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Background: There is limited evidence on the effectiveness of the existing rehabilitation interventions for old adults with long coronavirus disease (COVID), which is of particular concern among old adults. Methods: We systematically searched studies published in PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases from their inception to 15 November 2023. Randomised controlled trials (RCTs) compared rehabilitation interventions with other controls in old adults (mean/median age of 60 or older) with long COVID were included. We performed a meta-analysis to compare the effects of the rehabilitation interventions with the common control group. Mean difference (MD) or standardised mean difference (SMD) with its 95% confidence intervals (CI) were used as summary statistics. Moreover, subgroup analyses based on the intervention programmes, the severity of acute infection, and the age of participants were carried out. Results: A total of 11 RCTs involving 832 participants (64.37 ± 7.94 years, 52.2% were men) were included in the analysis. Compared with the control groups, rehabilitation interventions significantly improved 6-minute walking test (6 MWT; MD = 15.77 metres (m), 95% CI = 5.40, 26.13, P < 0.01), 30-second sit-to-stand test (MD = 4.11 number of stands (n), 95% CI = 2.46, 5.76, P < 0.001), all aspects of quality of life, independence in activities of daily living (SMD = 0.31, 95% CI = 0.14, 0.48, P < 0.001), and relieved fatigue (SMD = -0.66, 95% CI = -1.13, -0.19, P < 0.01), depression (SMD = -0.89, 95% CI = -1.76, -0.02, P < 0.05) and anxiety (SMD = -0.81, 95% CI = -1.58, -0.05, P < 0.05). However, the improvement of hand grip strength and pulmonary function was not statistically significant (P > 0.05). Subgroup analyses showed that improvements in 6 MWT, fatigue, anxiety, and depression were more pronounced in old patients who received exercise training, while those who received respiratory rehabilitation had more pronounced improvements in pulmonary function and quality of life. Conclusions: Old adults with long COVID who underwent rehabilitation interventions experienced significant improvement in functional capacity, fatigue, quality of life, independence in activities of daily living, and mental health outcomes compared with usual/standard care. These findings suggest that screening, management, and rehabilitation interventions for long COVID in older adults should be strengthened to improve their complete health status and functional status, thereby reducing the long-term disease burden caused by long COVID and fostering healthy aging during the post-pandemic era.

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Background: In low- and middle-income countries (LMICs) and territories, maternal infections impose a non-negligible disease burden. We aimed to analyse the secular trends, age distribution, and associated factors of maternal sepsis and other maternal infections (MSMI) across 131 LMICs from 1990 to 2019. Methods: We collected yearly data of incidences, deaths, and disability adjusted life years (DALYs) on MSMI in 131 LMICs from 1990 to 2019 from the Global Burden of Disease 2019 (GBD 2019). The sociodemographic index (SDI) and universal health coverage effective coverage index (UHCI) were also acquired. Relative percent change and estimated annual percentage change (EAPC) were used to assess the secular trends. Correlation analyses were also employed to explore the associations between the burden of MSMI with SDI and UHCI. Results: Between 1990 and 2019, the age-standardised incident rates (ASIRs), age-standardised maternal mortality ratios (ASMMRs) and age-standardised DALYs rates of low-income countries (LICs) were much higher than that of lower-middle-income countries (LMCs) and upper-middle income countries (UMCs), although they all continued to decline. At least six of 131 LMICs had ASMMR greater than 70.00 per 100 000 live births in 2019. The incidences of MSMI increased first till 20-24 years and then decreased with age both in 1990 and 2019, while the ASMMRs were higher in the youngest and the oldest age group. With the growth of SDI and UHCI in 2109, the decreasing trend of ASIR, ASMMR, and age-standardised DALYs rates slowed down. Conclusions: Although the progress has been made in reducing the burden of MSMI in 131 LMICs, the disease burden in LICs far exceeded that of LMCs and UMCs. Socio-economic status and universal health coverage were both associated with the MSMI burden, and further research is needed to explore the underlying factors contributing to these disparities and to identify effective strategies for reducing the burden of MSMI.

