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Abstracts Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.

Banana de-handing is an important part of banana post-harvesting operation. The traditional artificial de-handing model has problems such as labor intensity, inaccurate cutting, uneven cutting surface, unstable catching, and damage of banana fruit, etc. The mapping relationship between the characteristic parameters of the movement posture of the cutter and the influencing factors of the contact stress of banana crown cutting in unstructured environments, and the changing rules of the bumping contact stress of complex multi-shaped banana fruit with the physical property parameters of the cushioning material are the theoretical and technical difficulties that urgently need to be solved in the realization of banana mechanical de-handing. The future research (research on the coupling mechanism of visual cognition-mechanism cutting and low-destructive catching method of full-field continuous de-handing of bananas under multi-constraint scenarios) should: (1) create a database of banana crown, obtain the optimal banana crown recognition model, develop a recognition and locating system of the cutting line of banana crown and obtain its spatial location information; (2) establish the discrete element mechanical model of banana crown and the interaction model between banana crown and the cutter, clarify the stress change and the force wave transmission characteristics of the cutting process, construct the multi-objective optimization equation of the cutting performance, obtain the best combination of cutting parameters, and ascertain the mechanisms of synergistic locating and continuous cutting of banana crown; (3) establish the contact mechanical model of banana fruit drop-bump, parse the bumping characteristics between banana fruit and cushioning material, construct mathematical equations to quantitatively assess damage results, and determine the detract catching method of banana fruit that matches the de-handing mode in multi-constraint scenarios. This study showed that the real-time identification and spatial positioning of fruit, the mechanical properties of crown and the optimization of cutting performance, the damage mechanism of fruit and its loss-reducing harvesting method are the three key breakthroughs in realizing the robotization of de-handing. The current bottleneck problems and future research directions of intelligent banana de-handing were pointed out in this paper, which can provide a theoretical basis for the optimal design of banana de-handing devices and provide technical support for promoting the practical application of intelligent de-handing equipment.

Abstract This study aimed to investigate the expression levels and clinical implications of interferon α inducible protein 27 (IFI27) and the N6-methyladenosine (m6A) regulator Alkylation repair homolog 5 (ALKBH5) in head and neck squamous cell carcinoma (HNSCC). We employed bioinformatics methods to analyze the differential expression of IFI27 in HNSCC and its prognostic implications. Additionally, we explored the pathways and mechanisms associated with its enrichment. Immunohistochemistry (IHC) was used to detect the expression of IFI27 protein in HNSCC and adjacent normal tissues. IFI27 expression was significantly up-regulated in HNSCC (P

Multilabel remote sensing image classification (MLRSIC) can provide comprehensive object-level semantic descriptions of remote sensing images. However, most existing methods struggle to effectively integrate visual features of images and high-level semantic information of labels, which limits their ability to obtain fine-grained image features with rich semantic information for classification. To address these issues, we propose a novel cross-modal compositional learning (CMCL) model for MLRSIC, which fully utilizes label information to improve classification performance. CMCL introduces rich label semantic information into the image feature extraction process, which enhances the visual features of each class with the label semantic. Meanwhile, CMCL constructs a feature space shared by image features and label correlation features for classification. The multilabel image classification task is modeled as the feature distance measurement task, and the visual features of images and the semantic information of labels are mutually promoted by the method. Experimental results on UCM, AID, and DFC15 multilabel datasets show that the proposed CMCL outperforms existing state-of-the-art methods.

At present, the application scenarios based on BIM+GIS technology are widely used in various infrastructure industries. However, in the process of 2D to 3D transformation, the application scenarios of multi-source heterogeneous data fusion in the reconstruction and expansion projects of long lines and highways have not yet been studied. This paper focuses on the reconstruction and expansion project of long-line expressway, classifies the data according to the characteristics of the project, establishes the model coding suitable for the whole life cycle, and proposes a model coding processing method based on json mapping form, which improves the maintenance of the model and coding. This paper proposes a set of data lightening methods for the whole process, aiming at data lightening for terrain and structural models with large volumes, and realizing the load lightening capability after large volumes of data enter the platform. At the same time, in order to ensure the consistency of model information data content and spatial location accuracy, a set of BIM and GIS data coupling verification method and a positioning method of coordinate system transformation between new and old structures are established. Finally, the application value of multi-source heterogeneous data fusion is verified through the reconstruction and expansion project data of a long expressway. The results show that the whole life cycle encoding mode using json mapping form improves the usability of the model and encoding. The lightweight processing of large data improves the loading capability of data.

