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Abstract Background Pulmonary fibrosis (PF) is an aging-related progressive lung disorder. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis. Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine, yet it remains unclear how IL-10 deficiency-induced immunosenescence participates in the development of PF. Methods Firstly we evaluated the susceptibility to fibrosis and IL-10 expression in aged mice. Then 13-month-old wild-type (WT) and IL-10 knockout (KO) mice were subjected to bleomycin(BLM) and analyzed senescence-related markers by PCR, western blot and immunohistochemistry staining of p16, p21, p53, as well as DHE and SA-β-gal staining. We further compared 18-month-old WT mice with 13-month-old IL-10KO mice to assess aging-associated cell senescence and inflamation infiltration in both lung and BALF. Moreover, proliferation and apoptosis of alveolar type 2 cells(AT2) were evaluated by FCM, immunofluorescence, TUNEL staining, and TEM analysis. Recombinant IL-10 (rIL-10) was also administered intratracheally to evaluate its therapeutic potential and related mechanism. For the in vitro experiments, 10-week-old naïve pramily lung fibroblasts(PLFs) were treated with the culture medium of 13-month PLFs derived from WT, IL-10KO, or IL-10KO + rIL-10 respectively, and examined the secretion of senescence-associated secretory phenotype (SASP) factors and related pathways. Results The aged mice displayed increased susceptibility to fibrosis and decreased IL-10 expression. The 13-month-old IL-10KO mice exhibited significant exacerbation of cell senescence compared to their contemporary WT mice, and even more severe epithelial-mesenchymal transition (EMT) than that of 18 month WT mice. These IL-10 deficient mice showed heightened inflammatory responses and accelerated PF progression. Intratracheal administration of rIL-10 reduced lung CD45 + cell infiltration by 15%, including a 6% reduction in granulocytes and a 10% reduction in macrophages, and increased the proportion of AT2 cells by approximately 8%. Additionally, rIL-10 significantly decreased α-SMA and collagen deposition, and reduced the expression of senescence proteins p16 and p21 by 50% in these mice. In vitro analysis revealed that conditioned media from IL-10 deficient mice promoted SASP secretion and upregulated senescence genes in naïve lung fibroblasts, which was mitigated by rIL-10 treatment. Mechanistically, rIL-10 inhibited TGF-β-Smad2/3 and PTEN/PI3K/AKT/ERK pathways, thereby suppressing senescence and fibrosis-related proteins. Conclusions IL-10 deficiency in aged mice leads to accelerated cell senescence and exacerbated fibrosis, with IL-10KO-PLFs displaying increased SASP secretion. Recombinant IL-10 treatment effectively mitigates these effects, suggesting its potential as a therapeutic target for PF. Graphical Abstract

Abstract Background The management of non-communicable diseases (NCDs) has benefited from telehealth services. As these services which include teleconsultation services and e-prescriptions are relatively new in Malaysia, the data generated provide an unprecedented opportunity to study medication use patterns for the management of NCDs in the country. We analyze e-prescriptions from a local telehealth service to identify medication use patterns and potential areas to optimize medication use in relation to clinical practice guidelines. Methods A cross sectional observational study was conducted by retrieving e-prescription records retrospectively from a telehealth service. 739,482 records from January 2019 to December 2021 were extracted using a designated data collection form. Data cleaning, standardization and data analysis were performed using Python version 3.11. The diagnoses were classified according to the International Classification of Disease 10 (ICD-10), while medications were classified using the Anatomical Therapeutic Chemical (ATC) system. Diagnoses, frequency of use for medication classes and individual medications were analyzed and compared to clinical practice guidelines. Results The top five NCD diagnoses utilized by the service were hypertension (37.7%), diabetes mellitus (25.1%), ischemic heart disease (24.3%), asthma (14.4%), and dyslipidemia (11.7%). Medications were prescribed mostly in accordance with guideline recommendations. However, angiotensin receptor blockers (ARBs) were significantly more frequently prescribed compared to angiotensin converting enzyme inhibitors (ACEIs). Several medication classes appeared underutilized, including ACEIs in hypertensive patients with diabetes or ischemic heart disease, sodium glucose cotransporter 2 inhibitors in diabetic patients with ischemic heart disease, and metformin in patients with diabetes. Conclusions Telehealth services are currently being utilized for the management of NCDs. Medication use for the management of NCDs through these services are mostly in accordance with guideline recommendations, but there exist areas that would warrant further investigation to ensure optimal clinical and economic outcomes are achieved.

Abstract Acute pancreatitis (AP) is a common disease caused by a variety of causes. Is uric acid associated with the onset of AP? The objective of this study was to assess whether uric acid concentration in AP patients was higher than that in healthy population, and whether there were associations between uric acid concentration and serological indicators related to AP. A total of 205 AP patients were included in this study. Two hundred and five people who underwent physical examination in our hospital were randomly selected as controls. We analyzed whether there was difference in uric acid concentrations between the two groups. If the difference was statistically significant, the correlations between uric acid concentration and serological indicators in AP patients was further analyzed. There was significant difference in uric acid concentration (P

Abstract Introduction COVID-19 has demonstrated the importance of competent staff with expertise in public health emergency preparedness and response in the civil aviation system. The civil aviation system is a critical sentinel and checkpoint to prevent imported cases and slow the spread of communicable diseases. Understanding the current competencies of staff to deal with public health emergencies will help government agencies develop targeted training and evidence-based policies to improve their public health preparedness and response capabilities. Methods This cross-sectional pilot study was conducted from November 2022 to October 2023, involving 118 staff members from various positions within China’s civil aviation system. A 59-item questionnaire was translated and developed according to a competency profile. Data were collected using the self-report questionnaire to measure the workforce’s self-perceptions of knowledge and skills associated with public health emergency proficiency, categorized into (1) general competency, (2) preparedness competency, (3) response competency, and (4) recovery competency. KMO & Bartlett test and Cronbach’s α reliability analysis were used to test the reliability and validity of the questionnaire. Descriptive statistics, independent sample T-test, ANOVA, and linear regression models were performed to analyze the competencies. Results A total of 107 staff members from the aviation system were surveyed in this study. The KMO & Bartlett test, (KMO = 0.919, P

Background: Chronic kidney disease (CKD) is associated with increased bleeding and thrombotic risks. Standard blood tests do not sufficiently quantify these risks. Global coagulation assays (GCAs) provide a more comprehensive assessment of coagulation. Objectives: We aimed to evaluate if GCAs are predictive of spontaneous major bleeding (sMB) in CKD. Methods: Adult patients with CKD (estimated glomerular filtration rate,

The increasing intensity of human activities has led to a critical environmental challenge: widespread metal pollution. Manganese (Mn) oxides have emerged as potentially natural scavengers that perform crucial functions in the biogeochemical cycling of metal elements. Prior reviews have focused on the synthesis, characterization, and adsorption kinetics of Mn oxides, along with the transformation pathways of specific layered Mn oxides. This review conducts a meticulous investigation of the molecular-level adsorption and oxidation mechanisms of Mn oxides on hazardous metals, including adsorption patterns, coordination, adsorption sites, and redox processes. We also provide a comprehensive discussion of both internal factors (surface area, crystallinity, octahedral vacancy content in Mn oxides, and reactant concentration) and external factors (pH, presence of doped or pre-adsorbed metal ions) affecting the adsorption/oxidation of metals by Mn oxides. Additionally, we identify existing gaps in understanding these mechanisms and suggest avenues for future research. Our goal is to enhance knowledge of Mn oxides' regulatory roles in metal element translocation and transformation at the microstructure level, offering a framework for developing effective metal adsorbents and pollution control strategies.

