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Abstract Purpose This study explored the effectiveness of a Problem-based Learning (PBL) teaching model on the WeChat public platform for radiation oncology residency training programs. Materials and methods The WeChat PBL program was initiated in 2019. The study recruited student participants, on a voluntary basis, who were in their first and second years of standardized training in radiation oncology. We selected classic and trending issues in radiation oncology as the two main teaching topics. Students in the PBL group searched for relevant literature, summarizing PowerPoint presentations or academic speeches on specific issues published on the professional WeChat public platform after an in-depth review by teachers. The final national standardized training examination scores for resident physicians were used to evaluate teaching effectiveness. The graduation scores of the PBL and non-PBL groups were compared, and a stratified analysis was conducted based on the year of participation to assess the teaching effectiveness of this model. Moreover, questionnaires were administered to evaluate students’ experiences. Results Among the 36 students who joined the study in 2019, 16 (44.0%) voluntarily joined the PBL teaching group. Nine students started teaching PBL in their first year of residency, accounting for 47.4% of that year, and seven started in their second year, accounting for 41.2%. The average graduation scores of the PBL group were superior to those of the non-PBL-focused group for the same grade. The rate of high scores among students in the PBL group (56.3%) was higher than that of students in the non-PBL group (25%). Specifically, first-year residents who joined the PBL group had an average score of 92.3 ± 2.2, significantly higher than their non-PBL counterparts, who scored an average of 88.6 ± 4.6, showing a statistically significant advantage (p = 0.042). All students were satisfied with the PBL WeChat teaching and would recommend the PBL WeChat course to others. Conclusion The PBL residency teaching model on the WeChat platform improved residency scores and garnered student satisfaction.

Abstract Objective To investigate the difference in bone-implant contact (BIC) and the rate of infratemporal fossa intrusion among different apex sites for quad zygomatic implants (ZIs) design in edentulous patients with severe alveolar bone resorption. Methods Patients with maxillary edentulism were evaluated. Alveolar bone resorption was assessed using the Cawood and Howell classification. Participants with Class IV or Class V/VI bone resorption were selected. The zygomatic bone was devided into upper, middle and lower thirds, with four potential implant apex locations identified in each third. Virtual planning for quad ZIs, along with measurements of BIC were performed. Additionally, the occurrence of ZIs intrusion into the infratemporal fossa was examined, and the distance between ZI and orbital cavity was measured. Results A total of 28 CBCT scans of edentulous patients, encompassing 56 zygomas, were analyzed. Thirty-nine single lateral posterior edentulous jaws were classified into Class IV subgroup, while 17 into Class V/IV subgroup. Among all patients and patients in subgroups, the anterior and posterior ZI exhibited the highest BIC at points A3 and B2, respectively. The average zygomatic BIC at A3 apex point was 18.3 ± 3.9 mm, and that at the B2 apex point was 16.3 ± 5.3 mm. Quad ZIs risk intrusion into the infratemporal fossa when positioned at B2, B3, and at all apex points of the lower zygoma segment. Three anterior ZIs at A3 point show less than 1 mm distance to orbital cavity. Overall, A3 and B1 apex points showed high BIC and low infratemporal intrusion rate for quad ZIs, irrespective of patient’s alveolar bone resorption status. Conclusions The optional apex point for anterior and posterior quad ZIs is A3 and B1, respectively, regardless of the patients’s alveolar bone resorption level. Alveolar bone resorption does not affect the BIC for quad ZIs. Anterior ZI positioned at A3 point may present high risk for orbital penetration and may not be reccomended in a Quad ZI approach. Trial registration The clinical research is registered under the number ChiCTR2100044472.

Abstract Molecular dynamics (MD) is an indispensable atomistic-scale computational tool widely-used in various disciplines. In the past decades, nearly all ab initio MD and machine-learning MD have been based on the general-purpose central/graphics processing units (CPU/GPU), which are well-known to suffer from their intrinsic “memory wall” and “power wall” bottlenecks. Consequently, nowadays MD calculations with ab initio accuracy are extremely time-consuming and power-consuming, imposing serious restrictions on the MD simulation size and duration. To solve this problem, here we propose a special-purpose MD processing unit (MDPU), which could reduce MD time and power consumption by about 103 times (109 times) compared to state-of-the-art machine-learning MD (ab initio MD) based on CPU/GPU, while keeping ab initio accuracy. With significantly-enhanced performance, the proposed MDPU may pave a way for the accurate atomistic-scale analysis of large-size and/or long-duration problems which were impossible/impractical to compute before.

Abstract Background Babesia duncani is a pathogen within the phylum Apicomplexa that causes human babesiosis. It poses a significant threat to public health, as it can be transmitted not only through tick bites but also via blood transfusion. Consequently, an understanding of the gene functions of this pathogen is necessary for the development of drugs and vaccines. However, the absence of conditional gene knockdown tools has hindered the research on this pathogen. The auxin-inducible degron (AID) system is a rapid, reversible conditional knockdown system widely used in gene function studies. Thus, there is an urgent need to establish the AID system in B. duncani to study essential gene functions. Methods The endogenous genes of the Skp1-Cullin-F-box (SCF) complex in B. duncani were identified and confirmed through multiple sequence alignment and conserved domain analysis. The expression of the F-box protein TIR1 from Oryza sativa (OsTIR1) was achieved by constructing a transgenic parasite strain using a homologous recombination strategy. Polymerase chain reaction (PCR), western blot, and indirect immunofluorescence assay (IFA) were used to confirm the correct monoclonal parasite strain. The degradation of enhanced green fluorescent protein (eGFP) tagged with an AID degron was detected through western blot and live-cell fluorescence microscopy after treatment of indole-3-acetic acid (IAA). Results In this study, Skp1, Cul1, and Rbx1 of the SCF complex in B. duncani were identified through sequence alignment and domain analysis. A pure BdTIR1 strain with expression of the OsTIR1 gene was constructed through homologous recombination and confirmed. This strain showed no significant differences from the wild type (WT) in terms of growth rate and proportions of different parasite forms. The eGFP tagged with an AID degron was successfully induced for degradation using 500 μM IAA. Grayscale analysis of western blot indicated a 61.3% reduction in eGFP expression levels, while fluorescence intensity analysis showed a 77.5% decrease in fluorescence intensity. Increasing the IAA concentration to 2 mM accelerated eGFP degradation and enhanced the extent of degradation. Conclusions This study demonstrated the functionality of the AID system in regulating protein levels by inducing rapid degradation of eGFP using IAA, providing an important research tool for studying essential gene functions related to invasion, egress, and virulence of B. duncani. Moreover, it also offers a construction strategy for apicomplexan parasites that have not developed an AID system. Graphical Abstract

Objective To compare the clinical effects of arthroscopically-assisted reduction and internal fixation (ARIF) combined with enhanced recovery after surgery (ERAS) and open reduction and internal fixation surgery (ORIF) in the treatment of posterior lateral tibial plateau fractures. MethodsSeventy patients with posterior lateral tibial plateau fractures in the Department of Orthopaedics, Xuzhou Central Hospital, from January 2020 to November 2022 were retrospectively selected and divided into ARIF group (with ERAS, n＝32) and ORIF group (without ERAS, n＝38) according to the treatment methods. All patients were evaluated for fracture type by imaging examination after admission. The operation time, length of hospital stay, early postoperative pain score (evaluated by visual analogue scale [VAS]), knee joint function (evaluated by hospital for special surgery [HSS] scale) at 3 months and thigh circumference difference at 6 months postoperatively were compared between the two groups. ResultsThe operation time in the ARIF group was significantly shorter than that in the ORIF group ([67.84±9.89] min vs [85.16±9.18] min, P＜0.001), and the length of hospital stay was significantly shorter in the ARIF group ([7.13±1.41] d vs [8.74±1.84] d, P＜0.001). On the third day after operation, the VAS score in the ARIF group was significantly lower than that in the ORIF group ([4.00±1.44] vs [5.39±1.24], P＜0.001). ARIF group had better joint function than ORIF group 3 months after operation, and the difference of 10 cm thigh circumference on patella in ARIF group was smaller than that in ORIF group 6 months after operation. ConclusionsCompared to ORIF, patients with posterior lateral tibial plateau fractures treated with ARIF combined with ERAS showed faster postoperative recovery, shorter hospital stay, and more precise clinical efficacy.

