FDA-approved small molecule kinase inhibitors for cancer treatment (2001-2015): Medical indication, structural optimization, and binding mode Part I.

The dysregulation of kinases has emerged as a major class of targets for anticancer drug discovery given its node roles in the etiology of tumorigenesis, progression, invasion, and metastasis of malignancies, which is validated by the FDA approval of 28 small molecule kinase inhibitor (SMKI) drugs for cancer treatment at the end of 2015. While the preclinical and clinical data of these drugs are widely presented, it is highly essential to give an updated review on the medical indications, design principles and binding modes of these anti-tumor SMKIs approved by the FDA to offer insights for the future development of SMKIs with specific efficacy and safety.

Source apportionment of organic carbon and nitrogen in sediments from river and lake in the highly urbanized Changjiang Delta.

While the impact of human activities on organic matter pollution is recognized, how these impacts vary seasonally in the Changjiang Delta needs further investigation. This study addresses this gap by investigating seasonal variations in organic matter sources and ecological responses to human activities in Changjiang Delta sediments. Total organic carbon (TOC), total nitrogen (TN), and carbon (δ13C) and nitrogen (δ15N) isotopic compositions of surface sediments collected from the Taipu River and Dalian Lake wetland were analyzed. Both water bodies exhibited similar seasonal trends for TOC and TN, with the Taipu River containing an average of 0.46% and 0.03% higher concentrations of TOC and TN, respectively, compared to Dalian Lake. Additionally, the organic index (OI) and organic nitrogen (ON) index were elevated in both water bodies during the wet season. Sediments from Dalian Lake remained uncontaminated to moderately contaminated, while those from the Taipu River were generally classified as moderately to heavily contaminated. Stable isotope analysis identified terrestrial C3 plants (averaging 25.5%), C4 plants (averaging 16.0%), and municipal wastewater (averaging 16.0%) as the main contributors to organic matter in the sediments. These findings suggest that terrestrial plant material and municipal wastewater are key targets for managing organic matter contamination in the Changjiang Delta. Implementing strategic land-use planning and targeted interventions to minimize these inputs can significantly improve water quality and ecosystem health.

Causal role of immune cells in uveitis: a Mendelian randomization study.

Background: Uveitis refers to a group inflammation affecting the uvea, retina, retinal blood vessels as well as vitreous body, which is one of the common causes of blindness. There is growing evidence linking different types of immune cells to uveitis, although it remains uncertain if these associations imply causal relationships. Recent advancements in high-density genetic markers like SNPs or CNVs for genotyping, along with the progress in genome-wide association studies (GWAS) technologies, have improved our understanding of the immunological mechanisms involved in ocular diseases. Therefore, our objective was to investigate the potential causal link between immune cells and uveitis using a Mendelian randomization study. Methods: The exposure and outcome GWAS data for this study were sourced from an open-access database (https://gwas.mrcieu.ac.uk/). Two-sample MR analysis was utilized to evaluate the causal relationship between 731 immune cell features and uveitis. Various MR methods were employed to reduce bias and obtain dependable estimates of the causal link between the immune cell variables and the outcomes. Instrumental variable selection criteria were carefully chosen to enhance the accuracy and efficacy of the causal relationship between different immune cell types and the risk of uveitis. Results: Using two-sample MR, IVW modeling showed that GAD had significant effect on immunophenotypes. CD3 levels on CD45RA- CD4+ T cells (OR = 1.087, 95%CI = 1.029 ~ 1.147, p = 0.003) and CD3 levels on CM CD4+ T cells (OR = 1.086, 95%CI = 1.033 ~ 1.141, p = 0.001) were found to be elevated in cases of uveitis. HLA DR levels in CD14- CD16+ monocyte cells (OR = 0.735, 95% CI = 0.635 ~ 0.850, p < 0.001) and HLA DR levels in NK cells (OR = 0.910, 95% CI = 0.851 ~ 0.972, p = 0.005) were observed to be reduced in individuals with uveitis. Furthermore, Two cells were identified to be significantly associated with uveitis risk: HLA DR on in NK cells (OR = 0.938, 95%CI = 0.899 ~ 0.979, p = 0.003), HLA DR on CD14- CD16+ monocytes (OR = 0.924, 95%CI = 0.878 ~ 0.972, p = 0.002). Conclusion: This study highlights the intricate relationship between immune cells and generalized anxiety disorder using genetic methods, offering valuable insights for future clinical investigations.