Abstract S-nitrosylation (SNO) modification, a nitric oxide (NO)-mediated post-translational modification (PTM) of proteins, plays an important role in protein microstructure, degradation, activity, and stability. Due to the presence of reducing agents, the SNO modification process mediated by NO derivatives is often reversible and unstable. This reversible transformation between SNO modification and denitrification often influences the structure, activity, and function of proteins. The reversibility of SNO modifications also poses a challenge when verifying changes in the biological functions of proteins. Moreover, SNO modification of key signaling pathway proteins, such as caspase-3, NF-κB, and Bcl-2, can affect tumor proliferation, invasion, and apoptosis. The SNO-modified proteins play important roles in both promoting and inhibiting cancer, which indirectly confirms the duality and complexity of SNO modification functions. This article reviews the biological significance of various SNO-modified proteins in different cancers, providing a theoretical basis for determining whether the related changes of SNO-modified proteins are universal in cancers. Additionally, this review presents a comprehensive and detailed summary of the evolution of detection methods for SNO-modified proteins, providing a possible methodological basis for future research on SNO-modified proteins.

Abstract Adaptability to return to work is a process by which cancer survivors(CSs) utilize accessible resources to reconstruct themselves. While the stigma, financial situation and social support are known to influence their adaptability to return to work, the mechanisms by which these factors work remain unclear. This study proposes a moderated mediation model to signify a pathway linking stigma to the adaptability to return to work. Data were analyzed using the PROCESS macro for R version 4.3.1. A total of 238 CSs, aged between 18 and 60 years (73.5% female), of whom 42.1% had returned to work, completed the ARTWS, SIS, COST-PROM, SSRS, HeLMS. Stigma had a negative associations on the adaptability to return to work. Both financial toxicity and social support mediated the relationship between stigma and the adaptability to return to work. Health literacy moderated both the direct pathway and the second half of the pathway mediated by financial toxicity. Specifically, the negative effects of stigma and financial toxicity on the adaptability to return to work were significantly attenuated when health literacy levels were high. CSs with higher health literacy may not experience excessive stigma, and experience less financial toxicity than those with lower health literacy. CSs possessing greater social support will be more effective in utilizing external resources to buffer the influence of financial toxicity, and thus adapt better to work.

Abstract This study proved that the curves of carbon monoxide (CO), carbon dioxide (CO2), and CO + CO2 in the off-gas profile were forecastable, and realized a 32-s-ahead forecasting for them. It established a technical foundation for addressing the delay in off-gas profile display and for enabling pre-control in BOF steelmaking based on the forecasted curves’ features. First, a data pre-processing method was proposed based on the characteristics of the off-gas curves, where there are many samples, but each sample contains limited time-steps. It is termed the mixed-batch approach. The importance of the time series’ channels and time-steps were also analyzed by models with attention mechanism. Then, a deep-learning model is proposed to forecast the dynamic off-gas profile, named attention-based convolutional aggregation (ABCA). It incorporates artificial intelligence (AI) techniques, such as aggregation structures, causal dilation convolution, attention mechanisms, residual connections, etc. Its forecasting coefficient of determination (R 2 ) values for the curves of CO, CO2, and CO + CO2 reached 0.9386, 0.8566, and 0.9428, respectively, while the mean squared errors (MSEs) values were 47.3884, 11.9314, and 54.3583, respectively. These results outperform the benchmark state-of-the-art (SOTA) models. Additionally, ABCA was implemented in a forecasting tool for external validation. The results of external validation showed that ABCA has good forecasting accuracy and robustness. What is more, approaches in four aspects of pre-control of BOF steelmaking process with forecasted off-gas profile were also provided as pre-control examples.

Small wetlands are essential for preserving global biodiversity, yet they are frequently neglected in conservation strategies due to vague definitions and a lack of research attention. In this study, we conducted thirty-six surveys via the point count method in the Xiaohongxiang Wetland, Anning City, Yunnan Province, China, from November 2023 to June 2024. We aimed to evaluate the impact of various habitats surrounding Xiaohongxiang Wetland (wetlands, villages, farmlands, cherry plantations and pine forests) on the taxonomic, functional and phylogenetic diversity of avian species and investigate the significance of these habitats for ecological conservation and restoration efforts. A total of 62 species were recorded. Small wetlands are vital for supporting common waterbirds, but may not safeguard rare species effectively. While cherry plantations and pine forests enhance avian diversity near wetlands, their low functional diversity could limit the ecological niches available to birds. This indicates that monoculture plantations might restrict the habitat variety needed for a diverse bird community. Our study found no clear phylogenetic clustering or overdispersion amongst bird species across habitats, suggesting that community assembly is shaped by competitive exclusion, habitat filtering and neutral processes. Despite a limited sample size, our results highlight a gap between taxonomic and functional diversity, indicating that multidimensional biodiversity metrics are essential for thoroughly evaluating wetland restoration and habitat impacts on bird diversity.