Antibiotic resistance is fast spreading globally, leading to treatment failures and adverse clinical outcomes. This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization’s global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus. Several novel drug candidates have shown promising results from in vitro and in vivo studies, as well as clinical trials. The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small molecules with potential antibacterial effects screened by computational receptor docking. As drug discovery progresses, preclinical and clinical studies should also be extensively conducted on the currently available therapeutic agents to unravel their potential antibacterial effect and spectrum of activity, as well as safety and efficacy profiles.

Abstract Background Health policy competencies of regional organizations include mandates to create regional health laws and policies, as well as authorities that allow member states to undertake collective actions in the health field. The examination of the health policy competencies of regional organizations is essential, as it constitutes an important prerequisite for regional organizations to govern regional health. This study aims to map the development trajectory of health policy competencies in regional organizations worldwide and investigate their potential correlates. This will contribute to the enhanced promotion of both existing and new regional health cooperation. Methods This retrospective analysis utilized the health policy competencies of the 76 regional organizations worldwide from 1945 to 2015, as investigated in the Regional Organizations Competencies Database. By aggregating member state data from various sources such as the IHME Global Burden of Disease 2019, the World Bank, and the World Trade Organization, we extracted the mean values and coefficients of variation for the covariates in regional organization characteristics, socioeconomic and demographic factors, health status and health-system capacity. The correlation between changes in the health policy scope of regional organizations and independent variables was analyzed using Poisson pseudo-likelihood regression with multiple levels of fixed effects. Results From 1945 to 2015, the number of regional organizations with health policy competencies experienced a slow growth stage before 1991 and an explosive growth stage post-1991. By 2015, 48 out of the 71 existing regional organizations had developed their health policy competencies, yet 26 (54.2%) of these organizations possessed only 1–2 health policy competencies. An enhancement in the health policy scope of a regional organization correlated with its founding year, a greater number of policy fields, higher under-five mortality, and larger disparities in trade and healthcare access and quality indexes among member states. In contrast, larger disparities in population, under-five mortality and health worker density among member states, along with more hospital beds per capita, were negatively correlated with the expansion of a regional organization’s health policy scope. Conclusion Since 1991, there has been a surge of interest in health among regional organizations, although health remains a secondary priority for them. The health policy competencies of regional organizations are pivotal for promoting social equity within regional communities. Its establishment is also closely linked to the level and disparities among member states in aspects such as trade, population, child mortality rates, and health system capacity.

Reading therapy is an effective approach for improving mental states or addressing disabilities associated with individuals’ dyslexia. In traditional approaches, this process is performed through the intervention and supervision of an expert, which incurs time and cost. However, by utilizing artificial intelligence technologies, the reading therapy process can be automated. This article focuses on presenting an internet-based automated platform for reading therapy. In this method, audio and visual features during the reading therapy are processed using deep learning techniques to identify the individual’s emotional state based on their reading status. In this state, two separate convolutional neural networks are used to describe the facial image features and speech characteristics of the individual. Then, the described features from these two models are merged to determine the individual’s mental states using LSTM layers. Finally, a reinforcement learning model is used to provide feedback and design subsequent exercises. This reinforcement approach leads to continuous improvement of the evaluated process and plays a significant role in enhancing the efficiency of the internet-based reading therapy system. The performance of the proposed method has been evaluated based on information from 20 volunteers. According to the results, the proposed method can effectively improve individuals’ mental states and compete with the conventional supervisor-based approaches. The performance of the proposed deep learning models in identifying emotional states has also been investigated. The results indicate that this model achieves a minimum improvement of 9.71% in emotional state recognition compared to previous research, with an average correlation coefficient of 0.64485.

Torsades de Pointes (TdP) is a malignant polymorphic ventricular tachycardia with heart rate corrected QT interval (QTc) prolongation, which may be attributed to congenital and acquired factors. Although various acquired factors for TdP have been summarized, levosimendan administration in complex postoperative settings is relatively uncommon. Timely identification of potential causes and appropriate management may improve the outcome. Herein, we describe the postoperative case of a 56-year-old female with initial normal QTc who accepted the administration of levosimendan for heart failure, suffered TdP, cardiac arrest, and possible Takotsubo cardiomyopathy, further genetically confirmed as long QT syndrome type 1 (LQT1). The patient was successfully treated with magnesium sulfate, atenolol, and implantable cardioverter defibrillator implantation. There should be a careful evaluation of the at-risk populations and close monitoring of the electrocardiograms, particularly the QT interval, to reduce the risk of near-fatal arrhythmias during the use of levosimendan.

Abstract Primary health care (PHC) is the most effective way to improve people's health and well-being, and primary care services should act as the cornerstone of a resilient health system and the foundation of universal health coverage. To promote high quality development of PHC, an International Symposium on Quality Primary Health Care Development was held on December 4–5, 2023 in Beijing, China, and the participants have proposed and advocated the Beijing Initiative on Quality Primary Health Care Development. The Beijing Initiative calls on all countries to carry out and strengthen 11 actions: fulfill political commitment and accountability; achieve “health in all policies” through multisectoral coordination; establish sustainable financing; empower communities and individuals; provide community-based integrated care; promote the connection and integration of health services and social services through good governance; enhance training, allocation and motivation of health workforce, and medical education; expand application of traditional and alternative medicine for disease prevention and illness healing; empower PHC with digital technology; ensure access to medicinal products and appropriate technologies; and last, strengthen global partnership and international health cooperation. The Initiative will enrich the content of quality development of PHC, build consensus, and put forward policies for quality development of PHC in China in the new era, which are expected to make contributions in accelerating global actions.

Abstract When faced with incivility from service recipients, do volunteers feel damaged? As few previous studies have explored this issue, this study uses the conservation of resources theory to investigate the mechanisms through which incivility affects volunteer engagement and burnout, based on three-wave survey data from 1675 volunteers. This study develops a moderated mediation model to examine the effect of incivility on volunteer outcomes. We find that incivility affected volunteers’ subsequent outcomes, reducing engagement and increasing volunteer burnout by lowering volunteers’ psychological detachment. Volunteers’ hostile attribution bias played a moderating role, amplifying the negative impact of incivility on psychological detachment. Hostile attribution bias also enhanced the mediating effect of incivility on volunteer engagement and increased volunteer burnout by reducing psychological detachment. Besides developing a moderated mediation model, this study also proposes that managers should pay attention to strengthening volunteer training and providing psychological counseling to improve psychological detachment for volunteers experienced with incivility from service recipients.