Recent Progress in the Conversion of Methylfuran into Value-Added Chemicals and Fuels.

2-methylfuran is a significant organic chemical raw material which can be produced by hydrolysis, dehydration, and selective hydrogenation of biomass hemicellulose. 2-methylfuran can be converted into value-added chemicals and liquid fuels. This article reviews the latest progress in the synthesis of liquid fuel precursors through hydroxyalkylation/alkylation reactions of 2-methylfuran and biomass-derived carbonyl compounds in recent years. 2-methylfuran reacts with olefins through Diels-Alder reactions to produce chemicals, and 2-methylfuran reacts with anhydrides (or carboxylic acids) to produce acylated products. In the future application of 2-methylfuran, developing high value-added chemicals and high-density liquid fuels are two good research directions.

The association among negative life events, alexithymia, and depressive symptoms in a psychosomatic outpatient sample.

BACKGROUND: Depression is a life-threatening mental health problem. Various factors have been demonstrated to be associated with depressive symptoms, including negative life events (NLEs) and alexithymia. A retrospective study was conducted to investigate the relationship among negative life events, alexithymia, and depression symptoms in a psychosomatic outpatient sample in China. METHODS: A total of 2747 outpatients (aged 18 - 65) were included in this investigation. The Life Events Scale (LES), Toronto alexithymia scale (TAS-26), and 9-item Patient Health Questionnaire (PHQ-9) were used to assess NLEs, alexithymia, and depressive symptoms, respectively. A stepwise regression analysis model was established to investigate the relationship among alexithymia, NLEs, and depressive symptoms. RESULTS: Overall, 67.0% of the patient sample had a PHQ-9 score of 10 or higher. The stepwise regression analysis model showed a well-fitted model, in which NLEs and alexithymia explain a total of 34.2% of the variance of depressive symptoms in these participants. NLEs (ß = 0.256, p < 0.001) and dimensions of alexithymia (difficult describing feelings (ß = 0.192, p < 0.001) and identifying feelings (ß = 0.308, p < 0.001)) were positively correlated with symptoms of depression. CONCLUSIONS: Previous studies have confirmed the correlation between NLEs and depression, alexithymia and depression, respectively. In our study, we used a stepwise regression model to explain the relationship among those variables simultaneously, and found that NLEs and alexithymia could function as predictors of depressive symptoms. Based on this discovery, alexithymia-focused treatment strategies could be alternative in depressive patients with alexithymia, but this remains to be verified in the future.

Adherence to 24-Hour Movement Guidelines Among Chinese Older Adults: Prevalence, Correlates, and Associations With Physical and Mental Health Outcomes.

BACKGROUND: It is known that 24-hour movement behaviors, including physical activity (PA), sedentary behavior (SB), and sleep, are crucial components affecting older adults' health. Canadian 24-hour movement guidelines for older adults were launched in 2020, emphasizing the combined role of these 3 movement behaviors in promoting older adults' health. However, research on the prevalence and correlates of guideline adherence and its associations with health-related outcomes is limited, especially among Chinese older adults. OBJECTIVE: This study aimed to investigate the prevalence and correlates of meeting 24-hour movement guidelines among Chinese older adults. Furthermore, this study aimed to examine the associations of guideline adherence with older adults' physical and mental health outcomes. METHODS: Using a stratified cluster random sampling approach, a total of 4562 older adults (mean age 67.68 years, SD 5.03 years; female proportion: 2544/4562, 55.8%) were recruited from the latest provincial health surveillance of Hubei China from July 25 to November 19, 2020. Measures included demographics, movement behaviors (PA, SB, and sleep), BMI, waist circumference, waist-hip ratio (WHR), percentage body fat (PBF), systolic and diastolic blood pressure, physical fitness, depressive symptoms, and loneliness. Generalized linear mixed models were employed to examine the associations between variables using SPSS 28.0 (IBM Corp). RESULTS: Only 1.8% (83/4562) of participants met all 3 movement guidelines, while 32.1% (1466/4562), 3.4% (155/4562), and 66.4% (3031/4562) met the individual behavioral guidelines for PA, SB, and sleep, respectively. Participants who were older, were female, and lived in municipalities with lower economic levels were less likely to meet all 3 movement guidelines. Adhering to individual or combined movement guidelines was associated with greater physical fitness and lower values of BMI, waist circumference, WHR, PBF, depressive symptoms, and loneliness, with the exception of the relationship of SB+sleep guidelines with loneliness. Furthermore, only meeting SB guidelines or meeting both PA and SB guidelines was associated with lower systolic blood pressure. CONCLUSIONS: This is the first study to investigate adherence to 24-hour movement guidelines among Chinese older adults with regard to prevalence, correlates, and associations with physical and mental health outcomes. The findings emphasize the urgent need for promoting healthy movement behaviors among Chinese older adults. Future interventions to improve older adults' physical and mental health should involve enhancing their overall movement behaviors and should consider demographic differences.

