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.

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.

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.

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.

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.

The Asymmetric Total Synthesis of the Female-Produced Sex Pheromone of the Tea Tussock Moth.

The tea tussock moth is a pest that damages tea leaves, affecting the quality and yield of tea and causing huge economic losses. The efficient asymmetric total synthesis of the sex pheromone of the tea tussock moth was achieved using commercially available starting materials with a 25% overall yield in 11 steps. Moreover, the chiral moiety was introduced by Evans' template and the key C-C bond construction was accomplished through Julia-Kocienski olefination coupling. The synthetic sex pheromone of the tea tussock moth will facilitate the subsequent assessment and implementation of pheromones as environmentally friendly tools for pest management.

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 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.

A school-family blended multi-component physical activity program for Fundamental Motor Skills Promotion Program for Obese Children (FMSPPOC): protocol for a cluster randomized controlled trial.

BACKGROUND: Fundamental motor skills (FMSs) are crucial for children's health and comprehensive development. Obese children often encounter a considerable challenge in the development of FMSs. School-family blended PA programs are considered a potentially effective approach to improve FMSs and health-related outcomes among obese children, however, empirical evidence is still limited. Therefore, this paper aims to describe the development, implementation, and evaluation of a 24-week school-family blended multi-component PA intervention program for promoting FMSs and health among Chinese obese children, namely the Fundamental Motor Skills Promotion Program for Obese Children (FMSPPOC) employing behavioral change techniques (BCTs) and building on the Multi-Process Action Control (M-PAC) framework as well as using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework for improving and evaluating the program. METHODS: Using a cluster randomized controlled trial (CRCT), 168 Chinese obese children (8-12 years) from 24 classes of six primary schools will be recruited and randomly assigned to one of two groups by a cluster randomization, including a 24-week FMSPPOC intervention group and a non-treatment waiting-list control group. The FMSPPOC program includes a 12-week initiation phase and a 12-week maintenance phase. School-based PA training sessions (2 sessions/week, 90 min each session) and family-based PA assignments (at least three times per week, 30 min each time) will be implemented in the initiation phase (semester time), while three 60-min offline workshops and three 60-min online webinars will be conducted in the maintenance phase (summer holiday). The implementation evaluation will be undertaken according to the RE-AIM framework. For intervention effectiveness evaluation, primary outcome (FMSs: gross motor skills, manual dexterity and balance) and secondary outcomes (health behaviors, physical fitness, perceived motor competence, perceived well-being, M-PAC components, anthropometric and body composition measures) will be collected at four time-points: at baseline, 12-week mid-intervention, 24-week post-intervention, and 6-month follow-up occasions. DISCUSSION: The FMSPPOC program will provide new insights into the design, implementation, and evaluation of FMSs promotion among obese children. The research findings will also supplement empirical evidence, understanding of potential mechanisms, and practical experience for future research, health services, and policymaking. TRIAL REGISTRATION: Chinese Clinical Trial Registry; ChiCTR2200066143; 25 Nov 2022.

Seasonal heavy metal speciation in sediment and source tracking via Cu isotopic composition in Huangpu River, Shanghai, China.

The present study systematically analyzed and evaluated the variations in chemical speciation, pollution assessment, and source identification of heavy metals in sediments of Huangpu River. The methods employed included heavy metal concentration, chemical speciation and Cu isotopic compositions analysis. Results showed that the chemical speciation of sediment-bound heavy metals, characterized by significant seasonal variation, shifted from non-residual fractions dominating in spring and summer to residual fractions dominating in autumn and winter. Precipitation was identified as an important factor influencing the chemical speciation of sediment-bound heavy metals. Furthermore, ratio of the secondary phase to the primary phase, RSP (=Cnon-residual/Cresidual) values in Huangpu River sediments were higher than 1 in spring and summer, indicating that sediment-bound heavy metals in Huangpu River were mainly composed of non-residual fractions and could potentially be released into the river water. Principal component analysis (PCA) revealed that navigation, traffic, agricultural, and industrial activities could be the potential sources of heavy metal pollution. Notably, the δ65Cu values in Huangpu River sediments were observed to be isotopically lighter (from -0.37 to +0.18 ‰), suggesting that navigation might be the primary pollution source. These results will not only provide guidance in reducing heavy metal concentrations, but also serve as a crucial basis for policy making regarding heavy metal control.

