use of the ability of torque generation of two adjacent phases, the position where the torque of adjacent phases is equal is used as the turn-off angle of incoming phase. Finally, a 6/20 PMa-SRM prototype is simulated and verified. Compared with the conventional DITC strategy, the novel strategy not only diminish torque ripple and negative torque under different operating conditions, but also expands the operating range of the motor and improves the motor efficiency. [ABSTRACT FROM AUTHOR]

The mechanical properties and insulation damage of stator end windings in permanent magnet synchronous generator (PMSG) are investigated by theoretical analysis, finite element analysis (FEA) and experiment verification. First, a theoretical model of the winding electromagnetic force (EF) and vibration response before and after eccentricity faults are established. Then, the stress/strain distribution of the end windings under different working conditions is analyzed. Finally, the insulation damage behavior of end windings with initial cracks is studied and characterized using the stress intensity factor (SIF). The results indicate that the winding EF and vibration responses vary under different faults. The stress/strain at the joint of the winding is the largest, and the insulation layer has the maximum stress/strain under the same section. Additionally, the SIF amplitude of the crack at the winding joint is the largest. And the SIF amplitude of the crack will increase with the increase of fault degree/crack depth/crack length. The contribution of this paper lies in the comprehensive analysis of the winding EF distribution, vibration response, stress and strain, and insulation damage before and after eccentricity. This analysis can provide valuable reference for the health monitoring of PMSG eccentricity faults and the prevention of winding insulation damage. [ABSTRACT FROM AUTHOR]

Diabetes mellitus and obesity are growing health concerns. New pharmacologic interventions have recently begun to play a more notable role in the treatment pathway of these separate but related conditions. In particular, glucagon-like peptide-1 receptor agonists, such as semaglutides (Ozempic, Wegovy) and tirzepatide (Mounjaro), and sodium glucose co-transporter 2 inhibitors, such as dapagliflozin (Farxiga) and empagliflozin (Jardiance), have emerged as treatment options. Multiple clinical trials have demonstrated their efficacy in regulating metabolism, improving glycemic control, and managing long-term weight reduction. However, glucagon-like peptide-1 receptor agonists have also been associated with gastrointestinal side effects, including delayed gastric emptying as well as regurgitation and aspiration during general anesthesia or deep sedation, and sodium glucose co-transporter 2 inhibitors have been associated with severe diabetic ketoacidosis. Therefore, discontinuation of these medications before surgery is imperative. Given the popularity of these medications among the general public, it is essential for hand surgeons, to understand how to appropriately manage them perioperatively. The objective of this article was to review these new diabetes mellitus and weight loss medications, including their mechanisms of action, indications for use, and perioperative management guidelines. Additionally, we will take this opportunity to review perioperative guidelines for other common medications relevant to patients undergoing procedures involving the hand and upper extremity such as antithrombotic medications and rheumatoid arthritis-related immunosuppressive medications. Finally, we will describe how the electronic medical record system can be used to optimize perioperative medication management in this population. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is an incurable and overwhelming disease accompanied with serve disability and huge financial burden, where the overproduced reactive oxygen species (ROS) can exacerbate the secondary injury, leading to massive apoptosis of neurons. In this study, β-cyclodextrin (CD)-capped hyperbranched polymers containing selenium element (HSE-CD) were crosslinked with CD-modified hyaluronic acid (HA-CD) and amantadine-modified hyaluronic acid (HA-AD) to obtain a ROS-responsive ointment (R-O). The structures of synthesized polymers were characterized with 1H nuclear magnetic resonance, and the properties of ointment were investigated with rheology and antioxidation. Compared to non-ROS-responsive ointment (N-O), the R-O ointment had stronger efficiency in decreasing the ROS level in BV2 cells in vitro. In a controlled rat cortical impact (CCI) model, the R-O ointment could relieve the DNA damage and decrease apoptosis in injured area via reducing the ROS level. Besides, after the R-O treatment, the rats showed significantly less activated astrocytes and microglia, a lower level of pro-inflammatory cytokines and a higher ratio of M2/M1 macrophage and microglia. Moreover, compared to the TBI group the R-O ointment promoted the doublecortin (DCX) expression and tissue structure integrity around the cavity, and promoted the recovery of nerve function post TBI. Traumatic brain injury (TBI) is an incurable and overwhelming disease, leading to severe disability and huge social burden, where reactive oxygen species (ROS) are considered as one of the most significant factors in the secondary injury of TBI. A ROS responsive supramolecular ointment containing di-selenide bonds was injected in rats with controlled cortical impact. It relieved the DNA damage and decreased apoptosis in the injured area via reducing the ROS levels, downregulated neuroinflammation, and improved neurological recovery of TBI in vivo. This designed self-adaptive biomaterial effectively regulated the pathological microenvironment in injured tissue, and achieved better therapeutic effect. [Display omitted] [ABSTRACT FROM AUTHOR]

