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Abstract Background Our previous genome‑wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated. Methods We assessed the association between variant rs912304 and T1D, as well as islet autoimmunity and islet function, stratified by the diagnosed age of 12. We used epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to prioritize the most likely functional variant and potential causal gene. We also performed functional experiments to evaluate the role of the causal gene on islet function and its related mechanisms. Results We identified rs912304 as a risk variant for T1D subgroups with diagnosed age ≥ 12 but not

The electric power industry is a high-risk industry with frequent accidents. To ensure the life safety of employees and reduce the probability of accidents, it is necessary to utilize certain technical means to identify the main causative factors in electric fatal accident reports. This research proposes an accident causation identification method that combines text categorization and catastrophe association analysis. First, an improved text feature extraction method (TF-IDF-GloVe-LDA) is proposed by fusing term frequency-inverse document frequency (TF-IDF), global vectors for word representation (GloVe), and latent dirichlet allocation (LDA) algorithms. Then, an SVM classifier was used to categorize the 473 accident report texts into five categories, ACCIDENT, PROCESS, CAUSE, PROBLEM, and RESPONSE, based on the extracted text feature vectors. Second, for the 461 CAUSEs categorized from the accident report texts, the TF-IDF algorithm is utilized to mine them to obtain 62 accident causative factors. Using the word cloud map and semantic network, a visualization analysis is performed to reveal the intrinsic connection between causative factors. The human factor analysis and classification system (HFACS) is combined to construct a framework and a Boolean dataset for electric power fatal accident causative factors. Finally, the catastrophe progression method is utilized to improve the FP-growth algorithm and propose a catastrophe association analysis method. It is utilized to mine the Boolean dataset to obtain 28 association rules and construct the accident causal network. The main causative factors were ultimately identified by analyzing the critical causal chains within the network and examining the frequency and sensitivity of each node. The findings of this study indicate that a lack of effective management, supervision, and training serves as the fundamental cause of fatal accidents in the electric power industry when compared to equipment and environmental factors. This paper offered a fresh perspective on identifying primary accident causative factors in non-standardized text and exploring their intricate mechanisms of interaction, which holds significant implications for the pre-control management of accidents in the power industry.

Abstract Background Interest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies. This investigation examined the temporal trajectories of MRFs for dementia in England. Methods We used data from the English Longitudinal Study of Ageing, a panel study over eight waves collected between 2004 and 2019 (76,904 interviews in total). We calculated the PAFs for twelve MRFs (including six early- to mid-life factors and six late-life factors), as recommended by the Lancet Commission, and the individual weighted PAFs (IW-PAFs) for each risk factor. Temporal trends were analysed to understand the changes in the overall PAF and IW-PAF over the study period. Subgroup analyses were conducted by sex and socioeconomic status (SES). Results The overall PAF for dementia MRFs changed from 46.73% in 2004/2005 to 36.79% in 2018/2019, though this trend was not statistically significant. During 2004–2019, hypertension, with an average IW-PAF of 8.21%, was the primary modifiable determinant of dementia, followed by obesity (6.16%), social isolation (5.61%), hearing loss (4.81%), depression (4.72%), low education (4.63%), physical inactivity (3.26%), diabetes mellitus (2.49%), smoking (2.0%), excessive alcohol consumption (1.16%), air pollution (0.42%), and traumatic brain injury (TBI) (0.26%). During 2004–2019, only IW-PAFs of low education, social isolation, and smoking showed significant decreasing trends, while IW-PAFs of other factors either did not change significantly or increased (including TBI, diabetes mellitus, and air pollution). Upon sex-specific disaggregation, a higher overall PAF for MRFs was found among women, predominantly associated with later-life risk factors, most notably social isolation, depression, and physical inactivity. Additionally, hearing loss, classified as an early- to mid-life factor, played a supplementary role in the identified sex disparity. A comparable discrepancy was evident upon PAF evaluation by SES, with lower income groups experiencing a higher dementia risk, largely tied to later-life factors such as social isolation, physical inactivity, depression, and smoking. Early- to mid-life factors, in particular, low education and obesity, were also observed to contribute to the SES-associated divergence in dementia risk. Temporal PAF and IW-PAF trends, stratified by sex and SES, revealed that MRF PAF gaps across sex or SES categories have persisted or increased. Conclusions In England, there was little change over time in the proportion of dementia attributable to known modifiable risk factors. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them.

Abstract Background Proteolysis-targeting chimeras (PROTACs) are being developed for therapeutic use. However, they have poor pharmacokinetic profiles and their tissue distribution kinetics are not known. Methods A typical von Hippel-Lindau tumor suppressor (VHL)—PROTAC 14C-A947 (BRM degrader)—was synthesized and its tissue distribution kinetics was studied by quantitative whole-body autoradiography (QWBA) and tissue excision in rats following IV dosing. Bile duct-cannulated (BDC) rats allowed the elucidation of in vivo clearance pathways. Distribution kinetics was evaluated in the tissues and tumors of mice to support PK-PD correlation. In vitro studies enabled the evaluation of cell uptake mechanisms and cell retention properties. Results Here, we show that A947 quickly distributes into rat tissues after IV dosing, where it accumulates and is retained in tissues such as the lung and liver although it undergoes fast clearance from circulation. Similar uptake/retention kinetics enable tumor growth inhibition over 2–3 weeks in a lung cancer model. A947 quickly excretes in the bile of rats. Solute carrier (SLC) transporters are involved in hepatocyte uptake of PROTACs. Sustained BRM protein degradation is seen after extensive washout that supports prolonged cell retention of A947 in NCI-H1944 cells. A947 tissue exposure and pharmacodynamics are inversely correlated in tumors. Conclusions Plasma sampling for VHL-PROTAC does not represent the tissue concentrations necessary for efficacy. Understanding of tissue uptake and retention could enable less frequent IV administration to be used for therapeutic dosing.

Abstract Objective This study synthesizes evidence from the Loughborough Passing Test to evaluate the short-passing ability of soccer players and summarizes the reported variables that affect this ability to provide support for the development and improvement of short-passing abilities in soccer players. Methods In this systematic review using the PRISMA guidelines, a comprehensive search was conducted in Web of Science, PubMed, and EBSCOhost from inception to July 2023 to identify relevant articles from the accessible literature. Only studies that used the Loughborough test to assess athletes' short-passing ability were included. The quality of the included studies was independently assessed by two reviewers using the PEDro scale, and two authors independently completed the data extraction. Results Based on the type of intervention or influencing factor, ten studies investigated training, nine studies investigated fatigue, nine studies investigated supplement intake, and five studies investigated other factors. Conclusion Evidence indicates that fitness training, small-sided games training, and warm-up training have positive effects on athletes' short-passing ability, high-intensity special-position training and water intake have no discernible impact, mental and muscular exhaustion have a significantly negative effect, and the effect of nutritional ergogenic aid intake is not yet clear. Future research should examine more elements that can affect soccer players' short-passing ability. Trial registration https://inplasy.com/ ., identifier: INPLASY20237.