Abstract In random uncertain motor parameter identification field, there is low identification efficiency and ill-conditioned data coming from the second iteration involved in the uncertainty propagation and surrogate model between the motor parameters and the performance response. In this paper, the fourth-order moment method and trust region model management technology are combined to reduce the dependence of the surrogate model accuracy and improve the computational efficiency. In the framework, the inner layer calculates the cumulative probability under different motor performance response thresholds based on the fourth-order moment method, and obtain the probability density function of the calculated motor performance response. The outer layer transforms the random uncertain motor parameters identification into a deterministic optimization problem by minimizing the probability distribution between the calculated and the measured motor performance response. In the outer layer optimization, the trust region model management technology is used to divide the search interval of the entire parameter to be identified into a series of trust regions, construct a surrogate model on the trust region to calculate the motor performance response, and continuously update the trust region by comparing the response residuals between the calculated and measured motor performance response, so that the motor parameters to be identified continue to approach the interval where true values are located. At the same time, the genetic intelligent technology is introduced to further reduce the calculation cost. Finally, the probability distribution of random uncertain motor parameters is obtained according to the identified mean, standard deviation, skewness and kurtosis coefficients. The numerical results in the example verify that the random uncertain motor parameter identification can be effectively achieved by the proposed method.

Skin aging is an increasingly prominent topic in the context of healthy aging. During the aging process, the skin’s barrier function diminishes, its water content decreases, wrinkles begin to form, and changes occur in the gut microbiota composition. However, the relationship between gut microbiota and skin aging remains unclear. In this study, we explored skin rejuvenation in aged mice through fecal microbiota transplantation (FMT) using feces from young mice. The results demonstrated enhanced water retention, thickened stratum corneum, increased collagen content, and improved epithelial cell differentiation in aged mice following FMT. Notably, FMT particularly increased the abundance of Lactobacillus and Lactococcus in aged mice, which were nearly undetectable in untreated aged mice. Non-targeted and targeted metabolomics analyses indicated that FMT significantly elevated levels of tryptophan (Trp) and its microbiota metabolites (e.g., indole-3-lactic acid (ILA)) in the feces and serum of aged mice. Both Trp and ILA appeared to rejuvenate aged skin by activating the aryl hydrocarbon receptor (AhR) to promote epidermal cell differentiation. In conclusion, FMT from young mice rejuvenated aged skin via Trp-metabolizing bacteria (Lactobacillus and Lactococcus) and Trp-derived metabolites, suggesting that interventions targeting Trp metabolites may effectively improve skin aging.

Abstract Background Diabetes, occasionally diagnosed in orthodontic patients, can impede orthodontic tooth movement (OTM) by accumulating advanced glycation end products (AGEs) in the periodontium. This accumulation impairs the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) due to alterations in the force-loaded microenvironment, yet the underlying mechanisms remain elusive. Methods Bioinformatics analysis of GSE112122 identified alterations in the mechanical regulation of histone methylation enzyme Lysine Demethylase 6B (KDM6B). OTM models were established in healthy and Nicotinamide/ Streptozotocin-induced type II diabetic rats. The impact of AGEs on mechanically induced osteogenesis and its correlation with KDM6B were evaluated by assessing the therapeutic effects of periodontal ligament injections of the AGEs/RAGE inhibitor FPS-ZM1. To investigate transcriptomic changes, we extracted human PDLSCs, which were subjected to RNA sequencing following the overexpression of KDM6B. Experimental validation further identified potential self-reinforcing loops and their associated antioxidative mechanisms. Results Mechanical forces upregulated KDM6B expression and function in PDLSCs, modulating extensive downstream osteogenesis-related transcriptional changes. Experiments with AGEs-treated and FPS-ZM1-treated samples demonstrated that AGEs impaired osteogenesis by compromising KDM6B mechanical responsiveness. A positive feedback loop between KDM6B and Wnt pathways was identified, inhibited by AGEs. This loop regulated superoxide dismutase 2 (SOD2), facilitating antioxidative stress and preventing stem cell ageing. Conclusions This study elucidates a novel mechanism by which AGEs influence the osteogenic process and antioxidative capacity of PDLSCs through the KDM6B/Wnt self-reinforcing loop under orthodontic force. Targeting the AGE/RAGE pathway or enhancing KDM6B may enhance orthodontic treatments for diabetic patients.

Abstract Acute kidney injury (AKI) is a common clinical problem, and patients who survive AKI have a high risk of chronic kidney disease (CKD). The acute protective effects of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in AKI have been examined, there is still relatively little known regarding the impact of acute CDK4/6 inhibition on the chronic sequence of AKI. Therefore, we utilized the CDK4/6 inhibitor Palbociclib to examine the long-term effects of CDK4/6 inhibition in a rodent model of ischemic AKI. Palbociclib (Palb) was administered during the acute stage or post the acute stage of AKI and mice were sacrificed 21 days post injury. We found that Palb could cause renal senescence and renal fibrosis. Furthermore, dasatinib (D) plus quercetin (Q) were used to eliminate senescent cells in ischemic AKI murine model and Palb was administered post the treatment of D + Q. We found that Palb could reverse the senolytic and antifibrotic effects induced by D + Q, which indicates that the profibrotic effect of Palb could be ascribed to its pro-senescent effects. Our results demonstrate that CDK4/6 inhibitors treatment might be deleterious on the chronic sequence of AKI.