Abstract To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)—and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The Dmean, Dmax, and V5−40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p

Abstract Despite the broad potential applications of C-glycosides, facile synthetic methods remain scarce. Transforming glycosyltransferases with promiscuous or natural O-specific chemoselectivity to C-glycosyltransferases is challenging. Here, we employ rational directed evolution of the glycosyltransferase MiCGT to generate MiCGT-QDP and MiCGT-ATD mutants which either enhance C-glycosylation or switch to O-glycosylation, respectively. Structural analysis and computational simulations reveal that substrate binding mode govern C-/O-glycosylation selectivity. Notably, directed evolution and mechanism analysis pinpoint the crucial residues dictating the binding mode, enabling the rational design of four enzymes with superior non-inherent chemoselectivity, despite limited sequence homology. Moreover, our best mutants undergo testing with 34 substrates, demonstrating superb chemoselectivities, regioselectivities, and activities. Remarkably, three C-glycosides and an O-glycoside are produced on a gram scale, demonstrating practical utility. This work establishes a highly selective platform for diverse glycosides, and offers a practical strategy for creating various types of glycosylation platforms to access pharmaceutically and medicinally interesting products.

Abstract Objectives Socioeconomic factors significantly impact human health; however, the impact of exercise and income on musculoskeletal system health remains unclear. Our study aims to explore the relationship between exercise and income with musculoskeletal system health in young and middle-aged adults. Design This cross-sectional study used data from 7,515 adults aged 20–59 years, which were obtained from the US NHANES, 2011–2018. Participants’ musculoskeletal system health was evaluated on the basis of them having osteopenia, osteoporosis, or sarcopenia. Methods Ordinal regression was used to explore the correlation between income level, exercise volume, and musculoskeletal system health. Mediating effect analysis was used to assess whether the exercise volume affected the impact of income levels on musculoskeletal system health. Ordinal regression and restricted cubic spline curve were used to further analyze the relationship between exercise and income level. Results In the analysis of adjusted all covariates, the probability of having good musculoskeletal system health in high-income participants was higher than that of low- or middle-income participants. The probability of having good musculoskeletal system health in the actively exercising group higher than that of the participants exercised insufficiently or sufficiently. Mediating effect of exercise masked the effect of income on musculoskeletal system health. Participants with low income levels tended to spend more time exercising that those who had high income levels; exercise volume and income level had a significant non-linear relationship. Conclusion The findings presented will help identify young and middle-aged adults who are most at risk of developing musculoskeletal health problem and will likely benefit from certain lifestyle interventions.

Abstract Recent advancements in computer vision within the field of artificial intelligence (AI) have made significant inroads into the medical domain. However, the application of AI for classifying renal pathology remains challenging due to the subtle variations in multiple renal pathological classifications. Vision Transformers (ViT), an adaptation of the Transformer model for image recognition, have demonstrated superior capabilities in capturing global features and providing greater explainability. In our study, we developed a ViT model using a diverse set of stained renal histopathology images to evaluate its effectiveness in classifying renal pathology. A total of 1861 whole slide images (WSI) stained with HE, MASSON, PAS, and PASM were collected from 635 patients. Renal tissue images were then extracted, tiled, and categorized into 14 classes on the basis of renal pathology. We employed the classic ViT model from the Timm library, utilizing images sized 384 × 384 pixels with 16 × 16 pixel patches, to train the classification model. A comparative analysis was conducted to evaluate the performance of the ViT model against traditional convolutional neural network (CNN) models. The results indicated that the ViT model demonstrated superior recognition ability (accuracy: 0.96–0.99). Furthermore, we visualized the identification process of the ViT models to investigate potentially significant pathological ultrastructures. Our study demonstrated that ViT models outperformed CNN models in accurately classifying renal pathology. Additionally, ViT models are able to focus on specific, significant structures within renal histopathology, which could be crucial for identifying novel and meaningful pathological features in the diagnosis and treatment of renal disease.

Abstract This paper examines power user behavior and the design of marketing strategies, using a case study of Smart Community A. We explore how advanced analytical models are used to enhance energy efficiency and user services. First, we apply spectral clustering to refine user segmentation and identify distinct electricity consumption patterns among different groups. Then, the Hidden Markov Model (HMM) analyzes user behavior, uncovering shifts in consumption habits and enabling personalized service offerings. Next, the ARIMA model predicts electricity consumption trends, guiding grid scheduling and resource allocation. Based on these analyses, we develop targeted marketing strategies, such as dynamic pricing and energy-saving incentives, which boost user engagement and reduce energy usage. Through an IoT and big data-driven interactive marketing platform, we enhance user experience and foster a culture of energy conservation. Finally, a feedback mechanism ensures continuous improvement and maximizes the effectiveness of the marketing strategies.

Abstract The immiscibility of hydrogen-helium mixture under the temperature and pressure conditions of planetary interiors is crucial for understanding the structures of gas giant planets (e.g., Jupiter and Saturn). While the experimental probe at such extreme conditions is challenging, theoretical simulation is heavily relied in an effort to unravel the mixing behavior of hydrogen and helium. Here we develop a method via a machine learning accelerated molecular dynamics simulation to quantify the physical separation of hydrogen and helium under the conditions of planetary interiors. The immiscibility line achieved with the developed method yields substantially higher demixing temperatures at pressure above 1.5 Mbar than earlier theoretical data, but matches better to the experimental estimate. Our results suggest a possibility that H-He demixing takes place in a large fraction of the interior radii of Jupiter and Saturn, i.e., 27.5% in Jupiter and 48.3% in Saturn. This indication of an H-He immiscible layer hints at the formation of helium rain and offers a potential explanation for the decrease of helium in the atmospheres of Jupiter and Saturn.

Abstract Background With the increasing incidence of renal lesions, pretreatment differentiation between benign and malignant lesions is crucial for optimized management. This study aimed to develop a machine learning model utilizing radiomic features extracted from various regions of interest (ROIs), intratumoral ecological diversity features, and clinical factors to classify renal lesions. Methods CT images (arterial phase) of 1,795 renal lesions with confirmed pathology from three hospital sites were split into development (1184, 66%) and test (611, 34%) cohorts by surgery date. Conventional radiomic features were extracted from eight ROIs of arterial phase images. Intratumoral ecological diversity features were derived from intratumoral subregions. The combined model incorporating these features with clinical factors was developed, and its performance was compared with radiologists’ interpretation. Results Combining intratumoral and peritumoral radiomic features, along with ecological diversity features yielded the highest AUC of 0.929 among all combinations of features extracted from CT scans. After incorporating clinical factors into the features extracted from CT images, our combined model outperformed the interpretation of radiologists in the whole (AUC = 0.946 vs 0.823, P

Limited cells and factors, inadequate mechanical properties, and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds. Herein, we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure. The hydrogel scaffold possesses the characteristics of extracellular matrix; Meanwhile, the fabricated hybrid double network structure by polyacrylamide and CaCl2-crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability. Furthermore, the O2 generated by CaO2 nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8, which can significantly promote cell viability and proliferation in vitro, as well as angiogenesis and osteogenic differentiation with the assistance of Zn2+. More significantly, the synergy of O2 and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need, which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect in vivo. Overall, this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative.