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The porcine circovirus type 3 (PCV3) infection is an emerging disease associated with clinical signs of porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs. Currently, there is a lack of effective vaccines and therapeutics against this disease. Therefore, rapid, effective, sensitive, and specific detection methods are crucial for the timely identification, prevention, and control of PCV3. In this study, we developed one- and two-pot visual detection methods for PCV3 using a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas12a detection system combined with recombinase polymerase amplification (RPA). These two methods demonstrated no cross-reactivity with eight other swine viruses and exhibited minimum detection limits of five and two copies of viral DNA, respectively, revealing their high specificity and sensitivity. During a clinical sample detection within 30 min, the coincidence rates between the one- and two-pot detection methods and real-time quantitative polymerase chain reaction (qPCR) were 100%. In conclusion, both one- and two-pot RPA-CRISPR/Cas12a detection methods have significant potential for the rapid, sensitive, and specific visual detection of PCV3.

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OBJECTIVES: Globally, billions of people do not have access to safely managed drinking water and sanitation services. Interventions to improve drinking water, sanitation and hygiene could reduce the incidence of diarrhoea in low- and middle-income countries. This study aimed to investigate the association between these services and the incidence of diarrhoea. STUDY DESIGN: Worldwide, ecological observational study, utilising cross-sectional data. METHODS: Data from the Global Burden of Disease Study 2019 and World Bank were used in this study. Diarrhoeal disease episodes were defined as three or more loose bowel movements within 24 h. Estimated Annual Percentage Change was used to quantify trends in disease incidence over a specific time interval. Quasi-Poisson Generalised Linear Model was introduced to analyse the influence of basic drinking water and sanitation services on the incidence of diarrhoea. Subgroup analyses were carried out to determine potential variations in the incidence of diarrhoeal diseases according to sex, age and sociodemographic index (SDI) region. RESULTS: Between 2000 and 2019, the incidence rate of global diarrhoea remained consistent, with regional variations linked to SDIs. A 1% increase in access to basic drinking water was associated with a 0.41% (95% confidence interval [CI], 0.33%-0.50%) increase in the age-standardised incidence rate of diarrhoea; meanwhile, a 1% increase in sanitation service usage was associated with a 0.47% (95% CI, 0.40%-0.54%) reduction in the age-standardised incidence rate of diarrhoea. The correlation differed across SDI regions. The use of safely managed drinking water was associated with a reduction in diarrhoeal disease rates, but the effect was non-significant in High SDI regions. Higher diarrhoeal disease incidence was seen in younger and older populations. Individuals in the age groups 55-59 years and 10-14 years showed the greatest association of water service usage with diarrhoea, while an increase in sanitation service usage was related to decreased diarrhoea rates in most age groups, excluding children aged 5-14 years. CONCLUSIONS: Emphasising initiatives to enhance water quality, elevate the standards of drinking water safety management, and strengthening related infrastructure development in global health policies and development plans could have a positive impact on overall global health. Such comprehensive interventions have the potential to not only prevent waterborne diseases but also elevate the general health status of societies worldwide.