Abstract Background Internet addiction has an important influence on the development of physical and mental health of college students. The purpose of this study is to evaluate the current status and the correlation between college students’ negative emotion, fatigue level and Internet addiction disorder, and to provide reference for the care and management of college students. Methods We conducted a questionnaire survey on a cluster sample of college students from October to November 15, 2022. Internet addiction scale, fatigue assessment scale and positive and negative emotion scale were used for survey. Pearson correlation analysis and mediating effect test were performed to analyze the correlation and effects. Results A total of 1546 valid questionnaires were collected. The incidence of internet addiction in college student was 20.38%. The total score of internet addiction was 52.94 ± 12.47, the total fatigue score was 69.27 ± 3.19, the score of positive emotion of college students was 31. 41 ± 5.09, and the negative emotion score was 18.54 ± 5.68. The total score of internet addiction were positively correlated with score of negative emotion (all P

Autophagy is a highly conserved process in eukaryotes that is used to recycle the cellular components from the cytoplasm. It plays a crucial function in responding to both biotic and abiotic stress, as well as in the growth and development of plants. Autophagy-related genes (ATG) and their functions have been identified in numerous crop species. However, their specific tasks in potatoes (Solanum tuberosum L.), are still not well understood. This work is the first to identify and characterize the potato StATG18 subfamily gene at the whole-genome level, resulting in a total of 6 potential StATG18 subfamily genes. We analyzed the phylogenetic relationships, chromosome distribution and gene replication, conserved motifs and gene structure, interspecific collinearity relationship, and cis-regulatory elements of the ATG18 subfamily members using bioinformatics approaches. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) analysis suggested that StATG18 subfamily genes exhibit differential expression in various tissues and organs of potato plants. When exposed to heat stress, their expression pattern was observed in the root, stem, and leaf. Based on a higher expression profile, the StATG18a gene was further analyzed under heat stress in potatoes. The subcellular localization analysis of StATG18a revealed its presence in both the cytoplasm and nucleus. In addition, StATG18a altered the growth indicators, physiological characteristics, and photosynthesis of potato plants under heat stresses. In conclusion, this work offers a thorough assessment of StATG18 subfamily genes and provides essential recommendations for additional functional investigation of autophagy-associated genes in potato plants. Moreover, these results also contribute to our understanding of the potential mechanism and functional validation of the StATG18a gene’s persistent tolerance to heat stress in potato plants.

The spatial distribution and source analysis of heavy metals in soil are of great significance for the risk assessment and control of heavy metal pollution. Herein, a total of 87 topsoil samples (0–30 cm) were collected in the areas adjacent to a non-ferrous metal slag field of Gejiu City, Yunnan Province. The typical heavy metal concentrations, available phosphorus, available potassium, ammonium nitrogen, nitrate nitrogen, and pH in each soil sample were determined. Based on the above basic data, distribution and origins of heavy metals was analyzed. The results indicated that the mean contents of Pb, As, Cu, Zn, Ni and Cr in the topsoil of the study site were 247.82, 204.36, 104.83, 411.38, 29.73 and 67.59 mg kg-1, respectively. Exception of the Ni element, the contents of the remaining five heavy metals surpassed their respective background levels in study site. Especially, As element (with the highest accumulation effect) is 11.1l times of the background level, and the remaining four elements are 1.04–6.10 times of the background level in Yunnan. Single factor pollution index showed that the pollution degree of Pb, Cu and Zn was light, and the accumulation of As was a great threat to soil quality. Furthermore, the percentages of sites at mild pollution, moderate pollution and heavy pollution levels were 16.09%, 26.09% and 63.22%, respectively. Additionally, The order of potential ecological hazard degree of soil in the survey area was As > Pb > Cu = Ni > Zn = Cr. The spatial dispersion of heavy metals within the study region is impacted by both natural phenomena and human activities. The areas with severe pollution were the mining area in the northwest and planting sites in the east, middle and south of the study area. The main contribution sources of Ni were the mixed sources of natural parent material and industrial activities. The heavy metal element largely contributed by industrial activities and transportation is Pb. The main sources of metals As, Cu and Zn are the integrated sources of agricultural and industrial activities. The main source of Cr is natural source. Therefore, these useful results can guide the heavy metal pollution control and restoration of study site and this research work can also be used to other similar metal slag field and its affected area.

Abstract Cardiovascular disease, primarily caused by atherosclerotic plaque formation, is a significant health concern. The early detection of these plaques is crucial for targeted therapies and reducing the risk of cardiovascular diseases. This study presents PlaqueNet, a solution for segmenting coronary artery plaques from coronary computed tomography angiography (CCTA) images. For feature extraction, the advanced residual net module was utilized, which integrates a deepwise residual optimization module into network branches, enhances feature extraction capabilities, avoiding information loss, and addresses gradient issues during training. To improve segmentation accuracy, a depthwise atrous spatial pyramid pooling based on bicubic efficient channel attention (DASPP-BICECA) module is introduced. The BICECA component amplifies the local feature sensitivity, whereas the DASPP component expands the network’s information-gathering scope, resulting in elevated segmentation accuracy. Additionally, BINet, a module for joint network loss evaluation, is proposed. It optimizes the segmentation model without affecting the segmentation results. When combined with the DASPP-BICECA module, BINet enhances overall efficiency. The CCTA segmentation algorithm proposed in this study outperformed the other three comparative algorithms, achieving an intersection over Union of 87.37%, Dice of 93.26%, accuracy of 93.12%, mean intersection over Union of 93.68%, mean Dice of 96.63%, and mean pixel accuracy value of 96.55%.

Abstract The COVID-19 pandemic has dramatically threatened the Gulf Cooperation Council (GCC) countries which have a large proportion of foreign workers. The governments of GCC countries have proactively implemented a comprehensive set of policy measures, and up to our knowledge, a systematic analysis of qualitative and quantitative evidence on the government response is still lacking. We summarized the GCC countries’ government response and quantitatively measured that response using four indexes—the Government Response Index, the Stringency Index, the Vaccine Index, and the Initial Response Index, to analyse their response for future pandemic preparedness. Overall, the government response of all the GCC countries to the COVID-19 pandemic has been comprehensive, stringent, and timely. Notably, the GCC countries have implemented comprehensive vaccine policies. In addition, they have worked actively to protect foreign workers to improve their access to health services and secure their essential living conditions, regardless of their immigrant status. All the GCC countries dynamically adjusted their response to the evolving COVID-19 epidemiological burden and started to relax the stringency of the control policies after the Omicron wave, though the governments had different response magnitudes as measured by the four indexes. These findings have provided several important lessons for future pandemic response and preparedness for countries with similar economic, demographic, and health contexts in (1) prompt actions of containment and closure policies with dynamic adjusting, (2) strengthening health system policies, (3) comprehensive vaccination policies with universal access, (4) equitable and free access to testing, diagnosis, and treatment for all, and (5) strengthening the resilience of health systems.