Abstract Social phobia (SP) refers to excessive anxiety about social interactions. College students, with their exposure to academic, familial, and job-related pressures, are an ideal population for early screening and intervention of social phobia. Additionally, COVID-19 prevention measures including keeping social distance may further impact social phobia. This study aims to investigate the influencing factors of social phobia among Chinese college students and to tentatively explore the impact of COVID-19 prevention measures on social phobia. Respondents were recruited through Chinese Internet social platforms for an online survey. College students’ social phobia scores in pre- and early-COVID-19 periods were measured using Peters' short form of the Social Interaction Anxiety Scale and Social Phobia Scale (SIAS-6/SPS-6). Demographic information, family information, social relations, self-evaluation, and subjective feelings regarding the impact of COVID-19 preventive measures on social phobia were collected. A multivariable logistic regression model was used to analyze the influencing factors. A total of 1859 valid questionnaires were collected, revealing that the social phobia scores increased from 12.3 ± 11.9 to 13.4 ± 11.9 between pre- and early-COVID-19 periods, with an increase of 1.0 ± 6.4 (p

With rapid urbanization, retrieving information about residential complexes in a timely manner is essential for urban planning. To develop efficiency and accuracy of building extraction in residential complexes, a Segment Anything Model-based residential building instance segmentation method with an automated prompt generator was proposed combining LiDAR data and VHR remote sensing images in this study. Three key steps are included in this method: approximate footprint detection using LiDAR data, automatic prompt generation for the SAM, and residential building footprint extraction. By applying this method, residential building footprints were extracted in Pukou District, Nanjing, Jiangsu Province. Based on this, a comprehensive assessment model was constructed to systematically evaluate the spatial layout of urban complexes using six dimensions of assessment indicators. The results showed the following: (1) The proposed method was used to effectively extract residential building footprints. (2) The residential complexes in the study area were classified into four levels. The numbers of complexes classified as Excellent, Good, Average, and Poor were 10, 29, 16, and 1, respectively. Residential complexes of different levels exhibited varying spatial layouts and building distributions. The results provide a visual representation of the spatial distribution of residential complexes that belong to different levels within the study area, aiding in urban planning.

Background Although head elevation is an early first-line treatment for elevated intracranial pressure (ICP), the use of the head-down or prone position in managing neurocritical patients is controversial because a change in a position directly affects the intracranial and cerebral perfusion pressure, which may cause secondary brain injury and affect patient outcomes. This study compared the effects of two postural drainage positions (30° head-up tilt and 0° head flat) on the prognosis of neurocritical care patients with complicated pneumonia and a clinical pulmonary infection score (CPIS) ≥5 points to provide a reference for selecting appropriate postural drainage positions for patients with pneumonia in neurocritical care units. Methods A prospective randomized controlled study was conducted with 62 neurocritical care patients with complicated pneumonia. The patients were categorized into control (=31) and experimental (=31) groups in a 1:1 ratio using a simple randomized non-homologous pairing method. Emphasis was placed on matching the baseline characteristics of the two groups, including patient age, sex, height, weight, Glasgow Coma Scale score, heart rate, mean arterial pressure, cough reflex, and mechanical ventilation usage to ensure comparability. Both groups received bundled care for artificial airway management. The control group maintained a standard postural drainage position of 0° head-flat, whereas the experimental group maintained a 30° head-up tilt. The efficacy of the nursing intervention was evaluated by comparing the CPIS and other therapeutic indicators between the two groups after postural drainage. Results After the intervention, the within-group comparison showed a significant decrease in the CPIS (P

Loess areas have a unique geological environment, and geological disasters occur there frequently. In this work, the typical loess area Lvliang was used as the study area. Using the historical landslide catalog, 12 influencing factors were chosen by integrating multisource heterogeneous spatiotemporal big data such as remote sensing, ground investigation, and basic geography. Based on frequency ratio (FR) and improved TabNet deep learning technology, landslide susceptibility evaluation and uncertainty analysis were performed. The results showed that the TabNet evaluation model using FR and self-supervised learning performs well and has the highest FR in extremely high-prone areas. Compared with other methods, this method has the highest scores in areas under the curve and susceptibility index distribution and the lowest uncertainty. Moreover, the SHAP method was used for interpretability analysis of the model. Therefore, this study can provide new ideas for landslide susceptibility management.

Cancer, also known as malignant tumour or neoplasm, is a leading cause of death worldwide. One distinct feature from normal cells is that cancerous cells often overexpress protein on the cell membrane—for instance, the overexpression of human epidermal growth factor receptor 2. The expression of a specific protein on the cancerous cell surface acts as a marker that differentiates the normal cell and facilitates the recognition of cancerous cells. An emerging anticancer treatment, Antibody–Drug Conjugates (ADCs), utilises this unique feature to kill cancerous cells. ADCs consist of an antibody linked with a cytotoxic payload, mainly targeting the antigen found on cancerous cells. This design can increase the specificity in delivering the cytotoxin to the drug target, thus increasing the drug efficacy and reducing the side effect of cancer treatment due to off-target toxicities. There are tremendous quantities of clinical trials conducted to evaluate the safety and effectiveness of this magic drug in treating different types of cancers. However, only 12 ADCs have been approved by the FDA until now. This review provides the principles of ADCs and highlights the ADCs that FDA has approved. In addition, some of the ADCs that undergo clinical trials are discussed in this review. The application of computational techniques in addressing ADCs’ challenges and neoantigen-targeted cancer vaccines is also highlighted. Although ADCs have been seen as promising magic drugs in cancer treatment, the problems such as toxicity, the stability of the linker, the specificity of an antibody with antigen, and so on, remain a challenge in developing ADCs.

Abstract Background Screen time refers to the time an individual spends using electronic or digital media devices such as televisions, smart phones, tablets or computers. The purpose of this study was to conduct systematic review to analyze the relevant studies on the length and use of screen time of school-aged children, in order to provide scientific basis for designing screen time interventions and perfecting the screen use guidelines for school-aged children. Methods Screen time related studies were searched on PubMed, EMBASE, Clinical Trials, Controlled Trials, The WHO International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials, CNKI, and Whipple Journal databases from January 1, 2016 to October 31, 2021. Two researchers independently screened the literature and extracted the data, and adopted a qualitative analysis method to evaluate the research status of the length and usage of screen time of school-aged students. Results Fifty-three articles were included. Sixteen articles studied screen time length in the form of continuous variables. Thirty-seven articles studied screen time in the form of grouped variables. The average screen time of schoolchildren aged 6 to 14 was 2.77 h per day, and 46.4% of them had an average screen time ≥ 2 h per day. A growth trend could be roughly seen by comparing studies in the same countries and regions before and after the COVID-19 outbreak. The average rates of school-aged children who had screen time within the range of ≥ 2 h per day, were 41.3% and 59.4% respectively before and after January 2020. The main types of screen time before January 2020 were watching TV (20 literatures), using computers (16 literature), using mobile phones/tablets (4 literatures). The mainly uses of screens before January 2020 were entertainment (15 literatures), learning (5 literatures) and socializing (3 literatures). The types and mainly uses of screen time after January 2020 remained the same as the results before January 2020. Conclusions Excessive screen time has become a common behavior among children and adolescents around the world. Intervention measures to control children's screen use should be explored in combination with different uses to reduce the proportion of non-essential uses.