Many medical devices implanted in patients to mitigate diseases and medical conditions have different types of topographic features. While appropriate textures can promote the integration of host cells and reduce scar tissue formation, some textured implants with inappropriate topographies have been associated with inflammation, bacterial colonization, or even malignant complications. To better understand how surface topography affects host immune response to colonizing bacteria, a protocol was developed to investigate phagocytosis of bacterial cells attached on polydimethylsiloxane (PDMS) surfaces with different square-shaped recessive patterns. The interaction between activated RAW 264.7 macrophages and Escherichia coli in recessive wells was visualized in 3D using multiple fluorescent markers. The results revealed that there is a threshold dimension of topography, below which phagocytosis of attached bacterial cells is significantly impeded. Specifically, under our experimental condition, up to 100-fold reduction in phagocytosis was observed in square-shaped patterns with 5 µm side length and 10 µm depth compared to the flat control and patterns with 10 µm or longer side length. The spacing between wells also showed significant effects; e.g., phagocytosis in the wells further decreased when spacing increased to 50 µm. These results are helpful for understanding how undesired topographies may contribute to bacterial colonization and thus infection and other associated complications. Surface topography plays an important role in bacteria-material infections and thus the safety of implantable medical devices. Undesired topographic features can cause biofilm formation and related complications. However, how surface topography affects the capability of host immune cells to clear colonizing bacteria is not well understood. In this study, the interaction between macrophage RAW264.7 and colonizing E. coli cells on polydimethylsiloxane (PDMS) with recessive features is investigated. It was discovered that the size of recessive features and the spacing between these features have significant effects on phagocytosis of bacteria by macrophages. These new results are helpful for understanding the complex interaction among host cells, bacteria, and implanted biomaterials, which will help guide the rational design of safer medical devices. [Display omitted] [ABSTRACT FROM AUTHOR]

