The "supercompensation" effect of children's lockdown during COVID-19: based on the analysis of changes in physical activity, sleep, and psychology.

OBJECTIVE: To investigate the "supercompensation" effect of preschoolers during the coronavirus disease 2019 lockdown by comparing the changes in physical activity (PA), psychological, and sleep indicators before and after the lockdown. METHODS: A total of 127 children (aged 3-6 years) were recruited. Before and after the lockdown, the children's PA levels were measured using the ActiGraph GT3X+, and their psychological and sleep indicators were measured using the Strengths and Difficulties Questionnaire (SDQ) and Child Sleep Habit Questionnaire (CSHQ), respectively. RESULTS: Regarding PA, the children's total physical activity, low-intensity physical activity, and medium-intensity physical activity (MVPA) were higher after the lockdown than before the lockdown, with significant differences in MVPA (p < 0.05). Regarding psychology, the children's SDQ and multidimensional scores were better after the lockdown than before the lockdown, with a significant difference in SDQ scores (p < 0.05). Regarding sleep, the children's CSHQ scores were better after the lockdown than before the lockdown, with a highly significant difference in CSHQ scores (p < 0.01). CONCLUSION: After lockdown, children's PA, psychological, and sleep effects were "supercompensated." In particular, the PA of preschoolers before, during, and after the lockdown may show a "baseline-inhibition-supercompensation" process.

Evaluating the efficacy of GIPR agonists on non-alcoholic fatty liver disease: A Mediation Mendelian Randomization Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide while still lacks drugs for treatment or prevention. We aimed to investigate the causal role of glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs) on NAFLD and identify the mediated risk factors by which GIPRAs exert their therapeutic effects. METHODS: Genetic proxies of GIPRAs were identified as cis-SNPs of GIPR associated with both the gene expression level and HbA1c and analyses including colocalization and linkage disequilibrium (LD) were performed for validation. We then performed two-sample two-step mendelian randomization to determine the causal effect of GIPRAs on NAFLD. RESULTS: The MR analysis suggested genetic proxies of GIPRAs were causally associated with reduced risk of NAFLD (Odds ratio (OR): 0.46, 95 % confidence interval (95 % CI): 0.24-0.88, P = 0.02) and T2DM (OR: 0.10, 95 % CI: 0.07-0.13, P < 0.01). In addition, Mediation analysis showed evidence of indirect effect of GIPRAs on NAFLD via TRIG (0.88, [0.85-0.92], P < 0.01) and HDL-C (0.85, [0.80-0.90], P < 0.01). CONCLUSIONS: Our study provided strong evidence to support the causal role of GIPRAs on reducing the risk of NAFLD probably through improving lipid metabolism, especially TG and HDL-C, providing guidance for future clinical trials.

Relationship between 24-h activity behavior and body fat percentage in preschool children: based on compositional data and isotemporal substitution analysis.

OBJECTIVE: This study aims to elucidate the dose‒response relationship between 24-h activity behaviors and body fat percentage (BFP) in Chinese preschool children using a compositional isotemporal substitution model (ISM). METHODS: In a cross-sectional design, 881 children aged 3-6 from urban and rural areas of Jiangxi Province were sampled. Activity behaviors, including sedentary behavior (SB), low-intensity physical activity (LPA), and moderate- to high-intensity physical activity (MVPA), were measured using accelerometers. Sleep patterns were assessed through questionnaires, and BFP was determined by bioelectrical impedance analysis (BIA). The study employed compositional data analysis (CoDA) and ISM to estimate the impact of reallocating durations of different activity behaviors on BFP. RESULTS: Higher BFP was found in urban vs. rural children, decreasing with age. Overweight and obesity rates were 10.6% and 7.6%, respectively, above national averages. MVPA and LPA were negatively correlated with BFP, while SB was positively correlated. A 30-min MVPA reduction significantly increased zBFR, particularly in overweight children. Gender-specific nuances revealed that boys' MVPA negatively influenced zBFP (ß = -0.155), P < 0.05), while girls' SB positively impacted zBFP (ß = 0.636, P < 0.01). Isotemporal simulations emphasized amplified effects in overweight children, with boys' zBFR rising rapidly when MVPA was substituted and girls displaying a notable substitution effect between SB and LPA. CONCLUSION: BFP is closely linked to 24-h activity behaviors, notably in overweight and obese preschoolers. ISM identified MVPA as a critical influencer, with a 30-min reduction substantially increasing BFP. Gender disparities were evident, implicating MVPA in boys and LPA and SB in girls.