Psychosocial Determinants of Hand Hygiene, Facemask Wearing, and Physical Distancing During the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

BACKGROUND: Hand hygiene, facemask wearing, and physical distancing play a crucial role in the prevention of the COVID-19 pandemic. Identifying the key psychosocial determinants of these precautionary behaviors contributes to effective intervention and policymaking for COVID-19 and future pandemics. PURPOSE: This study aimed to systematically review and meta-analyze available evidence on psychosocial determinants of the general population's practice of three precautionary behaviors, based on the Risk, Attitudes, Norms, Abilities, and Self-regulation (RANAS) framework. METHODS: Literature was identified by searching seven databases and relevant review papers. Observational and experimental studies targeting the general population (≥18 years) published between January 2020 to September 2021 were included. Pooled effect sizes were calculated with the inverse-variance method using random-effects models. RESULTS: A total of 51 studies (64 samples) were included in the qualitative synthesis, of which 30 studies (42 samples) were included in the meta-analysis. RANAS-based constructs including knowledge, pros attitudes, and perceived norms were identified as significant determinants of all three behaviors in the meta-analysis. Perceived susceptibility and cons attitudes showed no significant associations with any behaviors. Perceived severity, perceived control, self-efficacy, and behavioral intention were significantly associated with one or two behaviors. Country (western vs. eastern hemispheres) significantly moderated the effects of certain risk and ability factors. CONCLUSIONS: More research is needed with respect to the intention-behavior relationship, self-regulatory and reflexive factors of precautionary behaviors, as well as the exploration of the potential moderating effect of sociodemographic factors.

Identifying the psychosocial factors affecting the practice of three precautionary behaviors (hand hygiene, facemask wearing, and physical distancing) contributes to effective intervention and policymaking for the COVID-19 and future pandemics. Given the lack of summarized evidence, we conducted a systematic review and meta-analysis. Through seven databases and relevant review papers, we summarized the research findings of 51 observational studies that targeted the general population (≥18 years) and were published between January 2020 and September 2021. We found that (a) more knowledge, positive behavioral attitudes, and better compliance with the norms were associated with better practices of all three precautionary behaviors; (b) perceived susceptibility to the disease and negative behavioral attitudes were not associated with any precautionary behaviors; (c) higher levels of perceived disease severity, perceived behavioral control, self-efficacy, and behavioral intention were associated with better practices of one or two behaviors. In addition, we found that country (western vs. eastern hemispheres) differed in the relationship between psychosocial factors and behavioral practices. Specifically, both the association of perceived susceptibility with hand hygiene and the association of perceived severity with physical distancing were stronger among western populations. In contrast, the contribution of self-efficacy on the practice of physical distancing was stronger among eastern populations.

Review on the contamination and remediation of polycyclic aromatic hydrocarbons (PAHs) in coastal soil and sediments.

The rapid economic and population growth in coastal areas is causing increasingly serious polycyclic aromatic hydrocarbons (PAHs) pollution in these regions. This review compared the PAHs pollution characteristics of different coastal areas, including industrial zones, commercial ports, touristic cities, aquacultural & agricultural areas, oil & gas exploitation areas and megacities. Currently there are various treatment methods to remediate soils and sediments contaminated with PAHs. However, it is necessary to provide a comprehensive overview of all the available remediation technologies up to date, so appropriate technologies can be selected to remediate PAHs pollution. In view of that, we analyzed the characteristics of the remediation mechanism, summarized the remediation methods for soil or sediments in coastal areas, which were physical repair, chemical oxidation, bioremediation and integrated approaches. Besides, this review also reported the development of new multi-functional green and sustainable systems, namely, micro-nano bubble (MNB), biochar, reversible surfactants and peracetic acid. While physical repair, expensive but efficient, was regarded as a suitable method for the PAHs remediation in coastal areas because of land shortage, integrated approaches would produce better results. The ultimate aim of the review was to ensure the successful restructuring of PAHs contaminated soil and sediments in coastal areas. Due to the environment heterogeneity, PAHs pollution in coastal areas remains as a daunting challenge. Therefore, new and suitable technologies are still needed to address the environmental issue.

Predicting hand washing, mask wearing and social distancing behaviors among older adults during the covid-19 pandemic: an integrated social cognition model.