Abstract Bacillus cereus is a common foodborne pathogen capable of producing cereulide and enterotoxin. Consumption of food contaminated with cereulide can even result in fatality. Bacteriophages are increasingly being utilized as biocontrol agents to combat specific pathogens in a variety of food products. However, there are currently no lytic phages available to target cereulide‐producing B. cereus. This study aims to isolate and characterize two novel phages, DC1 and DC2, and assess their potential for use in food substrates. These two phages possessed the widest host range among the reported lytic phages that target B. cereus. The whole genome analysis demonstrated that DC1 and DC2 belonged to the Tsarbombavirus genus of the Bastillevirinae subfamily, which is part of the Herelleviridae family. The one‐step growth curve analysis revealed that DC1 had a latent period of 30 min and a burst size of approximately 39 PFU (plaque‐forming units) per cell. On the other hand, DC2 exhibited a shorter latent period of 15 min and a larger burst size of 124 PFU per cell. Both phages had a burst period of 30 min. Furthermore, DC1 and DC2 displayed excellent stability within a wide range of pH levels and temperatures. After undergoing a brief phage‐soaking treatment, DC1 and DC2 effectively reduced the bacterial count in spiked food samples. Additionally, they inhibited the formation of biofilms and degraded already‐formed biofilms. Collectively, DC1 and DC2 exhibit great potential as biocontrol agents for the prevention and control of B. cereus contamination in foods.

Abstract Quantitative three-dimensional gait analysis has been used to evaluate the loading at the knee (i.e. external knee adduction moment, EKAM) during level ground walking in individuals with knee osteoarthritis (OA). The magnitude of EKAM can be influenced by some factors, such as knee marker position and foot placement angles in static calibration trials, which may lead to inaccurate functional assessments and intervention planning. This study aimed to clarify the effects of knee position during static calibration trials on the evaluation of knee loading during gait in individuals with medial knee OA. Seventeen individuals with medial knee OA completed three different static standing trials; (1) knee flexed at 0 degrees, (2) knee flexed at 15 degrees, and (3) knee flexed at 30 degrees before walking at their self-selected speed. A sixteen-camera three-dimensional VICON gait analysis system with four AMTI force platforms was used to collect the EKAM, knee adduction angular impulse (KAAI), knee joint center (KJC), and other knee kinematic and kinetic variables during gait. A repeated measures ANOVA was used to investigate the differences between conditions. The 1st peak of EKAM, the 1st peak EKAM arm, KAAI, and knee extension moment were significantly increased at the 15-degree and 30-degree conditions in comparison with the 0-degree condition (P

Abstract Background Lodging, a crucial agronomic trait linked to soybean yield, poses a significant challenge in soybean production. Nevertheless, there has been less research on soybean lodging compared to other important agronomic traits, hindering progress in breeding high-yield soybeans. Our goals were to investigate lodging, pinpoint quantitative trait loci (QTL) linked to lodging, and forecast potential candidate genes linked to this trait. To achieve this, we employed a recombinant inbred line (RIL) population derived from a cross between Guizao 1 and B13 (GB) across various environments. Results The lodging score of the RIL population was found to be significantly positively correlated with flowering time, maturity time, plant height, number of main stem nodes, stem diameter, and internode length, with correlation coefficients ranging from 0.457 to 0.783. A total of 84 QTLs associated with soybean lodging and related traits were identified using the GB population. The contribution of phenotypic variance ranged from 1.26 to 66.87%, with LOD scores ranging from 2.52 to 69.22. Additionally, within these QTLs, a stable major QTL associated with lodging was newly discovered in the GB population. Out of the ten major QTLs associated with other related traits, nine of them were situated within the qLD-4-1 interval of the major lodging score locus, displaying phenotypic variations ranging from 12.10 to 66.87%. Specific alterations in gene expression were revealed through the analysis of resequencing data from the two parental lines, potentially indicating their significant roles in lodging. Subsequently, it was determined through qRT-PCR that four genes are likely to be the major genes controlling soybean lodging. Conclusions This study’s findings offer valuable insights into the genetic underpinnings of soybean lodging resistance traits. By comprehending the potential genetic factors associated with lodging, this research lays the groundwork for breeding high-yield soybeans with improved lodging resistance.

Abstract Salicylic acid (SA) plays an essential role in plant defense against biotrophic and semi‐biotrophic pathogens. Following pathogen recognition, SA biosynthesis dramatically increases at the infection site of the host plant. The manner in which pathogens sense and tolerate the onslaught of SA stress to survive in the plant following infection remains to be understood. The objective of this work was to determine how the model phytopathogen Xanthomonas campestris pv. campestris (Xcc) senses and effluxes SA during infection inside host plants. First, RNA‐Seq analysis identified an SA‐responsive operon Xcc4167–Xcc4171, encoding a MarR family transcription factor HepR and an RND (resistance‐nodulation‐cell division) family efflux pump HepABCD in Xcc. Electrophoretic mobility shift assays and DNase I footprint analysis revealed that HepR negatively regulated hepABCD expression by specifically binding to an AT‐rich region of the promoter of the hepRABCD operon, Phep. Second, isothermal titration calorimetry and further genetic analysis suggest that HepR is a novel SA sensor. SA binding released HepR from its cognate promoter Phep and then induced the expression of hepABCD. Third, the RND family efflux pump HepABCD was responsible for SA efflux. The hepRABCD cluster was also involved in the regulation of culture pH and quorum sensing signal diffusible signaling factor turnover. Finally, the hepRABCD cluster was transcribed during the XC1 infection of Chinese radish and was required for the full virulence of Xcc in Chinese radish and cabbage. These findings suggest that the ability of Xcc to co‐opt the plant defense signal SA to activate the multidrug efflux pump may have evolved to ensure Xcc survival and virulence in susceptible host plants.

Abstract Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan–Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan–Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P

Abstract Background The relationship between healthy lifestyle and frailty remains unclear. Healthy weight is crucial for overall well-being, but using body mass index (BMI) to evaluate weight management is inefficient. This study clarifies the association between healthy lifestyle or its factors (non-smoking, moderate drinking, healthy weight, healthy diet, sufficeint physical activity, and non-sedentary) and frailty, and the feasibility of using the weight-adjusted waist index (WWI) reflecting central obesity as an intermediate indicator. Methods This study included 4,473 participants from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). Healthy lifestyle quality was assessed by summing the scores of each healthy lifestyle factor. Frailty was assessed using a 49-item frailty index (FI), categorizing participants into robust, pre-frail, and frail. Logistic regression to investigate the association between healthy lifestyle or its factors, WWI, and frailty. Smooth curve fitting and threshold effect analyses were used to elucidate the nonlinear association. Subgroup and two other sensitivity analyses were conducted to confirm the stability of the results. A causal mediation model examined the proportion of frailty mediated by WWI. Results The study identified 13.98% of the participants as frail. Optimal healthy lifestyle and frailty were negatively associated (OR: 0.39, 95%CI: 0.27–0.58). Five healthy lifestyle factors (non-smoking, healthy weight, healthy diet, sufficient physical activity, and non-sedentary) were associated with a lower prevalence of frailty, with odds ratios (OR) ranging from 0.48 to 0.61. We also analyzed the association between a healthy lifestyle and WWI (OR: 0.32, 95%CI: 0.27–0.37), WWI and frailty (OR: 1.85, 95%CI: 1.59–2.16). A positive association between WWI and FI was observed beyond the inflection point (9.99) (OR: 0.03, 95%CI: 0.02–0.03). Subgroup and sensitivity analyses confirmed stable associations between healthy lifestyle, WWI, and frailty. WWI partially mediated the association between a healthy lifestyle and frailty (mediating ratio = 20.50–20.65%). Conclusions An optimal healthy lifestyle and positive healthy lifestyle factors are associated with a lower incidence of frailty. WWI may mediate the relationship between a healthy lifestyle and frailty.

