Search

Abstract Little is known about the long-term effectiveness of risk-based treat-to-target cholesterol-lowering interventions on cardiovascular risk. Here, we show the emulated effectiveness of guideline-recommended low-density and non-high-density lipoprotein cholesterol-lowering interventions using the absolute risk reduction (ARR) and the restricted mean event-free time-based number needed to treat (NNT). With 5,375 participants, the 29-year risks for cardiovascular disease (CVD), all-cause mortality, and atherosclerotic CVD were 18.6%, 25.6%, and 17.7%, respectively. Long-term treat-to-target interventions showed significant reductions in CVD (ARR −2.3%, 95%CI −3.4% to −0.8%; NNT 115), all-cause mortality (−3.0%, −4.3% to −1.8%; 95), and atherosclerotic CVD (−2.6%, −3.5% to −1.2%; 104). Such effects appear more pronounced in women, smokers, and those with body mass index

Abstract Metabolic syndrome (MetS) is a cluster of conditions that increase the risk of cardiovascular disease and diabetes. This study aimed to investigate the association between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and MetS in a large, nationally representative US population. We analyzed data from 28,178 participants in the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Logistic regression models were used to evaluate the association between NPAR and MetS. Restricted cubic spline (RCS) models were employed to assess the dose-response relationship. Mediation analyses were conducted to explore potential mediating effects of serum uric acid and triglyceride-glucose (TyG) index. After adjusting for confounders, participants in the highest NPAR quartile had a 14% higher risk of MetS compared to those in the lowest quartile (OR 1.14, 95%CI 1.03–1.27, P = 0.010). RCS models revealed a monotonic increasing trend between NPAR and MetS risk (P for overall association = 0.002). Mediation analyses showed that serum uric acid and TyG index mediated 14.93% and 29.45% of the total effect of NPAR on MetS, respectively. Subgroup analyses indicated that the positive association between NPAR and MetS was more pronounced in Mexican Americans, individuals aged 20–65 years, those with lower income, males, current smokers, and moderate drinkers. Higher NPAR is associated with increased risk of MetS in the US adult population. This association is partially mediated by serum uric acid and TyG index. These findings suggest that NPAR may serve as a novel biomarker for MetS risk assessment and provide insights into potential mechanisms linking inflammation and metabolic disorders.

Introduction: To present a case of two macular holes (MHs) with myopic choroidal neovascularization (CNV) lesion. Case Presentation: A single case was evaluated. A 72-year-old woman presented with two small MHs in her left eye. One year ago, she had undergone vitrectomy for myopic foveal schisis, and a significant reduction of the schisis and a CNV lesion was observed after surgery. On examination, OCT (optical coherence tomography) showed the atrophic CNV and two MHs were located upper and lower close to the edge of the CNV. A PPV (pars plana vitrectomy) with two free ILM (internal limiting membrane) flaps implant was performed in her left eye. At 3 months after surgery, the two macular holes were both closed and the BCVA (best corrected visual acuity) was improved. Conclusions: Two MHs secondary to the regression of CNV after primary PPV combined with complete ILM peeling in eyes with macular schisis.

Abstract Chronic Obstructive Pulmonary Disease (COPD) significantly impacts patients’ quality of life and burdens healthcare systems. Magnesium is crucial for lung function and reducing respiratory disease risk. This study investigates the association between Magnesium Depletion Score (MDS) and COPD and explores whether inflammatory markers mediate this relationship. A cross-sectional analysis was conducted using data from 30,490 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. MDS was calculated based on diuretic use, proton pump inhibitors, renal function, and alcohol consumption. Univariable and multivariable logistic regression analyses were performed to assess the association between MDS and COPD, adjusting for potential confounders. Mediation analysis was used to examine the roles of neutrophils, serum albumin, and the Systemic Immune-Inflammation Index (SII). In the univariable logistic model, higher MDS was significantly associated with increased COPD risk. Specifically, compared to MDS = 0, the odds ratios (OR) for COPD were 2.50, 4.12, 6.13, 8.53, and 7.81 for MDS = 1, 2, 3, 4, and 5, respectively (all P

Abstract Background Human Papillomavirus (HPV) infection has garnered significant attention due to its high prevalence and association with various cancers and other health conditions. Composite lifestyle factors may influence the risk of HPV infection, yet their cumulative impact remains insufficiently explored. This study aims to explore the association between the Life’s Essential 8 (LE8) Score and HPV infection status, highlighting the potential role of lifestyle and health behaviors in HPV infection prevention. Methods Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005–2016, we analyzed the health and nutritional statuses of 6,773 participants after excluding those with missing HPV infection status, inability to calculate the LE8 Score, and missing covariate data. The LE8 Score was computed based on eight cardiovascular health metrics, encompassing both health factors (BMI, non-HDL cholesterol, blood pressure, and blood glucose) and health behaviors (physical activity, diet, sleep duration, and nicotine exposure). HPV infection status was determined through vaginal swab specimens analyzed using various Roche assays. Multivariate logistic regression, the restricted cubic splines (RCS) analysis and weighted quantile sum (WQS) regression were employed to assess the association between LE8 Score and HPV infection risk. Results Our findings indicate a significant inverse association between the LE8 Score and HPV infection risk. Participants with medium and high LE8 Scores exhibited a 21% and 31% lower risk of HPV infection, respectively, compared to those with low LE8 Scores in multivariate logistic regression models. The analysis also revealed that lifestyle factors, particularly nicotine exposure and blood pressure, significantly contributed to the observed association. Conclusion The study underscores the importance of healthy lifestyle behaviors in reducing the risk of HPV infection. Public health strategies promoting such behaviors could complement existing HPV prevention measures, potentially lowering the burden of HPV-related diseases. Future research should further investigate the mechanisms underlying this association and the effectiveness of lifestyle interventions in diverse populations.

Nosema ceranae, a parasite that parasitizes and reproduces in the gut of honeybees, has become a serious threat to the global apiculture industry. RNA interference (RNAi) technology can be used to inhibit N. ceranae growth by targeting silencing the thioredoxin reductase (TrxR) in N. ceranae. However, suitable carriers are one of the reasons limiting the application of RNAi due to the easy degradation of dsRNA in honeybees. As a vesicle composed of a lipid bilayer, liposomes are a good carrier for nucleic acid delivery, but studies in honeybees are lacking. In this study, liposomes were used for double-stranded RNA (dsRNA) dsTrxR delivery triggering RNAi to inhibit the N. ceranae growth in honeybees. Compared to naked dsTrxR, liposome-dsTrxR reduced N. ceranae numbers in the midgut and partially restored midgut morphology without affecting bee survival and gut microbial composition. The results of this study confirmed that liposomes could effectively protect dsRNA from entering the honeybee gut and provide a reference for using RNAi technology to suppress honeybee pests and diseases.