Summary: To achieve its goal of carbon emissions peak and neutrality, China requires synergistic efforts across all sectors. In this study, three scenarios—baseline, policy, and green low-carbon—were developed to explore the pathways for China’s emissions reduction across sectors from 2020 to 2060, and the timing of decoupling economic growth from CO2. The results showed that, under these scenarios, China’s carbon emissions peak in 2030, 2026, and 2025, with strong decoupling time, lagged one year behind peak attainment. The agriculture, forestry, livestock, and fishing (AFH) and mining and quarrying (MQ) sectors would be the first to achieve a carbon peak. Under all three scenarios, all of the other sectors—with the exception of electricity, gas, and water production and supply (EGW)—will achieve a carbon peak by 2030. Therefore, policymakers should set carbon peak goals based on sector characteristics and ensure energy security in the process of achieving carbon neutrality.

Background Telehealth services have gained popularity in Malaysia, providing convenient consultations during the COVID-19 pandemic. However, there is limited research on their usage, user demographics and prescribed medications. This study aims to fill that gap by investigating telehealth service utilisation in community pharmacies and identifying trends in common diagnoses and medications prescribed. Methods A retrospective observational study was conducted using a telehealth services database in Malaysian community pharmacies. Consultation records from January 2019 to December 2021 were extracted using a data collection form. The study identified the service usage over time, demographic profiles of users and the most common diagnoses and prescribed medications. Diagnoses were classified using the International Classification of Disease, 10th Revision (ICD-10), and medications were classified using the Anatomical Therapeutic Chemical (ATC) system. Results The study included 835,826 telehealth service records, with 88.8% being assisted consultations with e-prescriptions and 11.2% direct consultations. The user population consisted of primarily Malaysians (96.9%), with a mean age of 50 ± 21 years. Both telehealth services saw an increase in unique users over the 3-year study period. There was a moderate correlation between active COVID-19 cases and monthly user count. Assisted consultations were more widely used than direct consultations. Conclusion This study found an increased usage of telehealth services and its potential to remain as a healthcare system feature in community pharmacies. Further investigation into the impact on medication safety, quality and healthcare delivery is warranted.

This study explores the status quo of preventive care use and social capital among middle-aged and elderly people (≥45 years old) in China, and employs a multi-level model to analyze whether social capital at different levels is associated with preventive care use. The data are derived from the 2018 China Health and Retirement Longitudinal Study (CHARLS), which includes 11,503 respondents and 450 communities. Preventive care use covers the utilization of routine physical examination services. Individual social capital is measured by the level of social network and social activities participation. Social network includes contacting with children or other people, for example, by phone, text message. Social activities participation is measured by the involvement in social activities, for example, playing mahjong, going to community club. Community social capital is evaluated by the richness of community facilities. Results reveals that the utilization of preventive care is 48.94% among middle-aged and elderly in China. The most used preventive service is routine blood test. The intra-class correlation (ICC) coefficient indicates that preventive health behaviors of the respondents are clustered at communities where they live. Multi-level regression shows that influence of social network is not significant to preventive care use (p ＞ 0.05). Community facilities and individual social activities participation are significantly associated with preventive care use (p

Abstract Background Isodicentric Y chromosome (idic(Y)) is the most commonly reported aberration of the human Y chromosome, which is an important cause of abnormal sexual development. The breakpoints of isodicentric Y chromosome mostly occurred in Yq11.2 and Yp11.3, however, the breakpoints in Yq12 are relatively rare. Case presentation We described a 10-year-old boy presenting hypospadias, micropenis and short stature, as well as unilateral cryptorchidism without normal testicular seminiferous tubules structure by biopsy. Whole exome sequencing didn’t find any pathogenic/likely pathogenic variants related to phenotypes of this patient. Copy number variation sequencing showed the duplication of whole Y chromosome. Subsequently, karyotyping and FISH analyses demonstrated his genetic diagnosis was mosaic 45,X[8]/46,X,psu idic(Y)(q12)[32], with the breakpoint in Yq12. Conclusions Our case proved that it would be beneficial to integrate high-throughput sequencing with cytogenetic technique for precise diagnosis, treatment and genetic counselling.

Fake news detection is one of the most alluring problems that has grabbed the interest of Machine Learning (ML) and Natural Language Processing (NLP) experts in recent years. The majority of existing studies on detecting fake news are written in English, restricting its application outside the English-speaking population. The lack of annotated corpora and technologies makes it difficult to identify false news in the scenario of low-resource languages, despite the growth in multilingual web content. Moreover, existing works cannot collect more semantic and contextual characteristics from documents in a particular multilingual text corpus. To bridge up these challenges and deal with the multilingual fake news detection challenge, we develop a new semantic graph attention-based representation learning framework to extract structural and semantic representations of texts. Our experiments on TALLIP fake news datasets showed that the classification performance had been significantly enhanced, ranging from 1% to 7% in terms of accuracy metric, and our proposed framework outperformed the state-of-the-art techniques for the multilingual fake news detection task.

Objectives: To systematically summarize and compare the health management projects on the aged population funded by the National Institutes of Health (NIH) in the US and the National Natural Science Foundation of China (NSFC) in China. Methods: All elderly-related projects from 2007 to 2022 were retrieved by searching the project titles, abstracts, and keywords such as “older adults,” “elderly,” “aged,” “health management,” and so on. Python, CiteSpace, and VOSviewer were used to extract, integrate, and visualize the relevant information. Results: A total of 499 NSFC projects and 242 NIH projects were retrieved. For both countries, prestigious universities and institutions received the most funded projects; the projects that got the most funds were longitudinal studies. Both countries attach great importance to investment in the health management of the aged population. However, different focuses existed in health management projects for older adults in the two countries due to distinct national conditions and development levels. Conclusions: The analysis results of this study can provide a reference for other countries with similar challenges of population aging. Effective measures should be taken to promote the transformation and implementation practice of the project achievements. Nurses can benefit from these projects and facilitate the translation of relevant research findings into clinical practice to improve nursing quality for older adults.

Chilli anthracnose is a major infectious disease of the genus Capsicum. Chemical control is the primary means of controlling this disease; however, the excessive use of chemical pesticides can adversely affect ecological security and human health. Here, our aim was to explore the synergistic effects of chemical and biological pesticides in the control of chilli anthracnose. The bacterial strain LY7, which is antagonistic to the anthracnose-causing fungus Colletotrichum scovillei, inhibited the growth of C. scovillei by 83.52%. Through morphological and genetic analyses, this strain was identified as Bacillus velezensis. Then, the compatibility of LY7 with three common chemical fungicides was determined. The in vitro protective and therapeutic efficacies of the 1 × 109 CFU/mL (colony-forming unit/mL) bacterial solution were 66.38% and 35.18%, respectively, but both were significantly lower than those of prochloraz, the most compatible fungicide. We then conducted field efficacy trials to elucidate the best combination of prochloraz and LY7; the highest control efficiency was achieved with a suspension of 1.0 × 108 CFU/mL of LY7 mixed with 0.75 g/L prochloraz (3:7 ratio). Electron microscopy revealed the inhibitory effects of LY7 and prochloraz on C. scovillei mycelial growth. These results suggest that an LY7-based biofungicide can partially replace prochloraz, serving as an integrated management strategy to control chilli anthracnose.