Molecular characterization of adenosine monophosphate deaminase 1 and the correlation analysis between its mRNA expression levels and inosine monophosphate content in large yellow croaker (Larimichthys crocea).

Declining flesh quality has drawn considerable attention in the farmed large yellow croaker (LYC; Larimichthys crocea) industry. Inosine monophosphate (IMP) is the primary flavor substance in aquatic animals. Adenosine monophosphate deaminase 1 (AMPD1) plays a critical role in IMP formation by catalyzing the deamination of AMP to IMP in the purine nucleotide cycle. To further evaluate the correlation between ampd1 mRNA expression levels and IMP content in the LYC muscle tissue, the relevant open reading frame (ORF) of L. crocea (Lcampd1) was cloned, and the IMP content and Lcampd1 mRNA expression in the muscles of LYCs of different sizes were examined. The ORF cDNA of Lcampd1 was 2211 bp in length and encoded a polypeptide of 736 amino acids (AAs). The deduced protein, LcAMPD1, possesses conserved AMPD active regions (SLSTDDP) and shows high homology with AMPD proteins of other teleost fishes. The genomic DNA sequence of Lcampd1 exhibits a high degree of evolutionary conservation in terms of structural organization among species. Phylogenetic analysis of the deduced AA sequence revealed that teleost fish and mammalian AMPD1 were separate from each other and formed a cluster with AMPD3, suggesting that AMPD1 and AMPD3 arose by duplication of a common primordial gene. In healthy LYC, Lcampd1 mRNA was expressed only in the muscle tissue. The IMP content in the muscle of LYCs with different average body weights was measured by high-performance liquid chromatography; the results showed that the IMP content in the muscle of LYCs with greater body weight was significantly higher than that in LYC with lower body weight. Moreover, a similar trend in Lcampd1 expression was observed in these muscle tissues. The Pearson correlation analysis further showed that the Lcampd1 mRNA expression was positively correlated with IMP content in the muscles of different-sized LYCs. These results suggest the potential function of Lcampd1 in determining the IMP content in LYC and provide a theoretical basis for flesh quality improvement, as well as a scientific basis for the development of the molecular breeding of LYC.

ProtoCLIP: Prototypical Contrastive Language Image Pretraining.

Contrastive language image pretraining (CLIP) has received widespread attention since its learned representations can be transferred well to various downstream tasks. During the training process of the CLIP model, the InfoNCE objective aligns positive image-text pairs and separates negative ones. We show an underlying representation grouping effect during this process: the InfoNCE objective indirectly groups semantically similar representations together via randomly emerged within-modal anchors. Based on this understanding, in this article, prototypical contrastive language image pretraining (ProtoCLIP) is introduced to enhance such grouping by boosting its efficiency and increasing its robustness against the modality gap. Specifically, ProtoCLIP sets up prototype-level discrimination between image and text spaces, which efficiently transfers higher level structural knowledge. Furthermore, prototypical back translation (PBT) is proposed to decouple representation grouping from representation alignment, resulting in effective learning of meaningful representations under a large modality gap. The PBT also enables us to introduce additional external teachers with richer prior language knowledge. ProtoCLIP is trained with an online episodic training strategy, which means it can be scaled up to unlimited amounts of data. We trained our ProtoCLIP on conceptual captions (CCs) and achieved an + 5.81% ImageNet linear probing improvement and an + 2.01% ImageNet zero-shot classification improvement. On the larger YFCC-15M dataset, ProtoCLIP matches the performance of CLIP with 33% of training time.

A cohort study of factors influencing the physical fitness of preschool children: a decision tree analysis.