The construction of lunar bases is one of the core enabling technologies in current lunar exploration and development plans of various countries. However, to eliminate the constraints of high transportation costs and limited manned space technology, a new research plan is to employ multi robot teams to build lunar bases. The key to this solution is how to achieve path planning for complex tasks for multiple robots. Therefore, this article takes the exploration and collection area, lunar soil collection, and lunar soil transportation in the lunar base construction scene as complex task inputs, and studies a multi robot path planning modeling method based on Petri net model. Firstly, a Petri net model for multi robot motion was constructed. Meanwhile, linear temporal logic(LTL) language was used to describe the related tasks of lunar base construction. Finally, simulation validation was conducted in Matlab software and compared with the modeling method using switching systems. The results show that the total modeling time required for using the Petri net model is reduced by two orders of magnitude compared to the modeling time for a single task switching system model, indicating that the established Petri net multi robot model has advantages such as avoiding dimension explosion and computational efficiency.

Abstract Graphene growth on widely used dielectrics/insulators via chemical vapor deposition (CVD) is a strategy toward transfer-free applications of CVD graphene for the realization of advanced composite materials. Here, we develop graphene-skinned alumina fibers/fabrics (GAFs/GAFFs) through graphene CVD growth on commercial alumina fibers/fabrics (AFs/AFFs). We reveal a vapor-surface-solid growth model on a non-metallic substrate, which is distinct from the well-established vapor-solid model on conventional non-catalytic non-metallic substrates, but bears a closer resemblance to that observed on catalytic metallic substrates. The metalloid-catalytic growth of graphene on AFs/AFFs resulted in reduced growth temperature (~200 °C lower) and accelerated growth rate (~3.4 times faster) compared to that obtained on a representative non-metallic counterpart, quartz fiber. The fabricated GAFF features a wide-range tunable electrical conductivity (1-15000 Ω sq−1), high tensile strength (>1.5 GPa), lightweight, flexibility, and a hierarchical macrostructure. These attributes are inherited from both graphene and AFF, making GAFF promising for various applications including electrical heating and electromagnetic interference shielding. Beyond laboratory level preparation, the stable mass production of large-scale GAFF has been achieved through a home-made roll-to-roll system with capacity of 468-93600 m2/year depending on product specifications, providing foundations for the subsequent industrialization of this material, enabling its widespread adoption in various industries.

Reinforcement learning is now being applied more and more in a variety of scenarios, the majority of which are based on the deep Q network (DQN) technology. However, the algorithm is heavily influenced by multiple factors. In this paper, we take the lunar lander as a case to study how various hyper-parameters affect the performance of the DQN algorithm, based on which we tune to get a model with better performance. At present, it is known that the DQN model has an average reward of 280+ on 100 test episodes, and the reward value of the model in this article can reach 290+. Meanwhile, its robustness is tested and verified by introducing additional uncertainty tests into the original problem. In addition, to speed up the training process, imitation learning is incorporated in our model, using heuristic function model guidance method to obtain demonstration data, which accelerates training speed and improves performance. Simulation results have proven the effectiveness of this method.

Understanding how environmental factors influence the responsiveness of crop yield to growing season precipitation (GSP) can reduce the risk of yield fluctuations, ensuring stable crop production. This study involved the cultivation of rainfed potatoes at three locations within the climatic transition zone of Northwest China. We employed stepwise linear regression and machine learning techniques to pinpoint the key environmental factors influencing potato tuber yield and the yield-precipitation relationship. The slope of the water-limited yield potential relationship for potatoes was determined to be 172.1 ​kg ​ha−1 ​mm−1, with an intercept at 121.2 ​mm. The potato tuber yield exhibited an upward trend with increasing GSP but declined once the precipitation exceeded 400 ​mm. However, GSP alone explained up to 30% of the variability in potato tuber yield. Factors such as soil moisture at planting, maximum temperatures during the tuber stolon initiation and bulking stages, diurnal temperature fluctuations at maturity, and excessive precipitation events during the growing season significantly influenced potato tuber yield, and consequently, the relationship between yield and GSP. Conversely, climatic factors accounted for more than 63% of the variation in potato tuber yield, with the multiple linear regression model yielding the best results. This was especially evident when the yield-precipitation relationship was categorized into two groups based on the amount and distribution of GSP, maximum temperature, and radiation levels. This analysis suggested that preventing unnecessary water evaporation when precipitation is low, improving drainage when precipitation is high, and planting potato on an optimal date can advance potato production.

Abstract We aimed to implement four data partitioning strategies evaluated with four federated learning (FL) algorithms and investigate the impact of data distribution on FL model performance in detecting steatosis using B-mode US images. A private dataset (153 patients; 1530 images) and a public dataset (55 patient; 550 images) were included in this retrospective study. The datasets contained patients with metabolic dysfunction-associated fatty liver disease (MAFLD) with biopsy-proven steatosis grades and control individuals without steatosis. We employed four data partitioning strategies to simulate FL scenarios and we assessed four FL algorithms. We investigated the impact of class imbalance and the mismatch between the global and local data distributions on the learning outcome. Classification performance was assessed with area under the receiver operating characteristic curve (AUC) on a separate test set. AUCs were 0.93 (95% CI 0.92, 0.94) for source-based partitioning scenario with FedAvg, 0.90 (95% CI 0.89, 0.91) for a centralized model, and 0.83 (95% CI 0.81, 0.85) for a model trained in a single-center scenario. When data was perfectly balanced on the global level and each site had an identical data distribution, the model yielded an AUC of 0.90 (95% CI 0.88, 0.92). When each site contained data exclusively from one single class, irrespective of the global data distribution, the AUC fell in the range of 0.34–0.70. FL applied to B-mode US images provide performance comparable to a centralized model and higher than single-center scenario. Global data imbalance and local data heterogeneity influenced the learning outcome.

Abstract Direct chemical vapor deposition (CVD) growth of graphene on dielectric/insulating materials is a promising strategy for subsequent transfer-free applications of graphene. However, graphene growth on noncatalytic substrates is faced with thorny issues, especially the limited growth rate, which severely hinders mass production and practical applications. Herein, graphene glass fiber fabric (GGFF) is developed by graphene CVD growth on glass fiber fabric. Dichloromethane is applied as a carbon precursor to accelerate graphene growth, which has a low decomposition energy barrier, and more importantly, the produced high-electronegativity Cl radical can enhance adsorption of active carbon species by Cl–CH2 coadsorption and facilitate H detachment from graphene edges. Consequently, the growth rate is increased by ~3 orders of magnitude and carbon utilization by ~960-fold, compared with conventional methane precursor. The advantageous hierarchical conductive configuration of lightweight, flexible GGFF makes it an ultrasensitive pressure sensor for human motion and physiological monitoring, such as pulse and vocal signals.