Associations of Reallocating Sedentary Time to Physical Activity and Sleep with Physical and Mental Health of Older Adults.

INTRODUCTION: 24-hour movement behaviors: moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB) and sleep are crucial factors affecting older adults' health. Using a compositional data analysis approach, this study examined the associations of time spent in these four movement behaviors with cardiometabolic health, physical fitness, and mental health among older adults. Furthermore, this study identified the estimated changes in aforementioned health outcomes by reallocating SB time to other movement behaviors. METHODS: A population-based cross-sectional study of 4,562 participants (67.68 ± 5.03 years; 55.8% female) were implemented in Hubei China between 25-Jul and 19-Nov 2020. Measures included demographics, movement behaviors, cardiometabolic indicators (body mass index, BMI; waist circumference; waist-hip ratio, WHR; percentage body fat; systolic and diastolic blood pressure), physical fitness, and mental health outcomes (depressive symptoms and loneliness). Compositional data analyses were implemented in R. RESULTS: MVPA and sleep time was associated with greater health outcomes (all P < 0.001), except blood pressure (P = 0.13-0.83). LPA time was associated with waist circumference (B = 0.313, P = 0.009), WHR (B = 0.003, P = 0.003), physical fitness (B = 0.36, P < 0.001), and mental health indicators (both P < 0.001). Reallocating 30-min SB to MVPA and sleep was associated with predicated improvements in all health outcomes, except blood pressure, while reallocating 30-min SB to LPA resulted in predicted improvements in physical fitness (0.187 units), depressive symptoms (-0.264 units) and loneliness (-0.395 units). For dose-effect relationships, reallocating 5-60 min of SB to MVPA showed greatest benefits for all health outcomes. CONCLUSIONS: This study provides timely empirical evidence for future interventions and policymaking on promoting healthy aging during the post-covid-19 era. The findings underline the importance of including 24-hour movement behaviors in future health promotion among older adults.

In-classroom physical activity breaks program among school children in Sri Lanka: study protocol for a randomized controlled trial.

Background: The problem of sedentary behavior among primary school children is alarming, with numbers gradually increasing worldwide, including Sri Lanka. Physical activity interventions within classroom settings have been acknowledged as a critical strategy to increase students' movement behaviors while enhancing their academic achievement and health. Yet, the busy curriculum and challenging educational demands encourage more sedentary classroom behavior. Hence, this study aims to develop and evaluate an in-classroom physical activity breaks (IcPAB) intervention among fifth graders in Sri Lanka. Methods: The study will adopt a randomized controlled trial (RCT), comprising an in-classroom physical activity breaks program group and a control group to evaluate the effects of IcPAB on academic achievement, movement behaviors and health outcomes. The intervention design is based on the capability (C), opportunity (O) and motivation (M) behavior (B) (COM-B) model. A least 198 fifth graders will be recruited from two schools in Uva province, Sri Lanka. The recruitment process will start in late 2022. Class teachers of the intervention group will implement 5-min activity breaks at least three times a day after completing a training session. The primary variables include mathematics and reading achievement. The secondary variables include physical activity levels, steps count, sedentary behavior, body mass index, aerobic fitness, and perceived stress. Data collection will be implemented at pre-test and post-test, respectively. Intervention fidelity and the process will also be evaluated. Discussion: The IcPAB is designed to prevent pure educational time loss by introducing curriculum-integrated short bouts of physical active breaks into the classroom routine. If the IcPAB is effective, it can (1) improve the mathematics and reading achievement of fifth-grade girls and boys, which is a significant factor determining the performance at the Grade Five National Scholarship Examination in Sri Lanka; (2) improve movement behaviors as well as physical and mental health outcomes among primary school students. Sequentially, the IcPAB will enrich school-based physical activity intervention approaches which can in turn bring academic and health benefits to primary school children in Sri Lanka. Trial registration: The first version of the trial was registered with the ISRCTN registry (Ref: ISRCTN52180050) on 20/07/2022.

