Evaluation of AlphaFold2 Structures for Hit Identification across Multiple Scenarios.

The introduction of AlphaFold2 (AF2) has sparked significant enthusiasm and generated extensive discussion within the scientific community, particularly among drug discovery researchers. Although previous studies have addressed the performance of AF2 structures in virtual screening (VS), a more comprehensive investigation is still necessary considering the paramount importance of structural accuracy in drug design. In this study, we evaluate the performance of AF2 structures in VS across three common drug discovery scenarios: targets with holo, apo, and AF2 structures; targets with only apo and AF2 structures; and targets exclusively with AF2 structures. We utilized both the traditional physics-based Glide and the deep-learning-based scoring function RTMscore to rank the compounds in the DUD-E, DEKOIS 2.0, and DECOY data sets. The results demonstrate that, overall, the performance of VS on AF2 structures is comparable to that on apo structures but notably inferior to that on holo structures across diverse scenarios. Moreover, when a target has solely AF2 structure, selecting the holo structure of the target from different subtypes within the same protein family produces comparable results with the AF2 structure for VS on the data set of the AF2 structures, and significantly better results than the AF2 structures on its own data set. This indicates that utilizing AF2 structures for docking-based VS may not yield most satisfactory outcomes, even when solely AF2 structures are available. Moreover, we rule out the possibility that the variations in VS performance between the binding pockets of AF2 and holo structures arise from the differences in their biological assembly composition.

Epidemiological features of suicidal ideation among the elderly in China based meta-analysis.

BACKGROUND: Studies on the prevalence of suicidal ideation (SI) and its associated factors among the elderly in China show considerable variability. This meta-analysis aims to clarify the epidemiological features of SI in this population. METHODS: We systematically searched English and Chinese databases for relevant literature up to September 15, 2022. The extracted data facilitated the calculation of prevalence and odds ratios (ORs) for factors associated with SI among China's elderly. RESULTS: We analyzed 31 cross-sectional studies, comprising a total of 79,861 participants from over 20 provinces and municipalities. The pooled prevalence of SI was found to be 11.47% [95% confidence interval (CI): 7.82-15.71%]. Significant variations in prevalence were influenced by residence, physical health (including chronic diseases and daily living capabilities), mental health (depressive symptoms and life satisfaction), economic status, and time-specific assessment tools. Notably, the prevalence from 2011-2020 (15.59%, 95% CI: 9.08-23.44%) was almost double that of 2001-2010 (7.85%, 95% CI: 5.08-11.16%). The SI prevalence in the eastern region (8.06%, 95% CI 5.59-10.94%) was significantly lower than in the central and western regions (16.97%, 95% CI 12.04-22.53%). Fourteen factors exhibited a significant pooled OR greater than 1 (p < 0.05), and two factors had ORs less than 1 (p < 0.05), indicating notable association with SI among the elderly. CONCLUSION: SI among China's elderly showed relatively high prevalence and considerable heterogeneity across different characteristics and associated factors. This underscores the need for targeted intervention strategies and standardized temporal assessments of SI to effectively address suicide risk in this population.

Non-unique Hamiltonians for discrete symplectic dynamics.

An outstanding property of any Hamiltonian system is the symplecticity of its flow, namely, the continuous trajectory preserves volume in phase space. Given a symplectic but discrete trajectory generated by a transition matrix applied at a fixed time-increment (τ > 0), it was generally believed that there exists a unique Hamiltonian producing a continuous trajectory that coincides at all discrete times (t = nτ with n integers) as long as τ is small enough. However, it is now exactly demonstrated that, for any given discrete symplectic dynamics of a harmonic oscillator, there exist an infinite number of real-valued Hamiltonians for any small value of τ and an infinite number of complex-valued Hamiltonians for any large value of τ. In addition, when the transition matrix is similar to a Jordan normal form with the supradiagonal element of 1 and the two identical diagonal elements of either 1 or -1, only one solution to the Hamiltonian is found for the case with the diagonal elements of 1, but no solution can be found for the other case.