Abstract Mantle heterogeneity in lithology and geochemistry is often attributed to recycled subducted materials. While distinct mantle end‐members are identified by radiogenic isotopes, the specific recycled materials contributing to this heterogeneity remain debated. This study presents Mo‐Sr‐Nd‐Pb isotopic data for OIB‐like alkali basalts from the Maguan area in the southeastern Tibetan Plateau, focusing on slab inputs' role in mantle heterogeneity. The Miocene (ca. 13 Ma) Maguan alkali basalts are divided into two types based on petrographic and geochemical characteristics, showing similar Sr‐Nd‐Pb isotopic signatures but different Mo isotopic compositions. Type I basalts exhibit a wide δ98/95Mo range (−0.31‰ to −1.03‰, average −0.47‰ ± 0.06‰, 2SD = 0.40‰, n = 13), while type II basalts have heavy and constant δ98/95Mo values (−0.11‰ to −0.17‰, average −0.14‰ ± 0.01‰, 2SD = 0.05‰, n = 6). The unique low δ98/95Mo value (−1.03‰) in type I basalts is among the lowest reported in OIB‐like continental basalts. Type I basalts likely originate from an enriched asthenospheric mantle metasomatized by melts from recycled dehydrated oceanic crust and sediments, whereas type II basalts are derived from partial melting of an enriched asthenospheric mantle metasomatized by melts from recycled serpentinized peridotites. The residual Tethys oceanic slabs in the deep mantle significantly contribute to the mantle source of the Maguan basalts. The formation of Maguan Miocene magmas may be linked to mantle upwelling induced by the subduction of the West Burma plate. This study highlights the Mo isotopic system's utility in tracing complex slab fluxes generating mantle geochemical heterogeneity.

At present, the accuracy of remote sensing estimation models of plant alpha diversity is generally low, and high-precision estimation models in deciduous broadleaved forest (DBF), deciduous coniferous forest (DCF) and evergreen coniferous forest (ECF) are still lacking. The main purpose of this study is to construct high-precision remote sensing models for plant alpha diversity in multiple ecosystems at global scale. Normalized Difference Vegetation Index (NDVI) were derived from Sentinel-2 data. NDVI and NDVI based spectral diversity/heterogeneity indices were selected as predictive variables, and alpha diversity indices were selected as response variables. Simple linear regression (SLR), partial linear regression (PLSR), and random forest (RF) models were used to evaluate the predictive ability of the predictive variables against the response variables under six ecosystems (evergreen broadleaved forest (EBF), DBF, ECF, DCF, shrub, and grassland), and to compare the estimated robustness of various spectral diversity indices. In terms of prediction accuracy, the SLR models were the worst, and the PLSR model were average. RF performed best, outperforming most current models. Especially in DBF, ECF, shrub and grassland, the determination coefficient R2 of RF models can be as high as 0.9. In terms of the prediction of α-diversity, the prediction effect of species richness was better than that of Shannon index, Simpson index and Pielou index. The higher the vegetation complexity, the more accurate the assessment of vegetation α-diversity tends to be, especially in DBF, shrub and grassland. According to the importance of predictive variables and model stability evaluation results, NDVI, standard deviation of NDVI (SD), and NDVI derived Shannon’s diversity index (Sha), Cumulative Residual Entropy (CRE), Pielou’s evenness index (Pie), Hill’s numbers (Hill), Berger-Parker’s diversity index (Ber), Parametric Rao’s index of quadratic entropy (paRao) are all powerful indicators for predicting plant alpha diversity. Among them, the prediction performance of NDVI and SD is better. This study is not only an exploration of the practicability of R package “rasterdiv”, but also an attempt to construct high-precision remote sensing estimation models of plant alpha diversity at global scale.

Over the past decade, the rapid development of artificial intelligence has propelled the transition of autonomous vehicles from laboratories to real-world applications. However, autonomous vehicles are a long way from fully integrating into most people's lives. Previous studies indicate that the word-of-mouth effect is often used by consumers to determine the quality of innovative technologies. Word-of-mouth recommendation can not only increase the income of enterprises by attracting new customers, but also greatly reduce the promotion and publicity expenses of enterprises. Through the word-of-mouth effect, the intention to recommend can contribute to the growth of the autonomous driving market. Therefore, current research explores the mechanisms among the perceived risk of privacy safety, perceived defect, perceived behavioral control, intention to use, and intention to recommend through path analysis. Our findings, based on 433 online questionnaires, indicate that the perceived risk of privacy safety, perceived defects, and perceived behavioral control influence the intention to recommend. Notably, perceived risk of privacy safety and perceived defect directly affects the intention to recommend and also correlates with perceived behavioral control. These findings provide some empirical evidence for the recommendation of autonomous vehicles and the expansion of consumer groups.

Abstract Background Thromboinflammation involving platelet adhesion to endothelial surface-associated von Willebrand factor (VWF) has been implicated in the accelerated progression of non-culprit plaques after MI. The aim of this study was to use arterial endothelial molecular imaging to mechanistically evaluate endothelial-associated VWF as a therapeutic target for reducing remote plaque activation after myocardial infarction (MI). Methods Hyperlipidemic mice deficient for the low-density lipoprotein receptor and Apobec-1 underwent closed-chest MI and were treated chronically with either: (i) recombinant ADAMTS13 which is responsible for proteolytic removal of VWF from the endothelial surface, (ii) N-acetylcysteine (NAC) which removes VWF by disulfide bond reduction, (iii) function-blocking anti-factor XI (FXI) antibody, or (iv) no therapy. Non-ischemic controls were also studied. At day 3 and 21, ultrasound molecular imaging was performed with probes targeted to endothelial-associated VWF A1-domain, platelet GPIbα, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) at lesion-prone sites of the aorta. Histology was performed at day 21. Results Aortic signal for P-selectin, VCAM-1, VWF, and platelet-GPIbα were all increased several-fold (p 50% (p

Abstract Accurate simulation of lightning‐induced overvoltage for overhead distribution lines is helpful to prevent lightning trip accidents. An electromagnetic return‐stroke model was used to represent lightning and then a 3D finite‐difference time‐domain (FDTD) method was adopted to simulate the lightning‐induced overvoltage on a distribution line without a field‐line coupling model. How lightning‐induced overvoltage behave for different ground conductivity and varying distance between the distribution line and the lightning channel was analysed. The results showed that the overvoltage waveforms at the centre point of the line corresponding to lightning strikes on the lossy ground and an ideal ground (σ = ∞) were similar; however, the peak amplitudes of the waveform were affected by soil conductivity at a close distance. The relationship between magnitude of the overvoltage and distance can be described by a second‐order exponential decay equation. Finally, the overvoltage calculated using the proposed model was compared with those obtained based on Agrawal's model and measurements made using the newly developed intelligent insulator on site. From these comparisons, it could be concluded that the FDTD method with the electromagnetic return‐stroke model produces reasonably accurate results of the attenuated oscillation waveform, which can better reproduce the overvoltage on operational distribution lines.