Objective: Based on the decision tree model, to explore the key influencing factors of children's physical fitness, rank the key influencing factors, and explain the complex interaction between the influencing factors. Methods: A cohort study design was adopted. 1,276 children (ages 3-6) from 23 kindergartens in Nanchang, China, were chosen for the study to measure the children's physical fitness at baseline and a year later and to compare the physical fitness scores at the two stages. The study was conducted following the Chinese National Physical Fitness Testing Standard (Children Part); To identify the primary influencing factors of changes in physical fitness, a decision tree model was developed, and a questionnaire survey on birth information, feeding patterns, SB, PA, dietary nutrition, sleep, parental factors, and other relevant information was conducted. Results: The levels of physical fitness indicators among preschool children showed a significant increase after 1 year. The accuracy of the CHAID model is 84.17%. It showed that 7 variables were strongly correlated with the physical changes of children's fitness, the order of importance of each variable was weekend PA, weekend MVPA, mother's BMI, mother's sports frequency, father's education, mother's education, and school day PA. Three factors are related to PA. Four factors are related to parental circumstances. In addition to the seven important variables mentioned, variables such as breakfast frequency on school day, puffed food, frequency of outing, school day MVPA, parental feeling of sports, father's occupation, and weekend breakfast frequency are all statistically significant leaf node variables. Conclusion: PA, especially weekend PA, is the most critical factor in children's physical fitness improvement and the weekend MVPA should be increased to more than 30 min/d based on the improvement of weekend PA. In addition, parental factors and school day PA are also important in making decisions about changes in fitness for children. The mother's efforts to maintain a healthy BMI and engage in regular physical activity are crucial for enhancing the physical fitness of children. Additionally, other parental factors, such as the parents' educational levels and the father's occupation, can indirectly impact the level of physical fitness in children.

Integrated analysis of Mendelian Randomization and Bayesian colocalization reveals bidirectional causal association between inflammatory bowel disease and psoriasis.

BACKGROUND: Observational studies have suggested an association between inflammatory bowel disease [IBD] and psoriasis. However, the detailed genetic basis, causality, and direction of this association remain unclear. METHODS: Bidirectional two-sample Mendelian Randomization [MR] analysis was conducted using summary statistics from published genome-wide association studies. Bayesian Colocalization and multivariable MR [MVMR] analyses were performed to identify candidate variants and risk genes involved in the shared genetic basis between IBD, psoriasis, and their subtypes. RESULTS: Genetically predicted IBD and Crohn's disease [CD] were associated with an increased risk of psoriasis, psoriasis vulgaris [PsV], and psoriatic arthritis [PsA] (IBD on psoriasis: pooled odds ratio [OR] 1.09, 95% confidence interval [CI] 1.04-1.14, p = .0001; CD on psoriasis: pooled OR 1.10, 95% CI 1.06-1.15, p < .0001) and vice versa (psoriasis on IBD: pooled OR 1.11, 95%CI 1.02-1.21), whereas CD only exhibited a unidirectional association with psoriasis. Colocalization analysis revealed eight candidate genetic variants and risk genes (including LINC00824, CDKAL1, IL10, IL23R, DNAJC27, LPP, RUNX3, and RGS14) associated with a shared genetic basis. Among these, IL23R, DNAJC27, LPP, and RGS14 were further validated by MVMR analysis. CONCLUSION: Our findings indicated bidirectional causal associations between IBD and psoriasis (including PsV and PsA), which were attributed primarily to CD rather than Ulcerative colitis [UC]. Furthermore, we identified several candidate variants and risk genes involved in the shared genetic basis of IBD and psoriasis. Acquiring a better understanding of the shared genetic architecture underlying IBD and psoriasis would help improve clinical strategies.

Constipation and cardiovascular disease: A two-sample Mendelian randomization analysis.

Background: Although several observational studies have suggested positive associations between constipation and cardiovascular disease (CVD), a solid causal association has not been demonstrated. Therefore, a two-sample Mendelian randomization (MR) study was performed to investigate the causal associations between constipation and CVD. Methods: Independent genetic variants strongly associated with constipation were obtained from the FinnGen consortium. Summary-level data for CVD, including coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), stroke, and its subtypes, were collected from a few extensive genome-wide association studies (GWASs). The inverse-variance weighted methods, weighted median, and MR-Egger were used for the MR estimates. The Cochran's Q test, MR-Egger intercept tests, MR-PRESSO, MR Steiger test, leave-one-out analyses, and funnel plot were used in the sensitivity analysis. Results: Genetically determined constipation was suggestively associated with AF risk (odds ratio (OR), 1.07; 95% confidence interval (CI), 1.01, 1.14; p = 0.016). Constipation and other CVD do not appear to be causally related. It was demonstrated that the results were robust through sensitivity analyses. Conclusion: This MR study demonstrated suggestive causal associations of constipation on AF, despite no associations achieving a significance value after multiple testing corrections. There was no evidence of an association between constipation and the risk of CAD, MI, HF, stroke, or stroke subtypes.

Corrigendum: Inhibitory effects of Rhaponticin on osteoclast formation and resorption by targeting RANKL-induced NFATc1 and ROS activity.

[This corrects the article DOI: 10.3389/fphar.2021.645140.].