Two new varieties from Xizang, China, i.e. Agapetes interdicta var. flaviflora and A. forrestii var. parvifolia, are described and illustrated. Agapetes interdicta var. flaviflora differs from the nominate variety in having yellow and smaller corollas with shorter lobes and anthers with shorter appendages at the base. Agapetes forrestii var. parvifolia is distinguished from the nominate variety in the smaller leaves with an acute apex, nearly transverse secondary veins and puberulent peduncle. Taxonomic notes on these taxa are also provided.

Background Population aging has heightened, raising concerns about elderly health. Oral frailty, a novel frailty phenotype in the elderly, directly impacts the quality of life. A thorough grasp of oral frailty's prevalence in the elderly is crucial for formulating effective preventive and interventional strategies. Objective To systematically evaluate the prevalence of oral frailty in the elderly. Methods The CNKI, Wanfang Data, VIP, CBM, PubMed, Web of Science, Embase, CINAHL and Cochrane Library databases were searched for literature related to the study purpose with a time limit of the construction of the database to 19 April 2024. Literature was independently screened, information extracted and quality assessed by 2 researchers, and meta-analysis was performed using Stata 14.0 software. Results A total of 19 cross-sectional studies were included, with a total sample size of 11 776 cases and a risk of bias quality score of 6-9, all of which were of moderate or high quality. Meta-analysis showed that the prevalence of oral frailty in elderly people was 29.5% (95%CI=24.1%-35.2%), and the prevalence of pre-oral frailty was 47.9% (95%CI=40.5%-55.4%). Subgroup analyses showed that the progressive increase in the prevalence of oral frailty in the elderly with advancing age. Higher prevalence rates of oral frailty were observed in individuals screened using the Oral Frailty Index-8 (P

Abstract Background The distribution of fat and muscle mass in different regions of the body can reflect different pathways to mortality in individuals with diabetes. Therefore, we investigated the associations between whole‐body and regional body fat and muscle mass with cardiovascular disease (CVD) and non‐CVD mortality in type 2 diabetes (T2D). Methods Within the National Health and Nutrition Examination Survey 1999–2006, 1417 adults aged ≥50 years with T2D were selected. Dual‐energy X‐ray absorptiometry was used to derive whole‐body, trunk, arm, and leg fat mass and muscle mass indices (FMI and MMI). Mortality data until 31 December 2019 were retrieved from the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. Results A total of 1417 participants were included in this study (weighted mean age [standard error]: 63.7 [0.3] years; 50.5% female). Over a median follow‐up of 13.6 years, 797 deaths were recorded (371 CVD‐related and 426 non‐CVD deaths). Higher FMI in the arm was associated with increased risk of non‐CVD mortality (fourth quartile [Q4] vs. first quartile [Q1]: HR 1.82 [95% CI 1.13–2.94]), whereas higher FMI in the trunk or leg was not significantly associated with CVD or non‐CVD mortality. Conversely, higher arm MMI was associated with a lower risk of both CVD (Q4 vs. Q1: HR 0.51 [95% CI 0.33–0.81]) and non‐CVD (Q4 vs. Q1: HR 0.56 [95% CI 0.33–0.94]) mortality. There was a significant interaction between smoking status and arm FMI on non‐CVD mortality (P for interaction = 0.007). Higher arm FMI was associated with a higher risk of non‐CVD mortality among current or former smokers (Q4 vs. Q1: HR 2.67 [95% CI 1.46–4.88]) but not non‐smokers (Q4 vs. Q1: HR 0.85 [95% CI 0.49–1.47]). Conclusions Fat mass and muscle mass, especially in the arm, are differently associated with CVD and non‐CVD mortality in people with T2D. Our findings underscore the predictive value of body compositions in the arm in forecasting mortality among older adults with T2D.

Abstract Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, the procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks of radiation-induced enteropathy upon reaching threshold doses. Stem cells within the intestinal crypts, through their controlled proliferation and differentiation, support the critical functions of the intestinal epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem cells (ISCs) regulation is intricately orchestrated by diverse signaling pathways, among which are the WNT, BMP, NOTCH, EGF, Hippo, Hedgehog and NF-κB, each contributing to the complex control of these cells' behavior. Complementing these pathways are additional regulators such as nutrient metabolic states, and the intestinal microbiota, all of which contribute to the fine-tuning of ISCs behavior in the intestinal crypts. It is the harmonious interplay among these signaling cascades and modulating elements that preserves the homeostasis of intestinal epithelial cells (IECs), thereby ensuring the gut's overall health and function. This review delves into the molecular underpinnings of how stem cells respond in the context of radiation enteropathy, aiming to illuminate potential biological targets for therapeutic intervention. Furthermore, we have compiled a summary of several current treatment methodologies. By unraveling these mechanisms and treatment methods, we aspire to furnish a roadmap for the development of novel therapeutics, advancing our capabilities in mitigating radiation-induced intestinal damage.