Abstract Introduction This study aims to quantitatively assess diffuse chorioretinal atrophy (DCA) in pathologic myopia and establish a standardized classification system utilizing artificial intelligence. Methods A total of 202 patients underwent comprehensive examinations, and 338 eyes were included in the study. The methodology involved image preprocessing, sample labeling, employing deep learning segmentation models, measuring and calculating the area and density of DCA lesions. Lesion severity of DCA was graded using statistical methods, and grades were assigned to describe the morphology of corresponding fundus photographs. Hierarchical clustering was employed to categorize diffuse atrophy fundus into three groups based on the area and density of diffuse atrophy (G1, G2, G3), while high myopic fundus without diffuse atrophy was designated as G0. One-way analysis of variance (ANOVA) and nonparametric tests were conducted to assess the statistical association with different grades of DCA. Results On the basis of the area and density of DCA, the condition was classified into four grades: G0, G1 (0

Abstract Objective To investigate the recovery of binocular stereopsis recovery and its influencing factors in children with intermittent exotropia after successful correction of eye position. Methods Prospective clinical study. A total of 178 patients, aged 9 ∼ 14 (10.8 ± 1.7) years, who were successfully corrected after intermittent exotropia surgery at the Beijing Tongren Hospital Affiliated to Capital Medical University from October 2023 to September 2023 were collected, the follow-up duration was six-month or longer. Paired t test, Pearson correlation analysis and multivariable linear regression analysis were used to probe preoperative clinical features that may predict the stereopsis six months after surgery. Results Six months after surgery, the angle of deviation of the patients met the orthotopic standard, and there was significant difference compared with that before surgery (distant: -2.7△±3.2△ vs. -30.5△±8.4△, t=-25.3, P

Abstract Objective This study assessed the outcomes of elderly patients with limited‐stage small cell lung cancer (LS‐SCLC), which may be linked to the timing of thoracic radiotherapy (TRT) following chemotherapy. Methods Elderly patients (n = 78) with LS‐SCLC were divided into three groups depending on the timing of radiotherapy. The patients in the TRT group were stratified into early (TRT after 1–2 cycles of chemotherapy, n = 29), medium‐term (TRT after 3–4 cycles of chemotherapy, n = 33), and late (TRT after 5–6 cycles of chemotherapy, n = 16) TRT groups. The overall survival (OS) and progression‐free survival (PFS) were assessed and compared. Results The medium‐term TRT group demonstrated significantly longer mPFS (20.12 months) and better mOS (35.97 months) than those in the other groups (PFS: P = 0.021;OS: P = 0.035). A pairwise comparison of the three groups revealed that those who received medium‐term TRT exhibited significantly improved PFS than the early (mPFS: 20.12 vs. 10.36 mouths, P = 0.018) and late (mPFS: 20.12 vs. 9.17 months, P = 0.016) TRT. The medium‐term TRT group demonstrated significantly improved OS than the early TRT (mOS: 35.97 vs. 25.22 months, P = 0.007) but not in comparison with the late TRT (mOS: 35.97 vs. 21.63 months, P = 0.100). Conclusion In elderly patients with LS‐SCLC, the addition of TRT after 3–4 cycles of chemotherapy appears to be a viable and potentially beneficial treatment approach.

Abstract Background Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. Methods We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. Results In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. Conclusion Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.

ABSTRACTDomain adaptation can effectively enhance a model’s performance on target domain data with limited data. However, when some target domain labels are obtainable, training the model with both source and target domain data simultaneously can lead to worse performance due to the lower density of target domain data. If a large amount of target domain data is labeled without discrimination, it will necessitate a considerable expenditure of human resources. To address this issue, this paper proposes a human-in-one-loop active domain adaptation framework based on Target Domain Feature Generation to solve the problems. The oracle participates in only one iteration of data labeling, and a target domain classifier will take over the subsequent rest iterations. An image generator based on multiple CycleGANs forms an iterative co-training mechanism, which can continuously generate more high-quality labeled fake target domain data in iterations to improve the performance of the target domain classifier. The Top-N labeled data selection method with high confidence is devised to select the most accurately predicted data for labeling, reducing manual labeling workload. This framework can achieve an average accuracy of 0.8869 on six domain pairs, doubling the classical domain adaptation method DSN, requiring only a small amount of manual labeling.

Aim: A keloid is a fibroproliferative cutaneous disorder secondary to skin injury, caused by an imbalance in fibroblast proliferation and apoptosis. However, the pathogenesis is not fully understood. In this study, candidate genes for keloid were identified and used to construct a diagnostic model. Methods: Three datasets related to keloids were downloaded from NCBI Gene Expression Omnibus. Fibroblast-related genes were screened, and fibroblast scores for the samples were determined. Then, a weighted gene co-expression network analysis (WGCNA) was used to identify modules and genes associated with keloids and the fibroblast score. Differentially expressed genes (DEGs) between keloid and control samples were identified and compared with fibroblast-related genes and genes in the modules. Overlapping genes were evaluated using functional enrichment analyses. Signature genes were further screened, and a diagnostic model was constructed. Finally, correlations between immune cell frequences and signature genes were analyzed. Results: In total, 124 fibroblast-related genes were obtained, and the fibroblast score was an effective indicator of the sample type. WGCNA revealed five modules that were significantly correlated with both the disease state and fibroblast scores, including 1760 genes. Additionally, 589 DEGs were identified, including 16 that overlapped with fibroblast-related genes and genes identified in the WGCNA. These genes were related to cell proliferation and apoptosis and were involved in FoxO, Rap1, p53, Ras, MAPK, and PI3K-Akt pathways. Finally, a six fibroblast-related gene signature (CCNB1, EGFR, E2F8, BTG1, TP63, and IGF1) was identified and used for diagnostic model construction. The proportions of regulatory T cells and macrophages were significantly higher in keloid tissues than in controls. Conclusion: The established model based on CCNB1, EGFR, E2F8, BTG1, TP63, and IGF1 showed good performance and may be useful for keloid diagnosis.

Introduction: Obesity is a major risk factor associated with multiple pathological conditions including diabetes and cardiovascular disease. Endothelial dysfunction is an early predictor of obesity. However, little is known regarding how early endothelial changes trigger obesity. In the present work we report a novel endothelial-mediated mechanism essential for regulation of metabolic homeostasis, driven by c-Myc.Methods: We used conditional knockout (EC-Myc KO) and overexpression (EC-Myc OE) mouse models to investigate the endothelial-specific role of c-Myc in metabolic homeostasis during aging and high-fat diet exposure. Body weight and metabolic parameters were collected over time and tissue samples collected at endpoint for biochemical, pathology and RNA-sequencing analysis. Animals exposed to high-fat diet were also evaluated for cardiac dysfunction.Results: In the present study we demonstrate that EC-Myc KO triggers endothelial dysfunction, which precedes progressive increase in body weight during aging, under normal dietary conditions. At endpoint, EC-Myc KO animals showed significant increase in white adipose tissue mass relative to control littermates, which was associated with sex-specific changes in whole body metabolism and increase in systemic leptin. Overexpression of endothelial c-Myc attenuated diet-induced obesity and visceral fat accumulation and prevented the development of glucose intolerance and cardiac dysfunction. Transcriptome analysis of skeletal muscle suggests that the protective effects promoted by endothelial c-Myc overexpression are associated with the expression of genes known to increase weight loss, energy expenditure and glucose tolerance.Conclusion: Our results show a novel important role for endothelial c-Myc in regulating metabolic homeostasis and suggests its potential targeting in preventing obesity and associated complications such as diabetes type-2 and cardiovascular dysfunction.

BackgroundThe protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear.MethodsFecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman’s correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites.ResultsThe diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that L-valine could alleviate sepsis-induced intestinal damage.ConclusionAlterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury.