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BACKGROUND: Depression is the leading cause of mortality among mental health disorders. Evidence about the associations of socioeconomic status, social activities, and loneliness with depression is scarce. We aimed to identify whether social activities and loneliness mediate the association between socioeconomic status and depression, and the extent of interactive or joint relationships between social activities, loneliness, and socioeconomic status on depression. METHODS: In this population-based, cross-national cohort study we used data from five nationally representative surveys across 24 countries between Feb 15, 2008, and Feb 27, 2019: the Health and Retirement Study (HRS); the English Longitudinal Study of Ageing (ELSA); the Survey of Health, Ageing and Retirement in Europe (SHARE); the China Health and Retirement Longitudinal Study (CHARLS); and the Mexican Health and Ageing Study (MHAS). We included participants who were aged 50 years and older with reported information on socioeconomic status, social activities, and loneliness at baseline, and who had been assessed at least twice. We excluded participants with depressive symptoms at baseline; those with missing data on depressive symptoms and covariates; and those lost to follow-up. We defined socioeconomic status as high and low using latent class analysis based on family income, education, and employment status. Depression was assessed using the Center for Epidemiological Studies Depression Scale (CES-D) or EURO-D. We applied Cox proportional hazard models to estimate the association of socioeconomic status with depression. We used random-effects models to obtain pooled results. Joint and interactive effects of socioeconomic status, social activities, and loneliness on depression were explored, and the mediating roles of social activities and loneliness in the association between socioeconomic status and depression were explored using causal mediation analysis. FINDINGS: A total of 69 160 participants were included in our study and, during a median follow-up of 5 years, a total of 20 237 participants developed depression with a pooled incidence of 7·2 (95% CI 4·4-10·0) per 100 person-years. Compared with participants with high socioeconomic status, those with low socioeconomic status had a higher risk of depression (pooled hazard ratio [HR] 1·34; 95% CI 1·23-1·44). The proportion of the associations between socioeconomic status and depression mediated by social activities and loneliness were 6·12% (1·14-28·45) and 5·54% (0·71-27·62), respectively. We only observed a significant multiplicative interaction of socioeconomic status and loneliness with depression (pooled HR 0·84; 0·79-0·90). Compared with participants with high socioeconomic status and who were socially active and not lonely, those with low socioeconomic status and who were socially inactive and lonely had a higher risk of depression (pooled HR 2·45; 2·08-2·82). INTERPRETATION: Social inactivity and loneliness positively mediated a small proportion of the association between socioeconomic status and depression, indicating that other approaches in addition to interventions targeting social isolation and loneliness are required to mitigate the risk of depression in older adults. Additionally, the joint effects of socioeconomic status, social activities, and loneliness highlight the benefits of simultaneous and integrated interventions to reduce the global burden of depression. FUNDING: National Natural Science Foundation of China.

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PURPOSE: With limited studies exploring the dose-response of caffeine consumption on repeated sprint ability in hypoxia, this study aimed to determine the optimal caffeine dose (low, moderate or high) during repeated sprints in hypoxia to exhaustion. METHODS: On separate visits, twelve active males randomly performed four experimental trials in normobaric hypoxia (inspired oxygen fraction: 16.5 ± 0.2%). Participants ingested placebo (PLA) or caffeine capsules (3, 6 or 9 mg/kg or LOW, MOD and HIGH, respectively) 1 h before exercise and then underwent a repeated cycling sprint test (10 s sprint/20 s active recovery) to exhaustion. Total sprint number and work done, peak and mean power output, blood lactate concentration, cardiorespiratory and perceptual responses were recorded. RESULTS: Total sprint number was greater in MOD and HIGH compared to PLA (20 ± 7 and 18 ± 8 vs. 13 ± 4; all P < 0.05), with MOD also higher than LOW (15 ± 6; P = 0.02). Total work done was greater in MOD (111 ± 40 kJ) and HIGH (100 ± 35 kJ) compared to LOW (83 ± 29 kJ) and PLA (76 ± 25 kJ) (all P < 0.05). However, there were no significant differences in total sprint number or total work done between MOD and HIGH (all P > 0.05). Blood lactate concentration was higher in both MOD and HIGH compared to PLA (all P < 0.05). However, peak and mean power outputs, fatigue index, and ratings of perceived exertion did not differ across different caffeine dosages (all P > 0.05). CONCLUSION: A moderate dose of caffeine (6 mg/kg) is the optimal amount for enhancing repeated cycling sprint ability when compared to low and high doses in moderate normobaric hypoxia.

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Introduction: Since their identification in 1974, circoviruses have caused clinicopathological diseases in various animal species, including humans. However, their origin, transmission, and genetic evolution remain poorly understood. Methods: In this study, the genome sequences of circovirus were obtained from GenBank, and the Bayesian stochastic search variable selection algorithm was employed to analyzed the evolution and origin of circovirus. Results: Here, the evolutionary origin, mode of transmission, and genetic recombination of the circovirus were determined based on the available circovirus genome sequences. The origin of circoviruses can be traced back to fish circovirus, which might derive from fish genome, and human contributes to transmission of fish circovirus to other species. Furthermore, mosquitos, ticks, bats, and/or rodents might play a role as intermediate hosts in circovirus intra- and inter-species transmission. Two major lineages (A and B) of circoviruses are identified, and frequent recombination events accelerate their variation and spread. The time to the most recent common ancestor of circoviruses can be traced back to around A.D. 600 and has been evolving at a rate of 10-4 substitutions site-1 year-1 for a long time. Discussion: These comprehensive findings shed light on the evolutionary origin, population dynamics, transmission model, and genetic recombination of the circovirus providing valuable insights for the development of prevention and control strategies against circovirus infections.

