Terminal trajectory of HbA1c for 10 years supports the HbA1c paradox: a longitudinal study using Health and Retirement Study data.

Objectives: We aimed to assess the potential time-varying associations between HbA1c and mortality, as well as the terminal trajectory of HbA1c in the elderly to reveal the underlying mechanisms. Design: The design is a longitudinal study using data from the Health and Retirement Study. Setting and participants: Data were from the Health and Retirement Study. A total of 10,408 participants aged ≥50 years with available HbA1c measurements at baseline (2006/2008) were included. Methods: Longitudinal HbA1c measured at 2010/2012 and 2014/2016 were collected. HbA1c values measured three times for their associations with all-cause mortality were assessed using Cox regression and restricted cubic splines. HbA1c terminal trajectories over 10 years before death were analyzed using linear mixed-effect models with a backward time scale. Results: Women constitute 59.6% of the participants with a mean age of 69 years, with 3,070 decedents during the follow-up (8.9 years). The mortality rate during follow-up was 29.5%. Increased mortality risk became insignificant for the highest quartile of HbA1c compared to the third quartile (aHR 1.148, 1.302, and 1.069 for a follow-up of 8.9, 6.5, and 3.2 years, respectively) with a shorter follow-up, while it became higher for the lowest quartile of HbA1c (aHR 0.986, 1.068, and 1.439 for a follow-up of 8.9, 6.5, and 3.2 years, respectively). Accordingly, for both decedents with and without diabetes, an initial increase in HbA1c was followed by an accelerating terminal decline starting 5-6 years before death. Conclusions and implications: The time-varying association between HbA1c and mortality mapped to the terminal trajectory in HbA1c. High and low HbA1c may have different clinical relationships with mortality. The HbA1c paradox may be partially explained by reverse causation, namely, early manifestation of death.

Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

BACKGROUND: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. METHODS: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. RESULTS: The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at - 80°C, 3 months at - 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. CONCLUSION: haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

Synergistic antitumor effects of Peiminine and Doxorubicin on breast cancer through enhancing DNA damage via ZEB1.

Peiminine, the primary biologically active compound from Fritillaria thunbergii Miq., has demonstrated significant pharmacological activities. Doxorubicin is one of the most potent chemotherapeutic agents for breast cancer (BC). This study was designed to investigate the efficacy and underlying mechanisms of Peiminine combined with Doxorubicin in treating BC. Our results demonstrated that the combination of Peiminine and 1 mg/kg Doxorubicin exhibited more significant suppression of tumor growth compared with the monotherapy in MDA-MB-231 xenograft nude mice model, which is comparable to the effect of 3 mg/kg Doxorubicin in vivo. Notably, the 3 mg/kg Doxorubicin monotherapy resulted in organ toxicity, specifically in the liver and heart, whereas no toxicity was observed in the combination group. In vitro, this combined treatment exhibited a synergistic reduction on the viability of BC cells. Peiminine enhanced the cell cycle arrest and DNA damage induced by Doxorubicin. Furthermore, the combination treatment effectively blocked DNA repair by inhibiting the MAPKs signaling pathways. And ZEB1 knockdown attenuated the combined effect of Peiminine and Doxorubicin on cell viability and DNA damage. In conclusion, our study found that the combination of Peiminine and Doxorubicin showed synergistic inhibitory effects on BC both in vivo and in vitro through enhancing Doxorubicin-induced DNA damage. These findings support that their combination is a novel and promising therapeutic strategy for treating BC.

Lipid metabolism-related genes are involved in the occurrence of asthma and regulate the immune microenvironment.