Viscous slickwater has a higher viscosity and better sand-carrying ability than conventional slickwater at the same concentration. At a concentration of 0.4 wt.%, the viscosity of the viscous slickwater is 4.7 times that of the conventional slickwater. It is generally believed that viscosity is one of the main influencing factors on the sand-carrying ability of the fluid. However, this study has shown that the good sand-carrying ability of the viscous slickwater is more attributed to its viscoelasticity. Through rheology and sand-carrying tests, it has been found that the viscoelastic properties vary when fluids have the same viscosity; this then leads to a significant difference in the settling rate of sand and the sand-carrying threshold of the fluid in a fracture at a certain flow rate. The routine method of characterizing the viscoelastic property of the slickwater was to observe the cross point of the elastic modulus (G′) and viscous modulus (G″) curves. The smaller the frequency of the cross point, the better the viscoelastic property of the fluid. However, it has been found in experiments that even when the cross point is the same, there is still a significant difference in the sand-carrying ability of fluids. Therefore, sand-carrying experiments are conducted under a similar cross point and different magnitudes of modulus, of which the results indicate that as the elastic modulus increases, the settling rate of sand decreases. The flow rate threshold occurring as sand settles obtained from laboratory experiments is compared with the field condition during hydraulic fracturing. From laboratory experiments, the threshold of inner-fracture flow rate that prevents the sand settling is found to be 8.02 m/min for 0.6 wt.% viscous slickwater with a sand ratio of 30%. In the field operation, the operation conditions meet the sand-carrying threshold obtained from laboratory experiments. Observations from the field test confirm the applicability of the threshold plot proposed according to laboratory measurements, which can provide guidance for optimizing the fracturing scheme in the field.

ObjectiveCognitive impairment is a detrimental complication of stroke that compromises the quality of life of the patients and poses a huge burden on society. Due to the lack of effective early prediction tools in clinical practice, many researchers have introduced machine learning (ML) into the prediction of post-stroke cognitive impairment (PSCI). However, the mathematical models for ML are diverse, and their accuracy remains highly contentious. Therefore, this study aimed to examine the efficiency of ML in the prediction of PSCI.MethodsRelevant articles were retrieved from Cochrane, Embase, PubMed, and Web of Science from the inception of each database to 5 December 2022. Study quality was evaluated by PROBAST, and c-index, sensitivity, specificity, and overall accuracy of the prediction models were meta-analyzed.ResultsA total of 21 articles involving 7,822 stroke patients (2,876 with PSCI) were included. The main modeling variables comprised age, gender, education level, stroke history, stroke severity, lesion volume, lesion site, stroke subtype, white matter hyperintensity (WMH), and vascular risk factors. The prediction models used were prediction nomograms constructed based on logistic regression. The pooled c-index, sensitivity, and specificity were 0.82 (95% CI 0.77–0.87), 0.77 (95% CI 0.72–0.80), and 0.80 (95% CI 0.71–0.86) in the training set, and 0.82 (95% CI 0.77–0.87), 0.82 (95% CI 0.70–0.90), and 0.80 (95% CI 0.68–0.82) in the validation set, respectively.ConclusionML is a potential tool for predicting PSCI and may be used to develop simple clinical scoring scales for subsequent clinical use.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=383476.

Abstract Background The high incidence of catastrophic health expenditure (ICHE) among middle-aged and elderly population is a major deterrent for reducing the financial risk of disease. Current research is predominantly based on the assumption of spatial homogeneity of nationwide population characteristics, ignoring the differences in regional characteristics. Thus, our study aimed to explore the impact of various influencing factors on the ICHE from a spatiotemporal perspective. Methods We used data from the China Health and Retirement Longitudinal Study (waves 1 to 4), to conduct a retrospective cohort study across 28 provinces, from 2011 to 2018. We measured regional incidences of catastrophic health expenditure using methods recommended by the World Health Organization. Ordinary least squares (OLS) and geographical and temporal weighted regression (GTWR) were used as the global and local estimation models, respectively. The Fortheringham method was used to test the spatiotemporal non-stationarity. Results National ICHE showed a gradual increase from 2011 to 2015, but suddenly decreased from 2015 to 2018, also showing the spatial heterogeneity. And the southwest area and Hebei showed persistently high ICHE (Qinghai even reached the highest value of 27.5% in 2015). Out-of-pocket payment, gross domestic product, PM2.5, ageing, incidence of non-communicable diseases and disabilities, number of nurses, and health insurance coverage in the global estimation passed the significance test, and the GTWR model showed a better model fit (0.769) than the OLS model (0.388). Furthermore, except for health insurance coverage, all seven variables had spatiotemporal non-stationarity among their impacts on ICHE. Conclusion In this longitudinal study, we found spatiotemporal non-stationarity among the variable relationships, supporting regional governments’ adoption of regional-target policies. First, after the completion of universal health insurance coverage, the spatiotemporal non-stationarity of the prevalence of non-communicable diseases and disability and ageing should be the focus of the next phase of health insurance design, where improvements to compensation coverage and benefit packages are possible policy instruments. Second, the governance and causes of catastrophic health expenditure need to be laid out from a macro perspective rather than only from the individual/household perspective, especially for the potential impact of economic development, air pollution and nursing resources.

Abstract Background Chronotype and chrononutrition, both are emerging research interests in nutritional epidemiology. However, its association with glycemic control in the Asia population is less clear. A better understanding of how activity/eating time can influence glucose levels in Asian prediabetic individuals may improve strategies for blood glucose control in Asian countries. The present paper describes the research protocol which aims to determine the associations of chronotype and chrononutrition with glucose tolerance among Malaysian prediabetic individuals. Methods This is a prospective longitudinal study named Chrono-DM™, that targets to recruit 166 newly diagnosed prediabetic individuals from the community clinics in Malacca, Malaysia. Respondents will be followed-up for 6 months: (1) baseline (1st oral glucose tolerance test (OGTT)); (2) second visit (at 3rd month); and (3) third visit (2nd OGTT at 6th month). Data collection includes sociodemographic and anthropometry measurements (weight, height, body fat, visceral fat, waist and hip circumference). Dietary intake and meal timing are collected using the 3-day dietary record while data on sleep pattern, light exposure, chronotype and chrononutrition will be collected using validated questionnaires. Physical activity will be recorded using a validated IPAQ questionnaire and pedometer during periods of using continuous glucose monitoring (CGM) sensor. CGM, fasting blood sugar (FBS), OGTT and HbA1c are performed to assess glycemic outcomes. Discussion The Chrono-DM™ study represents a novel approach to determining the association of chronotype and chrononutrition with glycemic control. We anticipate that this study will not only review the association of chronotype with glycemia measure but also provide greater insight into optimal meal time for glycemic control among prediabetic individuals in the Asian population. Trial registration NCT05163964 (Clinicaltrial.gov). Trial registration date: 20 December 2021.