Abstract Background Immunization is a cornerstone of public health. Despite great success, China’s National Immunization Program (NIP) faces challenges, such as the integration of several World Health Organization-recommended vaccines and other systemic issues. The Innovation Laboratory for Vaccine Delivery Research (VaxLab), supported by the Bill & Melinda Gates Foundation and established in 2021 at Duke Kunshan University, focuses on enhancing China’s NIP through research and policy advocacy. This editorial aims to summarize the key findings of the manuscripts published in the collection contributed by VaxLab team and set the future research agenda. Key findings The collection contains eleven manuscripts discussing China’s immunization landscape and strategies to improve coverage, particularly for non-NIP vaccines like human papillomavirus vaccine (HPV), pneumococcal conjugate vaccine (PCV), Haemophilus influenzae type b vaccine (Hib), and rotavirus vaccines. Key findings include: (i) The COVID-19 vaccination campaign demonstrated China’s capacity for rapid, large-scale immunization efforts, suggesting potential for broader vaccine coverage improvements; (ii) Efforts in combating cervical cancer through the HPV vaccine indicate progress but also highlight challenges like vaccine supply and equitable access; (iii) The lag in adopting higher-valent paediatric combination vaccines in China needs attention to address regulatory and health system hurdles; (iv) Disparities in access to non-NIP vaccines underscore the need for government initiatives to improve vaccine coverage, especially for remote areas and marginalized populations; (v) Original studies emphasize the influence of caregivers’ knowledge, health workers’ financial incentives, and concerns about vaccine efficacy on immunization rates; (vi) Case studies from the Weifang City of China and Indonesia to introduce PCV offer insights on successful vaccine introduction strategies and the impact of innovative financing and government support. Conclusion The articles emphasize the need for government leadership, strategic policymaking, and public awareness to enhance vaccine coverage and equity. The VaxLab will continue strengthening China’s NIP by focusing on vaccine financing, emphasizing diversity, equity, and inclusion, and improving maternal vaccination coverage. Research will extend to Southeast Asian and Western Pacific regions, especially in middle-income countries facing challenges in vaccine financing and delivery. The collective efforts outlined in this collection show a commitment to evolving and adapting immunization strategies to meet global health goals and to provide equitable access to vaccines for all. Graphical Abstract

Purpose: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). Methods: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1–28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks. Results: In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P

Abstract Many countries have adopted higher-valent pediatric combination vaccines to simplify vaccination schedules and minimize health expenditures and social costs. However, China is conservative in the use of pediatric combination vaccines. By reviewing and synthesizing quantitative and qualitative data, in this commentary we identify gaps and challenges to combination vaccine use and make recommendations for promoting use of higher-valent pediatric combination vaccines in China. Challenges are in four dimensions: (1) legislation and regulation, (2) immunization schedule design, (3) vaccine awareness and price, and (4) research and development capacity. To optimize the use of combination vaccines to reduce vaccine-preventable disease burden, we make recommendations that address key challenges: (1) develop policies and regulations to strengthen enforcement of the Vaccine Administration Law and remove regulatory hurdles that hinder combination vaccine research and development, (2) establish an evidence-informed policy-making mechanism for combination vaccines, (3) resolve immunization schedule conflicts between monovalent and combination vaccines, and (4) implement effective interventions to increase vaccine awareness and reduce price. Graphical Abstract

Random phase interference is the main factor leading to uneven optical power distribution, which will affect the positioning accuracy of the four-quadrant detector. This paper uses the power spectrum inversion method to simulate the light spot power distribution affected by random phase interference, and studies the subdivision capability characteristics of the four-quadrant detector under different random phase interference. The simulation experiment results show that when the radius of the light spot received by the detector is 1/2 the radius of the detector, both detection range and positioning accuracy can be taken into account. When the random phase interference is enhanced, the detector's subdivision capability decreases. When the random phase interference is small, the detector can achieve more than 100 subdivisions. When the random phase interference is large, the light spot can only achieve 3 subdivision at the edge of the detector target surface. An experimental system was built to test the subdivision capability of the four-quadrant detector, the experimental test results were basically consistent with the simulation results. The research results provide a technical reference for the application of four-quadrant detector. in free space environments.

Abstract Crane usage is pervasive on construction sites, however, it is associated with a notably high accident rate. The analyzing of crane accident risks is essential for accident prevention, control, and ensuring the safety of lifting operations. Hence, significant emphasis should be placed on understanding the interaction among various risk factors. This paper proposes a quantitative coupling method for human, machine, management, and environmental risk factors in crane accidents, leveraging Bayesian networks (BN) and the N-K model. Firstly, text mining technology and fault tree analysis are employed to analyze the causes of crane accidents and categorize the associate risk factors. Secondly, the types of risk coupling resulting from human, machine, management, and environmental risk factors are defined. Thirdly, the BN model is developed based on the analysis of crane accident risksand its N-K model. Fourthly, the parameters of the risk coupling nodes in the developed BN are determined based on the calculation results of the N-K model. Finally, for the risk coupling types with high coupling values and the first-level node and second-level node, the failure probability is analyzed through posterior probability and sensitivity analysis. The results indicate that factors related to man and management significantly impact crane accidents and warrant enhanced attention. The interplay among multiple risk factors significantly influences the probability of crane accidents, necessitating careful attention.

Abstract Background Hepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis‑related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC. Methods The data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan–Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman’s rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2). Results We identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells. Conclusions The DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC.

Gut microbiota of centenarians has garnered significant attention in recent years, with most studies concentrating on the analysis of microbial composition. However, there is still limited knowledge regarding the consistent signatures of specific species and their biological functions, as well as the potential causal relationship between gut microbiota and longevity. To address this, we performed the fecal metagenomic analysis of eight longevous populations at the species and functional level, and employed the Mendelian randomization (MR) analysis to infer the causal associations between microbial taxa and longevity-related traits. We observed that several species including Eisenbergiella tayi, Methanobrevibacter smithii, Hungatella hathewayi, and Desulfovibrio fairfieldensis were consistently enriched in the gut microbiota of long-lived individuals compared to younger elderly and young adults across multiple cohorts. Analysis of microbial pathways and enzymes indicated that E. tayi plays a role in the protein N-glycosylation, while M. smithii is involved in the 3-dehydroquinate and chorismate biosynthesis. Furthermore, H. hathewayi makes a distinct contribution to the purine nucleobase degradation I pathway, potentially assisting the elderly in maintaining purine homeostasis. D. fairfieldensis contributes to the menaquinone (vitamin K2) biosynthesis, which may help prevent age-related diseases such as osteoporosis-induced fractures. According to MR results, Hungatella was significantly positively correlated with parental longevity, and Desulfovibrio also exhibited positive associations with lifespan and multiple traits related to parental longevity. Additionally, Alistipes and Akkermansia muciniphila were consistently enriched in the gut microbiota of the three largest cohorts of long-lived individuals, and MR analysis also suggests their potential causal relationships with longevity. Our findings reveal longevity-associated gut microbial signatures, which are informative for understanding the role of microbiota in regulating longevity and aging.