A blended face-to-face and eHealth lifestyle intervention on physical activity, diet, and health outcomes in Hong Kong community-dwelling older adults: a study protocol for a randomized controlled trial.

Background: Aging individuals are vulnerable to various Noncommunicable Diseases (NCDs). Different behaviors are closely related to a decreased risk of suffering from NCDs: sufficient Physical Activity (PA) (e.g., at least 150 mins Moderate-to-vigorous Physical Activity (MVPA) per week) and a healthy daily diet (e.g., at least five portions of Fruit and Vegetable Intake (FVI), 5-6 taels (189.0-226.8 g) Meat, Fish, Egg and Alternatives (MFEA)). Traditional face-to-face interventions were effective in behavior change. However, it was revealed to be resource-intensive and limited transfer due to poor self-regulation skills outside of face-to-face sessions. Thus, eHealth could be a supplement for older adults outside traditional face-to-face settings. The blended approach combining these two interventions might optimize the intervention effects on lifestyle behavior initiation and maintenance, but little research can be found among Hong Kong older adults. Therefore, the study aims to test a blended intervention to promote PA, diet, and health outcomes among Hong Kong community-dwelling older adults. Methods: This study will adopt a 10-week three-arm randomized controlled trial. The blended group will receive weekly (1) two 60-min face-to-face sessions with one for PA and one for diet, and (2) two web-based sessions with one for PA and one for diet. The face-to-face group will receive the same intervention content as the face-to-face sessions in the blended group. The control condition will receive a biweekly telephone call. The outcomes will include MVPA (minutes/week), FVI (portions/day), MFEA consumption (taels/day), social-cognitive factors (self-efficacy, planning, social support, action control), physical health outcomes (clinical indicators, senior physical fitness), mental health outcomes (depression, loneliness) and health-related quality of life. Data collection will be implemented at the pre-test, post-test, and 3-month follow-up test. Discussion: This is the first study evaluating a blended intervention promoting multiple health behaviors among Hong Kong community-dwelling older adults. If the effect of the blended intervention is superior to the traditional face-to-face group and the control group, it will enrich lifestyle intervention approaches and can be applied to older adults, helping them obtain health benefits. Furthermore, a better understanding of mechanisms will also have implications for theory-building. Clinical trial registration: https://www.isrctn.com/ISRCTN32329348, ISRCTN32329348.

Predictive factors of psychiatric syndrome in patients with systemic lupus erythematosus.

Introduction: Early detection of neuropsychiatric systemic lupus erythematosus (NPSLE) remains a challenge in clinical settings. Previous studies have found different autoantibodies as markers for NPSLE. This study aimed to describe the distribution of psychiatric syndromes in a group of patients with systemic lupus erythematosus (SLE) and to investigate the association between psychiatric syndromes and specific autoantibodies. Methods: This retrospective study was conducted at a single medical center in China. We reviewed medical records of hospitalized patients with SLE who were consulted by psychiatrists due to potential mental disorders. Results of serum autoantibodies and general laboratory tests were collected. The correlation between clinical variables was examined. Binary logistic regression analyses were used to determine factors related to NPSLE and different psychiatric diagnoses. Results: Among the 171 psychiatric manifestations in 160 patients, 141 (82.4%) were attributed to SLE. Acute confusional state (ACS) had the highest prevalence (57.4%). Anti-cardiolipin (ACL) antibody (X2 = 142.261, p < 0.001) and anti-ß2 glycoprotein I (-ß2GP1) antibody (X2 = 139.818, p < 0.001) varied significantly between groups, with the highest positive rate found in patients with mood disorders (27.3% and 18.2%). SLE disease activity index - 2000 (SLEDAI-2K) score excluding item ACS and item psychosis was a predictor of NPSLE (OR 1.172 [95% CI 1.105 - 1.243]). Conclusions: Disease activity reflected by SLEDAI-2K score is a predictor for NPSLE. Antiphospholipid antibodies are associated with mood disorders in SLE. Further separate investigation of neuropsychiatric disorders is needed in order to better comprehend NPSLE's pathological mechanism.