BACKGROUND: Lipid metabolism plays a pivotal role in asthma pathogenesis. However, a comprehensive analysis of the importance of lipid metabolism-related genes (LMRGs) in regulating the immune microenvironment in asthma remains lacking. The transcriptome matrix was downloaded from the Gene Expression Omnibus (GEO) dataset. Differentially expressed analysis and weighted gene coexpression network analysis (WGCNA) were conducted on the GSE74986 dataset to select hub LMRGs, and gene set enrichment analysis (GSEA) was conducted to explore their biological functions. The CIBERSORT algorithm was used to determine immune infiltration in the asthma and control groups, and the correlation of diagnostic biomarkers and immune cells was performed via Spearman correlation analysis. Subsequently, a competitive endogenous RNA (ceRNA) network was constructed to investigate the hidden molecular mechanism of asthma. The expression levels of the hub genes were further validated in the GSE143192 dataset, and RT‒qPCR and immunofluorescence were performed to verify the reliability of the results in the OVA asthma model. Lastly, the ceRNA network was confirmed by qRT-PCR and RNAi experiments in the characteristic cytokine (IL-13)-induced asthma cellular model. RESULTS: ASAH1, ACER3 and SGPP1 were identified as hub LMRGs and were mainly involved in protein secretion, mTORC1 signaling, and fatty acid metabolism. We found more infiltration of CD8+ T cells, activated NK cells, and monocytes and less M0 macrophage infiltration in the asthma group than in the healthy control group. In addition, ASAH1, ACER3, and SGPP1 were negatively correlated with CD8+ T cells and activated NK cells, but positively correlated with M0 macrophages. Within the ceRNA network, SNHG9-hsa-miR-615-3p-ACER3, hsa-miR-212-5p and hsa-miR-5682 may play crucial roles in asthma pathogenesis. The low expression of ASAH1 and SGPP1 in asthma was also validated in the GSE74075 dataset. After SNHG9 knockdown, miR-615-3p expression was significantly upregulated, while that of ACER3 was significantly downregulated. CONCLUSION: ASAH1, ACER3 and SGPP1 might be diagnostic biomarkers for asthma, and are associated with increased immune system activation. In addition, SNHG9-hsa-miR-615-3p-ACER3 may be viewed as effective therapeutic targets for asthma. Our findings might provide a novel perspective for future research on asthma.

Chemical Evolution and Biological Evaluation of Natural Products for Efficient Therapy of Acute Lung Injury.

Acute lung injury (ALI) is one of the most common complications in COVID-19 and also a syndrome of acute respiratory failure with high mortality rates, but lacks effective therapeutic drugs. Natural products provide inspiration and have proven to be the most valuable source for bioactive molecule discovery. In this study, the chemical evolution of the natural product Tanshinone IIA (Tan-IIA) to achieve a piperidine-fused scaffold through a synthetic route of pre-activation, multi-component reaction, and post-modification is presented. Through biological evaluation, it is pinpointed that compound 8b is a standout candidate with remarkable anti-inflammation and anti-oxidative stress properties, coupled with low toxicity. The mechanistic study unveils a multifaceted biological profile of 8b and shows that 8b is highly efficient in vivo for the treatment of ALI. Therefore, this work not only provides an effective strategy for the treatment of ALI, but also offers a distinctive natural product-inspired drug discovery.

Directed Dual Charge Pumping Tunes the d-Orbital Configuration of Pt Cluster Boosting Hydrogen Evolution Kinetic.

Achieving high catalytic activity with a minimum amount of platinum (Pt) is crucial for accelerating the cathodic hydrogen evolution reaction (HER) in proton exchange membrane (PEM) water electrolysis, yet it remains a significant challenge. Herein, a directed dual-charge pumping strategy to tune the d-orbital electronic distribution of Pt nanoclusters for efficient HER catalysis is proposed. Theoretical analysis reveals that the ligand effect and electronic metal-support interactions (EMSI) create an effective directional electron transfer channel for the d-orbital electrons of Pt, which in turn optimizes the binding strength to H*, thereby significantly enhancing HER efficiency of the Pt site. Experimentally, this directed dual-charge pumping strategy is validated by elaborating Sb-doped SnO2 (ATO) supported Fe-doped PtSn heterostructure catalysts (Fe-PtSn/ATO). The synthesized 3%Fe-PtSn/ATO catalysts exhibit lower overpotential (requiring only 10.5 mV to reach a current density of 10 mA cm- 2 ), higher mass activity (28.6 times higher than commercial 20 wt.% Pt/C), and stability in the HER process in acidic media. This innovative strategy presents a promising pathway for the development of highly efficient HER catalysts with low Pt loading.

Parenting style and child asthma control in families of school-age children with asthma: The mediating effects of children's general self-efficacy and medication adherence.