Background Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients’ condition.Methods An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided.Results A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP.Conslusions Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.

Objective: Mitomycin C (MMC), a DNA-damaging chemotherapeutic, is commonly used clinically for recurrent cervical carcinoma (CC), either alone or in combination. MMC generates DNA damage resulting in CC cell death yet also induces increased AKT-BAD phosphorylation associated with drug resistance and reduced clinical benefit. The present study evaluates the efficacy of combined MMC and a BAD phosphorylation inhibitor in CC. Methods: The association and function of phosphorylation of BAD on serine 99 (pBADS99) for cell survival of both MMC-resistant or sensitive-CC cells was explored. BAD was mutated to BADS99A to examine the requirement of BADS99 for CC cell survival and a novel small-molecule inhibitor of pBADS99 was utilized. Cell proliferation, survival, foci formation, and patient-derived organoids (PDOs) assays were utilized to determine efficacy, synergy and related mechanisms. Results: MMC IC50 was positively correlated to the cell line pBADS99/BAD ratio. Increased BADS99 phosphorylation was observed in both MMC-sensitive or -resistant CC cells after MMC treatment. Inhibition of pBADS99 in CC cell lines produced synergistic apoptosis through BAD-mediated apoptotic pathways and enhanced DNA damage in response to MMC. The concurrent use of pharmacological inhibition of pBADS99 and MMC was synergistic, resulting in diminished cell viability and inducing apoptotic cell death in MMC-sensitive and -resistant CC cell lines or patient-derived organoids. Conclusion: A combination of MMC with inhibition of BAD phosphorylation potentiated efficacy compared to single agent treatment. The potential further development of such strategies may provide outcome benefits to patients with CC.

Summary: p53 regulates multiple signaling pathways and maintains cell homeostasis under conditions of DNA damage and oxidative stress. Although USP7 has been shown to promote p53 stability via deubiquitination, the USP7-p53 activation mechanism has remained unclear. Here, we propose that DNA damage induces reactive oxygen species (ROS) production and activates ATM-CHK2, and CHK2 then phosphorylates USP7 at S168 and T231. USP7 phosphorylation is essential for its deubiquitination activity toward p53. USP7 also deubiquitinates CHK2 at K119 and K131, increasing CHK2 stability and creating a positive feedback loop between CHK2 and USP7. Compared to peri-tumor tissues, thyroid cancer and colon cancer tissues show higher CHK2 and phosphorylated USP7 (S168, T231) levels, and these levels are positively correlated. Collectively, our results uncover a phosphorylation-deubiquitination positive feedback loop involving the CHK2-USP7 axis that supports the stabilization of p53 and the maintenance of cell homeostasis.

Summary: The nematode Caenorhabditis elegans is a powerful model organism for studying the molecular and cellular mechanisms of innate immunity governed by the intestine. Here, we present a protocol to perform C. elegans survival assays to infection by the bacterial pathogen Pseudomonas aeruginosa PA14. Specifically, we describe steps for preparing C. elegans strains and PA14 bacteria for survival assays. This protocol will assist researchers to study genes involved in intestinal innate immunity and gut defense against pathogen infection.For complete details on the use and execution of this protocol, please refer to Liu et al.1 and Zheng et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Purpose Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of diabetes mellitus. In order to decrease the incidence of clinical adverse events, a novel bleeding and thrombosis score is developed in this research. Methods We conducted a retrospective analysis of patient data from two medical centers who were diagnosed with diabetes mellitus and treated with ticagrelor. We gathered information on every patient from the electronic database of the hospital and follow-up. The collected data were statistically analyzed to obtain risk factors for bleeding and ischemic events. Results A total of 851 patients with diabetes mellitus who have been administered ticagrelor are included in our investigation. A total of 76 patients have bleeding events and 80 patients have ischemic events. The analysis of multiple variables indicates that characteristics like the age of >65, having a previous occurrence of bleeding, experiencing anemia, using aspirin, and taking atorvastatin are linked to a higher likelihood of bleeding. Additionally, the age of >65, smoking, having a history of blood clots, and having a BMI ≥ 30 are found to increase the risk of ischemia. Conclusion The A 4 B score established in this study was better than the HAS-BLED score，and the same is true for the ABST score to the CHA 2 DS-VASc score. This new risk assessment model can potentially detect patients who are at high risk for bleeding and ischemic events. For high-risk patients, the dose of ticagrelor can be adjusted appropriately or the medication can be adjusted.(2023-09-11, ChiCTR2300075627)

BackgroundsAs a conserved signaling pathway, mitogen-activated protein kinase (MAPK) cascade regulates cellular signaling in response to abiotic stress. High temperature may contribute to a significant decrease in economic yield. However, research into the expression patterns of StMAPKK family genes under high temperature is limited and lacks experimental validation regarding their role in supporting potato plant growth.MethodsTo trigger heat stress responses, potato plants were grown at 35°C. qRT-PCR was conducted to analyze the expression pattern of StMAPKK family genes in potato plants. Plant with StMAPKK5 loss-of-function and gain-of-function were developed. Potato growth and morphological features were assessed through measures of plant height, dry weight, and fresh weight. The antioxidant ability of StMAPKK5 was indicated by antioxidant enzyme activity and H2O2 content. Cell membrane integrity and permeability were suggested by relative electrical conductivity (REC), and contents of MDA and proline. Photosynthetic capacity was next determined. Further, mRNA expression of heat stress-responsive genes and antioxidant enzyme genes was examined.ResultsIn reaction to heat stress, the expression profiles of StMAPKK family genes were changed. The StMAPKK5 protein is located to the nucleus, cytoplasm and cytomembrane, playing a role in controlling the height and weight of potato plants under heat stress conditions. StMAPKK5 over-expression promoted photosynthesis and maintained cell membrane integrity, while inhibited transpiration and stomatal conductance under heat stress. Overexpression of StMAPKK5 triggered biochemical defenses in potato plant against heat stress, modulating the levels of H2O2, MDA and proline, as well as the antioxidant activities of CAT, SOD and POD. Overexpression of StMAPKK5 elicited genetic responses in potato plants to heat stress, affecting heat stress-responsive genes and genes encoding antioxidant enzymes.ConclusionStMAPKK5 can improve the resilience of potato plants to heat stress-induced damage, offering a promising approach for engineering potatoes with enhanced adaptability to challenging heat stress conditions.