Abstract This study aimed to investigate the therapeutic potential of human adipose‐derived mesenchymal stem cells (hADSCs) modified with recombinant adeno‐associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate‐buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control‐hADSCs group), or rAAV VEGF165 vector (VEGF165‐hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium‐binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165‐hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain‐derived neurotrophic factor (BDNF) and glial cell‐derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV‐VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.

Abstract The recent high death tolls caused by large earthquakes are a further indication that earthquakes remain one of the most destructive natural hazards in the world and can seriously threaten the achievement of disaster reduction goals. To effectively reduce the existing seismic risk, the limited available mitigation resources should be allocated to areas with the most severe potential risk. However, identifying localized concentrations of risk requires detailed studies. Here, we propose a strategy to delineate regional high seismic risk zone at a fine resolution and with high confidence. We demonstrate this strategy by using the seismic hazard and loss estimation results for earthquake scenarios with a magnitude of Mw 7.5 for the Jiaocheng fault of the Shanxi Rift System, China. Our analyses reveal that the delineated zone accounts for only ~7% of the regional land area but for ~85% of the total financial loss. We recommend prioritizing seismic risk mitigation measures in such high-risk zones, especially for densely populated cities in seismically active areas, to better meet the disaster risk reduction targets in the Sendai Framework.

Abstract The mid-Holocene climate optimum saw warm temperatures in large parts of China, but its impact on seasonal environmental changes is not fully understood yet. Here, we use high-resolution geochemical analyses of 7000 to 6000 year-old oyster shells from the Yangtze River Delta to reconstruct climatic and oceanographic patterns. The stable isotope (δ18O, δ13C) and clumped isotope data reflect prominent seasonal changes in temperature, precipitation, and river discharge. Summer months experienced warm temperatures and a distinct increase in rainfalls and river discharge. In contrast, winter months were characterized by a dry season, which might have been longer than today. Stable isotope data also indicate regular summer upwelling in the study area. These results partly disagree with available climate models raising doubts on the models’ reliability. Thus, our palaeo-proxy data offers the possibility to evaluate and correct climate models and thereby improve predictions for the future considering on-going global warming.

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639–0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882–0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60–80%, >40–60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51–0.97) to 0.48 (95% CI, 0.36–0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

The Moon and Mars are adjacent to Earth and are starting stations for human exploration of the Universe. An in-depth study of the lithospheric structure of the Moon and Mars can reveal the composition and structure of their crust and mantle systems and deepen our understanding of their origins and thermal evolution histories, providing essential references for studies of Earth's origin and evolution. With the vigorous international development of deep space exploration in recent years, the accuracy and resolution of gravity field models for the Moon and Mars have increased. Significant scientific advances have been made in the studies of lunar and Martian lithospheric structures based on gravity data. This article briefly introduces exploration plans and gravity field models for the Moon and Mars and elaborates on achievements in the lithospheric structures of the Moon and Mars by applying their gravity fields. Finally, we present a summary and outlook on research into the lithospheric structures of the Moon and Mars. Methods to overcome uncertainties in gravitational fields for studying the lithospheric structures of the Moon and Mars have been proposed. We hope that this review can assist in promoting gravity exploration on the Moon and Mars and research into their lithospheric structures.

Purpose – This paper aims to analyze the stress and strain distribution on the track wheel web surface and study the optimal strain gauge location for force measurement system of the track wheel. Design/methodology/approach – Finite element method was employed to analyze the stress and strain distribution on the track wheel web surface under varying wheel-rail forces. Locations with minimal coupling interference between vertical and lateral forces were identified as suitable for strain gauge installation. Findings – The results show that due to the track wheel web’s unique curved shape and wheel-rail force loading mechanism, both tensile and compressive states exit on the surface of the web. When vertical force is applied, Mises stress and strain are relatively high near the inner radius of 710 mm and the outer radius of 1110 mm of the web. Under lateral force, high Mises stress and strain are observed near the radius of 670 mm on the inner and outer sides of the web. As the wheel-rail force application point shifts laterally toward the outer side, the Mises stress and strain near the inner radius of 710 mm of the web gradually decrease under vertical force while gradually increasing near the outer radius of 1110 mm of the web. Under lateral force, the Mises stress and strain on the surface of the web remain relatively unchanged regardless of the wheel-rail force application point. Based on the analysis of stress and strain on the surface of the web under different wheel-rail forces, the inner radius of 870 mm is recommended as the optimal mounting location of strain gauges for measuring vertical force, while the inner radius of 1143 mm is suitable for measuring lateral force. Originality/value – The research findings provide valuable insights for determining optimal strain gauge locations and designing an effective track wheel force measurement system.

To solve the problems of low accuracy, slow detection speed, and difficulty in deploying model parameters in surface defect detection of continuous casting production process, a lightweight surface defect detection algorithm YOLOv7-TSCR that integrates heavy parameterization and attention mechanism was proposed. Firstly, based on the Mish and SiLU activation functions and the SimAM attention mechanism, an improved high-efficiency layer aggregation module ELAN-S was constructed to effectively enhance the extraction of multi-scale defect features. Secondly, the C2f_RG module was designed to improve the feature fusion network, reducing the number of parameters while obtaining richer gradient flow information and enhancing feature fusion capabilities. Finally, based on the collected defect images from actual production, a dataset of casting defects was constructed and validated. The results show that YOLOv7-TSCR has significantly improved detection performance compared to other network models；With a reduced number of model parameters, the accuracy reaches 93.5%, the average accuracy increasesby 2.8%, and the detection speed reaches 120 FPS; The generalization comparison experiment on the NEU-DET public dataset proves that the algorithm has strong generalization. On the basis of ensuring high detection accuracy, the improved algorithm has a fast detection speed and a small number of parameters, which provides a technical reference for the efficient detection of surface defects in casting billets.