PURPOSE: Parenting style plays a pivotal role in children's chronic disease control. However, the relationship and underlying mechanism between parenting style and asthma control remain unclear. This study investigated the effects of parenting style on children's general self-efficacy, medication adherence and asthma control and the mediating effects of general self-efficacy and medication adherence among school-age children with asthma. DESIGN AND METHODS: A cross-sectional study with a convenience sampling approach was conducted. This study followed the STROBE guidelines. School-age children with asthma and their parents (N = 211) from pediatric respiratory clinics in China completed the General Questionnaire, Short-Egna Minnen av. Barndoms Uppfostran-Chinese, General Self-Efficacy Scale, Medication Adherence Questionnaire and Childhood Asthma Control Test. Structural equation modeling was used to examine the mediation models. RESULTS: Positive parenting style was positively correlated with child general self-efficacy, medication adherence and asthma control (r = 0.602, 0.572, 0.613, p < 0.001). Negative parenting style was negatively correlated with child general self-efficacy, medication adherence and asthma control (r = -0.535, -0.598, -0.586, p < 0.001). Structure Equation Modle (SEM) results indicated that the relationships between positive parenting style, negative parenting style and child asthma control were mediated by general self-efficacy (Effect Size [ES]: 0.209, 95%CI [0.075, 0.372]; and ES: -0.229, 95%CI [-0.387, -0.103], respectively) and medication adherence (ES: 0.128, 95%CI [0.032, 0.322]; and ES: -0.190, 95%CI [-0.432, -0.071], respectively) and together in serial (ES: 0.177, 95%CI [0.076, 0.295]; and ES: -0.118, 95%CI [-0.235, -0.020], respectively). CONCLUSIONS: Parenting style may impact child asthma through both child general self-efficacy and medication adherence. The study may provide useful intervention targets for improving asthma control. PRACTICE IMPLICATIONS: Nurses should encourage parents to increase positive parenting style while decreasing negative parenting style. Family interventions focusing on general self-efficacy and medication adherence may be advantageous to improve asthma control.

Caffeine intake is associated with less severe depressive symptoms in noncancer populations: an analysis based on NHANES 2007-2016.

Depression and cancer are both prevalent diseases worldwide. Numerous cancer patients experience psychological illnesses, especially depression, following a malignancy's dismal prognosis. Although some research has suggested that caffeine may be protective against depressive symptoms, it is still unclear how caffeine and cancer patients are related. Thus, we hypothesized that moderate daily caffeine intake may reduce the risk of depression in both the cancer and noncancer populations. Data were extracted and combined from the National Health and Nutrition Examination Survey from 2007 to 2016. After controlling for potential confounding factors, interaction effects analysis was used to clarify the interaction between caffeine and cancer on depressive symptoms. Linear regression analysis and restricted cubic splines were used to further analyze the relationship between caffeine and depression in cancer and noncancer populations. A total of 24,145 participants were included in the analysis. In the noncancer population, the quartile 3 group of caffeine intake showed a negative association between caffeine intake and Patient Health Questionnaire-9 (PHQ-9) scores (ß = -0.23, 95% confidence interval, -0.45 to -0.01; P = .041). No association between caffeine intake and PHQ-9 scores was observed in the cancer population. In both cancer and noncancer populations, restricted cubic splines indicated a nonlinear trend between caffeine and PHQ-9 scores, with the lowest PHQ-9 scores when caffeine intake was 119.52 mg. In the noncancer population, moderate daily caffeine intake (quartile 3 group; range, 119.5-236.5 mg) was associated with reduced depressive symptoms, whereas in the cancer population, no association was found between caffeine intake and depression.

Effect of different ankle braces on lower extremity kinematics and kinetics following special-induced fatigue for volleyball players with functional ankle instability.