Abstract Background Arthritis notably elevates mortality risk. It remains unclear whether the cardiovascular health (CVH) metrics improves the risk of all-cause mortality in patients with all types of arthritis. Methods This study data from the National Health and Nutrition Examination Survey to probe the link between CVH and all-cause mortality among arthritis sufferers in the United States. CVH evaluation employed the Life's Essential 8 metrics. Mortality outcomes were scrutinized using Cox proportional hazard regression models. Additionally, a restricted cubic spline analysis delineated the linear relationship between CVH and mortality. The study also delved into the singular impact of each CVH component on mortality. Results In the cohort of 5919 patients with arthritis, improved CVH was linked to lower all-cause mortality. Specifically, each 10-point increment in CVH score was associated with a substantial decline in all-cause mortality risk [unadjusted hazard ratio (HR): 0.77, 95% Confidence Interval (95% CI): 0.71–0.83, P

The growing demand for automation in the apple-harvesting industry remains challenging due to the complex and dynamic nature of orchard environments. This study presents an enhanced deep learning model designed to improve the accuracy and adaptability of recognition algorithms for robotic arm-based harvesting. Specifically, an optimized You Only Look Once (YOLO) v8n model was developed by integrating a dilation-wise residual–dilated re-parameterization block module, a generalized feature pyramid network, and the Scylla Intersection-over-Union loss function. The enhanced model was trained and evaluated on a comprehensive dataset, achieving precision, recall, F1 score, and mAP50 values of 81.43 %, 68.48 %, 74.40 %, and 81.68 %, respectively. These results indicate improvements of 1.06 %, 1.42 %, 1.28 %, and 1.61 % over the original YOLOv8n, while preserving comparable model parameters, computational efficiency, and detection speed. Furthermore, the enhanced model demonstrated superior overall performance compared to YOLOv5, YOLOv6, and RT-DETR. To validate its adaptability and robustness, the enhanced model was rigorously tested against the original YOLOv8n model diverse conditions, including varying growth stage, lighting environments, field of view, and levels of occlusion. In outdoor field experiments conducted under cloudy, low-light, and artificial lighting conditions, the model achieved localization errors of 2.43 mm (X-axis), 3.70 mm (Y-axis), and 1.28 mm (Z-axis), representing reductions of 19.27 %, 12.67 %, and 23.05 %, respectively. Furthermore, counting accuracy improved to 69.39 %, reflecting a 2.42 % increase over the original model. The results demonstrate the enhanced model's reliable performance and heightened precision for robotic arm-based apple harvesting in complex and challenging orchard environments. The study also provides a comprehensive analysis of the model's strengths, limitations, and avenues for future research. Ultimately, this work contributes to advancing agricultural automation, paving the way for smarter, more efficient, and sustainable farming practices.

ObjectivesTransforming growth factor β1 (TGFβ1)-interleukin 11 (IL11) is a newly found critical signaling pathway in fibrotic diseases such as Graves’ orbitopathy (GO). It has now been confirmed that enhanced glycolysis plays a key role in the pathogenesis of GO. However, little is known about the relationship between glycolysis and IL11-mediated fibrosis in GO. This study aimed to identify the relationship between glycolysis and TGFβ1-IL11 signaling pathway and investigate the role of IL11 in glycolysis-facilitated fibrosis in GO.MethodsOrbital connective tissues were collected from GO and control patients. Primary orbital fibroblasts (OFs) were cultured from clinical tissues. Patient-derived xenografts were established via intraorbital transplantation of GO orbital tissue in humanized NCG mice. Protein levels were measured using Capillary Western Immunoassay (WES). Small interfering RNA (siRNA) was used to construct transfected OF strains. Lactate production was measured to assess glycolysis status. Animal models were assessed by T2-weighted magnetic resonance (MR) scan. Immunohistochemistry staining was applied to patients’ orbital connective tissues.ResultsOrbital connective tissues were collected from GO patients. Immunohistochemical (IHC) staining of GO tissues revealed the phenomenon of pyruvate dehydrogenase kinase 2 (PDK2)-enhanced glycolysis and upregulated IL11-IL11Rα pathway. In vitro experiments showed successful induction of fibrosis of patient-derived orbital fat/connective tissues, which could be alleviated by dichloroacetic acid (DCA). MRI images and analysis of hematoxylin and eosin (HE) and Masson-stained section demonstrated enhanced glycolysis in GO, facilitating fibrosis of the orbital tissue. Targeting PDK2 decreased IL11 expression to suppress fibrosis. In vivo experiment confirmed anti-fibrotic effect of inhibition of glycolysis.ConclusionsPDK2-enhanced glycolysis exacerbates fibrosis via IL11-IL11Rα signaling pathway, shedding light on a potential therapeutic role of metabolic modulators such as DCA in GO treatment.