To prepare an ophthalmic solution with a cell-permeable TAT peptide (TAT-N24) as the main cell-permeable peptide inhibitor of p55PIK signaling and observe its therapeutic effect on suture-induced corneal neovascularization (CNV) in rats. Sprague-Dawley rats were used to establish a corneal suture (CS) model of CNV. The vehicle and 0.9% TAT-N24 ophthalmic solution was topically administered. CNV induction was assessed on the basis of the clinical performance of each group. Hematoxylin-eosin staining was used to observe pathological changes, and immunohistochemical staining and confocal immunofluorescence were used to determine the localization of factors associated with corneal tissue. The mRNA expression levels of hypoxia-inducible factor (HIF-1α), vascular endothelial growth factor (VEGF-A), nuclear transcription factor κB (NF-κB p65), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin (IL)-6 were determined using real-time quantitative polymerase chain reaction. Western blotting was performed to detect the protein expression levels of HIF-1α and NF-κB p65. TAT-N24 slowed CNV production and reduced the expression of HIF-1α and inflammatory factors in CS models. The mRNA levels of HIF-1α, VEGF-A, NF-kB, TNF-α, IL-1β, and IL-6 significantly decreased. Moreover, the protein levels of HIF-1α and NF-κB p65 were significantly decreased. TAT-N24 can treat CNV and ocular inflammation by inhibiting the HIF-1α/NF-κB signaling pathway in CS. In the early treatment of corneal foreign body trauma, topical application of TAT-N24 can not only reduce the inflammatory response but also inhibit corneal neovascularization.

The effective and long-term treatment of cartilage defects is an unmet need among patients worldwide. In the past, several synthetic and natural biomaterials have been designed to support functional articular cartilage formation. However, they have mostly failed to enhance the terminal stage of chondrogenic differentiation, leading to scar tissue formation after the operation. Growth factors substantially regulate cartilage regeneration by acting on receptors to trigger intracellular signaling and cell recruitment for tissue regeneration. In this study, we investigated the effect of recombinant insulin-like growth factor 1 (rIGF-1), loaded in fibrin microbeads (FibIGF1), on cartilage regeneration. rIGF-1-loaded fibrin microbeads were injected into full-thickness cartilage defects in the knees of goats. The stability, integration, and quality of tissue repair were evaluated at 1 and 6 months by gross morphology, histology, and collagen type II staining. The in vivo results showed that compared to plain fibrin samples, particularly at 6 months, FibIGF1 improved the functional cartilage formation, confirmed through gross morphology, histology, and collagen type II immunostaining. FibIGF1 could be a promising candidate for cartilage repair in the clinic.

Abstract Background The aim of this study was to investigate the associations of osteosarcopenic obesity (OSO) and its components with complete blood cell count-derived inflammation indices. Methods In this cross-sectional study, data of 648 participants aged ≥60 years (men/women: 232/416, mean age: 67.21 ± 6.40 years) were collected from January 2018 to December 2020. Areal bone mineral density and body fat percentage were used to define osteopenia/osteoporosis and obesity, respectively. The criteria of the 2019 Asian Working Group for Sarcopenia were used to diagnose sarcopenia. Based on the number of these conditions, participants were divided into four groups: OSO/0, OSO/1, OSO/2, and OSO/3. Logistic regression analysis was conducted to identify associations between blood cell count-derived inflammation indices and the number of disorders with abnormal body composition. Results Systemic inflammation response index (SIRI), white blood cells, neutrophil-to-lymphocyte ratio (NLR), aggregate inflammation systemic index (AISI), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) showed statistically significant differences among the four groups (P

RNA chemical modifications are a new but rapidly developing field. They can directly affect RNA splicing, transport, stability, and translation. Consequently, they are involved in the occurrence and development of diseases that have been studied extensively in recent years. However, few studies have focused on the correlation between chemical modifications and drug effects. Here, we provide a landscape of six RNA modifications in pharmacogene RNA (pharmacoepitranscriptomics) to fully clarify the correlation between chemical modifications and drugs. We performed systematic and comprehensive analyses on pharmacoepitranscriptomics, including basic characteristics of RNA modification and modification-associated mutations and drugs affected by them. Our results show that chemical modifications are common in pharmacogenes, especially N6-methyladenosine (m6A) modification. In addition, we found a very close relationship between chemical modifications and anti-tumor drugs. More interestingly, the results demonstrate the importance of m6A modification for anti-tumor drugs, especially for drugs in triple-negative breast cancer (TNBC), ovarian cancer, and acute myelocytic leukemia (AML). These results indicate that pharmacoepitranscriptomics could be a new source of drug-effect biomarkers, especially for m6A and anti-tumor drugs.

ObjectivesPleural invasion (PI) is identified as an adverse prognostic factor for non-small cell lung cancer (NSCLC), but its value in small cell lung cancer (SCLC) remains unclear. We aimed to evaluate the survival effect of PI on overall survival (OS) in SCLC, meanwhile, we established a predictive nomogram based on related risk factors for OS in SCLC patients with PI.MethodsWe extracted the data of patients diagnosed with primary SCLC between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. The propensity score matching (PSM) method was used to minimize the baseline difference between the non-PI and PI groups. Kaplan-Meier curves and the log-rank test were used for survival analysis. Univariate and multivariate Cox regression analyses were applied to identify the independent prognostic factors. Randomly divided the patients with PI into training (70%) and validation (30%) cohorts. A prognostic nomogram was established based on the training cohort and was evaluated in the validation cohort. The C-index, receiver operating characteristic curves (ROC), calibration curves, and decision curve analysis (DCA) were applied to assess the performance of the nomogram.ResultsA total of 1,770 primary SCLC patients were enrolled, including1321patients with non-PI and 449 patients with PI. After PSM, the 387 patients in the PI group matched the 387 patients in the non-PI group. By Kaplan-Meier survival analysis, we observed the exact beneficial effect of non-PI on OS in both original and matched cohorts. Multivariate Cox analysis showed similar results to demonstrate a statistically significant benefit for patients with non-PI in both original and matched cohorts. Age, N stage, M stage, surgery, radiotherapy, and chemotherapy were independent prognostic factors for SCLC patients with PI. The C-index of the nomogram in the training and validation cohort was 0.714 and 0.746, respectively. The ROC curves, calibration curves, and DCA curves also demonstrated good predictive performance in the training and validation cohorts of the prognostic nomogram.ConclusionOur study shows that PI is an independent poor prognostic factor for SCLC patients. The nomogram is a useful and reliable tool to predict the OS in SCLC patients with PI. The nomogram can provide strong references to clinicians to facilitate clinic decisions.

The present study was conducted to determine whether adipose derived mesenchymal stromal cells (AD-MSCs) or bone marrow derived-MSCs (BM-MSCs) would provide superior tenogenic expressions when subjected to cyclical tensile loading. The results for this would indicate the best choice of MSCs source to be used for cell-based tendon repair strategies. Both AD-MSCs and BM-MSCs were obtained from ten adult donors (N=10) and cultured in vitro. At passaged-2, cells from both groups were subjected to cyclical stretching at 1 Hz and 8% of strain. Cellular morphology, orientation, proliferation rate, protein, and gene expression levels were compared at 0, 24, and 48 hours of stretching. In both groups, mechanical stretching results in similar morphological changes, and the redirection of cell alignment is perpendicular to the direction of stretching. Loading at 8% strain did not significantly increase proliferation rates but caused an increase in total collagen expression and tenogenic gene expression levels. In both groups, these levels demonstrated no significant differences suggesting that in a similar loading environment, both cell types possess similar tenogenic potential. In conclusion, AD-MSCs and BM-MSCs both demonstrate similar tenogenic phenotypic and gene expression levels when subjected to cyclic tensile loading at 1 Hz and 8% strain, thus, suggesting that the use of either cell source may be suitable for tendon repair.