Unlocking the power of activated carbon-mediated peracetic acid activation for efficient antibiotics abatement in groundwater: Coupling the processes of electron transfer, radical production, and adsorption.

The activation of peracetic acid (PAA) by activated carbon (AC) is a promising approach for reducing micropollutants in groundwater. However, to harness the PAA/AC system's potential and achieve sustainable and low-impact groundwater remediation, it is crucial to quantify the individual contributions of active species. In this study, we developed a combined degradation kinetic and adsorption mass transfer model to elucidate the roles of free radicals, electron transfer processes (ETP), and adsorption on the degradation of antibiotics by PAA in groundwater. Our findings reveal that ETP predominantly facilitated the activation of PAA by modified activated carbon (AC600), contributing to ∼61% of the overall degradation of sulfamethoxazole (SMX). The carbonyl group (CO) on the surface of AC600 was identified as a probable site for the ETP. Free radicals contributed to ∼39% of the degradation, while adsorption was negligible. Thermodynamic and activation energy analyses indicate that the degradation of SMX within the PAA/AC600 system requires a relatively low energy input (27.66 kJ/mol), which is within the lower range of various heterogeneous Fenton-like reactions, thus making it easily achievable. These novel insights enhance our understanding of the AC600-mediated PAA activation mechanism and lay the groundwork for developing efficient and sustainable technologies for mitigating groundwater pollution. ENVIRONMENTAL IMPLICATION: The antibiotics in groundwater raises alarming environmental concerns. As groundwater serves as a primary source of drinking water for nearly half the global population, the development of eco-friendly technologies for antibiotic-contaminated groundwater remediation becomes imperative. The innovative PAA/AC600 system demonstrates significant efficacy in degrading micropollutants, particularly sulfonamide antibiotics. By integrating degradation kinetics and adsorption mass transfer models, this study sheds light on the intricate mechanisms involved, emphasizing the potential of carbon materials as sustainable tools in the ongoing battle for clean and safe groundwater.

Latent classes of symptom trajectories among major depressive disorder patients in China.

OBJECTIVE: This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. METHODS: A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. RESULTS: Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LIMITATIONS: Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. CONCLUSIONS: The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.

Association of Cardiovascular Health With Risk of Incident Depression and Anxiety.

OBJECTIVE: To investigate the association between cardiovascular health (CVH), defined by the American Heart Association's Life's Essential 8 (LE8) score, and incident depression and anxiety. DESIGN: A prospective cohort study using data from UK Biobank. SETTING: Participants were enrolled from March 2006 to October 2010. PARTICIPANTS: Participants without cardiovascular diseases and common mental disorders at baseline and having complete data on metrics of LE8 were included. MEASUREMENTS: CVH was assessed by LE8 score including eight components. The overall CVH was categorized as low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80). RESULTS: We included 115,855 participants (mean age: 55.7 years; female: 52.6%). During a median follow-up of 12.4 years, 3,194 (2.8%) and 4,005 (3.5%) participants had incident depression and anxiety, respectively. Compared with participants having low CVH, those having moderate and high CVH had 37% (HR = 0.63, 95% CI: 0.57-0.70) and 52% (HR = 0.48, 95% CI: 0.41-0.55) lower risk of incident depression. Similarly, moderate and high CVH were related to a lower risk of incident anxiety (HR = 0.81, 95% CI: 0.73-0.89 and HR = 0.68, 95% CI: 0.60-0.78). Restricted cubic spline showed that LE8 score was inversely related to incident depression and anxiety in a linear manner, and the risk of incident depression and anxiety decreased by 17% (HR = 0.83, 95% CI: 0.80-0.85) and 10% (HR = 0.90, 95% CI: 0.88-0.92) for 10-point increment in LE8 score, respectively. CONCLUSIONS: Higher CVH, evaluated by LE8 score, is strongly associated with a lower risk of incident depression and anxiety, suggesting the significance of optimizing CVH by adopting LE8.

Comprehensive evaluation of antibiotics pollution the Yangtze River basin, China: Emission, multimedia fate and risk assessment.