Background: The aim of this study is to examine the effects of different ankle braces on functional ankle instability (FAI) participants following special-induced fatigue, which will provide advice for preventing ankle sprains in volleyball game. Methods: A total of 18 male collegiate volleyball players with FAI were recruited. The kinematics and kinetics data were acquired from the participants during single-leg drop landing using the infrared motion capture system (Mars2H, Nokov, China) and the force platform (Bertec, USA). A 2 × 2 within subjects design ANOVA was adopted to analyze the data. Results: Whether fatigue or not, soft and semi-rigid brace reduced the ankle inversion (P = 0.025). Moreover, soft brace reduced the sagittal range of motion (ROM) of the ankle joint before fatigue (P = 0.05). In addition, the semi-rigid brace shortened the time to stability in the medial and lateral directions (P = 0.039) as well as the vertical directions (P < 0.001). The semi-rigid brace reduced the ground reaction force post-fatigue (P = 0.001). Conclusion: Soft ankle brace reduced the sagittal range of motion pre-fatigue. Since volleyball requires athletes to jumping and landing repeatedly, and the ankle sagittal ROM was an important cushion during landings. Thus, soft ankle brace might result in overuse injury for lower extremity. However, the semi-rigid ankle brace increased the dynamic stability in the medial and vertical directions, and reduced the ankle inversion angle and forward ground reaction force post-fatigue. This ensured that the volleyball player's ankle was in a neutral position during landing, reducing the risk of excessive inversion caused by contact with the opposing player during spike and block.

Dual roles of sub-nanometer NiO in alkaline hydrogen evolution reaction: breaking the Volmer limitation and optimizing d-orbital electronic configuration.

Pt-based nanoclusters toward the hydrogen evolution reaction (HER) remain the most promising electrocatalysts. However, the sluggish alkaline Volmer-step kinetics and the high-cost have hampered progress in developing high-performance HER catalysts. Herein, we propose to construct sub-nanometer NiO to tune the d-orbital electronic structure of nanocluster-level Pt for breaking the Volmer-step limitation and reducing the Pt-loading. Theoretical simulations firstly suggest that electron transfer from NiO to Pt nanoclusters could downshift the Ed-band of Pt and result in the well-optimized adsorption/desorption strength of the hydrogen intermediate (H*), therefore accelerating the hydrogen generation rate. NiO and Pt nanoclusters confined into the inherent pores of N-doped carbon derived from ZIF-8 (Pt/NiO/NPC) were designed to realize the structure of computational prediction and boost the alkaline hydrogen evolution. The optimal 1.5%Pt/NiO/NPC exhibited an excellent HER performance and stability with a low Tafel slope (only 22.5 mv dec-1) and an overpotential of 25.2 mV at 10 mA cm-2. Importantly, the 1.5%Pt/NiO/NPC possesses a mass activity of 17.37 A mg-1 at the overpotential of 20 mV, over 54 times higher than the benchmark 20 wt% Pt/C. Furthermore, DFT calculations illustrate that the Volmer-step could be accelerated owing to the high OH- attraction of NiO nanoclusters, leading to the Pt nanoclusters exhibiting a balance of H* adsorption and desorption (ΔGH* = -0.082 eV). Our findings provide new insights into breaking the water dissociation limit of Pt-based catalysts by coupling with a metal oxide.

Sleep duration affects the sequential change of body mass index and muscle strength: a contribution to dynapenic obesity.

BACKGROUND: With aging, body mass index (BMI) increases and muscle strength declines, resulting in dynapenic obesity. It remains unknown whether and how sleep duration contributes to the sequence of BMI and muscle strength change in the progression of dynapenic obesity. METHODS: Data were derived from the first two waves of China Health and Retirement Longitudinal Study. Sleep duration was self-reported. BMI was calculated and grip strength (GS) was measured to reflect muscle strength. The effect of baseline sleep duration on the sequential change of BMI and GS was assessed using two mediation models considering the nonlinear associations between them. The moderating effect of metabolic disorder was also tested. RESULTS: Totally 4986 participants aged ≥ 50 years (50.8% females) with complete information on variables were included. Baseline BMI fully mediated the nonlinear association between sleep duration and follow-up GS change, but baseline GS did not mediate between sleep duration and follow-up BMI change for older men and women. Short sleep duration positively affected BMI-induced GS change (ß = 0.038; 95%CI, 0.015-0.074), while this favorable effect became nonsignificant for moderate sleep duration (ß = 0.008; 95% CI, -0.003-0.024) and turned negative with prolonged sleep duration (ß = - 0.022; 95%CI, - 0.051 to - 0.003). This nonlinear mediation effect was more pronounced in older women who are relatively metabolically healthy at baseline. CONCLUSION: For older adults in China, the influence of sleep duration on BMI-induced GS change but not the GS-induced BMI change suggested the contribution of sleep duration to the sequential course in the progression of dynapenic obesity. Sleep duration deviated either above or below normal range may confer adverse impact on GS through BMI. Strategies addressing sleep and obesity jointly to improve muscle function and delay the progression of dynapenic obesity are required.