Abstract In this study, three kinds of electrohydrodynamic atomization (EHDA) processes (electrospraying, electrospinning, and coaxial electrospinning) are implemented to create hydroxypropyl methylcellulose (HPMC) based ultra‐thin products for providing the fast dissolution of a poorly water‐soluble drug ketoprofen (KET). An EHDA apparatus, characterized by a novel spinneret, is homemade for conducting the three processes. The three types of products are electrospun nanofibers E1, electrosprayed microparticles E2, and core‐shell nanofibers E3. SEM and TEM results indicate that they have the anticipated morphologies and inner structures. X‐ray diffraction and Fourier Transform Infrared results verify that KET is mainly amorphous in all the composites due to its fine compatibility with HPMC. In vitro dissolution tests demonstrate that the drug rapid release performances has an order of E3>E1>E2≫KET powders. The fast dissolution mechanisms are suggested and the advantages of the three products are compared. The super performance of E3 in furnishing the rapid release is attributed to a synergistic action of small size (of the shell thickness), high porosity, amorphous state of drug, and the solubility of HPMC. EHDA nanostructures can support the development of nano drug delivery systems (DDSs) through tailoring the spatial distribution of drug molecules within the nano products.

ABSTRACTAzoles are the primary antifungal drugs used to treat infections caused by Aspergillus fumigatus. However, the emergence of azole resistance in A. fumigatus has become a global health concern despite the low proportion of resistant isolates in natural populations. In bacteria, antibiotic resistance incurs a fitness cost that renders strains less competitive in the absence of antibiotics. Consequently, fitness cost is a key determinant of the spread of resistant mutations. However, the cost of azole resistance and its underlying causes in A. fumigatus remain poorly understood. In this observation, we revealed that the 10 out of 15 screened azole-resistant isolates, which possessed the most common azole-targeted cyp51A mutations, particularly the presence of tandem repeats in the promoter region, exhibit fitness cost when competing with the susceptible isolates in azole-free environments. These results suggest that fitness cost may significantly influence the dynamics of azole resistance, which ultimately contributes to the low prevalence of azole-resistant A. fumigatus isolates in the environment and clinic. By constructing in situ cyp51A mutations in a parental azole-susceptible strain and reintroducing the wild-type cyp51A gene into the azole-resistant strains, we demonstrated that fitness cost is not directly dependent on cyp51A mutations but is instead associated with the evolution of variable mutations related to conidial germination or other unknown development-related processes. Importantly, our observations unexpectedly revealed that some azole-resistant isolates showed no detectable fitness cost, and some even exhibited significantly increased competitive fitness in azole-free environments, highlighting the potential risk associated with the prevalence of these isolates.IMPORTANCEAzole resistance in the human fungal pathogen Aspergillus fumigatus presents a global public health challenge. Understanding the epidemic trends and evolutionary patterns of azole resistance is critical to prevent and control the spread of azole-resistant isolates. The primary cause is the mutation of the drug target 14α-sterol-demethylase Cyp51A, yet its impact on competitive ability remains uncertain. Our competition assays revealed a diverse range of fitness outcomes for environmental and clinical cyp51A-mutated isolates. We have shown that this fitness cost is not reliant on cyp51A mutations but might be linked to unknown mutations induced by stress conditions. Among these isolates, the majority displayed fitness costs, while a few displayed enhanced competitive ability, which may have a potential risk of spread and the need to closely monitor these isolates. Our observation reveals the variation in fitness costs among azole-resistant isolates of A. fumigatus, highlighting the significant role of fitness cost in the spread of resistant strains.

Abstract Background Non-National Immunization Program (NIP) vaccines have played an important role in controlling vaccine-preventable diseases (VPDs) in China. However, these vaccines are paid out of pocket and there is room to increase their coverage. We focused on four selected non-NIP vaccines in this study, namely Haemophilus influenzae type b (Hib) vaccine, human papillomavirus (HPV) vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine. We aimed to conduct a scoping review of their vaccination rates and the major barriers faced by health systems, providers, and caregivers to increase coverage. Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). We searched five English databases (PubMed, Web of Science, EMBASE, Scopus, and WHO IRIS) and four Chinese databases using the search strategy developed by the study team. Two independent reviewers screened, selected studies, and examined their quality. We summarized the non-NIP vaccine coverage data by vaccine and applied the 5A framework (Access, Affordability, Acceptance, Awareness, Activation) to chart and analyze barriers to increasing coverage. Results A total of 28 articles were included in the analysis (nine pertaining to vaccine coverage, and another 19 reporting challenges of increasing uptake). Among the four selected vaccines, coverage for the Hib vaccine was the highest (54.9–55.9% for 1 dose or more from two meta-analyses) in 2016, while the coverage of the other three vaccines was lower than 30%. Eight of the nine included articles mentioned the regional disparity of coverage, which was lower in under-developing regions. For example, the three-dose Hib vaccination rate in eastern provinces was 38.1%, whereas the rate in central and western provinces was 34.3% and 26.2%, respectively in 2017. Within the 5A framework, acceptance, awareness, and affordability stood out as the most prominent themes. Among the 12 identified sub-themes, high prices, low vaccine awareness, concerns about vaccine safety and efficacy were the most cited barriers to increasing the uptake. Conclusions There is an urgent need to increase coverage of non-NIP vaccines and reduce disparities in access to these vaccines across regions. Concerted efforts from the government, the public, and society are required to tackle the barriers and challenges identified in this study, both on the demand and supply side, to ensure everybody has equal access to life-saving vaccines in China. Particularly, the government should take a prudent approach to gradually incorporate non-NIP vaccines into the NIP step by step, and make a prioritizing strategy based on key factors such as disease burden, financial resources, and market readiness, with special attention to high-risk populations and underdeveloped regions. Graphical Abstract

Abstract Background The impact of multimorbidity on long-term care (LTC) use is understudied, despite its well-documented negative effects on functional disabilities. The current study aims to assess the association between multimorbidity and informal LTC use in China. We also explored the socioeconomic and regional disparities. Methods The study included 10,831 community-dwelling respondents aged 45 years and older from the China Health and Retirement Longitudinal Study in 2011, 2015, and 2018 for analysis. We used a two-part model with random effects to estimate the association between multimorbidity and informal LTC use. Heterogeneity of the association by socioeconomic position (education and income) and region was explored via a subgroup analysis. We further converted the change of informal LTC hours associated with multimorbidity into monetary value and calculated the 95% uncertainty interval (UI). Results The reported prevalence of multimorbidity was 60·0% (95% CI: 58·9%, 61·2%) in 2018. We found multimorbidity was associated with an increased likelihood of receiving informal LTC (OR = 2·13; 95% CI: 1·97, 2·30) and more hours of informal LTC received (IRR = 1·20; 95% CI: 1·06, 1·37), ceteris paribus. Participants in the highest income quintile received more hours of informal LTC care (IRR = 1·62; 95% CI: 1·31, 1·99). The estimated monetary value of increased informal LTC hours among participants with multimorbidity was equivalent to 3·7% (95% UI: 2·2%, 5·4%) of China’s GDP in 2018. Conclusion Our findings substantiate the threat of multimorbidity to LTC burden. It is imperative to strengthen LTC services provision, especially among older adults with multimorbidity and ensure equal access among those with lower income.