Abstract Most of the existing edge aware filters have a number of parameters. The optimal settings of these parameters guarantee the best performance but they depend on the input image. It would be difficult for inexperienced users to empirically get the optimal parameters. This paper proposes a new metric for choosing the optimal parameter settings of edge aware filtering, which is called metric of edge aware filtering (MEAF). MEAF evaluates the quality of filtered images from three aspects: the color distance, the distance of the prominent structure, and smoothness. The colour distance is calculated by rooted mean square error. The distance of the prominent structure is calculated by the proposed SSIM map masked by Sobel edges (MASKED‐SSIM). In MASKED‐SSIM, Sobel detector is used to detect the prominent structure from the input image and the calculation of structure distance is constrained on the prominent structures. Number of gradients and relative total variation are further defined to measure the smoothness of the filtered image. MEAF is an objective metric, which is specially designed for choosing the optimal parameters of edge aware filtering and can be used universally for arbitrary input image. Experiments on 12 state‐of‐the‐art edge aware filters show the effectiveness of MEAF.

With the construction and development of the distribution Internet of things in China, the three-phase imbalance treatment in the distribution area has gradually attracted attention as an optional function, and a large number of intelligent terminal manufacturers have begun to study this aspect. In this paper, research is carried out on the three-phase imbalance treatment function based on commutation control. The evaluation index system of imbalance treatment based on commutation is proposed in combination with the imbalance harm and the influence of treatment, and the three-phase imbalance treatment effect is evaluated by combining the analytic hierarchy process and improved entropy weight method. An example is given to verify the effectiveness of the evaluation method proposed in this paper.

Choanephora rot of Chenopodium plants (CRC) was observed at the flowering stages in seven plantations of Shanxi Province, China. CRC had caused leaf, stem, and panicle neck rot of C. quinoa, panicle neck and stem rot of C. formosanum, and stem rot of C. album. Typical symptoms included water-soaked, rapid soft rotting, and abundant sporulation on the whole panicle necks, stems, and leaves. Based on morphological characteristics, phylogenetic analyses, and pathogenicity tests, the pathogens were identified as Choanephoraceae cucurbitarum. Sporangiola and sporangiospore of C. cucurbitarum germinated at 30 °C and were able to germinate by two h post-inoculation (hpi). The germination rates of sporangiola and sporangiospore significantly increased at 3 to 4 hpi, and the germination rates ranged from 91.53 to 97.67%. The temperature had a significant effect on the pathogenicity of C. cucurbitarum the optimum pathogenic temperatures for stems of C. quinoa, C. formosanum and C. album were 30 °C after one day post-inoculation. Choanephoraceae cucurbitarum could infect white and red quinoa panicle necks between 20 and 30 °C, and the average lesion lengths were 0.21 to 3.62 cm. Among the five tested fungicides (boscalid, dimethomorph, isopyrazam, propiconazole, and tebuconazole), isopyrazam showed higher sensitivity to sporangiola germination of C. cucurbitarum, with an EC50 value of 0.6550 μg/mL. Isopyrazam and tebuconazole strongly inhibited the sporangiospore germination of C. cucurbitarum, which showed EC50 values of 0.4406 and 0.3857 μg/mL. To our knowledge, the present study found for the first time that C. cucurbitarum is a pathogen causing panicle neck of C. formosanum and stem rot of C. formosanum and C. album, while CRC first appeared in the quinoa panicle necks, and gradually expanded to stems and leaves.

The composites with multiple types of nano-carbon fillers have better electrical conductivity and piezoresistive properties as compared with composites with a single type of nano-carbon fillers. As previously reported, the nano-carbon fillers with various aspect ratios, such as carbon nanotube (CNT) and carbon black (CB), have synergistic enhanced effects on the piezoresistive performance of composite sensors. However, most of the works that have been reported are experimental investigations. The efficient and usable numerical simulation investigation needs to be further developed. In this study, based on an integrated 3D statistical resistor network model, a numerical simulation model was created to calculate the piezoresistive behavior of the CNT/CB/ Polyvinylidene Fluoride (PVDF) composite. This model also takes into account the tunneling effect between nearby nano-fillers. It is found from numerical simulation results that the piezoresistive sensitivity of composite simulation cells can be influenced by the fraction of CNT and CB. In the case that the CNT content is 0.073 wt.%, the best force-electrical piezoresistive sensitivity can be achieved when the CB loading is up to 0.2 wt.%. To verify the validity of the simulation model, the previous experimental investigation results are also compared. The experimental results confirm the validity of the model. The investigation is valuable and can be utilized to design a strain sensor for this nano-composite with increased sensitivity.

In order to realize the monitoring and maintenance of the internal environment of the pipeline，a cam-linkage mechanism is designed as a multi-legged pipeline robot，and the motion analysis and mechanism improvement of the single-leg mechanism are carried out，so as to improve the shortcomings of the initial connecting rod mechanism，such as low motion precision and large inertia force. The mechanism scheme is theoretically modeled，and then the motion analysis of the mechanism is carried out by using the method of the joint simulation of 3D modeling software SolidWorks and motion analysis software Adams. The mechanism is improved by changing relevant parameters of the mechanism. Through comparative analysis，it can be seen that the cam-linkage scheme has more advantages than the initial scheme. Change the size of the cam，the foot of the mechanism in the normal direction of the displacement of the greater，the foot will be lifted higher，and the same time can walk a longer distance. The results also show that the cam-linkage mechanism has less inertia force and impact，more stable operation，and easy to realize specific motion law.

Abstract It is a big challenge for unsupervised video segmentation without any object annotation or prior knowledge. In this article, we formulate a completely unsupervised video object segmentation network which can pop out the most salient object in an input video by self‐growth, called Pop‐Net. Specifically, in this article, a novel self‐growth strategy which helps a base segmentation network to gradually grow to stick out the salient object as the video goes on, is introduced. To solve the sample generation problem for the unsupervised method, the sample generation module which fuses the appearance and motion saliency is proposed. Furthermore, the proposed sample optimization module improves the samples by using contour constrains for each self‐growth step. Experimental results on several datasets (DAVIS, DAVSOD, VideoSD, Segtrack‐v2) show the effectiveness of the proposed method. In particular, the state‐of‐the‐art methods on completely unfamiliar datasets (no fine‐tuned datasets) are performed.

Abstract Background Residents’ preference for primary health care (PHC) determined their utilization of PHC. This study aimed to assess the determinants of PHC service preference among the residents and the trend in PHC service preference over time in China. Methods We employed the nationally representative longitudinal data from 2012 to 2018 based on the China Family Panel Studies. The analysis framework was guided by the Andersen model of health service utilization. We included a total of 12,508 individuals who have been successfully followed up in the surveys of 2012, 2014, 2016, and 2018 without any missing data. Logistic regressions were performed to analyze potential predictors of PHC preference behavior. Results The results indicated that individuals’ socio-economic circumstances and their health status factors were statistically significant determinants of PHC preference. Notably, over time, the residents’ likelihood of choosing PHC service represented a decreasing trend. Compare to 2012, the likelihood of PHC service preference decreased by 18.6% (OR, 0.814; 95% CI, 0.764–0.867) in 2014, 30.0% (OR, 0.700; 95% CI, 0.657–0.745) in 2016, and 34.9% (OR, 0.651; 95% CI, 0.611–0.694) in 2018. The decrease was significantly associated with the changes in residents’ health status. Conclusions The residents’ likelihood of choosing PHC service represented a decreasing trend, which was contrary to the objective of China’s National Health Reform in 2009. We recommend that policymakers adjust the primary service items in PHC facilities and strengthen the coordination of service between PHC institutions and higher-level hospitals.