Qualitative and quantitative anatomical characteristics and radial variations of the major cell components in Paulownia tomentosa wood were examined using optical microscopy and X-ray diffraction to aid in wood identification and as quality indices. The vessel arrangement on the transverse surface was either ring-porous or semi-ring-porous. Most vessels had solitary pores, while some vessels had multiple radial pores. The axial parenchyma was generally confluent and partially of aliform type. Tyloses with high frequency in the vessel lumen and multiseriate rays (2 to 5 cells) were typical. The vessel diameter of earlywood and latewood was approximately 240 and 107 μm, respectively, with a range of 165 to 289 μm in earlywood and 55 to 149 μm in latewood. Ray height and fiber length were approximately 178 and 740 μm, respectively. The vessel diameter in both earlywood and latewood and the fiber length increased gradually with an increasing number of growth rings. Ray height was constant from the pith to the middle section and decreased toward the bark. The anatomical characteristics and radial variation of major components of P. tomentosa can be used as wood identification keys and quality indices.

Abstract Exosomes play a crucial role in intercellular communication and can be used as biomarkers for diagnostic and therapeutic clinical applications. However, systematic studies in cancer-associated exosomal nucleic acids remain a big challenge. Here, we developed ExMdb, a comprehensive database of exosomal nucleic acid biomarkers and disease-gene associations curated from published literature and high-throughput datasets. We performed a comprehensive curation of exosome properties including 4,586 experimentally supported gene-disease associations, 13,768 diagnostic and therapeutic biomarkers, and 312,049 nucleic acid subcellular locations. To characterize expression variation of exosomal molecules and identify causal factors of complex diseases, we have also collected 164 high-throughput datasets, including bulk and single-cell RNA sequencing (scRNA-seq) data. Based on these datasets, we performed various bioinformatics and statistical analyses to support our conclusions and advance our knowledge of exosome biology. Collectively, our dataset will serve as an essential resource for investigating the regulatory mechanisms of complex diseases and improving the development of diagnostic and therapeutic biomarkers.

Abstract Background Despite advances in medical imaging technology, the accurate preoperative prediction of lymph node status remains challenging in ovarian cancer. This retrospective study aimed to investigate the feasibility of using ultrasound-based radiomics combined with preoperative clinical characteristics to predict lymph node metastasis (LNM) in patients with high-grade serous ovarian cancer (HGSOC). Results Patients with 401 HGSOC lesions from two institutions were enrolled: institution 1 for the training cohort (n = 322) and institution 2 for the external test cohort (n = 79). Radiomics features were extracted from the three preoperative ultrasound images of each lesion. During feature selection, primary screening was first performed using the sample variance F-value, followed by recursive feature elimination (RFE) to filter out the 12 most significant features for predicting LNM. The radscore derived from these 12 radiomic features and three clinical characteristics were used to construct a combined model and nomogram to predict LNM, and subsequent 10-fold cross-validation was performed. In the test phase, the three models were tested with external test cohort. The radiomics model had an area under the curve (AUC) of 0.899 (95% confidence interval [CI]: 0.864–0.933) in the training cohort and 0.855 (95%CI: 0.774–0.935) in the test cohort. The combined model showed good calibration and discrimination in the training cohort (AUC = 0.930) and test cohort (AUC = 0.881), which were superior to those of the radiomic and clinical models alone. Conclusions The nomogram consisting of the radscore and preoperative clinical characteristics showed good diagnostic performance in predicting LNM in patients with HGSOC. It may be used as a noninvasive method for assessing the lymph node status in these patients.

Abstract Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.

Sanghuangprous vaninii is a medicinal macrofungus cultivated extensively in China. Both the mycelia and fruiting bodies of S. vaninii have remarkable therapeutic properties, but it remains unclear whether the mycelia may serve as a substitute for the fruiting bodies. Furthermore, S. vaninii is a perennial fungus with therapeutic components that vary significantly depending on the growing year of the fruiting bodies. Hence, it is critical to select an appropriate harvest stage for S. vaninii fruiting bodies for a specific purpose. With the aid of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), metabolomics based on ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS) was used to preliminarily determine 81 key active metabolites and 157 active pharmaceutical metabolites in S. vaninii responsible for resistance to the six major diseases. To evaluate the substitutability of the mycelia and fruiting bodies of S. vaninii and to select an appropriate harvest stage for the fruiting bodies of S. vaninii, we analyzed the metabolite differences, especially active metabolite differences, among the mycelia and fruiting bodies during three different harvest stages (1-year-old, 2-year-old, and 3-year-old). Moreover, we also determined the most prominent and crucial metabolites in each sample of S. vaninii. These results suggested that the mycelia show promise as a substitute for the fruiting bodies of S. vaninii and that extending the growth year does not necessarily lead to higher accumulation levels of active metabolites in the S. vaninii fruiting bodies. This study provided a theoretical basis for developing and using S. vaninii.

IntroductionThe aim of this cross-sectional study was to investigate the association between breakfast patterns and executive function among adolescents in Shanghai, China.MethodsIn 2022, we randomly recruited 3,012 adolescents aged 12–13 years from all administrative districts in Shanghai. Breakfast information was collected by parents using a one-day recall method. Executive function was measured using the Behavior Rating Inventory of Executive Function-Parent Version. Latent Class Analysis was performed to identify breakfast patterns based on the food groups in the Diet Quality Questionnaire for China.ResultsBreakfast patterns were classified into three categories: “Egg and milk foods”, “Grain foods”, and “Abundant foods”, except for adolescents who skipped breakfast. Logistic regression was used to estimate the multivariate odds ratio (ORs) and 95% confidence intervals (95% CI) for the association between breakfast patterns and potential executive dysfunction. Adolescents in the “Abundant foods” class had a lower risk of executive dysfunction in terms of initiate (OR: 0.36; 95% CI: 0.17–0.76), and organization of materials (OR: 0.18; 95% CI: 0.04–0.94), compared to those who skipped breakfast. Similarly, the breakfast patterns of “Grain foods” and “Egg and milk foods” were associated with a lower risk of executive dysfunction, including initiate and working memory.DiscussionOur findings suggest that breakfast patterns were associated with executive function. The improvement of breakfast patterns among adolescents should be a significant public health intervention.

Background Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. Methods and Results A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person‐years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long‐term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19–2.21) than those with Lp(a)

BackgroundStrengthening the construction of community resilience and reducing disaster impacts are on the agenda of the Chinese government. The COVID-19 pandemic could alter the existing community resilience. This study aims to explore the dynamic change trends of community resilience in China and analyze the primary influencing factors of community resilience in the context of COVID-19, as well as construct Community Resilience Governance System Framework in China.MethodsA community advancing resilience toolkit (CART) was used to conduct surveys in Guangdong, Sichuan, and Heilongjiang provinces in China in 2015 and 2022, with community resilience data and information on disaster risk awareness and disaster risk reduction behaviors of residents collected. The qualitative (in-depth interview) data from staffs of government agencies and communities (n = 15) were pooled to explore Community Resilience Governance System Framework in China. Descriptive statistics analysis and t-tests were used to investigate the dynamic development of community resilience in China. Hierarchical regression analysis was performed to explore the main influencing factors of residential community resilience with such socio-demographic characteristics as gender and age being controlled.ResultsThe results indicate that community resilience in China has improved significantly, presenting differences with statistical significance (p

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.