Positive Self-perceptions of Aging Increase Physical Resilience to Facilitate Social Re-engagement of Older Adults Who Fall: Analysis Based on Health and Retirement Study Data.

OBJECTIVE: To determine whether self-perceptions of aging (SPAs) predict physical resilience after a fall and whether SPA and physical resilience affect subsequent social engagement in older adults with a fall. DESIGN: Prospective cohort study. SETTING: General community. PARTICIPANTS: Older adults who reported a fall within 2 years after baseline data collection (N=1707, mean age 72.9 years, 60.9% women). MAIN OUTCOME MEASURE: Physical resilience indicates the ability to resist or recover from functional decline from a stressor. The change in frailty status from directly after the fall to up to 2 years of follow-up was used to generate 4 physical resilience phenotypes. Social engagement was dichotomized based on the presence at 1 of the 5 social activities at least once a month. The 8-item Attitudes Toward Own Aging Scale was used to assess SPA at baseline. Multinomial logistic regression and nonlinear mediation analysis were used. RESULTS: Positive prefall SPA predicted more resilient phenotypes after a fall. Both positive SPA and physical resilience affected subsequent social engagement. Physical resilience partially mediated the association between SPA and social re-engagement (mediated percentage of 14.5%, P=.004). This mediation effect was fully driven by those with previous falls. CONCLUSION: Positive SPA promotes physical resilience in older adults with a fall, both of which affect subsequent social engagement. Physical resilience partially mediated the effect of SPA on social engagement but only for previous fallers. Multidimensional recovery incorporating psychological, physiological, and social aspects should be stressed in the rehabilitation of older adults who fall.

The relationship between dyspnea-related kinesiophobia and physical activity in people with COPD: Cross-sectional survey and mediated moderation analysis.

BACKGROUND: Changing the behavior of physical activity (PA) in COPD patients remains a challenge, because this population faces the same barriers to PA as the general population, as well as disease-specific barriers, especially dyspnea-related kinesiophobia. OBJECTIVES: This study aimed to assess the status of dyspnea-related kinesiophobia in people with COPD, and investigate its impact on PA levels, further examine the mediated moderation effects of exercise perception and social support on this relationship. METHODS: A cross-sectional survey was conducted with COPD patients recruited from four tertiary hospitals in Jinan Province, China. We used Breathlessness Beliefs Questionnaire to identify dyspnea-related kinesiophobia. International Physical Activity Questionnaire-short-form, Exercise Benefits/Barriers Scale, and Social Support Rating Scale were used to assess PA, exercise perception and social support, respectively. The data were statistically processed using correlation analysis and a test of mediated moderation model. RESULTS: A total of 223 COPD patients were included, and all of them had a symptom of dyspnea-related kinesiophobia. Dyspnea-related kinesiophobia was negatively correlated with exercise perception, subjective social support and PA. Exercise perception partially mediated the impact of dyspnea-related kinesiophobia on PA levels, and subjective social support indirectly influences PA by moderating the relationship between dyspnea-related kinesiophobia and exercise perception. CONCLUSIONS: People with COPD commonly have dyspnea-related kinesiophobia and experienced physical inactivity. The mediated moderation model provides a better understanding of how dyspnea-related kinesiophobia, exercise perception, and subjective social support work together to influence PA. Interventions seeking to improve the levels of PA in COPD patients should consider these elements.

Onychiol B attenuates lipopolysaccharide-induced inflammation via MAPK/NF-κB pathways and acute lung injury in vivo.

Acute lung injury (ALI) is a devastating respiratory disorder characterized by rapid alveolar injury, uncontrolled inflammatory response, etc. Onychiol B is a cyathane diterpene originally isolated from fern plants. In this study, onychiol B can inhibit the production and secretion of pro-inflammatory cytokines such as NO, iNOS, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells by restraining the NF-κB and the p38 MAPK pathway. In addition, it prevents the production of ROS and reduces the loss of mitochondrial membrane potential in LPS-stimulated RAW264.7 cells. Furthermore, in the acute lung injury mouse model induced by LPS injected into the trachea, onychiol B alleviates pulmonary edema, reverses inflammatory mediator TNF-α, IL-6, and IL-ß secretion in lung. In general, our data show that significant anti-ALI effects of onychiol B would render it a potential candidate for the treatment of inflammatory diseases.

Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease.

Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here, we develop and characterize an ultrasensitive, highly responsive, ratiometric lactate sensor, named FiLa, enabling the monitoring of subtle lactate fluctuations in living cells and animals. Utilizing FiLa, we demonstrate that lactate is highly enriched in mammalian mitochondria and compile an atlas of subcellular lactate metabolism that reveals lactate as a key hub sensing various metabolic activities. In addition, FiLa sensors also enable direct imaging of elevated lactate levels in diabetic mice and facilitate the establishment of a simple, rapid, and sensitive lactate assay for point-of-care clinical screening. Thus, FiLa sensors provide powerful, broadly applicable tools for defining the spatiotemporal landscape of lactate metabolism in health and disease.

Global prevalence of autism spectrum disorder and its gastrointestinal symptoms: A systematic review and meta-analysis.

Background: Autism spectrum disorder (ASD) is a severe public health concern, and Gastrointestinal (GI) symptoms are becoming more common among co-morbidities. The evidence has to be updated depending on differences in different parts of the world. This systematic review and meta-analysis aimed to better understand the existing epidemiological condition and help make health-related decisions. Methods: Searches in PubMed, Web of Science, Embase databases are limited to 14 March 2022. We reviewed the global prevalence of ASD and the prevalence of GI in people with ASD. Data were extracted by two independent researchers. Literature quality assessment using the National Institutes of Health Study Quality Assessment Tool. Results: We discovered that the global pooled prevalence of ASD was 98/10,000 (95% confidence interval, 95%CI: 81/10,000-118/10,000, I 2 = 99.99%, p < 0.001), with 48.67% (95%CI: 43.50 -53.86, I 2 = 99.51%) of individuals with ASD reporting GI symptoms. Based on the subgroup analyses, we found a higher prevalence of ASD in males (90/10,000, 95%CI: 71/10,000-112/10,000, I 2 = 99.99%) than females (21/10,000, 95%CI: 15/10,000-27/10,000, I 2 = 99.99%). Prevalence of pooling is higher in developing countries (155/10,000, 95% CI: 111/10,000-204/10,000, I 2 = 99.87%) than in developed countries (85/10,000, 95%CI: 67/10,000-105/10,000, I 2 = 99.99%). Conclusion: The global prevalence of ASD and the prevalence of GI symptoms in ASD are both significant. The prevalence of ASD is much higher in men than in women. Further attention to ASD and its related comorbidities will be required in the future to inform coping strategy adaptation.

What caregivers believe affected the quality of implementation of asthma-related family management models (AFMM) during COVID-19: A phenomenological qualitative study.

PURPOSE: The recurrent COVID-19 epidemic in China has disrupted many aspects of daily life for children with asthma and their caregivers, while negatively impacting their asthma family management models (AFMM). This phenomenological qualitative study identifies what affects the quality of implementation of AFMM in this population and outlines potential coping strategies for the caregivers. METHODS: We used purposive sampling to conduct semistructured interviews with primary caregivers of school-age children with asthma from community healthcare centers (CHCs), which focused on understanding what factors influenced caregivers' implementation of AFMM during quarantine. The Colaizzi seven-step method was used to independently code and categorize the transcript and to generate themes and identify associated key subthemes. RESULTS: Twenty-four caregivers were interviewed, and they provided greater insight into barriers and motivators to implement AFMM. The three themes and nine relevant subthemes generated, (a) the "individual-family" internal-level factors: weak health literacy and beliefs, quietly changing family relationships, the dramatic increase in the care burden, gradual adjustment of negative psychology; (b) the "hospital-community" external-level factors: the endless power of peer support, strict community quarantine policy; and (c) the "health system-public" social-level factors: the enormous potential of internet-based telemedicine, improved public awareness of prevention, government's prompt assistance. CONCLUSIONS: This qualitative study reveals that the quality of AFMM implementation during pandemic is impacted by three different levels. Therefore, a targeted and comprehensive caring model that provides caregivers with the necessary coping strategies around these three levels is needed to achieve better asthma control outcomes.