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STUDY QUESTION: Is parity associated with all-cause and cause-specific mortality among women in a nationally representative cohort of the US population, and does depression mediate this association? SUMMARY ANSWER: Nulliparous women have a higher risk of all-cause and cause-specific mortality, with depression partially mediating the relationship between parity and women's all-cause and cause-specific mortality. WHAT IS KNOWN ALREADY: Parity, a significant state in reproductive life, has enduring implications for women's health. There is also a complex relationship between depression, a prevalent mental and emotional disorder, and female fertility. Previous studies have elucidated the relationships between parity and depression, both of which are associated with mortality. However, findings from studies examining parity and women's mortality have been inconsistent. Moreover, few studies have investigated whether the effect of parity on mortality is mediated by depression. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study using data from seven cycles of the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort comprised adult women with available parity and survival follow-up data. Parity data were self-reported and sourced from the Reproductive Health Questionnaire. Depression scores were derived from the Patient Health Questionnaire 9, and cause-specific deaths were identified using the International Statistical Classification of Diseases, 10th Revision (ICD-10). Weighted multivariable Cox regression was applied to analyze the association between parity, depression, and mortality. Weighted linear regression was performed to examine the relationship between parity and depression. Mediation analyses were employed to determine whether and to what extent depression mediated the effect of parity on mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Our study ultimately encompassed 16 962 American women. Following multivariable adjustment, compared to nulliparous women, those with one to three live births exhibited a 17% and 33% reduction in all-cause and cancer mortality, respectively (all-cause mortality: HR = 0.83, 95% CI = 0.69-0.99, P = 0.040; cancer mortality: HR = 0.67, 95% CI = 0.45-0.99, P = 0.045). Women with more than four live births demonstrated lower all-cause mortality and mortality from other (not cancer or cardiovascular disease) diseases (all-cause mortality: HR = 0.73, 95% CI = 0.58-0.93, P = 0.011; other diseases mortality: HR = 0.66, 95% CI = 0.47-0.91, P = 0.013). No correlation was detected between parity and the risk of cardiovascular disease mortality among women. Furthermore, depression was found to partially mediate the impact of parity on all-cause mortality and mortality from other diseases in women. LIMITATIONS, REASONS FOR CAUTION: Firstly, a single index of parity was used as an exposure factor, and other reproductive factors such as birth spacing, age at first birth, and mode of delivery were not taken into account. Secondly, despite accounting for important potentially confounders in our analysis, such as BMI, smoking status, and educational level, the influence of unmeasured confounders (e.g., social class, latent reproductive system diseases) on reproductive behavior or mortality cannot be dismissed. Thirdly, women's vulnerability to depression fluctuates across reproductive stages, and the effect of depression on female fertility varies over time. Due to data constraints, we were unable to obtain information on women's mental health status at different reproductive stages. Fourthly, due to the data accessibility limitations of NHANES, we were unable to specifically explore the relationship between parity and different specific types of cancer, a limitation that may obscure potential correlations. Additionally, despite our efforts to control for various confounding factors in subgroup analyses, the smaller sample sizes in some subgroups may limit the statistical power, affecting the ability to detect effects. Finally, studies exploring the association between parity and depression are cross-sectional designs, making it difficult to infer causality. These results should be interpreted with caution, and further research is warranted to corroborate our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our study underscores the elevated risk of all-cause and cause-specific mortality in nulliparous women and reveals that depression partially mediates the negative correlation between parity and women's all-cause mortality and mortality from other diseases. These results should be interpreted with caution, and further investigation is needed to support our findings. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2023YFC2705700), the Key Research & Developmental Program of Hubei Province (2022BCA042), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