Ethnopharmacological relevance: Murrayae Folium et Cacumen (MFC) is a plant considered to be a traditional Chinese medicine with culinary value as well. The dry leaves and twigs of Murraya paniculata and M. exotica are used to treat stomach aches, rheumatism, toothaches, swelling, and insect and snake bites. They are also used to prepare spicy chicken dishes.Aim of the review: This review comprehensively summarizes the available information on the botanical characterization, phytochemistry, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC.Methods: Relevant scientific literature up to August 2023 was included in the study. Chinese and English studies on MFC were collected from databases, including PubMed, Elsevier, Web of Science, Springer, Science Direct, Wiley, ACS, and CNKI (Chinese). Doctoral and Master’s dissertations were also included.Results: In total, 720 compounds have been identified and reported in the literature, including flavonoids, coumarins, alkaloids, sterols, phenylpropenols, organic acids, spirocyclopentenones, and volatile oils. Flavonoids and coumarins are the two most important bioactive compounds responsible for these pharmacological activities. MFC has anti-inflammatory, anti-bacterial, anti-microbial, anti-diabetic, anti-tumor, anti-oxidant, anti-depressant, potential anti-Alzheimer’s disease, chondroprotective, and analgesic properties. The pharmacological effects include interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways, downregulating EpCAM expression, inhibiting NF-κB and ERK signals, inhibiting the EP/cAMP/PKA signaling pathway and miR-29a/Wnt/β-catenin signaling activity, and upregulating Foxo3a expression.Conclusion: This review demonstrates that the chemical constituents, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC support its use in traditional Chinese botanical medicines. MFC contains a wide range of chemical compounds. Flavonoids and coumarins promote strong pharmacological activity and, are low-toxicity natural phytomedicines that are widely used in medicine, food, ornamentation, and cosmetics, making MFC a promising compound for development and use in the treatment of several medical conditions.

Abstract Electrostrictors, materials developing mechanical strain proportional to the square of the applied electric field, present many advantages for mechanical actuation as they convert electrical energy into mechanical, but not vice versa. Both high relative permittivity and reliance on Pb as the key component in commercial electrostrictors pose serious practical and health problems. Here we describe a low relative permittivity (

Abstract Cuproptosis is a unique type of cell death that may influence tumour formation by targeting lipoylated tricarboxylic acid cycle proteins. Solute carrier family 31 member 1 (SLC31A1), an important copper transporter, influences dietary copper absorption in the cell membrane. However, various SLC31A1 properties in pan-cancer profiles remain unknown. This study investigated the role of SLC31A1 in human malignancies and analysed its prognostic value. Raw data were obtained from The Cancer Genome Atlas database and processed using numerous internet databases, including UALCAN, GEPIA, cBioPortal, TIMER2.0, and Human Protein Atlas. SLC31A1 expression was found to be elevated in cervical, endometrial, and breast cancers compared to that in normal tissues, but reduced in clear cell renal cell carcinoma, liver hepatocellular carcinoma, and lung adenocarcinoma. Furthermore, SLC31A1 expression was strongly associated with overall survival and disease-free survival in several cancers. SLC31A1 gene mutations and methylations were identified in 33 cancers. SLC31A1 expression was positively correlated with immune cells in immune infiltration data. Single-cell sequencing revealed that SLC31A1 may play key roles in DNA repair, DNA damage, and proliferation. These findings may lead to better understanding of SLC31A1 in pan-cancer profiles and suggest that SLC31A1 could be a viable predictive biomarker, particularly in gynaecological cancers.

Abstract Background Patients with epithelial ovarian carcinoma (EOC) are usually diagnosed at an advanced stage with tumour cell invasion. However, identifying the underlying molecular mechanisms and biomarkers of EOC proliferation and invasion remains challenging. Results Herein, we explored the relationship between tumour microenvironment (TME) reprogramming and tissue invasion based on single-cell RNA sequencing (scRNA-seq) datasets. Interestingly, hypoxia, oxidative phosphorylation (OXPHOS) and glycolysis, which have biologically active trajectories during epithelial mesenchymal transition (EMT), were positively correlated. Moreover, energy metabolism and anti-apoptotic activity were found to be critical contributors to intratumor heterogeneity. In addition, HMGA1, EGR1 and RUNX1 were found to be critical drivers of the EMT process in EOC. Experimental validation revealed that suppressing EGR1 expression inhibited tumour cell invasion, significantly upregulated the expression of E-cadherin and decreased the expression of N-cadherin. In cell components analysis, cancer-associated fibroblasts (CAFs) were found to significantly contribute to immune infiltration and tumour invasion, and the accumulation of CAFs was associated with poorer patient survival. Conclusion We revealed the molecular mechanism and biomarkers of tumour invasion and TME reprogramming in EOC, which provides effective targets for the suppression of tumour invasion.

Effectors are considered to be virulence factors secreted by pathogens, which play an important role during host-pathogen interactions. In this study, the candidate effector Pt9226 was cloned from genomic DNA of Puccinia triticina (Pt) pathotype THTT, and there were six exons and five introns in the 877 bp sequence, with the corresponding open reading frame of 447 bp in length, encoding a protein of 148 amino acids. There was only one polymorphic locus of I142V among the six Pt pathotypes analyzed. Bioinformatics analysis showed that Pt9226 had 96.46% homology with the hypothetical putative protein PTTG_26361 (OAV96349.1) in the Pt pathotype BBBD. RT-qPCR analyses showed that the expression of Pt9226 was induced after Pt inoculation, with a peak at 36 hpi, which was 20 times higher than the initial expression at 0 hpi, and another high expression was observed at 96 hpi. No secretory function was detected for the Pt9226-predicted signal peptide. The subcellular localization of Pt9226Δsp-GFP was found to be multiple, localized in the tobacco leaves. Pt9226 could inhibit programmed cell death (PCD) induced by BAX/INF1 in tobacco as well as DC3000-induced PCD in wheat. The transient expression of Pt9226 in 26 wheat near-isogenic lines (NILs) by a bacterial type III secretion system of Pseudomonas fluorescens EtHAn suppressed callose accumulation triggered by Ethan in wheat near-isogenic lines TcLr15, TcLr25, and TcLr30, and it also suppressed the ROS accumulation in TcLr15. RT-qPCR analysis showed that the expression of genes coded for pathogenesis-related protein TaPR1, TaPR2, and thaumatin-like protein TaTLP1, were suppressed, while the expression of PtEF-1α was induced, with 1.6 times at 72 h post inoculation, and TaSOD was induced only at 24 and 48 h compared with the control, when the Pt pathotype THTT was inoculated on a transient expression of Pt9226 in wheat TcLr15. Combining all above, Pt9226 acts as a virulence effector in the interaction between the Pt pathotype THTT and wheat.