Relationships among thriving at work, organisational commitment and job satisfaction among Chinese front-line primary public health workers during COVID-19 pandemic: a structural equation model analysis.

OBJECTIVES: This study aims to explore the mediating effect and influence mechanism of organisational commitment on the association among thriving at work and job satisfaction among frontline primary public health workers (PHWs) in China during the COVID-19 pandemic. DESIGN: This study is a cross-sectional written survey. SETTING: We included 20 primary care units in northern provinces of China. PARTICIPANTS: A total of 601 PHWs who worked in primary organisations and against COVID-19 on the front line were included. METHODS: We collected the data from the participants' written questionnaire (Minnesota Satisfaction Questionnaire, thriving at work scale and organisational commitment scale), and programmed AMOS V.26.0 to develop a structural equation model (SEM) based on the relationships among the three variables. RESULTS: The thriving at work scores of the primary PHWs were (M=3.17, SD=0.65), and job satisfaction was (M=3.05, SD=0.69); the scores of their thriving at work, organisational commitment and job satisfaction were all significantly correlated (p<0.01); and the SEM indicated that organisational commitment had a significant partial mediating effect between thriving at work and job satisfaction. The overall effect value was 0.867, and the mediated effect value was 0.422, accounting for 48.7% of the total effect size. CONCLUSION: The thriving at work and job satisfaction scores of primary PHWs in China are moderate, and thriving at work not only affects job satisfaction directly, but also indirectly through organisational commitment. This study suggests that health policy-makers should promote job satisfaction among PHWs through relative inventions aiming to improve their thriving at work and organisational commitment.

Construction of Severe Eosinophilic Asthma Related Competing Endogenous RNA Network by Weighted Gene Co-Expression Network Analysis.

Background: Currently, disease control in patients with severe eosinophilic asthma is not optimistic. Competing endogenous RNA (ceRNA) networks have been found to play a key role in asthma in recent years. However, it is unclear whether ceRNA networks play an important part in severe eosinophilic asthma. Methods: Firstly, gene expression profiles related to severe eosinophilic asthma were downloaded from the Gene Expression Omnibus (GEO) database. Secondly, the key modules were identified by the weighted gene co-expression network analysis (WGCNA). Thirdly, genes in modules highly associated with severe eosinophilic asthma were selected for further construction of the ceRNA network. Fourthly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on hub genes. Finally, the results of this study were validated on the GSE143303, GSE137268, and GSE147878 datasets. Results: 22 severe eosinophilic asthmatics and 13 healthy controls were extracted for WGCNA. We found that the genes in the black module (r = -0.75, p < 0.05) and yellow module (r = 0.65, p < 0.05) were highly associated with severe eosinophilic asthma. EP300 was discovered to serve the key connecting function in the ceRNA network. Surprisingly, lncRNAs seem to eliminate the role of EP300 in the black module and we discovered that CCT8 and miRNA-mRNA formed a circRNA-miRNA-mRNA network in the yellow module. We found that EP300 and FOXO3 in the black module were regulated by steroid hormones in the enrichment analysis, which were related to the medication used by the patient. Through validation of other datasets, we found that the hub genes in the yellow module were the key genes in the treatment of severe eosinophilic asthma. In particular, RPL17 and HNRNPK might specifically regulate severe eosinophilic asthma. Conclusion: RPL17 and HNRNPK might particularly regulate severe eosinophilic asthma. Our results could be useful to provide potential immunotherapy targets and prognostic markers for severe eosinophilic asthma.

Optogenetic control of RNA function and metabolism using engineered light-switchable RNA-binding proteins.

RNA-binding proteins (RBPs) play an essential role in regulating the function of RNAs in a cellular context, but our ability to control RBP activity in time and space is limited. Here, we describe the engineering of LicV, a photoswitchable RBP that binds to a specific RNA sequence in response to blue light irradiation. When fused to various RNA effectors, LicV allows for optogenetic control of RNA localization, splicing, translation and stability in cell culture. Furthermore, LicV-assisted CRISPR-Cas systems allow for efficient and tunable photoswitchable regulation of transcription and genomic locus labeling. These data demonstrate that the photoswitchable RBP LicV can serve as a programmable scaffold for the spatiotemporal control of synthetic RNA effectors.