In early February 2024, severe low-temperature rainfall/snowfall and freezing weather events occurred in the eastern parts of Guizhou and the middle and lower reaches of the Yangtze River. Coinciding with the travel period of the Spring Festival, the event caused serious impacts on travel, energy supply guarantees, and people's daily lives. To reveal the exceptional characteristics of the weather event, observation data from the National Meteorological Information Center, NCEP/NCAR reanalysis data, and Huaihua dual-polarization radar data were used to analyze the characteristics and causes of rainfall/snowfall and freezing weather events. The results are as follows: (1) Severe freezing disasters lasting 4-6 days occurred in eastern Guizhou, northern and central parts of Hunan, eastern and southern parts of Hubei, and northern and western parts of Anhui. These disasters were primarily caused by two rounds of low-temperature rain and snow weather. The first round occurred around February 1 to 4, with the most severe period appearing on the 3rd. It was characterized by heavy snowfall and freezing rain, leading to rapid accumulation of snow and ice. The second round occurred from February 5 to 6, with freezing rain predominating in eastern Guizhou and northern and central parts of Hunan, and sleet predominating along the Yangtze River in Hubei and other areas, which sustained or further increased the ice accumulation. (2) The geopotential height anomaly of the mid to high latitudes in Asia showed a distribution of low in the west and high in the east, and the southern trough was active. Both provided important weather conditions for the low-temperature rain and snow weather. The strong southwest jet stream climbs along the front to form a tilted upward airflow, enhancing the precipitation intensity behind the front, and leading to the first round of the weather event. The weakening of the southern trough and the maintenance of the southern front area, the mid-to-low low-level jet, and the surface stationary front resulted in the second round of the weather event. (3) Affected by the formation and maintenance of the South China stationary front and the Yunnan-Guizhou stationary front, the range of inversion was wide, with a significant warm layer in the southern region of the Yangtze River, resulting in different phases of precipitation on the south and north sides of the Yangtze River. Meanwhile, there were significant differences in the vertical direction of the temperature and humidity fields on the north and south sides of the Yangtze River. When heavy snowfall dominated north of the Yangtze River, the temperature and humidity fields exhibited deep cold-wet characteristics, with a typical ice-phrase structure. However, when heavy freezing rain dominated south of the Yangtze River, the temperature and humidity fields exhibited a"strong warm-wet and cold-wet"feature. (4) The rapidly increasing amount of rainwater, ice, and snow formed strong wet snow and severe freezing rain on February 3-4. The low-level supercooled water of both light and heavy rain droplets coexisted in the southern region of the Yangtze River on the night of the 3rd day, while it was dominated by light rain on the night of the 5th day.

Abstract Background The metastasis of cancer cells is influenced by both their intrinsic characteristics and the tumor microenvironment (TME). However, the molecular mechanisms underlying pre-nodal metastases of breast cancer remain unclear. Methods We integrated a total of 216,963 cells from 54 samples across 6 single-cell datasets to profile the cellular landscape differences between primary tumors and pre-nodal metastases. Results We revealed three distinct metastatic epithelial cell subtypes (Epi1, Epi2 and Epi3), which exhibited different metastatic mechanisms. Specifically, the marker gene KCNK15 of the Epi1 subtype exhibited increased gene expression along the cell differentiation trajectory and was specifically regulated by the transcription factor ASCL1. In the Epi3 subtype, we highlighted NR2F1 as a regulator targeting the marker gene MUCL1. Additionally, we found that the Epi2 and Epi3 subtypes shared some regulons, such as ZEB1 and NR2C1. Similarly, we identified specific subtypes of stromal and immune cells in the TME, and discovered that vascular cancer-associated fibroblasts might promote capillary formation through CXCL9+ macrophages in pre-nodal metastases. All three subtypes of metastatic epithelial cells were associated with poor prognosis. Conclusions In summary, this study dissects the intratumoral heterogeneity and remodeling of the TME in pre-nodal metastases of breast cancer, providing novel insights into the mechanisms underlying breast cancer metastasis.

Abstract Currently, there is still debate over the effectiveness of transcranial direct current stimulation (tDCS) in treating obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and anxiety disorders (ADs). To investigate the immediate and long-term effectiveness of tDCS in these diseases, we conducted a systematic review and quantitative analysis of existing literature on the treatment of OCD, PTSD, and ADs with tDCS. Following the PRISMA guidelines, we searched seven electronic databases and systematically retrieved articles published from May 2012 to June 2024 that compared the effects of active tDCS with sham stimulation in the treatment of these disorders. We included primary outcome measures such as the change scores in disorder-specific and general anxiety symptoms before and after treatment, as well as secondary outcomes such as changes in disorder-specific and general anxiety symptoms at follow-up. We also assessed the impact of tDCS on depressive symptoms. Fifteen papers met the eligibility criteria. Overall, the results of meta-analysis indicated that tDCS had a high effect in improving specific symptoms (SMD = −0.73, 95% CI: −1.09 to −0.37) and general anxiety symptoms (SMD = −0.75; 95% CI: −1.23 to −0.26) in OCD, PTSD and ADs, with effects lasting up to 1 month and showing a moderate effect size. Furthermore, tDCS demonstrated immediate and significant alleviation of depressive symptoms in these diseases. This study concludes that tDCS can serve as a non-invasive brain stimulation technology for treating these disorders, and the therapeutic effects can be maintained for a period of time.

Abstract Objective To elucidate the impact and predictive value of the Triglyceride Glucose Index (TyG) and the ratio of Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) in identifying the risk of diabetes progression in Chinese individuals with prediabetes. Methods This longitudinal study enrolled 15,012 prediabetic adults from the Rich Healthcare Group between 2010 and 2016. Diabetes was defined as self-reported diabetes or a fasting glucose level ≥ 7.0 mmol/L. The Cox proportional hazards models was utilized to assess the relationship between the two indices and the risk of developing diabetes. The predictive efficacy of the two markers was gauged by the area under the curve (AUC). Results Over a median follow-up period of 2.87 years, 1,730 (11.5%) prediabetic participants developed diabetes. The adjusted hazard ratios for the top quartile of the TyG index and the TG/HDL-C ratio were 2.03 (95% confidence interval [CI]: 1.71–2.40) and 2.59 (95% CI: 2.20–3.05), respectively, compared to the lowest quartile. A significant trend of increasing diabetes risk with higher quartiles of both indices was observed. The AUC for the adjusted prediction model for prediabetes-to-diabetes transition was 0.726 for the TyG index and 0.710 for the TG/HDL-C ratio. The difference in AUCs was statistically significant (P = 0.03). Conclusions The baseline TyG index or TG/HDL-C ratio was significantly associated with an increased risk of diabetes in prediabetic individuals. The TyG index demonstrated superior predictive accuracy, underscoring its importance in preventing diabetes in prediabetic individuals.

In 60Co based computed tomography (CT) of carbon components，reducing the number of sampling angles can significantly shorten detection time and improve detection efficiency. However，for conventional analytical reconstruction algorithms，sparse angle reconstruction images contain a large amount of noise and artifacts，which interfere with the detection of defects in the images and affect the quality evaluation of the inspected components by the detection system under fast detection conditions. This article proposes a sparse angle CT image reconstruction method based on neuralnetwork，which uses an untrained encoding decoding neural network to optimize the projection error of the reconstructed image，and uses the ADAM algorithm to optimize the total variation prior of the image. Compared with traditional deep learning reconstruction algorithms，this method does not require training sample sets and has stronger generalization ability and robustness. The results of simulation and practical experiments show that compared to traditional analytical and reconstruction algorithms，this method significantly improves the quality of reconstructed images，while retaining the detailed information of the detected components，and significantly suppresses artifacts and noise in the reconstructed images retaining image details and texture. This work can effectively improve image quality，eliminate the interference of artifacts on the identification of defects in graphics，and improve the ability to recognize defects in carbon components for the detection system.