Ferroptosis is greatly restricted by low reactive oxygen species (ROS) generation efficiency, and the inherent self-protection mechanism originating in heat shock proteins (HSPs) seriously impedes the efficiency of photothermal therapy (PTT). Herein, we designed an intelligent strategy utilizing cascade catalytic nanoassemblies (Au@COF@MnO 2) with triple-enzyme activity for amplifying ferroptosis therapy and improving the efficiency of PTT in tumor. Gold nanozyme was encapsulated within a hollow manganese dioxide (MnO 2) shell with the help of covalent organic frameworks (COFs). The nanoassemblies possess the ability of photothermal conversion. Mechanism studies suggested that glutathione (GSH) depletion by Au@COF@MnO 2 leads to the inactivation of glutathione peroxidase 4 (GPX4). This effect synergized with Mn2+-mediated reactive oxygen species (ROS) generation to enhance the accumulation of lipid peroxide (LPO), thereby inducing high-efficiency ferroptosis. Notably, gold nanozyme facilitated the conversion of glucose into gluconic acid and hydrogen peroxide (H 2 O 2). This process augmented the endogenous H 2 O 2 levels necessary for Fenton chemistry, which could effectively promote the generation of ROS. Simultaneously, glucose depletion downregulated the expression of HSPs induced by hyperthermia, consequently reducing cellular heat resistance for enhancing PTT. Therefore, the cascade catalytic nanoassembly not only exhibits high tumor inhibition and admirable biosafety, but also possesses trimodal imaging performance for imaging-guided tumor therapy in vivo , holding great potential for clinical application. This study engineered multi-responsive cascade catalytic nanoassembly (Au@COF@MnO 2) with triple enzymatic functions for amplifying ferroptosis therapy and improving the efficiency of PTT in tumor. The nanoassembly exhibited multi-responsive release and great photothermal conversion performance. Glucose consumption-evoked starvation downregulated the hyperthermia-induced expression of HSPs in tumor cells, thereby improving the efficacy of PTT. Mechanism studies suggested that GSH depletion by Au@COF@MnO 2 lead to the inactivation of GPX4, which synergized with Mn2+-mediated ROS generation to bolster the accumulation of LPO, thereby inducing high-efficiency ferroptosis. Moreover, the nanoassembly demonstrated trimodal (PT, PA, and MR) imaging in vivo , enabling the visualization of the tumor treatment with nanoassembly. Such nanoassembly exhibited high tumor inhibition and admirable biosafety in tumor therapy in vivo , holding a great potential for clinical application. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Profound perturbation of metabolome preceding T2D onset was revealed in a prospective Chinese population-based cohort. • Insulin resistance rather than β-cell dysfunction was strongly associated with metabolic shifts before T2D. • The impact of metabolites on T2D risk could be mediated by insulin resistance. • Discovery of previously unknown independent associations between metabolites and incident T2D. • The inclusion of metabolites selected by machine learning improved the predictive power of traditional clinical models. Type 2 diabetes (T2D) is a heterogeneous metabolic disease with large variations in the relative contributions of insulin resistance and β-cell dysfunction across different glucose tolerance subgroups and ethnicities. A more precise yet feasible approach to categorize risk preceding T2D onset is urgently needed. This study aimed to identify potential metabolic biomarkers that could contribute to the development of T2D and investigate whether their impact on T2D is mediated through insulin resistance and β-cell dysfunction. A non-targeted metabolomic analysis was performed in plasma samples of 196 incident T2D cases and 196 age- and sex-matched non-T2D controls recruited from a long-term prospective Chinese community-based cohort with a follow-up period of ∼ 16 years. Metabolic profiles revealed profound perturbation of metabolomes before T2D onset. Overall metabolic shifts were strongly associated with insulin resistance rather than β-cell dysfunction. In addition, 188 out of the 578 annotated metabolites were associated with insulin resistance. Bi-directional mediation analysis revealed putative causal relationships among the metabolites, insulin resistance and T2D risk. We built a machine-learning based prediction model, integrating the conventional clinical risk factors (age, BMI, TyG index and 2hG) and 10 metabolites (acetyl-tryptophan, kynurenine, γ-glutamyl-phenylalanine, DG(18:2/22:6), DG(38:7), LPI(18:2), LPC(P-16:0), LPC(P-18:1), LPC(P-20:0) and LPE(P-20:0)) (AUROC = 0.894, 5.6% improvement comparing to the conventional clinical risk model), that successfully predicts the development of T2D. Our findings support the notion that the metabolic changes resulting from insulin resistance, rather than β-cell dysfunction, are the primary drivers of T2D in Chinese adults. Metabolomes as a valuable phenotype hold potential clinical utility in the prediction of T2D. [ABSTRACT FROM AUTHOR]

[Display omitted] • A human iPSCs-based high-throughput anti-seizure compounds screening platform was built. • The human iPSCs-derived neurons can effectively and efficiently predict positive compounds. • This integrated anti-seizure drug discovering approach combines the advantages of human genetic background, HTS, and animal brain network. • Piperine, magnolol, α-asarone, and osthole can reduce epileptiform activity and seizures. • Natural compounds are promising candidates used for anti-seizure drug discovery. One-third of people with epilepsy continue to experience seizures despite treatment with existing anti-seizure medications (ASMs). The failure of modern ASMs to substantially improve epilepsy prognosis has been partly attributed to overreliance on acute rodent models in preclinical drug development as they do not adequately recapitulate the mechanisms of human epilepsy, are labor-intensive and unsuitable for high-throughput screening (HTS). There is an urgent need to find human-relevant HTS models in preclinical drug development to identify novel anti-seizure compounds. This paper developed high-throughput preclinical screening models to identify new ASMs. 14 natural compounds (α-asarone, curcumin, vinpocetine, magnolol, ligustrazine, osthole, tanshinone IIA, piperine, gastrodin, quercetin, berberine, chrysin, schizandrin A and resveratrol) were assessed for their ability to suppress epileptiform activity as measured by multi-electrode arrays (MEA) in neural cultures derived from human induced pluripotent stem cells (iPSCs). In parallel, they were tested for anti-seizure effects in zebrafish and mouse models, which have been widely used in development of modern ASMs. The effects of the compounds in these models were compared. Two approved ASMs were used as positive controls. Epileptiform activity could be induced in iPSCs-derived neurons following treatment with 4-aminopyridine (4-AP) and inhibited by standard ASMs, carbamazepine, and phenytoin. Eight of the 14 natural compounds significantly inhibited the epileptiform activity in iPSCs-derived neurons. Among them, piperine, magnolol, α-asarone, and osthole showed significant anti-seizure effects both in zebrafish and mice. Comparative analysis showed that compounds ineffective in the iPSCs-derived neural model also showed no anti-seizure effects in the zebrafish or mouse models. Our findings support the use of iPSCs-derived human neurons for first-line high-throughput screening to identify compounds with anti-seizure properties and exclude ineffective compounds. Effective compounds may then be selected for animal evaluation before clinical testing. This integrated approach may improve the efficiency of developing novel ASMs. [ABSTRACT FROM AUTHOR]