Antibiotics have attracted global attention because of their potential ecological and health risks. The emission, multimedia fate and risk of 18 selected antibiotics in the entire Yangtze River basin were evaluated by using a level Ⅳ fugacity model. High antibiotic emissions were found in the middle and lower reaches of the Yangtze River basin. The total antibiotic emissions in the Yangtze River basin exceeded 1600 tons per year between 2013 and 2021. The spatial distribution of antibiotics concentration was the upper Yangtze River > middle Yangtze River > lower Yangtze River, which is positively correlated with animal husbandry size in the basin. Temperature and precipitation increases may decrease the antibiotic concentrations in the environment. Transfer fluxes showed that source emission inputs, advection processes, and degradation fluxes contributed more to the total input and output. High ecological risks in the water environment were found in 2018, 2019, 2020, and 2021. The comprehensive health risk assessment through drinking water and fish consumption routes showed that a small part of the Yangtze River basin is at medium risk, and children have a relatively high degree of health risk. This study provides a scientific basis for the pollution control of antibiotics at the basin scale.

The validity and IRT psychometric analysis of Chinese version of Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10).

OBJECTIVE: The doctor-patient relationship (DPR) plays a crucial role in the Chinese healthcare system, functioning to improve medical quality and reduce medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China. METHODS: The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale. Convergent validity was evaluated by examining the correlation between DDPRQ-10 and depressive symptoms, burnout, and self-efficacy, using the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Maslach Burnout Inventory (MBI). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) frameworks were used to estimate the parameters of each item. RESULTS: The Chinese version of DDPRQ-10 showed satisfactory internal consistency (Cronbach's alpha = 0.931), and fitted in a modified two-factor model of positive feelings and negative feelings (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, SRMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). Significant correlations with PHQ-9 with DDPRQ-10 and both subscales were revealed (r = 0.293 ~ 0.333, p < .001), while DDPRQ-10 score also significantly correlated with doctors' MBI score (r = -0.467, p < .001). The MIRT model of full scale and IRT models of both subscales showed high discrimination of all items (a = 2.30 ~ 10.18), and the test information within the range of low-quality relationship was relatively high. CONCLUSION: The Chinese version of DDPRQ-10 displayed satisfactory reliability and validity and thus was appropriate for measuring the DPR in Chinese medical settings.

Loneliness and depression in older adults with multimorbidity: the role of self-efficacy and social support.

Introduction: As relatively little is known about self-efficacy and social support in individuals aged 65 years and older and whether they are facing a decline in life due to multimorbidity and previous COVID-19 infection, this study investigated hypotheses based on Social Cognitive Theory. Methods: It was tested whether depressive symptoms in multimorbid patients who were hospitalized for COVID-19 infection, and recover post infection during their hospital stay, do not differ from those of multimorbid patients hospitalized for other conditions. Furthermore, we tested whether depressive symptoms are associated with increased loneliness scores, low self-efficacy beliefs, and poorly perceived social support. Additionally, it was investigated whether self-efficacy is a mediator variable, and social support is a moderator variable between loneliness and depression. N = 135 patients with or without previous COVID-19 infection (mean age 64.76) were recruited. Paper questionnaires were collected at the time of inpatient hospital admission in the year 2021 and in a cross-sectional study design. The study compared n = 45 multimorbid patients who survived COVID-19 infection with those n = 90 who were not infected before. Results: No significant difference in depressive symptomology between these two groups revealed [t(133) = 130, p = 0.90, d = 0.024); F(3, 122) = 0.255, p = 0.86]. The study found a positive correlation between loneliness and anxiety and depression in both groups (rdepression = 0.419 and ranxiety = 0.496). Self-efficacy mediated the relation between loneliness and depression. The completely standardized indirect effect was ß = 0.111, percentile Bootstrap 95% CI 0.027-0.201. Discussion: The research findings suggest the importance of self-efficacy, and loneliness in the development of depressive symptoms, and have several practical implications for improving the mental health of multimorbid patients: Prospectively, treatment should not only focus on physical and cognitive health, but also on promoting self-efficacy and perceived social support, as well as address loneliness with psychoeducational interventions. Replication of the findings and conducting interventional research also employing lifestyle components should follow up, as this study tested associations but no causal relationships.

Development of a bispecific nanobody conjugate broadly neutralizes diverse SARS-CoV-2 variants and structural basis for its broad neutralization.