Injectable hydrogel encapsulating siMMP13 with anti-ROS and anti-apoptotic functions for osteoarthritis treatment.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive degeneration of articular cartilage, leading to pain, stiffness, and loss of joint function. The pathogenesis of OA involves multiple factors, including increased intracellular reactive oxygen species (ROS), enhanced chondrocyte apoptosis, and disturbances in cartilage matrix metabolism. These processes contribute to the breakdown of the extracellular matrix (ECM) and the loss of cartilage integrity, ultimately resulting in joint damage and dysfunction. RNA interference (RNAi) therapy has emerged as a promising approach for the treatment of various diseases, including hATTR and acute hepatic porphyria. By harnessing the natural cellular machinery for gene silencing, RNAi allows for the specific inhibition of target genes involved in disease pathogenesis. In the context of OA, targeting key molecules such as matrix metalloproteinase-13 (MMP13), which plays a critical role in cartilage degradation, holds great therapeutic potential. RESULTS: In this study, we developed an innovative therapeutic approach for OA using a combination of liposome-encapsulated siMMP13 and NG-Monomethyl-L-arginine Acetate (L-NMMA) to form an injectable hydrogel. The hydrogel served as a delivery vehicle for the siMMP13, allowing for sustained release and targeted delivery to the affected joint. Experiments conducted on destabilization of the medial meniscus (DMM) model mice demonstrated the therapeutic efficacy of this composite hydrogel. Treatment with the hydrogel significantly inhibited the degradation of cartilage matrix, as evidenced by histological analysis showing preserved cartilage structure and reduced loss of proteoglycans. Moreover, the hydrogel effectively suppressed intracellular ROS accumulation in chondrocytes, indicating its anti-oxidative properties. Furthermore, it attenuated chondrocyte apoptosis, as demonstrated by decreased levels of apoptotic markers. CONCLUSION: In summary, the injectable hydrogel containing siMMP13, endowed with anti-ROS and anti-apoptotic properties, may represent an effective therapeutic strategy for osteoarthritis in the future.

The assessment and detection rate of intrinsic capacity deficits among older adults: a systematic review and meta-analysis.

BACKGROUND: Assessing and monitoring intrinsic capacity (IC) is an effective strategy to promote healthy ageing by intervening early in high-risk populations. This review systematically analyzed the global detection rates of IC deficits and explored variations across diverse populations and data collection methods. METHODS: This study was preregistered with PROSPERO, CRD42023477315. In this systematic review and meta-analysis, we systematically searched ten databases from January 2015 to October 2023, for peer-reviewed, observational studies or baseline survey of trials that assessed IC deficits among older adults aged 50 and above globally following the condition, context and population approach. The main outcome was intrinsic capacity deficits which could be assessed by any tools. Meta-analyses were performed by a random-effect model to pool the detection rates across studies and subgroup analyses were conducted by populations and data collection methods. RESULTS: Fifty-six studies conducted in 13 countries were included in the review and 44 studies with detection rates of IC were included in the meta-analysis. The pooled detection rate of IC deficits was 72.0% (65.2%-78.8%) and deficits were most detected in sensory (49.3%), followed by locomotion (40.0%), cognition (33.1%), psychology (21.9%), and vitality (20.1%). Variations in detection rates of IC deficits were observed across studies, with higher rates observed in low- and middle-income countries (74.0%) and hyper-aged societies (85.0%). Study population and measurement tools also explained the high heterogeneity across studies. CONCLUSION: IC deficits are common among older adults, while heterogeneity exists across populations and by measurement. Early monitoring with standardized tools and early intervention on specific subdomains of IC deficits are greatly needed for effective strategies to promote healthy ageing.

Gender difference in the association between education and schizophrenia in Chinese adults.

BACKGROUND: Improving education level was evidenced to decrease the risk of schizophrenia, but whether this strength of education role depends on gender is not. This study aimed to investigate whether there was gender difference in the association between education and schizophrenia in Chinese adults. METHODS: Data were obtained from the Second China National Sample Survey on Disability in 2006, including 1,909,205 participants aged 18 years or older. Schizophrenia was ascertained according to the International Statistical Classification of Diseases, Tenth Revision. Logistics regression models were fitted to examine the combined effect of gender and education on schizophrenia. RESULTS: The lifetime prevalence of schizophrenia in female groups was higher than in male groups, with 0.44% (95%CI: 0.42-0.45%) and 0.36% (95%CI: 0.35-0.37%), respectively. Compared with schizophrenia male patients, more females with schizophrenia experienced severe or extreme difficulty in understanding and communicating. However, more males with schizophrenia suffered from severe or extreme difficulty in the function of daily activities. The combined effect of education and schizophrenia was statistically significant, indicating that, as the level of education increased, schizophrenia risk of females decreased faster than the risk of males. CONCLUSIONS: This study showed that additional years of education associated with lower risk of schizophrenia, and this association was stronger in females than in males. As education elevated, the risk of schizophrenia decreased more for women than for men. The findings indicate that improving education level may have an effect on reducing the gender disparities in mental health of China. Actions to prevent schizophrenia and address its gender disparities will require attention to the improving educational opportunities.