To evaluate the effectiveness of using vascular clips to seal targeted lymphatics in gynecological malignancies for the prevention of postoperative pelvic lymphocele and symptomatic lymphocele after laparoscopic pelvic lymphadenectomy. Retrospective analysis. Single-center academic hospital. In total, 217 patients with gynecological malignancies were included. Patients were classified into two groups: group 1 (vascular clips were used to seal the targeted lymphatics) and group 2 (electrothermal instruments were used to seal the targeted lymphatics). The patients were followed up 4–6 weeks after surgery to evaluate the incidence of lymphoceles by ultrasound or CT. Symptomatic lymphoceles are defined as those that cause infection, deep vein thrombosis with or without swelling of the extremities, edema (swelling) of the extremities or perineum, hydronephrosis, and/or moderate to severe pain. One hundred and thirteen patients were enrolled in group 1, and 104 patients were enrolled in group 2. Lymphoceles were observed in 46 (21.2%) patients. Fewer lymphoceles occurred in group 1 than in group 2 (8 [7.1%] vs. 38 [36.5%], p <.001). The percentage of significantly sized lymphoceles was lower in group 1 than that in group 2 (4 [3.5%] vs. 30 [28.8%], p <.001]. Symptomatic lymphoceles occurred in 18 patients (8.3%), and only one (1.0%) occurred in group 1, while 17 (16.3%) occurred in group 2 (p <.001). A multivariate analysis revealed that vascular clips were the only independent factor for preventing lymphocele (OR = 7.65, 95% CI = [3.30–17.13], p <.001) and symptomatic lymphocele (OR = 22.03, 95% CI = [2.84–170.63], p =.003). The results indicate that the use of vascular clips may be useful for the prevention of the development of lymphocele and symptomatic lymphocele secondary to pelvic lymphadenectomy performed via laparoscopy. [ABSTRACT FROM AUTHOR]

This study aims to use Meta-analytical structural equation modeling (MASEM) to clarify the relationship between burden, depression, and quality of life in informal caregivers of stroke survivors. The databases of PubMed, Cochrane Library, Embase, China Knowledge Resource Integrated Database, Wan Fang Database, and Chinese Biomedical Database were comprehensively searched before January 16, 2023. Two researchers performed an independent initial search by using a unified search strategy. Observational studies investigating the relation between burden, depression, and quality of life in informal caregivers of stroke survivors were included. The studies that met the inclusion criteria were appraised by "Quality Assessment and Validity Tool for Correlational Studies". PRISMA guidelines were used for this study. Data extraction was performed independently by 2 researchers. The following data were extracted: study author, year of publication, country, language, sample size, age, sex (%women), the caregivers' relation with stroke survivor, measures, type of outcome reported in the study, study design, and main conclusion. The analysis included 18 articles that reported 23 effect sizes (N=3284). The MASEM findings showed that caregiver burden was positively associated with caregiver depression (β=0.474, 95% CI [0.398, 0.550]), caregiver depression was negatively associated with caregiver quality of life (β=-0.316, 95% CI [-0.545, -0.087]). Furthermore, the association between caregiver burden and quality of life was completely mediated by caregiver depression (β=-0.150, 95% CI [-0.271, -0.041]). Using the MASEM approach, we observed that caregiver depression completely mediated the relation between burden and quality of life in informal caregivers of stroke survivors. Although the results did not allow for causal inference, this result suggested that for burdened stroke survivors' informal caregivers efforts should be made to their mental health to eliminate the internal barriers, then eventually improve their quality of life. [ABSTRACT FROM AUTHOR]