BackgroundBone marrow mesenchymal stem cells (BMSCs) hold promise for repairing myocardial injury following acute myocardial infarction (AMI), but their clinical application is hindered by poor migration, homing efficiency, and survival rates. Previously, we demonstrated that ELABELA (ELA), a small peptide, enhances the survival of rat BMSCs under hypoxia-reoxygenation (H/R) conditions by activating ERK1/2. However, the role of ELA in promoting BMSCs migration and homing to injured cardiomyocytes remains unclear.MethodsPrimary BMSCs and neonatal rat ventricular myocytes (NRVMs) were isolated and cultured. NRVMs were exposed to H/R to mimic the microenvironment of AMI in vitro. The migration of BMSCs toward the injured myocardium was assessed in different treatment groups using transwell and chemotaxis assays. Additionally, in vivo studies were performed using a rat myocardial infarction/reperfusion injury (MI/RI) model with DIR-labeled BMSCs. Cardiac repair was evaluated through fluorescence imaging, echocardiography, and histological analysis. Transcriptome sequencing and bioinformatics analysis were employed to identify and validate the mechanisms by which ELA promoted the migration of BMSCs. A dual luciferase assay was used to investigate the interaction between Exo70 and miR-299a-5p. Subsequently, a series of experimental procedures were performed, including sequential silencing of APJ or Exo70, overexpression of miR-299a-5p, inhibition of ERK1/2 phosphorylation, assessment of BMSCs migration through transwell and scratch assays, detection of F-actin polymerization via immunofluorescence, and evaluation of the expression levels of each factor using qPCR and Western blotting.ResultsIn vitro, the migration ability of ELA-pretreated BMSCs was significantly augmented in the H/R environment. ELA pretreatment effectively heightened the homing capacity of BMSCs to the site of myocardial injury and their proficiency in repairing myocardial damage in vivo. Transcriptome sequencing revealed upregulation of Exo70 in ELA pretreated BMSCs, which promoted F-actin polymerization and migration. Overexpression of miR-299a-5p reduced Exo70 expression and impaired BMSCs migration. ELA also activated ERK1/2 phosphorylation, while inhibition of ERK1/2·with U0126 abrogated F-actin polymerization and migration, increasing miR-299a-5p levels and reducing Exo70.ConclusionELA enhances BMSCs migration and homing to injured cardiomyocytes by activating the APJ receptor, promoting ERK1/2 phosphorylation, downregulating miR-299a-5p, and upregulating Exo70, providing a potential therapeutic strategy for improving stem cell-based cardiac repair.

Abstract Circularly polarized luminescence (CPL) materials with delayed fluorescence have attracted much attention due to their ability to efficiently trap triplet state excitons, thereby improving the photoluminescence quantum yields of CPL materials. However, much effort has been normally focused on the utilization of T1 excitons but seldom on the utilization of higher excited triplet state Tn (n > 1) excitons. Rational manipulation of higher excited triplet state Tn (n > 1) excitons and suppression of Kasha's rule of CPL materials remains a major challenge. Herein, two gold complex enantiomers ((R/S)‐BPAuBC) based on axially chiral binaphthyls and 3,6‐Di‐tert‐butylcarbazole groups are synthesized and systematically investigated. These materials exhibit aggregation‐induced circularly polarized delayed fluorescence. Circularly polarized delayed fluorescence was found to be enabled by activating high‐level reverse intersystem crossing (hRISC). The anti‐Kasha phosphorescence at 77 K proves that the exciton has a large population in the high‐lying triplet state T2, which allows the effective hRISC process to cross back to the singlet state S1 and emit delayed fluorescence. In addition, CPL “on–off” switching is further achieved in nanoparticles by acid–base stimulus, showing its potential as an acid–base responsive material.

Objective: The aim of this paper is to discover differentially expressed genes related to ferroptosis (DEFRGs) in patients with ST-segment elevation myocardial infarction (STEMI) and to construct a reliable prognostic signature that incorporates key DEFRGs and easily accessible clinical factors. Methods: We did a systematic review of Gene Expression Omnibus datasets and picked datasets SE49925, GSE60993, and GSE61144 for analysis. We applied GEO2R to find DEFRGs and overlapped them among the picked datasets. We performed functional enrichment analysis to explore their biological functions. We built an optimal model with least absolute shrinkage and selection operator (LASSO) penalized Cox proportional hazards regression. We tested the clinical value of the signature with survival analysis, ROC curve, decision curve analysis and a prognostic nomogram. We also confirmed the model externally with plasma samples from our center's patients. Results: A prognostic signature combining three overexpressed DEFRGs (ACSL1, ACSL4, TSC22D3) and two clinical variables (serum creatinine level, Gensini score) was established. The signature effectively classified patients into low- and high-risk groups. Survival analysis, ROC curve analysis, and DCA showed its robust predictive performance and clinical utility of the signature within two years after the onset of the disease. The external validation cohort confirmed the significant difference in major adverse cardiovascular events (MACEs) between the low- and high-risk groups. Conclusion: This study revealed DEFRGs in patients with STEMI and developed a prognostic signature that integrates gene expression levels and clinical factors for stratifying patients and predicting the risk of MACEs.