Abstract Xanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot in Brassica vegetables, which can induce the host plant to produce salicylic acid and 4-hydroxybenzoic acid (4-HBA) during infection. Xcc was previously shown to sense and degrade host plant-derived 4-HBA via the sensor PobR and a PobA-dependent pathway. The degradation of 4-HBA is associated with Xcc virulence in cabbage. The present study generated a reporter strain XC1::PpobA-gusA to monitor pobA transcription. 4-HBA-like compounds were screened for their ability to interfere with pobA transcription. Benzoic acid (BA) was found to efficiently decrease pobA transcription in a dose-dependent manner. Xcc neither produced nor degraded BA; however, the exogenous addition of BA to the 4-HBA-containing Xcc culture significantly decreased the 4-HBA degradation rate. Furthermore, addition of BA into the Xcc culture did not significantly affect the transcription of pobA or pobR; however, addition of BA into the 4-HBA-containing culture significantly decreased the transcription of both genes. Isothermal titration calorimetry and an electrophoretic mobility shift assay revealed that BA binds to PobR with a moderate affinity, which interfered with the binding of 4-HBA/PobR complex to the pobA promoter and thereby inhibiting pobA transcription and 4-HBA degradation. The endogenous BA level of the infected cabbage leaves increased in response to Xcc infection. In the presence of BA, the virulence of Xcc on cabbage decreased significantly. Taken together, these results suggest that cabbage utilizes BA to interfere with 4-HBA degradation, thereby reducing Xcc virulence. Thus, BA has the potential to be developed as a bactericide against Xcc infection.

Abstract N-Myc is a key driver of neuroblastoma and neuroendocrine prostate cancer (NEPC). One potential way to circumvent the challenge of undruggable N-Myc is to target the protein homeostasis (proteostasis) system that maintains N-Myc levels. Here, we identify heat shock protein 70 (HSP70) as a top partner of N-Myc, which binds a conserved “SELILKR” motif and prevents the access of E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1), possibly through steric hindrance. When HSP70’s dwell time on N-Myc is increased by treatment with the HSP70 allosteric inhibitor, STUB1 is in close proximity with N-Myc and becomes functional to promote N-Myc ubiquitination on the K416 and K419 sites and forms polyubiquitination chains linked by the K11 and K63 sites. Notably, HSP70 inhibition significantly suppressed NEPC tumor growth, increased the efficacy of aurora kinase A (AURKA) inhibitors, and limited the expression of neuroendocrine-related pathways.

Abstract Dental pulp stem cells (DPSC) have shown osteogenic and bone regenerative potential. Improving the in situ bone regeneration potential of DPSC is crucial for their application as seed cells during bone defect reconstruction in clinics. This study aimed to develop DPSC-derived organoid-like microspheroids as effective seeds for bone tissue engineering applications. DPSC osteogenic microspheroids (70 μm diameter) were cultured in a polydimethylsiloxane-mold-based agarose-gel microwell-culture-system with or without cannabidiol (CBD)-treatment. Results of in vitro studies showed higher osteogenic differentiation potential of microspheroids compared with 2D-cultured-DPSC. CBD treatment further improved the osteogenic differentiation potential of microspheroids. The effect of CBD treatment in the osteogenic differentiation of microspheroids was more pronounced compared with that of CBD-treated 2D-cultured-DPSC. Microspheroids showed a higher degree of bone regeneration in nude mice calvarial bone defect compared to 2D-cultured-DPSC. CBD-treated microspheroids showed the most robust in situ bone regenerative potential compared with microspheroids or CBD-treated 2D-cultured-DPSC. According to mRNA sequencing, bioinformatic analysis, and confirmation study, the higher osteogenic potential of CBD-treated microspheroids was mainly attributed to WNT6 upregulation. Taken together, DPSC microspheroids have robust osteogenic potential and can effectively translate the effect of in vitro osteoinductive stimulation during in situ bone regeneration, indicating their application potential during bone defect reconstruction in clinics.

Abstract Wearable devices especially smartwatches are widely used in our daily life. With their increased use, a large amount of sensitive data are collected, stored, and managed in those devices. To protect sensitive data, encryption is often used but, traditional encryption is vulnerable to a novel coercive attack in which the adversary can capture the device’s user and coerce the user to disclose the decryption key. To defend against the coercive attack, Plausibly Deniable Encryption (PDE) has been designed which can allow the victim user to deny the existence of hidden sensitive data. The PDE systems have been explored broadly for smartphones. However, the PDE systems which are suitable for wearable devices are still missing in the literature. In this work, we have designed MobiWear, the first PDE system specifically designed for wearable devices. By leveraging PDE, image steganography as well as watermarking, MobiWear ensures plausible deniability and can be easily deployed at the application layer. In addition, MobiWear relies on sensors equipped with the wearable devices to enter passwords, accommodating the wearable devices which have small-size screens and are inconvenient for entering plaintext. Security analysis and experimental evaluation using a real-world prototype (ported to an LG G smartwatch) show that MobiWear can ensure the deniability with a small computational overhead as well as a tiny degradation of the perceived quality of the image.

Abstract Background Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), which accounts for approximately one-fifth of all BCs, are highly invasive with a high rate of recurrence and a poor prognosis. Several studies have shown that growth factor receptor-bound protein 7 (GRB7) might be a potential therapeutic target for tumor diagnosis and prognosis. Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated. The aim of this study was to investigate the biological function and regulatory mechanism of GRB7 in HER2+ BC. Methods Bioinformatics analysis was performed using the TCGA, GEO and CancerSEA databases to evaluate the clinical significance of GRB7. RT quantitative PCR, western blot and immunofluorescence were conducted to assess the expression of GRB7 in BC cell lines and tissues. MTT, EdU, colony formation, wound healing, transwell, and xenograft assays were adopted to explore the biological function of GRB7 in HER2+ BC. RNA sequencing was performed to analyze the signaling pathways associated with GRB7 in SK-BR-3 cells after the cells were transfected with GRB7 siRNA. Chromatin immunoprecipitation analysis (ChIP) and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of GRB7 in HER2+ BC. Results GRB7 was markedly upregulated and associated with poor prognosis in BC, especially in HER2+ BC. Overexpression of GRB7 increased the proliferation, migration, invasion, and colony formation of HER2+ BC cells, while depletion of GRB7 had the opposite effects in HER2+ BC cells and inhibited xenograft growth. ChIP-PCR and luciferase reporter assay revealed that TCF12 directly bound to the promoter of the GRB7 gene to promote its transcription. GRB7 facilitated HER2+ BC epithelial-mesenchymal transition (EMT) progression by interacting with Notch1 to activate Wnt/β-catenin pathways and other signaling (i.e., AKT, ERK). Moreover, forced GRB7 overexpression activated Wnt/β-catenin to promote EMT progression, and partially rescued the inhibition of HER2+ BC proliferation, migration and invasion induced by TCF12 silencing. Conclusions Our work elucidates the oncogenic role of GRB7 in HER2+ BC, which could serve as a prognostic indicator and promising therapeutic target.