BACKGROUND: Older adults are at a higher risk from COVID-19. Individual preventive behaviors including frequent hand washing, mask wearing, and social distancing play important roles in reducing the transmission of COVID-19 in the community. This study aimed to identify the determinants of three preventive behaviors of older adults during the COVID-19 pandemic by using an Integrated Social Cognition Model. METHODS: Using a prospective study design, 516 Chinese older adults from Hubei province of China (mean age = 67.55 years, SD = 6.60, 57.9% females) completed two online questionnaire surveys. The demographics, social cognition constructs (motivational self-efficacy, risk perception, attitude, subjective norm, health knowledge, intention, volitional self-efficacy, planning, action control) and three preventive behaviors were measured during the first-wave online survey from 18 May 2020 to 7 June 2020. One month later, three preventive behaviors were measured again during the second-wave online survey. Data were analyzed by structural equation modelling. RESULTS: Models showed attitude, motivational self-efficacy and subjective norm were consistent predictors of intention, motivational self-efficacy was a consistent predictor of volitional self-efficacy, planning and volitional self-efficacy were consistent predictors of action control, and health knowledge was a consistent predictor of behaviors across all three preventive behaviors. In addition, mediating relationships were found in the model of hand washing behavior. In particular, planning (ß = .109, p = .042) and action control (ß = .056, p = .047) mediated between volitional self-efficacy and hand washing respectively. Action control also mediated between planning and hand washing (ß = .087, p = .044). Moreover, the inclusion of past behaviors in three models attenuated most of the structural relations. CONCLUSIONS: The current study's findings basically supported the Integrated Social Cognition Model and identified key modifiable determinants of preventive behaviors. Based on this model, future interventions aiming to promote COVID-19 preventive behaviors among older adults are warranted.

A systematic review and meta-analysis on the preventive behaviors in response to the COVID-19 pandemic among children and adolescents.

PURPOSE: The purpose of this review was to synthesize the empirical evidence of relevant studies related to preventive behaviors in response to the COVID-19 pandemic among children and adolescents. Further to this, we aimed to identify the demographic, psychological, and social and environmental correlates of such behaviors. METHODS: Following PRISMA guidelines, eligible literature was identified by searching seven databases (PsycINFO, PubMed, MEDLINE, EMBASE, Cochrane Library, PROSPERO registry platform, and ClinicalTrials.gov website) and reference list of included studies and relevant review papers from 1st Jan 2020 to 28th Feb 2021. The standardized mean difference and correlation coefficients r were extracted to estimate the effect sizes. Analyses were conducted using R software. RESULTS: Of the 35,271 original papers, 23 eligible studies were included in the qualitative synthesis and all these studies were of moderate-to-high quality, of which 17 studies were further included into the quantitative analysis. Children and adolescents (6-20 yrs.) showed a poorer practice of COVID-19 preventive behaviors compared to younger adults (21-59 yrs.) with a small-to-medium effect size (SMD = -.25, 95%CI = -.41 to -.09). For the demographic correlates, children and adolescents' COVID-19 preventive practice was found to be significantly associated with gender (r = .14, 95%CI = .10 to .18), while not with age (r = -.02, 95%CI = -.14 to .10). Narratively, knowledge was found to be consistently and significantly correlated. For the psychological correlates, small-to-medium overall effects were identified for the association with attitudes (r = .26, 95%CI = .21 to .31) and perceived severity (r = .16, 95%CI = .01 to .30). For the family and social correlates, a non-significant association was identified between family economic status and COVID-19 preventive behaviors (r = .004, 95%CI = -.12 to .12). CONCLUSIONS: Interventions and relevant policies of promoting children and adolescent's preventive measures should be a priority. Further, empirical studies identifying the demographic, psychological, and family and social correlates of children and adolescents' preventive behaviors are needed.

Health Status Stability of Patients in a Medical Rehabilitation Program: What Are the Roles of Time, Physical Fitness Level, and Self-efficacy?

BACKGROUND: Individuals' physical and mental health, as well as their chances of returning to work after their ability to work is damaged, can be addressed by medical rehabilitation. AIM: This study investigated the developmental trends of mental and physical health among patients in medical rehabilitation and the roles of self-efficacy and physical fitness in the development of mental and physical health. DESIGN: A longitudinal design that included four time-point measurements across 15 months. SETTING: A medical rehabilitation center in Germany. POPULATION: Participants included 201 patients who were recruited from a medical rehabilitation center. METHODS: To objectively measure physical fitness (lung functioning), oxygen reabsorption at anaerobic threshold (VO2AT) was used, along with several self-report scales. RESULTS: We found a nonlinear change in mental health among medical rehabilitation patients. The results underscored the importance of medical rehabilitation for patients' mental health over time. In addition, patients' physical health was stable over time. The initial level of physical fitness (VO2AT) positively predicted their mental health and kept the trend more stable. Self-efficacy appeared to have a positive relationship with mental health after rehabilitation treatment. CONCLUSIONS: This study revealed a nonlinear change in mental health among medical rehabilitation patients. Self-efficacy was positively related to mental health, and the initial level of physical fitness positively predicted the level of mental health after rehabilitation treatment. CLINICAL REHABILITATION: More attention could be given to physical capacity and self-efficacy for improving and maintaining rehabilitants' mental health.