Preparation of Mechanically Stable Self-Assembled Peptides Hydrogels.

Peptide hydrogels are highly hydrophilic, three-dimensional network gels formed by the self-assembly of nanofibers or polymers, creating water-locking networks. Their morphology closely resembles that of the extracellular matrix, allowing them to exhibit both the biological functions of peptides and responsive gelation properties. These unique characteristics have led to their extensive application in tissue engineering, three-dimensional cell culture, cancer therapy, regenerative medicine, and other biomedical fields. This article describes three methods for preparing ECF-5 peptide hydrogels using self-assembling peptides with environmentally responsive gelation processes: (1) pH-responsive gelation: varying pH levels induce the protonation or deprotonation of amino acid residues, altering electrostatic interactions between peptide molecules and promoting their self-assembly into hydrogels; (2) Metal ion addition: polyvalent metal ions chelate with negatively charged amino acid residues, acting as bridges between peptides to form a network hydrogel; (3) Solvent exchange: hydrophobic peptides are initially dissolved in non-polar organic solvents and subsequently induce self-assembly into hydrogels upon transitioning to a polar aqueous environment. These methods utilize conventional experimental procedures to facilitate peptide self-assembly into hydrogels. By designing peptide sequences to align with specific gelation-inducing conditions, it is possible to achieve finely tuned micro/nanostructures and biological functions, highlighting the significant potential of peptide hydrogels in the biomedical domain.

Association between chronic disease status and transitions in depressive symptoms among middle-aged and older Chinese population: Insights from a Markov model-based cohort study.

BACKGROUND: The relationship between chronic disease status (CDS) and transitions in depressive symptoms (DS) remains unclear. This study explores the association between CDS and DS transitions. METHODS: This cohort study analyzed data from 8175 participants aged 45+, sourced from China Family Panel Studies (2016, 2018, 2020). DS were assessed using a brief version of Center for Epidemiologic Studies Depression Scale (CES-D). CDS was categorized into healthy, single disease, and multimorbidity. Markov models were used to estimate state transition intensities, mean sojourn times and hazard ratios (HRs). RESULTS: DS transitions occurred between adjacent and non-adjacent states, but transition intensity between adjacent states was higher than among non-adjacent states. Self-transition intensities of severe-DS, mild-DS, and non-DS progressively increased, with average durations of 1.365, 1.482, and 7.854 years, respectively. Both single disease and multimorbidity were significantly associated with an increased risk of transitioning from non-DS to mild-DS, with multimorbidity showing a stronger association. In contrast, HRs for single diseases transitioning from mild-DS to severe-DS were significantly lower than 1. Furthermore, their HRs were almost <1 in recovery transitions but not statistically significant. LIMITATIONS: Specific chronic diseases and their combinations were not analyzed. CONCLUSIONS: The progression of DS exhibits various pathways. CDS is associated with DS transitions, but the roles of single disease and multimorbidity may differ across different DS progression stages. Both conditions were significantly linked to the risk of new-onset DS, with multimorbidity posing a greater association. However, this relationship is not observed in other progression stages. These findings could provide insights for early prevention and intervention for DS.

Socioeconomic, Health Services, and Multimorbidity Disparities in Chinese Older Adults.

INTRODUCTION: As one of the world's most populous countries, China persistently confronts a significant multimorbidity burden. This study aimed to elucidate the multimorbidity burden experienced by Chinese older adults, explore its interplay with socioeconomic disparity, and investigate potential correlations between these provincial disparities and health services availability. METHODS: The fourth wave of China's national Urban and Rural Elderly Population study, conducted in 2015, was used to construct a multimorbidity index and elucidate the geographic differences in the multimorbidity burden. Incorporating macrolevel indicators about socioeconomic and health services availability, quantile regression and Spearman correlation analyses were employed to investigate the relationship between multimorbidity and socioeconomic disparities and examine the potential linkages between these provincial disparities and health services availability. Analyses were performed in 2023. RESULTS: The final analysis included a total of 213,857 older adults. At the provincial level, significant geographic disparities in multimorbidity burden were identified. After adjusting for individual social determinants of health, an independent association was found between the human development index and a higher multimorbidity index (coefficient= -0.22; 95% CI= -0.24, -0.19). Furthermore, a significant positive correlation emerged between human development index and both population and geographic densities of health services availability. Notably, geographic density displayed greater inequality (Gini coefficients=0.45-0.48) than population density (Gini coefficients=0.03-0.10). CONCLUSIONS: This study demonstrates that multimorbidity burden in China is linked to provincial socioeconomic disparities and that inequality in health services availability may account for this, which would advocate for a need to reduce disparities in health services availability.