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Problem: Chest radiography is a crucial tool for diagnosing thoracic disorders, but interpretation errors and a lack of qualified practitioners can cause delays in treatment. Aim: This study aimed to develop a reliable multi-classification artificial intelligence (AI) tool to improve the accuracy and efficiency of chest radiograph diagnosis. Methods: We developed a convolutional neural network (CNN) capable of distinguishing among 26 thoracic diagnoses. The model was trained and externally validated using 795,055 chest radiographs from 13 datasets across 4 countries. Results: The CNN model achieved an average area under the curve (AUC) of 0.961 across all 26 diagnoses in the testing set. COVID-19 detection achieved perfect accuracy (AUC 1.000, [95% confidence interval {CI}, 1.000 to 1.000]), while effusion or pleural effusion detection showed the lowest accuracy (AUC 0.8453, [95% CI, 0.8417 to 0.8489]). In external validation, the model demonstrated strong reproducibility and generalizability within the local dataset, achieving an AUC of 0.9634 for lung opacity detection (95% CI, 0.9423 to 0.9702). The CNN outperformed both radiologists and nonradiological physicians, particularly in trans-device image recognition. Even for diseases not specifically trained on, such as aortic dissection, the AI model showed considerable scalability and enhanced diagnostic accuracy for physicians of varying experience levels (all P < 0.05). Additionally, our model exhibited no gender bias (P > 0.05). Conclusion: The developed AI algorithm, now available as professional web-based software, substantively improves chest radiograph interpretation. This research advances medical imaging and offers substantial diagnostic support in clinical settings.

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BACKGROUND: The potential mutual effect of physical and psychological disorders on cognitive function is critical for preventing cognitive impairment among older adults. We aimed to investigate the mediating role of physical and psychological disorders in their associations with cognitive function. METHODS: We conducted a prospective cohort study using the Health and Retirement Study, involving 5308 adults aged 60 years or older. Physical disorders included seven self-reported physician-diagnosed conditions. Psychological disorder and cognitive function were ascertained using the 8-item Centers for Epidemiologic Research Depression scale and the 27-point HRS cognitive scale, respectively. Multivariable linear regression models were used to assess the association of the baseline scores of physical and psychological disorders with subsequent cognitive scores. Second-order cross-lagged panel models (CLPM) were used to assess the longitudinal mediating roles, respectively. RESULTS: The higher psychological disorder scores (ß = -0.15; P < 0.0001) and physical disorders scores (ß = -0.18; P < 0.0001) were, the worse the cognitive function was. CLPM revealed a significant longitudinal mediating effect of baseline physical disorders through changes in psychological disorder from 2002 to 2010 on the cognitive scores changes from 2002 to 2010 (ß = -0.02; P < 0.0001). Meanwhile, the longitudinal mediating effect of baseline psychological disorder scores through physical disorders changes from 2002 to 2010 on the cognitive scores changes from 2002 to 2010 was significant (ß = -0.004; P = 0.005). CONCLUSIONS: The mutual longitudinal mediating effects of psychological disorder and physical disorder indicate that among older adults, physical and psychological disorders accelerate cognitive impairment as a whole and mutually reinforcing process.