Abstract Introduction Here we investigate the clinical features of foveal detachment (FD), full-thickness macular hole (MH), and macular hole retinal detachment (MHRD) in myopic traction maculopathy (MTM). Methods In the retrospective observational case series, 314 eyes of 198 patients with myopic retinoschisis in Beijing Tongren Hospital were enrolled. We recorded gender, age, and axial length and evaluated fundus characteristics using optical coherence tomography. Epiretinal membranes (ERMs), vitreoretinal traction, and paravascular abnormalities (PVAs) were used to describe the vitreoretinal interface condition. Different retinoschisis layers (inner, middle, and outer retinoschisis) and the location with a range of outer retinoschisis were evaluated to reveal the retinal condition. Five patterns of the scleral shape: dome-shaped, sloped toward the optic nerve, symmetrical or asymmetrical around the fovea, and irregular were assessed to show retina-sclera condition. We regarded the FD, full-thickness MH, and MHRD as the advanced stage in MTM. Multivariate logistic regression assessed significant factors for the advanced stage with odds ratios (OR) and 95% confidence intervals (CI). Results There were 76 eyes with FD, 6 eyes with full-thickness MH, and 7 eyes with MHRD. The mean age was 52.9 ± 12.3 years. On univariate analysis, the eyes with the advanced stage were older and had higher rates of ERMs, PVAs, middle retinoschisis, outer retinoschisis, and irregular sclera shape. The number of retinoschisis layers and the grade of outer retinoschisis were higher in eyes with the advanced stage. After multivariate logistic regression, ERMs (OR 1.983; 95% CI 1.093–3.595; P = 0.024), middle retinoschisis (OR 2.967; 95% CI 1.630–5.401; P

Abstract Background The availability of physical activity (PA) facilities in neighborhoods is hypothesized to influence cardiovascular disease (CVD), but evidence from individual-level long-term cohort studies is limited. We aimed to assess the association between neighborhood exposure to PA facilities and CVD incidence. Methods A total of 4658 participants from the Chinese Multi-provincial Cohort Study without CVD at baseline (2007–2008) were followed for the incidence of CVD, coronary heart disease (CHD), and stroke. Availability of PA facilities was defined as both the presence and the density of PA facilities within a 500-m buffer zone around the participants’ residential addresses. Time-dependent Cox regression models were performed to estimate the associations between the availability of PA facilities and risks of incident CVD, CHD, and stroke. Results During a median follow-up of 12.1 years, there were 518 CVD events, 188 CHD events, and 355 stroke events. Analyses with the presence indicator revealed significantly lower risks of CVD (hazard ratio [HR] 0.80, 95% confidence interval ([CI] 0.65–0.99) and stroke (HR 0.76, 95% CI 0.60–0.97) in participants with PA facilities in the 500-m buffer zone compared with participants with no nearby facilities in fully adjusted models. In analyses with the density indicator, exposure to 2 and ≥ 3 PA facilities was associated with 35% (HR 0.65, 95% CI 0.47–0.91) and 28% (HR 0.72, 95% CI 0.56–0.92) lower risks of CVD and 40% (HR 0.60, 95% CI 0.40–0.90) and 38% (HR 0.62, 95% CI 0.46–0.84) lower risks of stroke compared with those without any PA facilities in 500-m buffer, respectively. Effect modifications between presence of PA facilities and a history of hypertension for incident stroke (P = 0.049), and a history of diabetes for incident CVD (P = 0.013) and stroke (P = 0.009) were noted. Conclusions Residing in neighborhoods with better availability of PA facilities was associated with a lower risk of incident CVD. Urban planning intervention policies that increase the availability of PA facilities could contribute to CVD prevention.

Abstract Background Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease with high penetrance caused by a germline variant of TP53 gene. We report the first case of endometrial cancer after yolk sac tumor with LFS. Case presentation The presented female patient underwent right adnexectomy at age 23 because of a yolk sac tumor of the ovary. At the age of 27, the patient was diagnosed with endometrial adenocarcinoma, received cytoreductive surgery and chemotherapy. Given that her personal cancer history along with a strong family history of cancer, her father passing away from lung cancer at age 48 and her grandmother dying of ovarian cancer at age 50, the patient was referred for genetic counseling and testing. Genetic screening revealed a heterozygous pathogenic TP53 c.844C > T, p.( R282 W) with NM_000546.5 variant, a class 5 (C5) variant. This is the first reported case of a yolk sac tumor accompanied by subsequent endometrial cancer that is associated with LFS. Conclusions We reported a first case of an endometrial cancer after yolk sac tumor patient with a tumor family history of harboring the germline TP53 pathogenic variation which expanded types of tumor that can be presented in patients with LFS. This case highlights the importance of genetic testing for patients with malignant tumors, as well as patients with a family history of malignant tumors. And our case highlights the necessity of screening for gynecologic tumor in LFS patients.

Summary: Background: The most recent updated hypertension guidelines recommend individuals with systolic blood pressure (SBP)/diastolic blood pressure (DBP) of 130–139/80–89 mmHg and high cardiovascular risk should receive antihypertensive drug treatment. This study aimed to assess the benefits and cost-effectiveness of medication for people aged ≥35 years with this blood pressure stratum and high cardiovascular risk in China. Methods: The benefits of drug treatment in adults aged ≥35 years with SBP/DBP of 130–139/80–89 mmHg and high cardiovascular risk were evaluated in decision-analytic simulation models. Decreasing numbers of cardiovascular disease (CVD) events and premature deaths from all causes and increasing quality-adjusted life-years (QALYs) from drug treatment were estimated in 10-year and lifetime horizons. The incremental cost-effectiveness ratios (ICER) for drug treatment were calculated. Findings: Among approximately 106.60 million Chinese adults aged ≥35 years with this blood pressure stratum and high cardiovascular risk, drug treatment was estimated to prevent 2,060,000 strokes and 660,000 myocardial infarctions over a 10-year time horizon. Adults prescribed antihypertensive drugs could gain 0.034 incremental QALYs. Over a lifetime horizon, adults who start treatment earlier could benefit more in preventing CVD and gaining incremental QALYs. The medication treatment is cost-effective either over a 10-year time horizon with an ICER of Int$13321.29 per QALY gained or over the remaining lifetime. Interpretation: Antihypertensive treatment of adults with SBP/DBP of 130–139/80–89 mmHg and high cardiovascular risk would gain substantial benefits with cost-effectiveness. The young and middle-aged population would derive the most benefit. Funding: National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Intraneuronal inclusions of alpha-synuclein (α-synuclein, α-syn) are commonly found in the brain of patients with Parkinson's disease (PD). The pathogenesis of the abundant α-syn protein in the blood has been extensively studied to understand its properties better. In recent years, peptidome analysis has received increasing attention. In this study, we identified and analyzed serum peptides from wild-type (WT) and the (Thy-1)-h[A30P] alpha-synuclein transgenic mice (SNCA-A30P mice) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). One thousand eight hundred fifty-six peptides from 771 proteins were analyzed. Among them, 151 peptides from 107 proteins were significantly differentially expressed. The glycoprotein VI platelet pathway (GP6) was the pathway's most significant differentially expressed signaling pathway. Cleavage sites of the differentially expressed peptides may reflect protease distribution and activity. We selected the most significantly differentially expressed peptide, VGGDPI, and found that it contained cathepsin K (Ctsk) and trypsin-1 cleavage sites, suggesting that Ctsk and trypsin-1 may be key peptidases in PD. α-syn is a protein associated with the pathogenesis of PD. mutations in several genes, including SNCA, which encodes α-syn, are associated with the development of PD. Bioinformatics analysis of the physiological pathways related to SNCA genes and apoptosis genes found the five most markedly up-regulated proteins: formin homology 2 domain-containing 1 (FHOD1), insulin receptor substrate 1(IRS1), TRPM8 channel-associated factor 1 (TCAF1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and interleukin-16 (IL-16). Therefore, the differentially expressed peptides in the five precursor protein domains may be potential bioactive peptides associated with α-syn and apoptosis. This study provides a validated peptidomics profile of SNCA-A30P mice and identifies potentially bioactive peptides linked to α-syn and apoptosis.