Developmental toxicity and metabolomics analyses of zebrafish (Danio rerio) embryos exposed to Fenoxaprop-p-ethyl.

Fenoxaprop-p-ethyl (FEN) is an aryloxy phenoxy propionate herbicide that has been widely used in paddy fields. Previous studies have indicated that FEN is highly toxic to aquatic organisms, but little is known about the developmental effects of FEN. This study investigated acute and developmental toxicity, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and metabolomic analyses in zebrafish embryos after 96 h of exposure. FEN exhibited high acute toxicity to zebrafish embryos and larvae. Exposure to FEN could reduce heartbeat and hatching rates and increase malformation rates in embryos. Oxidative damage was also caused in embryos. The results of metabolomics analysis showed that 102 differentially abundant metabolites were found in zebrafish embryos in the 0.05 mg/L FEN treatment group, and 60 differentially abundant metabolites were found in the 0.20 mg/L FEN treatment group. These differentially abundant metabolites mainly belonged to 9 metabolic pathways, of which folate pathways and ABC transport protein pathways had the greatest impact. These results suggested that FEN induced high acute and developmental toxicity in zebrafish embryos.

Trends and Distribution of Infertility - Asia Pacific Region, 1990-2021.

What is already known about this topic?: Infertility represents a significant global public health concern, impacting approximately 15% of couples of reproductive age worldwide. Despite this, data on infertility prevalence in the demographically diverse Asia-Pacific region remains sparse. What is added by this report?: This study examines the trends and distribution of infertility in the Asia-Pacific region from 1990 to 2021, revealing a significant increase in female infertility. The growth rate of secondary infertility has exceeded that of primary infertility. Additionally, an increase in the prevalence of polycystic ovary syndrome (PCOS) may be a significant contributor. The research also highlights geographical variations in the prevalence and trends of infertility across different countries. What are the implications for public health practice?: The findings emphasize the significance of sexual and reproductive health services and rights in safeguarding fertility.

Two-electron oxidized polyphenol chemistry-inspired superhydrophilic drug-carrying coatings for the construction of multifunctional nasolacrimal duct stents.

Nasolacrimal duct obstruction due to infection, inflammation, or excessive fibroblast proliferation may result in persistent tearing, intraocular inflammation, or even blindness. In this study, surface engineering techniques are applied to nasolacrimal duct stents for the first time. Based on the functioning of marine mussels, "one-pot" and "stepwise" methods were employed to construct a novel multifunctional superhydrophilic PDA/RAP coating using dopamine and rapamycin. Micron-sized rapamycin crystals combined with nano-sized polydopamine particles form a micro-nano topographical structure. Therefore, acting synergistically with in situ-generated hydrophilic groups (amino, carboxyl, and phenolic hydroxyl), they impart excellent and long-lasting superhydrophilicity to the nasolacrimal duct stent. The PDA/RAP coating effectively maintained the stability of the initial microenvironment during stent implantation by inhibiting the onset of acute inflammation and infection during the early stages of implantation. Meanwhile, the rapamycin crystals, supported by the superhydrophilic platform, exhibited a sustained-release capability that helped them to better exert their anti-inflammatory, antibacterial, and anti-fibroblast proliferative properties, ensuring conducive conditions for the rapid repair of nasolacrimal duct epithelial cells, verified by a series of experiments. In conclusion, the PDA/RAP hydrophilic coating has anti-inflammatory, antifibrotic, antibacterial, and antithrombotic properties, offering a new strategy to address restenosis following clinical nasolacrimal duct stent implantation.

FATP2 regulates osteoclastogenesis by increasing lipid metabolism and ROS production.

Lipid metabolism plays a crucial role in maintaining bone homeostasis, particularly in osteoclasts (OCs) formation. Here, we found that the expression level of FATP2, a transporter for long-chain and very-long-chain fatty acids, was significantly upregulated during OC differentiation and in the bone marrow of mice fed a high-fat diet (HFD). Notably, the use of FATP2 siRNA or a specific inhibitor (Lipofermata) resulted in significant inhibition of OC differentiation, while only slightly affecting osteoblasts. In pathological models of bone loss induced by LPS or ovariectomy, in vivo treatment with Lipofermata was able to rescue the loss of bone mass by inhibiting OC differentiation. RNA sequencing revealed that Lipofermata reduced fatty acid ß-oxidation and inhibited energy metabolism, while regulating ROS metabolism to decrease ROS production, ultimately inhibiting OC differentiation. Treatment with Lipofermata, either in vivo or in vitro, effectively rescued the overactivation of OCs, indicating that FATP2 regulated OC differentiation by modulating fatty acid uptake and energy metabolism. These findings suggested that targeting FATP2 may represent a promising therapeutic approach for pathological osteoporosis.