Cluster characteristics of physical activities among children inside and outside kindergartens and its relationship with athletic abilities / 中国学校卫生

Objective@#Based on physical activity (PA) and sedentary behavior (SB) variables on weekdays and weekends, the study aims to cluster the physical activities inside and outside kindergartens and to explore the cluster characteristics of different children using physical fitness indicators, so as to provide new strategies and methods for early childhood education and health.@*Methods@#From March to June 2019, 291 children aged 3-6 years from 6 kindergartens in Nanchang were recruited by a stratified cluster random sampling method. The ActiGraph GT3X-BT triaxial accelerometer was used to measure and analyze the PA and SB levels inside and outside the kindergarten. A twostep clustering algorithm model was employed for cluster analysis. Physical fitness were measured and evaluated according to the "National Physical Fitness Measurement Standard Manual (Preschool Section)". Differences in physical fitness among different clusters of children were compared, and the cluster characteristics of different children were analyzed.@*Results@#The clustering algorithm model indicated that based on six indicators, including PA and SB inside the kindergarten on weekdays, and PA and SB outside the kindergarten on both weekdays and weekends, children could be divided into three categories:active inside (high PA, low SB inside), active outside (high PA outside), and inactive (low PA, high SB both inside and outside). The average silhouette coefficient of the model was 0.3, indicating good clustering results. Both the active inside and active outside children showed significantly higher PA inside on weekdays, PA outside on weekdays and weekends, daily low intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) than the inactive children ( F=157.91, 80.79 , 95.86, 95.52, 124.74, P <0.05). After adjusting for gender and age, the physical fitness scores of both active outside ( 19.03 ±0.47) and active inside (19.11±0.40) were significantly higher than those of the inactive children (17.94±0.31). Additionally, active inside children (3.91±0.14) also showed significantly better performance in continuous double-leg jumps, compared to inactive children (3.45±0.11) ( P <0.05).@*Conclusion@#Children active inside and those active outside perform well in PA. Future research should focus on the proportion of structured and unstructured PA time to enhance the overall physical fitness of children.

Exosomes and Exosomal Cargos: A Promising World for Ventricular Remodeling Following Myocardial Infarction.

Exosomes are a pluripotent group of extracellular nanovesicles secreted by all cells that mediate intercellular communications. The effective information within exosomes is primarily reflected in exosomal cargos, including proteins, lipids, DNAs, and non-coding RNAs (ncRNAs), the most intensively studied molecules. Cardiac resident cells (cardiomyocytes, fibroblasts, and endothelial cells) and foreign cells (infiltrated immune cells, cardiac progenitor cells, cardiosphere-derived cells, and mesenchymal stem cells) are involved in the progress of ventricular remodeling (VR) following myocardial infarction (MI) via transferring exosomes into target cells. Here, we summarize the pathological mechanisms of VR following MI, including cardiac myocyte hypertrophy, cardiac fibrosis, inflammation, pyroptosis, apoptosis, autophagy, angiogenesis, and metabolic disorders, and the roles of exosomal cargos in these processes, with a focus on proteins and ncRNAs. Continued research in this field reveals a novel diagnostic and therapeutic strategy for VR.

Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study.

Background: Observational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally. Methods: Two-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10-8) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10-5). Summary-level statistics for CVDs, including coronary artery disease (CAD), myocardial infarction, heart failure, atrial fibrillation, stroke and its subtypes were collected. The ME estimation was performed using the inverse-variance weighted and Wald ratio methods. Sensitivity analysis was performed using the weighted median, MR-Egger, leave-one-out analysis, MR pleiotropy residual sum and outlier and MR Steiger. Results: Based on the locus-wide significance level, genetically predicted genus Oxalobacter was positively associated with the risk of CAD (odds ratio (OR) = 1.06, 95% confidence interval (CI), 1.03 - 1.10, P = 1.67 × 10-4), family Clostridiaceae_1 was negatively correlated with stroke risk (OR = 0.83,95% CI, 0.75-0.93, P = 7.76 × 10-4) and ischemic stroke risk (OR = 0.823,95% CI, 0.74-0.92, P = 4.15 × 10-4). There was no causal relationship between other genetically predicted gut microbiome components and CVDs risk. Based on the genome-wide statistical significance threshold, the results showed that the gut microbiome had no causal relationship with CVDs risk. Conclusion: Our findings reveal that there are beneficial or adverse causal effects of gut microbiome components on CVDs risk and provide novel insights into strategies for the prevention and management of CVDs through the gut microbiome.