To promote the deep processing of zucchini, heteropolymeric pectin fractions from zucchini was analyzed and their hypoglycemic activity was explored. Combining acid and base treatment, two pectin fractions were isolated, namely zucchini acid-extracted pectin (ZPA) and zucchini alkali-extracted pectin (ZPB). The yield, composition, and structural properties of two fractions were analyzed. Moreover, high-fat diet induced bumblebee diabetic model was established to explore the hypoglycemic activity of zucchini pectin. Results showed that the yield of ZPB was 2.45 times higher than that of ZPA. ZPA had an averaged molecular weight of 70297 Da and polydispersity index of 1.149, while ZPB had an averaged molecular weight of 126170 Da and polydispersity index of 1.677, indicating the more complex components of ZPB. Monosaccharides including arabinose, galactose, galacturonic acid, glucuronic acid, rhamnose, and mannose were found in both ZPA and ZPB, while glucose and ribose were only present in ZPA. It indicated that ZPA and ZPB were heteropolymeric pectins containing RG-I structure. ZPA had less but longer RG-I side chain, whereas ZPB had more and shorter RG-I side chain. Based on bumblebee diabetic model, ZPA and ZPB were found to significantly lower the blood glucose and trehalose level, indicating that zucchini pectin had potential hypoglycemic activity.

Abstract Background Nutrient limitations often lead to metabolic stress during cancer initiation and progression. To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. However, there is a discrepancy between the level of HO-1 mRNA and its protein, particularly in cells under stress. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear. Methods We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. We validated eIF2α O-GlcNAcylation through site-specific mutagenesis and azido sugar N-azidoacetylglucosamine-tetraacylated labeling. We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions. Results Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. However, the level of the metabolic stress effector ATF4 is not affected by eIF2α O-GlcNAcylation under these conditions. Conclusions Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications.

Recent studies have indicated that the invasive apple snail (Pomacea canaliculata) exhibits tolerance to the salinity levels present in coastal agricultural soils, suggesting that apple snails could potentially invade salt-affected coastal agricultural areas. However, the effects of the alien snail Pomacea canaliculata invasion on coastal saline soils, such as in terms of soil properties, microbial diversity, and abundance, remain poorly understood. To fill this gap, we conducted experiments involving three salinity levels (0, 2‰, and 5‰, w/w), coupled with varying snail densities (0, 5, and 10 snails per box), applied to agricultural soil. We analyzed soil chemical properties, enzyme activities, and bacterial communities. The findings revealed that heightened soil salinity increased soil electrical conductivity (EC) (exceeding 1312.67 μS cm−1). Under saline conditions, snail treatments significantly increased the soil organic matter (SOM) content from 15.82 mg kg−1 to 18.69 mg kg−1, and concurrently diminished the dissolved organic carbon (DOC) from 47.45 mg kg−1 to 34.60 mg kg−1. Both snail and salinity treatments resulted in ammonia nitrogen (NH4+-N) accumulation, while nitrate nitrogen (NO3−-N) concentrations remained low in salt-affected soils. A notable positive correlation existed between the EC and the activities of hydroxylamine reductase (HR) and peroxidase (POD), where HR exhibited a positive correlation with NH4+-N, and POD displayed a negative correlation with NO3−-N. Salinity substantially decreased the diversity and altered the composition of soil bacterial community, with the phyla Bacteroidota, Proteobacteria, and Firmicutes adapting to salt-affected soil environment and proliferating. Structural equation modeling (SEM) analysis indicated that snails exerted a direct influence on soil-available nitrogen (including NO3−-N and NH4+-N), while salinity impacted available nitrogen by modulating soil enzyme activities and bacterial communities. Our findings provide insights into how soil responds to the concurrent impacts of snail invasion and soil salinization, establishing some references for future research.

Background: In this study, the regularity of drug containing borneol proprietary Chinese medicine was mined, to provide reference for the clinical application and new drug research and development of borneol. Methods: The database of proprietary Chinese medicines on Pharmaceutical Intelligence Network was searched for internal and external prescriptions that contained borneols and the diseases they treat. Microsoft Office Excel 2019 and SPSS Modeler 18.0 were used to analyze the properties, flavors, meridians tropisms and association rule analysis of the medicines, and Origin 21.0 software was used to draw the association rules diagram. Results: Among them, 528 prescriptions of internal Chinese patent medicine containing borneol and 387 prescriptions of external Chinese patent medicine were included. The diseases treated by internal prescription were mainly neurological diseases and heart diseases, among which Chinese medicines with higher frequency of compatibility with borneol were bezoar, licorice, cinnabar, musk and scutellaria. The diseases treated by external prescription were mainly physical disabilities, paralysis diseases, sore and ulcer diseases and so on. Among them, menthol, camphor, frankincense, angelica, and carthami flos and so on are the most frequently combined with borneol. Conclusion: The prescription of Chinese patent medicine containing borneol is composed of cold or warm, pungent or bitter Chinese medicine. Internal prescription primarily targets the meridians of the heart, liver, and lungs, and is often combined with sedative, antipyretic and detoxicating drugs to treat stroke, infantile convulsion and angina pectoris. External prescription mainly acts on liver, heart and spleen meridian, and is often combined with drugs for clearing heat, promoting blood circulation and removing blood stasis to treat rheumatic arthralgia syndrome and sore and ulcer diseases.

Abstract Recycling of molybdenum isotopes in continental subduction zones remains debated. In this contribution, we re‐visit the Mo isotope compositions of the Sailipu post‐collisional ultrapotassic rocks in the Himalaya‐southern Tibet orogen. These ultrapotassic rocks have very varying δ98/95Mo values of −0.66 to −0.07‰ and Mo/Ce ratios of 0.0008–0.005, which are lower than those of mid‐ocean ridge basalts (MORB; δ98/95Mo = −0.20 ± 0.06‰, and Mo/Ce = 0.03) and oceanic subduction‐related (i.e., mantle source involving fluids, residual slab, or oceanic sediments) magmatic rocks (e.g., modern arc lavas, Cenozoic OIB‐type basalts in eastern China and the central Mariana Trough basalts in the back‐arc basin, syn‐collisional andesitic rocks in southern Tibet). Combined with the light Mo isotopes of the Himalayan schists and gneisses, we suggest that the light Mo isotopic signature of the Sailipu ultrapotassic rocks is derived from subducted Indian continental crust. This is consistent with the extremely low δ11B (−17.4 to −9.7‰) and B/Nb (0.16–1) values and enriched Sr‐Nd‐Pb isotopes of the Sailipu ultrapotassic rocks. Thus, this study reveals the recycling of light Mo‐B isotopes during continental subduction and demonstrates that Mo‐B isotopes can effectively distinguish between continental and oceanic subduction.