Abstract Background At present, the guidelines for urology recommend percutaneous nephrolithotomy (PCNL) as the preferred treatment for staghorn renal calculi (SRC). However, for complete SRC, it has been questioned by clinicians and patients due to high residual stone rate, complications, repeated hospitalizations and high treatment cost. Anatrophic nephrolithotomy (ANL) is a traditional and classic method for the treatment of SRC. Due to its high trauma and high technical requirements, it is difficult to carry out in primary hospitals, and gradually replaced by PCNL. The purpose of this study is to compare the efficacy of PCNL and ANL in the treatment of complete SRC. Methods Overall, 238 patients with complete SRC were divided into mini-PCNL in lateral supine position group, (n = 190) and ANL group (n = 94) according to treatment for a retrospective cohort study. The calculi parameters, renal function index, comorbidities of calculi, surgical complications, length and frequency of hospitalization, treatment costs, results of postoperative satisfaction survey were compared between the two groups. Results The risk of the residual stone rate after mini-PCNL in lateral supine position was 239 times (OR = 238.667, P

Abstract This paper provides an in-depth discussion on the comprehensive requirements analysis, design implementation, algorithm optimization, and experimental evaluation of an electric power marketing information system, aiming to build a modern information system that is efficient, secure, and user-friendly. In the requirements analysis phase, the importance of business process optimization, data management analysis, security compliance, system integration and scalability is emphasized, while the diversified needs of end customers are considered. For the design and implementation part, the system architecture is based on microservices and cloud-native technologies to ensure high performance and security; and modularized development is achieved through Spring Boot, Vue.js and other technology stacks. For algorithm optimization, LSTM is used for power demand prediction and anomaly detection by combining integrated learning and self-encoder, which improves the prediction accuracy and anomaly identification capability. Experimental evaluation shows that the system demonstrates good performance, security and scalability in cloud computing environment, and the cost-effectiveness is significantly better than traditional deployment.

Abstract Objective Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. Methods Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). Results The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. Conclusion The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Abstract Diabetic retinopathy (DR), a well-known microvascular complication of diabetes mellitus, remains the main cause of vision loss in working-age adults worldwide. Up to now, there is a shortage of information in the study regarding the contributing factors of DR in diabetes. Accumulating evidence has identified glycemic variability (GV), referred to fluctuations of blood glucose levels, as a risk factor for diabetes-related complications. Recent reports demonstrate that GV plays an important role in accounting for the susceptibility to DR development. However, its exact role in the pathogenesis of DR is still not fully understood. In this review, we highlight the current landscape and relevant mechanisms of GV in DR, as well as address the mechanism-based therapeutic strategies, aiming at better improving the quality of DR management in clinical practice.

Abstract Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.

Abstract Background The atherogenic index of plasma (AIP) is a critical metric for predicting cardiovascular outcomes. However, its associations with cardiovascular disease mortality (CVM) and all-cause mortality (ACM) remain unclear. This study aims to elucidate the relationship between baseline AIP levels and CVM and ACM among a broad cohort of US adults. Methods Utilizing data from the National Health and Nutrition Examination Survey (2005–2018), we analyzed 18,133 adults aged ≥ 18. Baseline triglycerides and high-density lipoprotein cholesterol levels were measured to calculate the AIP. Mortality outcomes were determined through linkage with the National Death Index database, with follow-up through December 31, 2019. Multivariable Cox proportional hazard models examined the associations between baseline AIP and mortality risks. Additionally, restricted cubic splines were utilized to investigate potential non-linear relationships, with subgroup analyses conducted across strata defined by age, gender, body mass index, diabetes, hypertension, and metabolic syndrome to assess variability in these associations. Results Over a median 95.0-month follow-up, there were 1870 all-cause deaths and 579 cardiovascular disease-related deaths. Our findings indicate a J-shaped association between the AIP and ACM (threshold = 0.0905); specifically, when baseline AIP exceeded 0.0905, a significant positive association with ACM emerged (hazard ratio, HR (95% confidence interval, CI): 1.61(1.08–2.37)). However, after adjusting for confounders, the relationship between AIP and CVM was not statistically significant (HR 1.31, 95% CI 0.93–1.86). Notably, in the 40–60-year age group, AIP was significantly positively associated with ACM and CVM, with HRs and 95% CIs of 1.51 (1.08v2.10) and 2.63 (1.39–4.98), respectively. Conclusions A J-shaped relationship was observed between baseline AIP levels and ACM within the general US population, with a threshold of 0.0905. Moreover, AIP could potentially be an effective predictor for future ACM or CVM, particularly among individuals aged 40–60. Further investigation is warranted to corroborate these findings.

Abstract Background Anti-vascular endothelial growth factor monoclonal antibody (anti-VEGF) or immune checkpoint inhibitors (ICIs) combined with chemotherapy are commonly administered to cancer patients. Although cancer patients receiving anti-VEGF or ICIs have been reported to experience an increased risk of acute kidney injury (AKI), comparative studies on the AKI incidence have not been evaluated. Methods Cancer patients receiving anti-VEGF or ICIs were retrospectively selected from the hospital information system of the First Affiliated Hospital of Wenzhou Medical University between Jan, 2020 and Dec, 2022 and were divided into two groups according to the treatment regimen: anti-VEGF group and ICIs group. The baseline characteristics were propensity-score matched. The primary outcome was sustained AKI. A comparison of cumulative incidence of sustained AKI was performed by Kaplan-Meier curves and log-rank test. Risks for outcomes were assessed using Cox proportional regression. Results A total of 1581 cancer patients receiving anti-VEGF (n = 696) or ICIs (n = 885) were included in the primary analysis. The ICIs group had a higher cumulative incidence of sustained AKI within one year than the anti-VEGF group (26.8% vs. 17.8%, P 35 g/l) was an important risk factor for a lower incidence of sustained AKI in the anti-VEGF group (HR 0.5; 95%CI 0.3 to 0.9; P = 0.027) and the ICIs group (HR 0.3; 95%CI 0.2 to 0.5; P

Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a major cause of malignant tumors and cancer-related deaths in China, accounting for approximately 85% of all cancer cases in the country. Several guidelines have been used to diagnose and treat liver cancer. However, these guidelines provide a broad definition for classifying advanced liver cancer, with an emphasis on a singular approach, without considering treatment options for individual patients. Therefore, it is necessary to establish a comprehensive and practical expert consensus, specifically for China, to enhance the diagnosis and treatment of HCC using the Delphi method. The classification criteria were refined for Chinese patients with HCC, and the corresponding optimal treatment regimen recommendations were developed. These recommendations took into account various factors, including tumor characteristics, vascular tumor thrombus grade, distant metastasis, liver function status, portal hypertension, and the hepatitis B virus replication status of patients with primary HCC, along with treatment prognosis. The findings and recommendations provide detailed, scientific, and reasonable individualized diagnosis and treatment strategies for clinicians.

Abstract Background There is currently a lack of comprehensive prevalence information on arthritis and its various classifications among adults in the U.S., particularly given the notable absence of detailed data regarding the Asian population. We examined the trends in the prevalence of arthritis, including osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and other types of arthritis, among U.S. adults by race between 2011 and 2018. Methods We analyzed data from the National Health and Nutrition Examination Survey (NHANES), spanning from 2011 to 2018. Our study focused on a nationally representative sample of U.S. adults aged 20 and older. Participants who answered “y es” to the research question “Doctors ever said you had arthritis?” were classified as having arthritis. Further classification into specific diseases was based on responses to the question “Which type of arthritis was it?” with options including “OA or degenerative arthritis, ” “RA, ” “PsA, ” or “Other. ” Results We analyzed 22,566 participants from NHANES (2011–2018), averaging 44.8 years, including 10,927 males. The overall arthritis prevalence rose significantly from 22.98% (95% CI: 21.47–24.55%) in 2011–12 to 27.95% (95% CI: 26.20–29.76%) in 2017–18 (P for trend