Psychosocial Mediators of Web-Based Interventions for Promoting a Healthy Lifestyle Among Chinese College Students: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Web-based multiple health behavior change (MHBC) interventions have demonstrated effectiveness in promoting physical activity (PA) and fruit and vegetable consumption (FVC) among Chinese college students. However, there is limited research examining their effects on promoting a healthy lifestyle (ie, adhering to both PA and FVC behavioral recommendations) among Chinese college students. In addition, the salient psychosocial mediators of successful MHBC interventions need to be researched. OBJECTIVE: This study aims to examine the effectiveness of a previous 8-week web-based MHBC program for promoting a healthy lifestyle and enhancing the psychosocial determinants (intention, self-efficacy, planning, and social support) of behavior change among Chinese college students. Furthermore, the study aims to identify whether changes in these psychosocial determinants mediate intervention effectiveness on the immediate and sustained lifestyle changes. METHODS: This was a secondary analysis for a 3-arm randomized controlled trial. Chinese college students (N=552) were randomly assigned to 1 of 3 groups: a PA-first group (4-week PA intervention followed by 4-week FVC intervention), an FVC-first group (4-week FVC intervention followed by 4-week PA intervention), and a placebo control group. The intervention content was designed based on the health action process approach model. Data for analyses were collected at baseline (T0), postintervention assessment (T1), and 12-week follow-up assessment (T2). RESULTS: At baseline, 13.9% (77/552) of the participants maintained a healthy lifestyle. After 8 weeks, more (200/552, 36.2%) participants achieved a healthy lifestyle. PA-first and FVC-first groups were, respectively, 3.24 times and 5 times more likely to adopt a healthy lifestyle than the control group at T1. After 12 weeks, 35.5% (196/552) of the participants adopted a healthy lifestyle. Intervention groups were approximately 2.99 times (PA first) and 4.07 times (FVC first) more likely to adopt a healthy lifestyle than the control group at T2. Intervention effects favored both intervention groups in self-efficacy and planning for PA and in intention and planning for FVC compared with the control condition. In addition, changes in PA self-efficacy and FVC intention mediated intervention effectiveness on the immediate lifestyle change after 8 weeks. Changes in FVC intention were identified as a salient mediator for facilitating sustained lifestyle change after 12 weeks. CONCLUSIONS: This study provides empirical evidence for the effectiveness of an 8-week theory- and web-based MHBC intervention program on promoting a healthy lifestyle, self-efficacy and planning for PA, and intention and planning for FVC among Chinese college students. These research findings add new knowledge to the underlying psychosocial mechanisms of successful MHBC interventions. Overall, this study has considerable implications for future web-based MHBC research and practice in terms of addressing PA self-efficacy and FVC intention and helping students to adopt and maintain a healthy lifestyle independently of whether PA or FVC is addressed first. TRIAL REGISTRATION: ClinicalTrials.gov NCT03627949; https://clinicaltrials.gov/ct2/show/NCT03627949.

The Effectiveness of Sequentially Delivered Web-Based Interventions on Promoting Physical Activity and Fruit-Vegetable Consumption Among Chinese College Students: Mixed Methods Study.