The inhibition of osteoclastogenesis by Lipofermata, a FATP2 inhibitor, was achieved through the reprogramming of energy metabolism and regulation of ROS levels. In both pathological bone loss and HFD-induced osteoporosis models, the expression levels of FATP2 were significantly upregulated, and Lipofermata demonstrated potential therapeutic effects in the pathological bone loss model.

Trends and Patterns of Respiratory Tuberculosis Mortality in Rural and Urban - China, 1987-2021.

What is already known about this topic?: In China, an estimated 780,000 individuals contract tuberculosis (TB) every year. With TB ranked as the second most prevalent disease in terms of the morbidity and mortality rates for legally infectious diseases, it imparts a substantial disease burden on families and society. What is added by this report?: This study identifies specific periods and cohort effects related to trends in respiratory TB mortality in both rural and urban regions of China. The mortality rates have been found to decrease at an annual rate of 5.5% in urban regions and 6.6% in rural ones, with a more marked decline evident in rural areas. These findings represent a significant milestone in the prevention and treatment of respiratory TB in China, especially in its rural locales. What are the implications for public health practice?: This research contributes to policymakers' comprehension, assisting in the early formulation of cogent optimization policies, thereby further supporting the United Nations Sustainable Development Goals (SDGs) and the Endeavor to End Respiratory TB Strategy. It is recommended that policymakers prioritize key groups such as children, young adults aged 20-30 in rural areas, and older men (60 years and over) in urban areas when developing these astute optimization policies.

Urban-rural disparities in the prevalence and trends of depressive symptoms among Chinese elderly and their associated factors.

BACKGROUND: This study aimed to examine urban-rural disparities in the prevalence and trends of depressive symptoms (DS) among Chinese elderly and associated factors. METHODS: A total of 8025, 7808, and 4887 respondents aged 60 years and above were selected from the China Family Panel Studies (CFPS) in 2016, 2018, and 2020, respectively. DS was assessed using a short version of Center for Epidemiologic Studies Depression Scale (CES-D). Twenty-two associated factors from six categories were included in random forest (RF) models. All urban-rural comparisons were conducted based on good model performance. RESULTS: The DS prevalence among all rural elderly was significantly higher than corresponding urban elderly. This disparity continued to widen among younger elderly, while it continued to narrow among older elderly. The top 10 common leading factors were sleep quality, self-rated health, life satisfaction, memory ability, child relationship, IADL disability, marital status, educational level, and gender. Urban-rural disparities in sleep quality, interpersonal trust, and child relationship continued to widen, while disparities in multimorbidity, hospitalization status, and frequency of family dinner continued to narrow. LIMITATION: This study may exist recall bias and lacks causal explanation. CONCLUSIONS: Significant and continuing disparities in the DS prevalence were observed between urban and rural elderly in China, showing opposite trends in younger and older elderly. The top 10 leading associated factors for DS were nearly consistent across urban and rural elderly, with sleep quality having strongest contribution. Urban-rural disparities in associated factors also showed different trends. This study provides a reference for mental health promotion among Chinese elderly.

Widening rural-urban gap in life expectancy in China since COVID-19.

INTRODUCTION: Disparities in life expectancy between rural and urban populations are well established but how it varies with epidemics and pandemics remains poorly understood. We aimed to quantify the rural-urban differences in the mortality burden of COVID-19 and to contribute to understanding the disparity trends in life expectancy between 1987 and 2021 in China. METHODS: We used monthly death counts from death registration systems. Rural-urban gap estimation and decomposition were carried out using period life tables to calculate life expectancy, the Arriaga decomposition technique to break down into age-specific and cause-specific mortality, and the Lee-Carter forecasts to estimate the expected gap. RESULTS: The rural-urban gap increased to 22.7 months (95% credible interval (CI) 19.6 to 25.8) in 2020 and further to 23.7 months (95% CI 19.6 to 26.7) in 2021, and was larger than expected under the continuation of the prepandemic trends. Compared with that in the recent 2003 SARS-CoV-2 epidemic and the 2009 influenza epidemic, excess rural-urban gaps in the COVID-19 pandemic changed from urban disadvantage to rural disadvantage, and the contributions shifted toward old age groups and circulatory diseases. Variations in the rural-urban gap since 1987 were positively correlated with the rural-urban disparity in public health expenditures, especially among ages <60 (p values <0.005). CONCLUSIONS: Our findings identified a widening rural-urban gap in life expectancy since COVID-19, and a shifting trend towards old ages and circulatory diseases, disrupting the diminishing trend of the gap over 35 years. The findings highlight the unequal impact of the pandemic on different communities in terms of mortality burdens.