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Porcine circovirus type 3 (PCV3) is closely associated with various diseases, such as the porcine dermatitis, nephropathy syndrome, and multisystemic clinicopathological diseases. PCV3-associated diseases are increasingly recognized as severe diseases in the global swine industry. Ring finger protein 2 (RNF2), an E3 ubiquitin ligase exclusively located in the nucleus, contributes to various biological processes. This ligase interacts with the PCV3 Cap. However, its role in PCV3 replication remains unclear. This study confirmed that the nuclear localization signal domain of the Cap and the RNF2 N-terminal RING domain facilitate the interaction between the Cap and RNF2. Furthermore, RNF2 promoted the binding of K48-linked polyubiquitination chains to lysine at positions 139 and 140 (K139 and K140) of the PCV3 Cap, thereby degrading the Cap. RNF2 knockdown and overexpression increased or decreased PCV3 replication, respectively. Moreover, the RING domain-deleted RNF2 mutant eliminated the RNF2-induced degradation of the PCV3 Cap and RNF2-mediated inhibition of viral replication. This indicates that both processes were associated with its E3 ligase activity. Our findings demonstrate that RNF2 can interact with and degrade the PCV3 Cap via its N-terminal RING domain in a ubiquitination-dependent manner, thereby inhibiting PCV3 replication.IMPORTANCEPorcine circovirus type 3 is a recently described pathogen that is prevalent worldwide, causing substantial economic losses to the swine industry. However, the mechanisms through which host proteins regulate its replication remain unclear. Here, we demonstrate that ring finger protein 2 inhibits porcine circovirus type 3 replication by interacting with and degrading the Cap of this pathogen in a ubiquitination-dependent manner, requiring its N-terminal RING domain. Ring finger protein 2-mediated degradation of the Cap relies on its E3 ligase activity and the simultaneous existence of K139 and K140 within the Cap. These findings reveal the mechanism by which this protein interacts with and degrades the Cap to inhibit porcine circovirus type 3 replication. This consequently provides novel insights into porcine circovirus type 3 pathogenesis and facilitates the development of preventative measures against this pathogen.

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BACKGROUND: School-aged children are in the stage of permanent tooth eruption to replace primary teeth and this can be reached at a life stage when their health habits are being formed due to a large amount of time in school. However, data on the global trend in incidence of caries in permanent teeth in school-aged children are sparse. This study aimed to assess the trends in incidence of caries in permanent teeth in children aged 5 through 14 years from 1990 through 2019 at the global, regional, and national levels. METHODS: The authors collected data on incidence of caries in permanent teeth in children aged 5 through 14 years from 1990 through 2019 from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to assess trends at the global, regional, and national levels. RESULTS: Globally, incident cases of caries in permanent teeth in children aged 5 through 14 years increased by 15.25% from 1990 through 2019, and the incidence rate remained stable during this period, with incidence rates of 34.04% in 1990 and 33.93% in 2019. The incidence rate increased at an average annual percentage change of 0.08% (95% CI, 0.06% to 0.10%) and 0.07% (95% CI, 0.05% to 0.09%) from 1990 through 2019 in low and low-middle sociodemographic index regions, respectively. An increasing trend also was observed in nearly one-half of GBD regions and more than one-half of the world's countries from 1990 through 2019 (P < .05). CONCLUSIONS: Global incidence of caries in permanent teeth remained stable at a high level in children aged 5 through 14 years, but there was a trend toward increasing rates in nearly one-half of sociodemographic index or GBD regions and more than one-half of the world's countries and territories from 1990 through 2019. These findings suggest that caries in permanent teeth is a priority health issue in school-aged children worldwide. PRACTICAL IMPLICATIONS: Reducing free sugar intake and implementing school-based effective caries prevention programs, such as school water fluoridation, provision of fluoride tablets at school, and school dental sealant programs, are needed for school-aged children.

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BACKGROUND: Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019. METHODS: This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019. RESULTS: In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65-69, 75-79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature. CONCLUSIONS: Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