The major pathologic hallmark of the alcoholic liver disease (ALD) is the representation of chronic alcohol-induced hepatocyte lipid accumulation. This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia (ACT) in chronic alcohol-induced liver injury mice, establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks. In long-term alcohol consumption mice, the significantly lost body weight, increased organ indexes, hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration, showing its hepatoprotective property. ACT suppressed the triglyceride, total cholesterol and low-density lipoprotein levels, and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice. Combining with the pathological observations, ACT displayed an anti-steatosis effects to restrain the progress of ALD. Based on proteomic analysis and enzyme-linked immunosorbent assay, ACT had been confirmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species. According to further data, ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1α and NF-κB signaling. In summary, ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.

Soil nutrients are vital for plant growth and survival and present a crucial role in terrestrial function and productivity. However, little is known about the effect mechanism of groundwater table on soil nutrients in an arid desert ecological system. This study investigated the impacts of groundwater depth on the concentrations of soil organic carbon (C), available nitrogen (N), phosphorus (P), and potassium (K) at shallow groundwater depths (0.4, 0.8, 1.2, 1.8, and 2.2 m) and field deep groundwater depths (2.5, 4.5, and 11.0 m) in a desert-oasis ecotone in Central Asia in 2015 and 2016. Soil nitrate-N, inorganic-N, soil available P, and K concentrations were significantly affected by shallow and field deep groundwater. Groundwater depths did not alter soil ammonium-N concentration. Soil organic C concentration was influenced by field deep groundwater depth. Structural equation model showed that groundwater depth directly affected soil nitrate-N and K concentrations and indirectly altered the soil inorganic-N, soil organic C and available P concentrations in shallow groundwater. Moreover, groundwater depth directly influenced soil nitrate-N and soil organic C, available P and K concentrations and indirectly affected soil inorganic-N concentration in deep groundwater. Hence, groundwater depth should be considered one of the most critical environmental factors affecting soil nutrient variation in an arid desert. This study provides new insights into the soil nutrient variation under a declining groundwater depth in a hyper-arid ecosystem.

Regulatory B cells have important roles in inflammation and autoimmune diseases. A newly discovered subpopulation of B cells with a CD19hiFcγRIIbhi phenotype inhibits the proliferation of CD4+ T cells by secreting interleukin (IL)-10. The expansion of CD19hiFcγRIIbhi B cells in mouse spleen can be induced by lipopolysaccharide (LPS) or CpG oligodeoxynucleotide stimulation. However, the mechanism of CD19hiFcγRIIbhi B cell expansion and its role in inflammatory diseases are unclear. Here, we report that, under inflammatory conditions, the proliferation and immunosuppressive function of CD19hiFcγRIIbhi B cells were decreased in high mobility group box1 (HMGB1) C106A mutant mice, compared with wild-type mice. The HMGB1 (C106A) mutation in B cells reduced STAT3 phosphorylation, restricting the expansion and suppressive function of CD19hiFcγRIIbhi B cells. Compared with CD19hiFcγRIIbhi B cells from wild-type mice, CD19hiFcγRIIbhi B cells from Hmgb1(C106A) mice significantly reduced the survival of mice with sepsis. Recombinant HMGB1 promoted the expansion of IL-10-producing CD19hiFcγRIIbhi B cells among LPS-activated B cells in vitro. Furthermore, the percentage of CD19hiFcγRIIbhi regulatory B cells in the peripheral blood was increased in patients with sepsis, compared with healthy controls. These findings implicate the role of HMGB1 in the expansion and immunosuppressive function of CD19hiFcγRIIbhi B cells.

Macamides are a class of amide alkaloids that are only found in maca and are widely considered to be its bioactive marker compounds. More than thirty macamide monomers have been identified in recent years; however, it is difficult to obtain a single macamide monomer from the maca plant because of their similar structures and characteristics. We used the carbodiimide condensation method (CCM) to efficiently synthesize five typical macamides, including N-benzyl-hexadecanamide (NBH), N-benzyl-9Z,12Z,15Z-octadecenamide, N-(3-methoxybenzyl)-9Z,12Z-octadecenamide, N-benzyl-9Z,12Z-octadecenamide, and N-(3-methoxybenzyl)-9Z,12Z,15Z-octadecadienamide. All the synthesized macamides were purified by a one-step HPLC with a purity of more than 95%. NBH is the most abundant macamide monomer in natural maca, and it was selected to evaluate the anti-fatigue effects of macamides. The results indicated that NBH could enhance the endurance capacity of mice by increasing liver glycogen levels and decreasing blood urea nitrogen, lactate dehydrogenase, blood ammonia, and blood lactic acid levels. Macamides might be the active substances that give maca its anti-fatigue active function.

Abstract Activation of adenosine monophosphate-activated protein kinase (AMPK) is able to produce significant anti-non-small cell lung cancer (NSCLC) cell activity. ASP4132 is an orally active and highly effective AMPK activator. The current study tested its activity against NSCLC cells. In primary NSCLC cells and established cell lines (A549 and NCI-H1944) ASP4132 potently inhibited cell growth, proliferation and cell cycle progression as well as cell migration and invasion. Robust apoptosis activation was detected in ASP4132-treated NSCLC cells. Furthermore, ASP4132 treatment in NSCLC cells induced programmed necrosis, causing mitochondrial p53-cyclophilin D (CyPD)-adenine nucleotide translocase 1 (ANT1) association, mitochondrial depolarization and medium lactate dehydrogenase release. In NSCLC cells ASP4132 activated AMPK signaling, induced AMPKα1-ACC phosphorylation and increased AMPK activity. Furthermore, AMPK downstream events, including mTORC1 inhibition, receptor tyrosine kinases (PDGFRα and EGFR) degradation, Akt inhibition and autophagy induction, were detected in ASP4132-treated NSCLC cells. Importantly, AMPK inactivation by AMPKα1 shRNA, knockout (using CRISPR/Cas9 strategy) or dominant negative mutation (T172A) almost reversed ASP4132-induced anti-NSCLC cell activity. Conversely, a constitutively active AMPKα1 (T172D) mimicked and abolished ASP4132-induced actions in NSCLC cells. In vivo, oral administration of a single dose of ASP4132 largely inhibited NSCLC xenograft growth in SCID mice. AMPK activation, mTORC1 inhibition and EGFR-PDGFRα degradation as well as Akt inhibition and autophagy induction were detected in ASP4132-treated NSCLC xenograft tumor tissues. Together, activation of AMPK by ASP4132 potently inhibits NSCLC cell growth in vitro and in vivo.