Abstract Background Remdesivir is considered to be a specific drug for treating coronavirus disease 2019. This systematic review aims to evaluate the clinical efficacy and risk of remdesivir alone and in combination with other drugs. Research design and methods The PubMed, Embase, SCIE, Cochrane Library, and American Clinical trial Center databases were searched up to 1 April 2022 to identify. Randomized controlled trials (RCTs) and observational studies comparing the efficacy of remdesivir monotherapy and combination therapy with that of control drugs. Results Ten RCTs and 32 observational studies were included in the analysis. Regarding the primary outcome, remdesivir use reduced mortality in patients with severe COVID-19 (RR = 0.57, 95% CI (0.48,0.68)) and shortened the time to clinical improvement (MD = -2.51, 95% CI (-2.75, -2.28)). Regarding other clinical outcomes, remdesivir use was associated with improved clinical status (RR = 1.08, 95%CI (1.01, 1.17)). Regarding safety outcomes, remdesivir use did not cause liver or kidney damage (RR = 0.87, 95%CI (0.68, 1.11)) (RR = 0.88, 95%CI (0.70,1.10)). Compared with remdesivir alone, remdesivir combined with other drugs (e.g., steroids, favipiravir, and convalescent plasma) had no effect on mortality. Conclusion The use of remdesivir can help to reduce the mortality of patients with severe COVID-19 and shorten the time to clinical improvement. There was no benefit of remdesivir combination therapy for other clinical outcomes. Trial registration PROSPERO registration number: CRD42022322859.

The impact of traumatic spinal cord injury (SCI) can be extremely devastating, as it often results in the disruption of neural tissues, impeding the regenerative capacity of the central nervous system. However, recent research has demonstrated that mesenchymal stem cells (MSCs) possess the capacity for multi-differentiation and have a proven track record of safety in clinical applications, thus rendering them effective in facilitating the repair of spinal cord injuries. It is urgent to develop an aligned scaffold that can effectively load MSCs for promoting cell aligned proliferation and differentiation. In this study, we prepared an aligned nanofiber scaffold using the porcine decellularized spinal cord matrix (DSC) to induce MSCs differentiation for spinal cord injury. The decellularization method removed 87% of the immune components while retaining crucial proteins in DSC. The electrospinning technique was employed to fabricate an aligned nanofiber scaffold possessing biocompatibility and a diameter of 720 nm. In in vitro and in vivo experiments, the aligned nanofiber scaffold induces the aligned growth of MSCs and promotes their differentiation into neurons, leading to tissue regeneration and nerve repair after spinal cord injury. The approach exhibits promising potential for the future development of nerve regeneration scaffolds for spinal cord injury treatment.

Abstract Autism spectrum disorder (ASD) presents a significant risk to human well‐being and has emerged as a worldwide public health concern. Twenty‐eight children with ASD and 33 healthy children (HC) were selected for the quantitative determination of their plasma metabolites using an ultraperformance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) platform. A total of 1997 metabolites were detected in the study cohort, from which 116 metabolites were found to be differentially expressed between the ASD and HC groups. Through analytical algorithms such as least absolute shrinkage selection operator (LASSO), support vector machine (SVM), and random forest (RF), three potential metabolic markers were identified as FAHFA (18:1(9Z)/9‐O‐18:0), DL‐2‐hydroxystearic acid, and 7(S),17(S)‐dihydroxy‐8(E),10(Z),13(Z),15(E),19(Z)‐docosapentaenoic acid. These metabolites demonstrated superior performance in distinguishing the ASD group from the HC group, as indicated by the area under curves (AUCs) of 0.935, 0.897, and 0.963 for the three candidate biomarkers, respectively. The samples were divided into training and validation sets according to 7:3. Diagnostic models were constructed using logistic regression (LR), SVM, and RF. The constructed three‐biomarker diagnostic model also exhibited strong discriminatory efficacy. These findings contribute to advancing our understanding of the underlying mechanisms involved in the occurrence of ASD and provide a valuable reference for clinical diagnosis.

Based on the fluid-efficient flow pattern global construction heat transfer enhancement mechanism, a novel evaporator, called the efficient flow pattern global construction evaporator (EFGE), is presented to improve the in-tube evaporation heat transfer at low quality. The numerical analysis and experimental study of EFGE's thermodynamic performance are performed. Results show that the temperature distribution characteristic of the fluid-efficient heat transfer flow pattern construction is better than that of the initial fluid. The evaporation heat transfer coefficient (HTC) of EFGE is 0.34–1.04 times that of a common parallel flow evaporator (PFE), and the pressure drop of EFGE is only 80%–116 % of that of a common PFE at the quality of 0.9. The theoretical nonuniformity of the evaporation HTC between low- and high-quality flow is approximately 12%–67 %, which is 55%–72 % of the pressure drop. The numerical analysis results agree with the finding that EFGE has better thermodynamic performance than PFE in terms of friction power reduction and minimum entropy generation number.

BackgroundPeople living with HIV (PLWH) are susceptible to social isolation as a result of stigma and discrimination, which not only diminishes adherence to antiretroviral therapy but also heightens the risks of hospital readmission, depression, and mortality. However, there is currently no systematic review addressing the occurrence and impact of social isolation in individuals with HIV. Therefore, this study undertook a comprehensive systematic review and meta-analysis of existing literature to examine the prevalence and influencing factors associated with social isolation among PLWH.Methods and analysisPubMed, EMBASE, CINAHL, Cochrane Library, Web of Science, Google Scholar, China Science and Technology Journal Database, The China National Knowledge Infrastructure, WanFang Data and Chinese Biomedicine Literature Database will be searched from the establishment of the database to the latest search date. Literature screening, data extraction and literature quality assessment will be done independently by two researchers and results will be cross-referenced. Data analysis will be performed using stata15.1 software. Risk of publication bias will be assessed using Begg's and Egger's methods. Heterogeneity between studies will then be assessed using the I2 index and its 95% CI and Q statistics. Sources of heterogeneity will be accounted for by subgroup and sensitivity analyses.ResultsThe results may reveal the prevalence of social isolation among PLWH and provide data support for understanding its etiology and prevention.ConclusionBy systematically reviewing the existing literature on social isolation among PLWH, this study aims to provide a comprehensive understanding of the prevalence of social isolation within this population, elucidate the detrimental effects it poses for people affected by HIV, and effectively inform targeted interventions for high-risk groups. Furthermore, these findings offer valuable insights to support evidence-based decision-making in public health policy.Systematic review registrationPROSPERO registration number: CRD42024499044.