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BACKGROUND: Malancao (MLC) is a traditional Chinese medicine with a long history of utilization in treating ulcerative colitis (UC). Nevertheless, the precise molecular mechanisms underlying its efficacy remain elusive. This study leveraged ultra-high-performance liquid chromatography coupled with exactive mass spectrometry (UHPLC-QE-MS), network pharmacology, molecular docking (MD), and gene microarray analysis to discern the bioactive constituents and the potential mechanism of action of MLC in UC management. AIM: To determine the ingredients related to MLC for treatment of UC using multiple databases to obtain potential targets for fishing. METHODS: This research employs UHPLC-QE-MS for the identification of bioactive compounds present in MLC plant samples. Furthermore, the study integrates the identified MLC compound-related targets with publicly available databases to elucidate common drug disease targets. Additionally, the R programming language is utilized to predict the central targets and molecular pathways that MLC may impact in the treatment of UC. Finally, MD are conducted using AutoDock Vina software to assess the affinity of bioactive components to the main targets and confirm their therapeutic potential. RESULTS: Firstly, through a comprehensive analysis of UHPLC-QE-MS data and public database resources, we identified 146 drug-disease cross targets related to 11 bioactive components. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted that common disease drug targets are primarily involved in oxidative stress management, lipid metabolism, atherosclerosis, and other processes. They also affect AGE-RAGE and apoptosis signaling pathways. Secondly, by analyzing the differences in diseases, we identified key research targets. These core targets are related to 11 active substances, including active ingredients such as quercetin and luteolin. Finally, MD analysis revealed the stability of compound-protein binding, particularly between JUN-Luteolin, JUN-Quercetin, HSP90AA1-Wogonin, and HSP90AA1-Rhein. Therefore, this suggests that MLC may help alleviate intestinal inflammation in UC, restore abnormal lipid accumulation, and regulate the expression levels of core proteins in the intestine. CONCLUSION: The utilization of MLC has demonstrated notable therapeutic efficacy in the management of UC by means of the compound target interaction pathway. The amalgamation of botanical resources, metabolomics, natural products, MD, and gene chip technology presents a propitious methodology for investigating therapeutic targets of herbal medicines and discerning novel bioactive constituents.

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Understanding Li-ion transport is key for the rational design of superionic solid electrolytes with exceptional ionic conductivities. LiNbOCl4 is reported to be one of the most highly conducting materials in the recently realized new class of soft oxyhalide solid electrolytes, exhibiting an ionic conductivity of ∼11 mS·cm-1. Here, we apply X-ray/neutron diffraction and pair distribution function analysis─coupled with density functional theory/ab initio molecular dynamics (AIMD)─to determine a structural model that provides a rationale for the high conductivity that we observe experimentally in this nanocrystalline solid. We show that it arises from unusually high framework flexibility at room temperature. This is due to isolated 1-D [NbOCl4]- anionic chains that exhibit energetically favorable orientational disorder that is─in turn─correlated to multiple, disordered, and equi-energetic Li+ sites in the lattice. As the Li ions sample the 3-D energy landscape with a fast predicted diffusion coefficient of 5.1 × 10-7 cm2/s at room temperature (σicalc = 17.4 mS·cm-1), the inorganic polymer chains can reorient or vice versa. The activation energy barrier for Li migration through the frustrated energy landscape is especially reduced by the elastic nature of the NbO2Cl4 octahedra evident from very widely dispersed Cl-Nb-Cl bond angles in AIMD simulations at 300 K. The phonon spectra are predominantly influenced by Cl vibrations in the low energy range, and there is a strong overlap between the framework (Cl, Nb) and Li partial density of states in the region between 1.2 and 4.0 THz. The framework flexibility is also reflected in a relatively low bulk modulus of 22.7 GPa. Our findings pave the way for the investigation of future "flex-ion" inorganic solids and open up a new direction for the design of high-conductivity, soft solid electrolytes for all-solid-state batteries.