IntroductionSynbiotics have revealed the possibility of improving constipation through gut microbiota. The synergistic efficacy of Bifidobacterium animalis subsp. lactis BL-99 (BL-99) and fructooligosaccharide (FOS) on constipation have not been investigated.MethodsLoperamide-induced constipated mice model was established to explore the effect of BL-99, FOS, and BL-99+FOS on changes of defecation-related parameters, gut microbiota and metabolites.Results and discussionThe results showed that BL-99, FOS, and BL-99+FOS each alleviated constipation, with the synbiotic showing significant efficacy in the first black stool defecation time, fecal number, fecal weight, and the gastrointestinal transit rate (P < 0.05). Additionally, significant increased in serum 5-HT and IL-10 were observed in the BL-99+FOS group, alongside an increased relative abundance of Lachnospiraceae_NK4A136_group, Blautia, and Clostridium sensu stricto 1, while significantly reducing the relative abundance of Alistipes and Bacteroides. These changes facilitated alterations in short-chain fatty acids (SCFAs) metabolism, and were closely associated with the expression of genes related to the 5-HT pathway and the modulation of serum inflammatory factors. This study provides a theoretical basis for BL-99 and FOS synbiotics to improve constipation by regulating the gut microbiota and metabolites.

Nowadays, high-strength press-hardened steels (PHS) have gained wide applications in automotive body-in-white owing to excellent mechanical properties. Nevertheless, the fatigue properties of high-strength PHS and associated failure mechanisms have not been clearly revealed, which restricts their potential applications in other parts of automobiles involving fluctuating and repetitive stresses, such as wheels or beams. In this work, the fatigue behavior of 1900 and 2000 MPa grade PHS is systematically studied, with the main focus on the associated deformation and fatigue cracking mechanisms. The fatigue behavior of these two steels is similar, and the ratio of fatigue strength to tensile strength is around 0.5. The fatigue damage mechanism of high-strength PHS is dominated by surface cracking, as the fine martensite structures reduce the stress concentration and cracking at small-sized inclusions. This work can provide guidance for the application of high-strength PHS in alternating loads scenarios.

Abstract Background Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China. Methods A total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018–2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis. Results A shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January–April and October–December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P

Objective To explore the application value of 80 kV deep learning image reconstruction （DLIR） algorithm in coronary CT angiography （CCTA）. Methods Sixty patients who underwent CCTA were divided into two groups based on the scanning protocols： 100 kV group （Group A， n = 30） and 80 kV group （Group B， n = 30）. In Group A， 60% ASIR-V （A-AV60） and DLIR high-level reconstruction （A-DLIR） was adopted. In Group B， DLIR high-level reconstruction （B-DLIR） was employed. The CT volumetric dose index （CTDIvol） and the dose length product （DLP） were recorded in both groups， and the effective dose （ED） was calculated. Regions of interest （ROI） were placed in the aortic root （AR）， left anterior descending coronary artery （LAD）， left circumflex coronary artery （LCX）， right coronary artery （RCA）， and the same-layer pectoral fat area. The CT values and noise values of each ROI were recorded. Signal-to-noise ratio （SNR） and contrast-to-noise ratio （CNR） were calculated. Subjective evaluation was performed on the original axis， curved planar reconstruction （CPR）， volume rendering （VR）， and maximum intensity projection （MIP） reconstructions after the second-generation freeze technology （Snapshot Freeze 2， SSF-2）， and the images in two groups were subject to subjective image quality evaluation. Results The ED in Group B was reduced by 45.14% compared to that in Group A. The CT values for AR， LAD， LCX， and RCA in the B-DLIR were higher than those in the A-AV60 and A-DLIR groups， and the differences were statistically significant （all P < 0.001）. The noise values for AR， LAD and LCX were similar， whereas statistical significance was observed in RCA between the A-DLIR and B-DLIR groups （P < 0.05）. The noise values in the A-DLIR and B-DLIR groups were smaller than that in the A-AV60 group， and the differences were statistically significant （both P < 0.001）. The SNR and CNR for AR， LAD， LCX and RCA were similar between the A-DLIR and B-DLIR groups， which were higher than those in the A-AV60 group （all P < 0.05）. The average subjective evaluation score of image quality in the B-DLIR group was higher than that in the A-AV60 group （P < 0.05）， whereas lower than that in the A-DLIR group （P < 0.05）. There were no significant differences in clarity， artifact and small branch visibility between the A-DLIR and B-DLIR groups （all P > 0.05）. Conclusions During CCTA， the 80 kV DLIR algorithm contributes to yielding high-quality images， further improves the diagnostic efficiency and reduces the irradiation dose.