BACKGROUND: Web-based interventions for multiple health behavior change (MHBC) appear to be a promising approach to change unhealthy habits. Limited research has tested this assumption in promoting physical activity (PA) and fruit-vegetable consumption (FVC) among Chinese college students. Moreover, the timing of MHBC intervention delivery and the order of components need to be addressed. OBJECTIVE: This study aims to examine the effectiveness of 2 sequentially delivered 8-week web-based interventions on physical activity, FVC, and health-related outcomes (BMI, depression, and quality of life) and the differences in the intervention effects between the 2 sequential delivery patterns. The study also aims to explore participants' experiences of participating in the health program. METHODS: We conducted a randomized controlled trial, in which 552 eligible college students (mean 19.99, SD 1.04 years, 322/552, 58.3% female) were randomly assigned to 1 of 3 groups: PA-first group (4 weeks of PA followed by 4 weeks of FVC intervention), FVC-first group (4 weeks of FVC followed by 4 weeks of PA intervention), and a control group (8 weeks of placebo treatment unrelated to PA and FVC). The treatment content of two intervention groups was designed based on the Health Action Process Approach (HAPA) framework. A total of four web-based assessments were conducted: at baseline (T1, n=565), after 4 weeks (T2, after the first behavior intervention, n=486), after 8 weeks (T3, after the second behavior intervention, n=420), and after 12 weeks (T4, 1-month postintervention follow-up, n=348). In addition, after the completion of the entire 8-week intervention, 18 participants (mean 19.56, SD 1.04 years, 10/18, 56% female) who completed the whole program were immediately invited to attend one-to-one and face-to-face semistructured interviews. The entire study was conducted during the fall semester of 2017. RESULTS: The quantitative data supported superior effects on physical activity, FVC, and BMI in the 2 sequential intervention groups compared with the control group. There were no significant differences in physical activity, FVC, and health-related outcomes between the 2 intervention groups after 8 weeks. The FVC-first group contributed to more maintenance of FVC compared with the PA-first group after 12 weeks. Four major themes with several subthemes were identified in the qualitative thematic analysis: PA and FVC behavior, health-related outcomes, correlates of behavior change, and contamination detection. CONCLUSIONS: This study provides empirical evidence for the effectiveness of sequentially delivered, web-based MHBC interventions on PA and FVC among Chinese college students. The timing issue of MHBC intervention delivery was preliminarily addressed. Qualitative findings provide an in-depth understanding and supplement the quantitative findings. Overall, this study may contribute considerably to future web-based MHBC interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03627949; https://clinicaltrials.gov/ct2/show/NCT03627949. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-019-7438-1.

Development and students' evaluation of a blended online and offline pedagogy for physical education theory curriculum in China during the COVID-19 pandemic.

The outbreak and continuation of the COVID-19 pandemic has challenged the implementation of physical education theory (PET) curriculums among global colleges and universities. This study aimed to describe the design and students' evaluation of a blended "Sports Multimedia Courseware Design" course among Chinese university students during the COVID-19 pandemic. Using information communication technologies, a 4-month blended course was developed, which consisted of 36 credits (18-credit online self-learning + 18-credit offline group-learning). A total of 1300 Chinese university students who majored in physical education, completed the blended course from Mar to Jun 2020, among which 238 (69.75% males; 21 ± 1.2 years) were randomly recruited to evaluate the course in terms of three aspects: (1) online self-learning, (2) offline group-learning, and (3) overall learning outcomes. A descriptive analysis was conducted using the IBM SPSS 27.0. Students' overall positive evaluation supported a successful development and implementation of the blended course. Over 90% of students fulfilled the learning tasks and satisfied with the online learning resources. About 83% of students indicated high levels of autonomous motivation and engagement in online self-learning. Approximately 88% of students showed positive attitudes to the offline group-learning content, while the participation rate (60%) was relatively lower than of the online self-learning. Over 50% of the students indicated self-improvements in diverse aspects after attending the blended course. Blended online and offline pedagogy shows apparent promise in delivering the PET course among Chinese university students during the COVID-19 pandemic. Further application and comprehensive evaluation are warranted in the future.

[Association between Gestational Diabetes Mellitus and Postpartum Depressive Episode].