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OBJECTIVE: To compare the association between body mass index (BMI) trajectories determined by different methods and the risk of overweight in early childhood in a prospective cohort study, and to identify children with higher risk of obesity during critical growth windows of early childhood. METHODS: A total of 1 330 children from Peking University Birth Cohort in Tongzhou (PKUBC-T) were included in this study. The children were followed up at birth, 1, 3, 6, 9, 12, 18, and 24 months and 3 years of age to obtain their height/length and weight data, and calculate BMI Z-score. Latent class growth mixture modeling (GMM) and longitudinal data-based k-means clustering algorithm (KML) were used to determine the grouping of early childhood BMI trajectories from birth to 24 mouths. Linear regression was used to compare the association between early childhood BMI trajectories determined by different methods and BMI Z-score at 3 years of age. The predictive performance of early childhood BMI trajectories determined by different methods in predicting the risk of overweight (BMI Z-score > 1) at 3 years was compared using the average area under the curve (AUC) of 5-fold cross-validation in Logistic regression models. RESULTS: In the study population included in this research, the three-category trajectories determined using GMM were classified as low, medium, and high, accounting for 39.7%, 54.1%, and 6.2% of the participants, respectively. The two-category trajectories determined using the KML method were classified as low and high, representing 50. 3% and 49. 7% of the participants, respectively. The three-category trajectories determined using the KML method were classified as low, medium, and high, accounting for 31.1%, 47.4%, and 21.5% of the participants, respectively. There were certain differences in the growth patterns reflected by the early childhood BMI trajectories determined using different methods. Linear regression analysis found that after adjusting for maternal ethnicity, educational level, delivery mode, parity, maternal age at delivery, gestational week at delivery, children' s gender, and breastfeeding at 1 month of age, the association between the high trajectory group in the three-category trajectories determined by the KML method (manifested by a slightly higher BMI at birth, followed by rapid growth during infancy and a stable-high BMI until 24 months) and BMI Z-scores at 3 years was the strongest. Logistic regression analysis revealed that the three-category trajectory grouping determined by the KML method had the best predictive performance for the risk of overweight at 3 years. The results were basically consistent after additional adjustment for the high bound score of the child' s diet balanced index, average daily physical activity time, and screen time. CONCLUSION: This study used different methods to identify early childhood BMI trajectories with varying characteristics, and found that the high trajectory group determined by the KML method was better able to identify children with a higher risk of overweight in early childhood. This provides scientific evidence for selecting appropriate methods to define early childhood BMI trajectories.

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Introduction: In many parts of Asia Pacific (APAC), insufficient intake of micronutrients that are important for conception and pregnancy remains a prevalent issue among women of reproductive age. It is crucial to gain insights into women's nutritional awareness and nutrition-related behaviors, as well as how these relate to their health literacy (HL). This understanding can help identify gaps and guide the development of appropriate intervention strategies. However, there appears to be limited relevant data available for the APAC region. We therefore examined nutritional awareness and behaviors among preconception and pregnant women in three APAC countries, and explored how these were related to women's HL. Methods: Cross-sectional online surveys were conducted among preconception (i.e., planning to conceive within the next 12 months or currently trying to conceive) and pregnant women in Australia (N = 624), China (N = 600), and Vietnam (N = 300). The survey questionnaire included a validated tool for HL (Newest Vital Sign) and questions to examine awareness and behaviors relating to healthy eating and prenatal supplementation during preconception and pregnancy. Results: Despite recommendations for a quality diet complemented by appropriate supplementation during preconception and pregnancy, many respondents in each country were not aware of the specific impact of adequate nutrition during these stages. While many respondents reported changes in their diet to eat more healthily during preconception and pregnancy, a substantial proportion were not taking prenatal supplements. Higher HL was related to greater nutritional awareness and higher use of prenatal supplements. Discussion: Our findings suggest that there are gaps in nutritional awareness and practices of many preconception or pregnant women in the three countries. Interventions to improve HL would be valuable to complement conventional knowledge-centric nutrition education, and enhance understanding and empower women to adopt appropriate nutritional practices throughout their preconception/pregnancy journey.

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The Seneca Valley virus (SVV) is a recently discovered porcine pathogen that causes vesicular diseases and poses a significant threat to the pig industry worldwide. Erythropoietin-producing hepatoma receptor A2 (EphA2) is involved in the activation of the AKT/mTOR signaling pathway, which is involved in autophagy. However, the regulatory relationship between SVV and EphA2 remains unclear. In this study, we demonstrated that EphA2 is proteolysed in SVV-infected BHK-21 and PK-15 cells. Overexpression of EphA2 significantly inhibited SVV replication, as evidenced by decreased viral protein expression, viral titers, and viral load, suggesting an antiviral function of EphA2. Subsequently, viral proteins involved in the proteolysis of EphA2 were screened, and the SVV 3C protease (3Cpro) was found to be responsible for this cleavage, depending on its protease activity. However, the protease activity sites of 3Cpro did not affect the interactions between 3Cpro and EphA2. We further determined that EphA2 overexpression inhibited autophagy by activating the mTOR pathway and suppressing SVV replication. Taken together, these results indicate that SVV 3Cpro targets EphA2 for cleavage to impair its EphA2-mediated antiviral activity and emphasize the potential of the molecular interactions involved in developing antiviral strategies against SVV infection.

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