Thiaplakortone B attenuates RANKL-induced NF-κB and MAPK signaling and dampens OVX-induced bone loss in mice.

Osteoclasts play an important role in maintaining the relative stability of bone mass. Abnormal number and function of osteoclasts are closely related to osteoporosis and osteolytic diseases. Thiaplakortone B (TPB), a natural compound derived from the Great Barrier Reef sponge Plakortis lita, has been reported to inhibit the growth of the malaria parasite, Plasmodium falciparum, but its effect on osteoclastogenesis has not been previously investigated. In our study, we found that TPB suppresses the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and resorption activity by tartrate-resistant acid phosphatase (TRAcP) staining, immunofluorescence staining of F-actin belts and hydroxyapatite resorption assay. Furthermore, using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis, we discovered that TPB inhibits osteoclast-specific genes and proteins expression. Mechanistically, TPB blocks multiple upstream pathways including calcium oscillation, NF-κB, mitogen-activated protein kinase (MAPK) and nuclear factor of activated T cells 1(NFATc1) signaling pathways. In vivo, TPB could dampen bone loss in an ovariectomy (OVX) mouse model by micro-CT assessment and histological staining. Therefore, TPB may serve as a potential therapeutic candidate for the treatment of osteoporosis and osteolysis.

Effects of Traditional Chinese Exercise on Oxidative Stress in Middle-Aged and Older Adults: A Network Meta-Analysis.

OBJECTIVE: To evaluate the best option among traditional Chinese exercises for reducing oxidative stress in middle-aged and older adults, using a network meta-analysis. METHODS: PubMed, Web of Science, and CNKI databases were used. We searched randomized controlled trials (RCTs) on middle-aged and older adults to influence oxidative stress by any traditional Chinese exercises from the beginning to 20 January 2022. A network meta-analysis of randomized control trials was performed comparing the changes in the concentration of glutathione peroxidase (GPX), malondialdehyde (MDA), and superoxide dismutase (SOD) as primary outcomes, following different therapeutic interventions with traditional Chinese exercises in middle-aged and older adults over 30 years old. Standardized mean differences (SMD) and 95% confidence intervals (CI) were used to assess the correlation between each group of interventions, and surface under the cumulative ranking (SUCRA) was used to rank the best interventions. RESULTS: The meta-analysis comprised 15 trials with a total of 927 participants and six interventions: (Wuqinxi (WQX), Baduanjin (BDJ), Tai Ji Quan (TJQ), Yijinjing (YJJ), Mawangdui Daoyin (MWD), and no exercise intervention (NEI)). Regarding GPX: WQX [SMD = 2.79 (1.75, 3.83)], TJQ [SMD = 0.47 (0.23, 0.70)], YJJ [SMD = 1.78 (1.18, 2.37)], MWD [SMD = 1.89 (1.36, 2.43)] were superior in increasing GPX relative to NEI. Regarding MDA: WQX [SMD = 1.68 (0.94, 2.42)], YJJ [SMD = 0.99 (0.28, 1.69)] were superior in reducing MDA relative to NEI. Regarding SOD: WQX [SMD = 1.05 (0.10, 2.01)] were superior in increasing SOD relative to NEI. WQX topped the SUCRA with GPX: 0.97, MDA: 0.91, and SOD: 0.94. Furthermore, WQX was more effective than TJQ in interfering with GPX [SMD = 2.32 (1.26, 3.39)] and MDA [SMD = 1.47 (0.26, 2.67)], and a significantly better intervention effect on SOD than YJJ [SMD = 1.52 (0.80, 2.24)] and MWD [SMD = 0.89 (0.03, 1.75)]. CONCLUSION: Traditional Chinese exercise can help middle-aged and older adults reduce oxidative stress. WQX may be the best traditional Chinese exercise of the exercises evaluated for reducing oxidative stress in middle-aged and older adults.

12-Deoxyphorbol-13-Hexadecanoate Abrogates OVX-Induced Bone Loss in Mice and Osteoclastogenesis via Inhibiting ROS Level and Regulating RANKL-Mediated NFATc1 Activation.