Objective To explore the association between gestational diabetes mellitus (GDM) and postpartum depressive (PPD) episode and the influencing factors of PPD episode. Methods The clinical data of pregnant women who filed in the Department of Obstetrics,Peking Union Medical College Hospital from March 1,2020 to February 28,2021 were collected.Oral glucose tolerance test (OGTT,75 g) and determination of glycosylated hemoglobin (HbA1c) were carried out in the second trimester,and fasting blood glucose and glycosylated albumin (GA) were determined in the third trimester.Mini-International Neuropsychiatric Interview (MINI,5.0 Chinese version) was used to diagnose depressive episode and anxiety disorder within (42±7) days after delivery.We analyzed the influencing factors of PPD episode by multiple Logistic regression to explore the relationship between GDM and PPD episode.Fasting glucose and GA in the third trimester,as well as the incidence of PPD episode,between women with and without GDM were compared. Results The GDM,75 g OGTT,and HbA1c in the second trimester,as well as fasting blood glucose and GA in the third trimester,showed no significant differences between the PPD group and the non-PPD group (all P>0.05).Postpartum generalized anxiety disorder (OR=4.656,95%CI=1.130-19.184, P=0.033),obsessive-compulsive disorder (OR=11.989,95%CI=1.004-143.113, P=0.049),and the history of mental disorder before pregnancy (OR=13.567,95%CI=2.191-83.991, P=0.005) were the risk factors of PPD episode.The fasting blood glucose and GA in the third trimester,the incidence of PPD episode,and the PPD episode comorbidities of generalized anxiety disorder and obsessive-compulsive disorder had no significant differences between pregnant women with and without GDM (all P>0.05).Conclusions There is no association between GDM and PPD episode under routine blood glucose management. Special attention should be paid to pregnant women with a history of mental disorder before pregnancy.

Binding of Duck Tembusu Virus Nonstructural Protein 2A to Duck STING Disrupts Induction of Its Signal Transduction Cascade To Inhibit Beta Interferon Induction.

Duck Tembusu virus (DTMUV), which is similar to other mosquito-borne flaviviruses that replicate well in most mammalian cells, is an emerging pathogenic flavivirus that has caused epidemics in egg-laying and breeding waterfowl. Immune organ defects and neurological dysfunction are the main clinical symptoms of DTMUV infection. Preinfection with DTMUV makes the virus impervious to later interferon (IFN) treatment, revealing that DTMUV has evolved some strategies to defend against host IFN-dependent antiviral responses. Immune inhibition was further confirmed by screening for DTMUV-encoded proteins, which suggested that NS2A significantly inhibited IFN-ß and IFN-stimulated response element (ISRE) promoter activity in a dose-dependent manner and facilitated reinfection with duck plague virus (DPV). DTMUV NS2A was able to inhibit duck retinoic acid-inducible gene-I (RIG-I)-, and melanoma differentiation-associated gene 5 (MDA5)-, mitochondrial-localized adaptor molecules (MAVS)-, stimulator of interferon genes (STING)-, and TANK-binding kinase 1 (TBK1)-induced IFN-ß transcription, but not duck TBK1- and interferon regulatory factor 7 (IRF7)-mediated effective phases of IFN response. Furthermore, we found that NS2A competed with duTBK1 in binding to duck STING (duSTING), impaired duSTING-duSTING binding, and reduced duTBK1 phosphorylation, leading to the subsequent inhibition of IFN production. Importantly, we first identified that the W164A, Y167A, and S361A mutations in duSTING significantly impaired the NS2A-duSTING interaction, which is important for NS2A-induced IFN-ß inhibition. Hence, our data demonstrated that DTMUV NS2A disrupts duSTING-dependent antiviral cellular defenses by binding with duSTING, which provides a novel mechanism by which DTMUV subverts host innate immune responses. The potential interaction sites between NS2A and duSTING may be the targets of future novel antiviral therapies and vaccine development.IMPORTANCE Flavivirus infections are transmitted through mosquitos or ticks and lead to significant morbidity and mortality worldwide with a spectrum of manifestations. Infection with an emerging flavivirus, DTMUV, manifests with clinical symptoms that include lesions of the immune organs and neurological dysfunction, leading to heavy egg drop and causing serious harm to the duck industry in China, Thailand, Malaysia, and other Southeast Asian countries. Mosquito cells, bird cells, and mammalian cell lines are all susceptible to DTMUV infection. An in vivo study revealed that BALB/c mice and Kunming mice were susceptible to DTMUV after intracerebral inoculation. Moreover, there are no reports about DTMUV-related human disease, but antibodies against DTMUV and viral RNA were detected in serum samples of duck industry workers. This information implies that DTMUV has expanded its host range and may pose a threat to mammalian health. However, the pathogenesis of DTMUV is largely unclear. Our results show that NS2A strongly blocks the STING-induced signal transduction cascade by binding with STING, which subsequently blocks STING-STING binding and TBK1 phosphorylation. More importantly, the W164, Y167, or S361 residues in duSTING were identified as important interaction sites between STING and NS2A that are vital for NS2A-induced IFN production and effective phases of IFN response. Uncovering the mechanism by which DTMUV NS2A inhibits IFN in the cells of its natural hosts, ducks, will help us understand the role of NS2A in DTMUV pathogenicity.