Association between multimorbidity and memory-related diseases among middle-aged and older adults: Evidence from the China Health and Retirement Longitudinal Study.

Objectives: This study aimed to examine the cross-sectional and longitudinal association between multimorbidity and memory-related diseases (MDs) among Chinese middle-aged and older adults. Methods: This study included 8,338 subjects who participated in the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression and Cox proportional hazards regression models were used to explore the association and effect of multimorbidity on MDs. Results: The overall prevalence of MDs was 2.52%, and the mean multimorbidity number was 1.87. In a cross-sectional analysis, compared with the no multimorbidity group, groups of multimorbidity with four or more non-communicable diseases (NCDs) were more likely to have MDs (OR: 6.49, 95%CI: 4.35-9.68). Within 2.7 years of follow-up, 82 cases of MDs (1.12%) were reported, and participants with multimorbidity were more likely to have new-onset MDs than participants without multimorbidity (HR: 2.93, 95%CI: 1.74-4.96). Conclusion: Multimorbidity is associated with MDs among Chinese middle-aged and older adults. This relationship gradually strengthens with the severity of multimorbidity, which indicates that early prevention for people with multimorbidity may reduce the risk of MDs.

Urban-Rural Disparity in Mortality Patterns of Respiratory Diseases Among Older Adults - China, 1987-2021.

What is already known about this topic?: Respiratory diseases (RDs) are the primary cause of death in older adults in China. However, there is limited evidence regarding the disparity in mortality rates of RDs between urban and rural areas among the elderly population. What is added by this report?: The age-standardized mortality rate (ASMR) due to RDs in the elderly population in both urban and rural areas of China has shown a consistent decrease. This trend is observed in both males and females. However, there was no significant change in the average annual percentage of ASMR for pneumonia among the urban elderly population and rural elderly men throughout the study period. What are the implications for public health practice?: Efforts should be made in China to reduce mortality from chronic lower respiratory disease and pneumonia among the elderly, particularly in urban populations.

Sigmoid Accelerated Molecular Dynamics: An Efficient Enhanced Sampling Method for Biosystems.

Gaussian accelerated molecular dynamics (GaMD) is recognized as a popular enhanced sampling method for tackling long-standing challenges in biomolecular simulations. Inspired by GaMD, Sigmoid accelerated molecular dynamics (SaMD) is proposed in this work by adding a Sigmoid boost potential to improve the balance between the highest acceleration and accurate reweighting. Compared with GaMD, SaMD extends the accessible time scale and improves the computational efficiency as tested in three tasks. In the alanine dipeptide task, SaMD can produce the free energy landscape with better accuracy and efficiency. In the chignolin folding task, the estimated Gibbs free energy difference can converge to the experimental value ∼30% faster. In the protein-ligand binding task, the bound conformations are closer to the crystal structure with a minimal ligand root-mean-square deviation of 1.7 Å. The binding of the ligand XK263 to the HIV protease is reproduced by SaMD in ∼60% less simulation time.

Healthy Lifestyles and Chronic Pain with New-Onset Metabolic-Related Multimorbidity among Older Adults - China, 2011-2018.

What is already known about this topic?: Chronic pain has been identified as a risk factor for cardiovascular diseases. Evidence shows that adopting a healthy lifestyle can help reduce the cardiometabolic risks associated with chronic pain. What is added by this report?: Results from this cohort study suggest a positive association between chronic pain and the development of new-onset metabolic-related multimorbidity, specifically metabolic multimorbidity and cardiometabolic comorbidity, within middle-aged and older Chinese adults. Furthermore, adopting healthy lifestyles can potentially mitigate or even reverse these associations. What are the implications for public health practice?: The results of our study emphasize the importance of promoting healthy lifestyles among older Chinese adults as a preventative measure against the medical burdens and cardiometabolic risks associated with chronic pain.