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and profound immune-escape capacity makes it an urgent need to develop broad-spectrum therapeutics. Nanobodies have recently attracted extensive attentions due to their excellent biochemical and binding properties. Here, we report two high-affinity nanobodies (Nb-015 and Nb-021) that target non-overlapping epitopes in SARS-CoV-2 S-RBD. Both nanobodies could efficiently neutralize diverse viruses of SARS-CoV-2. The neutralizing mechanisms for the two nanobodies are further delineated by high-resolution nanobody/S-RBD complex structures. In addition, an Fc-based tetravalent nanobody format is constructed by combining Nb-015 and Nb-021. The resultant nanobody conjugate, designated as Nb-X2-Fc, exhibits significantly enhanced breadth and potency against all-tested SARS-CoV-2 variants, including Omicron sub-lineages. These data demonstrate that Nb-X2-Fc could serve as an effective drug candidate for the treatment of SARS-CoV-2 infection, deserving further in-vivo evaluations in the future.

Enhancing Physical and Psychosocial Health of Older Adults in Saudi Arabia through Walking: Comparison between Supervised Group-Based and Non-Supervised Individual-Based Walking.

Walking is widely recognized as one of the most common and effective forms of physical activity, particularly for older adults. This study examined the comparative effects of two types of walking interventions, including supervised group-based intervention (SGBI) and non-supervised individual-based intervention (NSIBI), on frailty syndrome, cognitive functions or skills, and health-related quality of life among sedentary older Saudi individuals. A 15-week double-blinded, randomized controlled trial (RCT) including three groups (two were intervention groups while the other was the control group) was conducted among older adults who were inactive to examine the effect of different forms of walking interventions on frailty syndrome, cognitive functions, and health-related quality of life. A total of 107 participants, including 65 males and 42 females, were divided into three groups, which include SGBI, NSIBI, and the control group. Frailty syndrome was measured using the physical performance test (PPT), while cognitive function and health-related quality of life were assessed using the Mini-mental State Examination (MMSE) and the Short Form 36 (SF 36) health survey questionnaire. One-way repeated measures analysis of variance (ANOVA) and one-way analysis of covariance (ANCOVA) with the pre- and post-tests were performed for within- and between-group differences. while post-test data for the control group participants were absent due to the change in elderly center regulation, and they were excluded from the analysis. Hence, the comparison was stated only between the intervention groups. Both of the intervention groups (SGBI and NSIBI) showed significant within-subject differences in the Physical Function subscale of the health-related quality of life scale only, with F(1,20) = 23.03, p < 0.001, and F(1,18) = 27.22, p < 0.001, respectively. On the other hand, the Physical Performance Test revealed significant [F(2,51) = 9.21, p < 0.001] between-group differences in the post-test based on the baseline values. In addition, the average step count of older adults was increased from 4000 steps per session to around 7000 steps per session in the intervention group. The average heart rate of the NSIBI group did not show a visible change, and the resting heart rate of both groups showed a slightly declining trend throughout the intervention period. The walking intervention significantly increased participants' physical function, which is a component of health-related quality of life and physical performance (frailty level), along with average daily step counts for older adults in Saudi Arabia. Regular engagement in the recommended level of walking is strongly advisable for Saudi Arabian older adults to maintain their overall quality of life at this stage.

Structural and functional basis of low-affinity SAM/SAH-binding in the conserved MTase of the multi-segmented Alongshan virus distantly related to canonical unsegmented flaviviruses.

Alongshan virus (ALSV), a newly discovered member of unclassified Flaviviridae family, is able to infect humans. ALSV has a multi-segmented genome organization and is evolutionarily distant from canonical mono-segmented flaviviruses. The virus-encoded methyltransferase (MTase) plays an important role in viral replication. Here we show that ALSV MTase readily binds S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH) but exhibits significantly lower affinities than canonical flaviviral MTases. Structures of ALSV MTase in the free and SAM/SAH-bound forms reveal that the viral enzyme possesses a unique loop-element lining side-wall of the SAM/SAH-binding pocket. While the equivalent loop in flaviviral MTases half-covers SAM/SAH, contributing multiple hydrogen-bond interactions; the pocket-lining loop of ALSV MTase is of short-length and high-flexibility, devoid of any physical contacts with SAM/SAH. Subsequent mutagenesis data further corroborate such structural difference affecting SAM/SAH-binding. Finally, we also report the structure of ALSV MTase bound with sinefungin, an SAM-analogue MTase inhibitor. These data have delineated the basis for the low-affinity interaction between ALSV MTase and SAM/SAH and should inform on antiviral drug design.