Biodiversity of local communities has been found to generally decrease with elevation. However, the elevational patterns of intraspecific genetic diversity remain unclear, especially in passive dispersers and species with short life histories. In this study, we investigated the populations of a tropical dominant Cladoceran, Diaphanosoma dubium, along elevation in the largest watershed of South China. The studied populations were grouped into four regional groups based on elevation and habitat connectivity. No significant elevation pattern was observed for mitochondrial genetic diversity, but nuclear diversity was influenced by habitat type. The haplotype network showed a radial pattern with a common haplotype at the centre, and many private haplotypes existed in each regional group. Four clusters of D. dubium populations were identified and exactly corresponding to the four investigated regions, indicating a strong spatial genetic structure. Weak but significant isolation by distance (IBD) supported the critical role of environmental selection with elevation. Precipitation significantly explained population genetic variation at the watershed scale. Bidirectional gene flow was a common pattern that occurred among the four regional groups. Our results highlight that habitat selection with gene flow plays an important role in shaping the genetic pattern of tropical freshwater Cladocera along an elevational gradient.

Abstract The rhizosheath, or the layer of soil closely adhering to roots, can help plants to tolerate drought under moderate soil drying conditions. Rhizosheath formation is the result of poorly understood interactions between root exudates, microbes, and soil conditions. Here, we study the roles played by the soil microbiota in rhizosheath formation in barley (a dry crop). We show that barley rhizosheath formation is greater in acid soil than in alkaline soil, and inoculation with microbiota from acid soil enhances rhizosheath formation in alkaline soil. The rhizosheath-promoting activity is associated with the presence of Flavobacteriaceae and Paenibacillaceae bacteria that express genes for biosynthesis of indole-3-acetic acid (IAA, a common auxin), as determined by metagenomics and metatranscriptomics. Two bacterial strains isolated from rhizosheath (Chryseobacterium culicis and Paenibacillus polymyxa) produce IAA and enhance barley rhizosheath formation, while their IAA-defective mutants are unable to promote rhizosheath formation. Co-inoculation with the IAA-producing strains enhances barley grain yield in field experiments through an increase in spike number. Our findings contribute to our understanding of barley rhizosheath formation, and suggest potential strategies for crop improvement.

Abstract Breast cancer is the most common cancer and the leading cause of cancer death among females worldwide. During the past 15 years, quality of life (QOL) has become an important aspect of breast cancer treatment. The purpose of this study was to evaluate QOL of breast cancer patients in China, and investigate its associations with sociodemographic and clinical variables. A cross-sectional study was conducted in 246 breast cancer patients in China. Recruited patients were surveyed for QOL using the QOL instruments for cancer patients-breast cancer QLICP-BR (V2.0). We assessed the associations between potential influencing factors and QOL using multiple linear regression models. The general mean QOL score for our population was 70.24 with SD = 8.70. Results indicated that medical insurance, drinking history, alkaline phosphatase, serum chloride ion level, serum calcium ion level, serum phosphorus ion level, mean corpuscular volume, mean corpuscular hemoglobin, red cell volume distribution width and platelet had significant associations with QOL of breast cancer patients. Our results emphasized that many factors are affecting QOL of breast cancer patients, which may provide a reference for targeted management or intervention strategies of breast cancer patients to improve their QOL.

ABSTRACTIn this study, the quality characteristics of the following foodstuffs were studied: waxy rice, three varieties of Taiwanese banana, and banana rice cakes prepared using ripe or unripe fruit. The proportions of resistant starch (RS), total starch, and amylose were significantly higher in the ripe bananas than in the unripe bananas (p

Abstract Background Little is known about the relationship between early life body size and occurrence of life-course multiple chronic diseases (multimorbidity). We aim to evaluate associations of birth weight, childhood body size, and their changes with the risks of chronic diseases and multimorbidity. Methods This prospective cohort study included 246,495 UK Biobank participants (aged 40–69 years) who reported birth weight and childhood body size at 10 years old. Birth weight was categorized into low, normal, and high; childhood body size was reported as being thinner, average, or plumper. Multimorbidity was defined as having two or more of 38 chronic conditions retrieved from inpatient hospital data until 31 December, 2020. The Cox regression and quasi-Poisson mixed effects models were used to estimate the associations. Results We show that 57,071 (23.2%) participants develop multimorbidity. Low birth weight (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.26–1.33), high birth weight (HR 1.02, 95% CI > 1.00–1.05), thinner (HR 1.21, 95% CI 1.18–1.23) and plumper body size (HR 1.06, 95% CI 1.04–1.09) are associated with higher risks of multimorbidity. A U-shaped relationship between birth weight and multimorbidity is observed. Changing to be thinner or plumper is associated with multimorbidity and many conditions, compared to changing to be average. Conclusions Low birth weight, being thinner and changing to have a thinner body size in childhood are associated with higher risks of developing multimorbidity and many chronic conditions in adulthood. Early monitoring and maintaining a normal body size in childhood could have life-course benefits for preventing multimorbidity above and beyond individual conditions.

Background/Aims Long-term immunosuppressive therapies used to treat inflammatory bowel disease (IBD) are associated with an increased risk of infections, many of which can be prevented by vaccination. We assessed physicians’ current approaches and clinical practices regarding vaccinations for IBD patients in different Asian countries/regions. Methods An internet-based survey was conducted among members of the Asian Organization for Crohn’s and Colitis from September 2020 to November 2020. The questionnaire consisted of 2 parts covering general opinion on the relevance of vaccinations and clinical practice of vaccination. Results Overall, 384 Asian medical doctors responded to the survey. The majority of respondents considered it very (57.6%) or sufficiently (39.6%) important to perform vaccinations as recommended by the guidelines. About half of the Asian physicians (52.6%) were usually or always performing vaccinations. The influenza vaccine was the most frequently recommended vaccine for IBD patients. Half of the respondents (51.3%) did not recommend hepatitis A vaccine, especially in China (61.6%) and Japan (93.6%). The diphtheria, tetanus, and pertussis vaccine were never (35.2%) or rarely (29.4%) recommended. Conclusions The findings of this survey indicated similarities among countries/regions in terms of the current approaches and practices regarding vaccination of IBD patients; however, there are some differences that might reflect each country’s domestic vaccination guidelines and health insurance particularly with certain vaccines in some countries/regions. Although Asian physicians largely recommend vaccination, more awareness among doctors and Asian consensus regarding differences in IBD vaccination among countries/regions may be required.

Abstract Nuclear factor I B (NFIB) plays an important role in tumors. Our previous study found that NFIB can promote colorectal cancer (CRC) cell proliferation in acidic environments. However, its biological functions and the underlying mechanism in CRC are incompletely understood. Nicotinamide adenine dinucleotide (NAD+) effectively affects cancer cell proliferation. Nevertheless, the regulatory mechanism of NAD+ synthesis in cancer remains to be elucidated. Here we show NFIB promotes CRC proliferation in vitro and growth in vivo, and down-regulation of NFIB can reduce the level of NAD+. In addition, supplementation of NAD+ precursor NMN can recapture cell proliferation in CRC cells with NFIB knockdown. Mechanistically, we identified that NFIB promotes CRC cell proliferation by inhibiting miRNA-182-5p targeting and binding to NAMPT, the NAD+ salvage synthetic rate-limiting enzyme. Our results delineate a combination of high expression of NFIB and NAMPT predicted a clinical poorest prognosis. This work provides potential therapeutic targets for CRC treatment.