Abstract Background The intrusion of maxillary anterior teeth is often required and there are various intrusion modes with mini-implants in clear aligner treatment. The objective of this study was to evaluate the effectiveness of maxillary anterior teeth intrusion with different intrusion modes, aiming to provide references for precise and safe intrusion movements in clinical practice. Methods Cone-beam computed tomography and intraoral optical scanning data of a patient were collected. Finite element models of the maxilla, maxillary dentition, periodontal ligaments (PDLs), clear aligner (CA), attachments, and mini-implants were established. Different intrusion modes of the maxillary anterior teeth were simulated by changing the mini-implant site (between central incisors, between central and lateral incisor, between lateral incisor and canine), loading site (between central incisors, on central incisor, between central and lateral incisor, between lateral incisor and canine), and loading mode (labial loading and labiolingual loading). Ten conditions were generated and intrusive forces of 100 g were applied totally. Then displacement tendency of the maxillary anterior teeth and CA, and stress of the PDLs were analyzed. Results For the central incisor under condition L14 and for the canine under conditions L11, L13, L23, and L33, the intrusion amount was negative. Under other conditions, the intrusion amount was positive. The labiolingual angulation of maxillary anterior teeth exhibited positive changes under all conditions, with greater changes under linguoincisal loading. The mesiodistal angulation of canine exhibited positive changes under labial loading, while negative changes under linguoincisal loading except for condition L14. Conclusions The intrusion amount, labiolingual and mesiodistal angulations of the maxillary anterior teeth were affected by the mini-implant site, loading site, and loading mode. Labial and linguoincisal loading may have opposite effects on the intrusion amount of maxillary anterior teeth and the mesiodistal angulation of canine. The labiolingual angulation of the maxillary incisors would increase under all intrusion modes, with greater increases under linguoincisal loading.

Abstract Background Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs. Methods Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts. Results At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p

Abstract DNA N6-adenine methylation (6mA) has recently gained importance as an epigenetic modification in eukaryotes. Its function in lineages with high levels, such as early-diverging fungi (EDF), is of particular interest. Here, we investigated the biological significance and evolutionary implications of 6mA in EDF, which exhibit divergent evolutionary patterns in 6mA usage. The analysis of two Mucorales species displaying extreme 6mA usage reveals that species with high 6mA levels show symmetric methylation enriched in highly expressed genes. In contrast, species with low 6mA levels show mostly asymmetric 6mA. Interestingly, transcriptomic regulation throughout development and in response to environmental cues is associated with changes in the 6mA landscape. Furthermore, we identify an EDF-specific methyltransferase, likely originated from endosymbiotic bacteria, as responsible for asymmetric methylation, while an MTA-70 methylation complex performs symmetric methylation. The distinct phenotypes observed in the corresponding mutants reinforced the critical role of both types of 6mA in EDF.

Abstract Assessing the impact of past and future urban land expansion on ecosystem services (ESs) is essential for the sustainable management of urban landscapes. Despite recent progress, it remains challenging to determine the influence mechanism of different urbanization stages and areas on ESs and their trade-offs/synergies. Here, we analyzed the responses of four ESs and their trade-offs/synergies to the spatial and temporal differentiation of urbanization in the Su-Xi-Chang region of China from 1990 to 2050. The results showed that the relationship between ESs and urbanization followed a U-shaped curve from 1990 to 2050. Between 1990 and 2020, urbanization weakened trade-offs and enhanced lose-lose situations, exhibiting an S-shaped curve. From 2020 to 2050, lose-lose situations are expected to diminish, and the curve is projected to display a downward trend. Our findings suggest the implementation of compact urban development, sustainable agricultural practices, reforestation, and the conversion of farmland to lakes.

Objectives: The American Heart Association defined cardiovascular–kidney–metabolic (CKM) syndrome as a novel multi-stage disorder. We examined the associations of CKM stages with premature mortality and the role of social determinants of health (SDOHs). Design: A prospective cohort study. Setting and participants: A nationally representative sample of US adults from NHANES 1999–2018. Measurements: CKM included 5 stages (stages 0–4), reflecting progressive pathophysiology. Premature mortality (deaths before 75 years) were ascertained via linkage to the National Death Index with follow-up until 2019. Cox proportional-hazards models adjusted for age, sex, race/ethnicity, medical history, and other confounding factors were used to calculate the hazard ratios (HR) and 95% CIs for CKM-mortality associations. Results: Among 27,909 participants (mean age 49.7 years, 49.0% females), 1762 premature deaths occurred over a median follow-up of 8.3 years. Compared with stage 0, the adjusted HRs for all-cause premature mortality at CKM stages 1–4 were 0.88 (95% CI 0.66–1.17), 1.31 (0.99–1.73), 1.94 (1.31–2.87), and 2.19 (1.61–2.98), respectively. For CVD premature mortality, the adjusted HRs for CKM stages 1–4 were 1.12 (0.46–2.72), 1.74 (0.71–4.28), 3.93 (1.53–10.12), and 6.48 (2.95–14.20), respectively. Among adults at CKM stages 3–4, unfavorable SDOHs, particularly not living with a partner, low family income, lack of private health insurance, unemployment, or ≥2 cumulative SDOHs (4.16, 95% CI 3.35–5.18) were associated with increased all-cause premature mortality. Among those at CKM stages 0–2, unfavorable SDOHs were also related to increased premature mortality. Conclusion: CKM stages 3–4, but not stages 1–2, were associated with increased risks of premature mortality compared with stage 0. The risks were increased by unfavorable SDOHs across CKM stages.