Abstract Background Blood homocysteine (Hcy) level has become a sensitive indicator in predicting the development of cardiovascular disease. Studies have shown an association between individual mineral intake and blood Hcy levels. The effect of mixed minerals’ intake on blood Hcy levels is unknown. Methods Data were obtained from the baseline survey data of the Shanghai Suburban Adult Cohort and Biobank(SSACB) in 2016. A total of 38273 participants aged 20–74 years met our inclusion and exclusion criteria. Food frequency questionnaire (FFQ) was used to calculate the intake of 10 minerals (calcium, potassium, magnesium, sodium, iron, zinc, selenium, phosphorus, copper and manganese). Measuring the concentration of Hcy in the morning fasting blood sample. Traditional regression models were used to assess the relationship between individual minerals’ intake and blood Hcy levels. Three machine learning models (WQS, Qg-comp, and BKMR) were used to the relationship between mixed minerals’ intake and blood Hcy levels, distinguishing the individual effects of each mineral and determining their respective weights in the joint effect. Results Traditional regression model showed that higher intake of calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese was associated with lower blood Hcy levels. Both Qg-comp and BKMR results consistently indicate that higher intake of mixed minerals is associated with lower blood Hcy levels. Calcium exhibits the highest weight in the joint effect in the WQS model. In Qg-comp, iron has the highest positive weight, while manganese has the highest negative weight. The BKMR results of the subsample after 10,000 iterations showed that except for sodium, all nine minerals had the high weights in the joint effect on the effect of blood Hcy levels. Conclusion Overall, higher mixed mineral’s intake was associated with lower blood Hcy levels, and each mineral contributed differently to the joint effect. Future studies are available to further explore the mechanisms underlying this association, and the potential impact of mixed minerals’ intake on other health indicators needs to be further investigated. These efforts will help provide additional insights to deepen our understanding of mixed minerals and their potential role in health maintenance.

Background Regular rehabilitation during or after cancer treatment can bring numerous benefits to colorectal cancer survivors. However, there is a lack of convenient and mobile rehabilitation support systems tailored specifically for this group. The metaverse, as a virtual reality environment, offers an innovative platform for implementing rehabilitation. Hence, our study aims to develop a metaverse-based multimodal rehabilitation program and assess its effects on enhancing outcome measures such as quality of life in colorectal cancer patients. Methods and analysis This study was designed as a randomized, single-blind controlled trial design featuring two arms: a rehabilitation group and a conventional care group. Sixty colorectal cancer survivors who have undergone curative surgery followed by adjuvant chemotherapy will be recruited for this study. The intervention will take place within the metaverse over a 4-week period. Assessments will be conducted at baseline and after 4 weeks. The intervention is grounded in the behavior change wheel framework and encompasses dietary intervention, exercise intervention, psychological support, and behavior management. Through the implementation of diverse strategies such as training, education, and motivation, our objective is to enhance patients’ capacity, opportunities, and motivation, ultimately fostering healthy behaviors. Outcome measures will encompass quality of life, fear of recurrence, and lifestyle. Results The analysis includes statistical description and inference. Quantitative data will be summarized using mean ± standard deviation for normally distributed data and medians with percentiles for non-normally distributed data. Categorical data will be presented as frequencies and percentages. Statistical tests will detect significant differences between pre- and post-intervention periods. Subgroup analysis will explore CRC stage, age, and gender in relation to outcome measures to identify factors affecting intervention efficacy. Conclusions The findings from this research will offer valuable insights and practical implications for the implementation of remote interventions and family-based interventions in the context of colorectal cancer survivorship. Trial Registration NCT05956990 (Registered 21 July 2023)

Background: Chemoradiotherapy (CRT) is the main treatment for elderly patients with non-metastatic rectal cancer who are ineligible for or decline surgery, but the optimal modality remains unclear. Objectives: This study was to validate the safety and efficacy of comprehensive geriatric assessment (CGA) guided radiotherapy in older patients. Design: An exploratory analysis of a single-arm, multicenter, Phase II trial. Methods: Patients aged over 70 and diagnosed with rectal cancer were enrolled and evaluated by CGA. CGA-guided radiotherapy was individually conducted in a multidisciplinary setting. Patients in fit, intermediate, and frail groups were scheduled to receive CRT, long-course radiotherapy, and short-course radiotherapy (SCRT) alone respectively. Patients who were unfit for or refused surgery were analyzed for acute toxicities and survival outcomes. Results: In a total of 109 enrolled patients, 47 individuals who did not undergo surgery were included, with 26, 9, and 12 categorized into fit, intermediate, and frail groups. Only 11 (23.4%) grade 3 or above toxicities were observed overall. Within a median follow-up of 69.0 months, the 3-year overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) rates were 44.3% (95% CI: 32.1%–61.2%), 25.5% (95% CI: 15.7%–41.6%) and 61.0% (95% CI: 47.8%–77.6%) in total. The 5-year OS, PFS, and CSS reached 15.0% (95% CI: 7.4%–30.3%), 14.6% (95% CI: 7.3%–29.4%), and 36.2% (95% CI: 22.0%–59.4%), with no significant difference among the three subgroups. SCRT ( p

Ophiopogon japonicus (Thunb.) Ker Gawl., is a traditional Chinese medicine (TCM) with a history of thousands of years. O. japonicus polysaccharides (OJPs), as one of the main active ingredient, are a kind of representative pharmacological bioactive macromolecules and mainly composed of Glc and Fru with molecular weight between 2.48 and 325 kDa. OJPs have a variety of biological activities, such as hypoglycemic, cardioprotective, immunomodulatory, improvement of obesity, and renal protective activity. In this review, the extraction, purification and structural characterization of OJPs were systematically reviewed, and its biological function, molecular mechanism and structure–activity relationship were analyzed. Additionally, this review summarized and found that structural modifications such as liposome modification, sulfation modification, and polyethylene glycol modification have improved the pharmacological activity and bioavailability of OJPs. Overall, this work will help to better understand OJPs and provide a theoretical review of their further development and utilization in the field of medicine and health food.

BackgroundAnti-melanoma differentiation-associated gene 5 positive dermatomyositis (MDA5+ DM) is a life-threatening disease due to rapidly progressive interstitial lung disease (RP-ILD). We aimed to investigate the expression profile of T cell subsets in MDA5+ DM patients, seeking for possible disease-causing T cell subsets and potential biomarkers to distinguish ILD, especially RP-ILD patients.MethodsPeripheral blood T cell subpopulations were immunophenotyped in 24 MDA5+ DM patients and 21 healthy controls (HCs) by flow cytometry. The proportion of T cell subsets and clinical characteristics were analyzed. The quantitative determination of cytokines in the plasma was measured by using a microsphere-based immunofluorescence assaying kit.ResultsThe proportion of naïve and CD38+ T cells were much higher, whereas the proportion of central memory T cells were lower in MDA5+ DM patients than in HCs. Notably, the proportion of CD38+CD4+ T cells and CD38+CD8+ T cells on T cells in in RP-ILD group were significantly elevated compared to C-ILD, non-ILD group and HCs. Moreover, serum IFN-α levels were significantly increased in MDA5+ DM patients with RP-ILD. Further, the frequencies of CD38+CD4+ T cells and CD38+CD8+ T cells were positively correlated with IFN-α levels. Finally, ROC analysis indicated that CD38+CD4+ T cells and CD38+CD8+ T cells could be potential biomarkers for predicting ILD/RP-ILD in MDA5+ DM patients.ConclusionDysregulated CD38 expression on T cell subsets was associated with lung involvement, especially RP-ILD in MDA5+ DM patients. CD38+ T cell subsets could be used as potential biomarkers for predicting ILD/RP-ILD in MDA5+ DM patients.