In dynamic space networks, achieving high precision and fast initial pointing of the optical line of sight (LOS) is the key goal in developing this technology. It is the premise and basis of realizing optical LOS capture. Based on the composition and working principle of space optical networking systems, and the effect of real-time position and attitude changes on LOS initial pointing between networks, the matrix transformation and transfer principle is used to establish a multi-link LOS initial pointing model and analyze the factors affecting the size of the field of uncertainty (FOU). In a dynamic space optical networking experiment, the “one-to-two” simultaneous LOS pointing test is carried out, which shows that the model can realize the function of multi-link LOS initial pointing. The sizes of the FOU of the test terminal are 8.67 mrad and 8.34 mrad, respectively, with an average capture time of 18.3 s.

Abstract In the computer-aided diagnosis system, the use of medical database data mining and knowledge discovery technology is of great significance and necessity of development. To understand the health status of left-behind children in ethnic minority areas, a questionnaire survey and computer-aided technology were used to diagnose and investigate the health status of left-behind children aged 6–12 years in Xiangxi, Hunan Province, such as body shape, physical function and personal cognition. The comparison results show that the body shape, function and perception of left-behind children are not optimistic. The countermeasures are to strengthen policy support, school physical education and the supervision consciousness of the guardian, make the government, schools and families form a joint force, establish a scientific work and leisure system, improve the quality of life, and effectively build the health level of left-behind children.

Abstract Background There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. Methods Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn’s disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. Results Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. Conclusions The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.

Abstract Quantum simulation enables study of many-body systems in non-equilibrium by mapping to a controllable quantum system, providing a powerful tool for computational intractable problems. Here, using a programmable quantum processor with a chain of 10 superconducting qubits interacted through tunable couplers, we simulate the one-dimensional generalized Aubry-André-Harper model for three different phases, i.e., extended, localized and critical phases. The properties of phase transitions and many-body dynamics are studied in the presence of quasi-periodic modulations for both off-diagonal hopping coefficients and on-site potentials of the model controlled respectively by adjusting strength of couplings and qubit frequencies. We observe the spin transport for initial single- and multi-excitation states in different phases, and characterize phase transitions by experimentally measuring dynamics of participation entropies. Our experimental results demonstrate that the recently developed tunable coupling architecture of superconducting processor extends greatly the simulation realms for a wide variety of Hamiltonians, and can be used to study various quantum and topological phenomena.

Algal–bacterial symbiotic system is ubiquitous in natural water and has an important impact on water quality and environment such as algal toxins from extracellular secretions. In general, the species diversity and abundance of this system can be dynamically regulated by quorum sensing (QS). However, very little is known about extracellular secretions of algal–bacterial symbiotic system under the QS process. In this study, the effects of N-acylhomoserine lactones (AHLs) on the algal–bacterial symbiotic system were investigated. When the supplemental concentration was between 250 and 500 μg/L, the biological dry weight, Chl-a, and phycocyanin of algae cells and the fluorescence intensity of extracellular humic acid and fulvic acid increased greatly. Whereas, when the supplemental concentration was greater than 750 μg/L, the concentration of Chl-a and phycocyanin showed opposite patterns. This result indicates that AHLs can mediate communication between algae cells and bacteria, and bacteria can regulate the growth of algae by secreting signal molecules. The results of this study also provide useful information for blue-green algae outbreaks prediction by changing trend of AHLs in water. HIGHLIGHTS The amount of endogenous AHLs is closely related to algal growth.; The exogenous AHLs can regulate algae-bacterial symbiotic system.; The changing trend of AHLs in water may predict blue-green algae outbreaks.;

Progress in medicine requires not only innovation and development in the medical field but also the integration of the technology of other fields into the medical field. As an important technological advancement, three-dimensional (3D) reconstruction transforms traditional two-dimensional images into 3D images that are more consistent with the physiological habits of human eyes. It has been applied to the bones, heart, liver, and maxillofacial area, promoting the progress of medical technology and surgeons. This article introduces the progress of 3D reconstruction technology in the clinical application of pancreatic surgery, from the preoperative, intraoperative, and postoperative perspectives, as well as the education of young surgeons. It also puts forward new ideas for the further development of pancreatic surgery.

Here the author study Self-trapped exciton emission for multiphoton excited luminescence in ZnO nanoparticle which until now have not been explored. They provide a reason for the emission enhancement and apply these materials in optical imaging for a proof of concept.

Neurochemicals, crucial for nervous system function, influence vital bodily processes and their fluctuations are linked to neurodegenerative diseases and mental health conditions. Monitoring these compounds is pivotal, yet the intricate nature of the central nervous system poses challenges. Researchers have devised methods, notably electrochemical sensing with micro-nanoscale electrodes, offering high-resolution monitoring despite low concentrations and rapid changes. Implantable sensors enable precise detection in brain tissues with minimal damage, while microdialysis-coupled platforms allow in vivo sampling and subsequent in vitro analysis, addressing the selectivity issues seen in other methods. While lacking temporal resolution, techniques like HPLC and CE complement electrochemical sensing’s selectivity, particularly for structurally similar neurochemicals. This review covers essential neurochemicals and explores miniaturized electrochemical sensors for brain analysis, emphasizing microdialysis integration. It discusses the pros and cons of these techniques, forecasting electrochemical sensing’s future in neuroscience research. Overall, this comprehensive review outlines the evolution, strengths, and potential applications of electrochemical sensing in the study of neurochemicals, offering insights into future advancements in the field.

This paper presents the development of a photoelectrochemical sensor for hypochlorous acid (HOCl) detection, employing a phenothiazine-based organic photosensitizer (Dye-PZ). The designed probe, Dye-PZ, follows a D-π-A structure with phenothiazine as the electron-donating group and a cyano-substituted pyridine unit as the electron-accepting group. A specific reaction of the phenothiazine sulfur atom with HOCl enables selective recognition. The covalent immobilization of Dye-PZ onto a titanium dioxide nanorod-coated fluorine-doped tin oxide electrode (FTO/TiO2) using bromo-silane coupling agent (BrPTMS) resulted in the fabrication of the photoanode FTO/TiO2/BrPTMS/Dye-PZ. The photoanode exhibited a significant photoresponse under visible-light irradiation, with a subsequent reduction in photocurrent upon reaction with HOCl. The oxidation of the phenothiazine sulfur atom to a sulfoxide diminished the internal charge transfer (ICT) effect. Leveraging this principle, the successful photoelectrochemical sensing of HOCl was achieved. The sensor showed high stability, excellent reproducibility, and selective sensitivity for HOCl detection. Our study provides a novel approach for the development of efficient photoelectrochemical sensors based on organic photosensitizers, with promising applications in water quality monitoring and biosensing.