Osteoporosis is a major health problem in the elderly. Almost every bone can fracture due to the increased bone fragility in osteoporosis, posing a major challenge to public health. 12-Deoxyphorbol-13-hexadecanoate (DHD), one of the main bioactive components of Stellera chamaejasme L. (Lang Du), is considered to have antitumor, antibacterial, and antifungal properties. However, the role of DHD in osteoporosis is still elusive. In this study, we demonstrated for the first time that DHD inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in a dose- and time-dependent manner without exhibiting cytotoxicity in vitro. Mechanistically, we found that DHD not only represses the expression of osteoclasts marker genes by suppressing RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways but also scavenges reactive oxygen species (ROS) through enhancing cytoprotective enzymes expression. Furthermore, DHD inhibits the activation of nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclasts formation. Preclinical studies revealed that DHD protects against bone loss in ovariectomy (OVX) mice. In sum, our data confirmed that DHD could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathways and promoting the expression of ROS scavenging enzymes, thereby preventing OVX-induced bone loss. Thus, DHD may act as a novel therapeutic agent to manage osteoporosis.

The impacts of surgical mask in young healthy subjects on cardiopulmonary function and muscle performance: a randomized crossover trial.

OBJECTIVE: To explore the impacts of surgical mask in normal subjects on cardiopulmonary function and muscle performance under different motor load and gender differences. DESIGN: Randomized crossover trial. SETTING: The Fifth Affiliated Hospital of Guangzhou Medical University, June 16th to December 30th, 2020. PARTICIPANTS: Thirty-one college students (age: male 21.27 ± 1.22 years; female 21.31 ± 0.79 years) were recruited and randomly allocated in two groups. INTERVENTIONS: Group 1 first received CPET in the mask-on condition followed by 48 h of washout, and then received CPET in the mask-off condition. Group 2 first received CPET in the mask-off condition followed by 48 h of washout, then received CPET in the mask-on condition. The sEMG data were simultaneously collected. MAIN OUTCOME MEASURES: The primary outcome was maximum oxygen uptake (VO2 max) from CPET, which was performed on a cycle ergometer-this is the most important parameter associated with an individual's physical conditioning. The secondary parameters included parameters reflecting exercise tolerance and heart function (oxygen uptake, anaerobic valve, maximum oxygen pulse, heart rate reserve), parameters reflecting ventilation function (respiration reserve, ventilation volume, tidal volume, breathing frequency), parameters reflecting gas exchange (end-tidal oxygen and carbon dioxide partial pressure, oxygen equivalent, carbon dioxide equivalent, and the relationship between dead space and tidal volume) and parameters reflecting skeletal muscle function [oxygen uptake, anaerobic valve, work efficiency, and EMG parameters including root mean square (RMS)]. RESULTS: Comparing the mask-on and mask-off condition, wearing surgical mask had some negative effects on VO2/kg (peak) and ventilation (peak) in both male and female health subjects [VO2/kg (peak): 28.65 ± 3.53 vs 33.22 ± 4.31 (P = 0.001) and 22.54 ± 3.87 vs 26.61 ± 4.03 (P < 0.001) ml/min/kg in male and female respectively; ventilation (peak): 71.59 ± 16.83 vs 82.02 ± 17.01 (P = 0.015) and 42.46 ± 10.09 vs 53.95 ± 10.33 (P < 0.001) liter in male and female respectively], although, based on self-rated scales, there was no difference in subjective feelings when comparing the mask-off and mask-on condition. Wearing surgical masks showed greater lower limb muscle activity just in male subjects [mean RMS of vastus medialis (load): 65.36 ± 15.15 vs 76.46 ± 19.04 µV, P = 0.031]. Moreover, wearing surgical masks produced a greater decrease in △tidal volume (VTpeak) during intensive exercises phase in male subjects than in female [male - 0.80 ± 0.15 vs female - 0.62 ± 0.11 l P = 0.001]. CONCLUSIONS: Wearing medical/surgical mask showed a negative impact on the ventilation function in young healthy subjects during CPET, especially in high-intensity phase. Moreover, some negative effects were found both in ventilation and lower limb muscle actives in male young subjects during mask-on condition. Future studies should focus on the subjects with cardiopulmonary diseases to explore the effect of wearing mask. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( ChiCTR2000033449 ).

Hesperidin Ameliorates Dexamethasone-Induced Osteoporosis by Inhibiting p53.

Osteoporosis is one of the most frequent skeletal disorders and a major cause of morbidity and mortality in the expanding aging population. Evidence suggests that hesperidin may have a therapeutic impact on osteoporosis. Nevertheless, little is known about the role of hesperidin in the development of osteoporosis. Bioinformatics analyses were carried out to explore the functions and possible molecular mechanisms by which hesperidin regulates osteogenic differentiation. In the present study, we screened and harvested 12 KEGG pathways that were shared by hesperidin-targeted genes and osteoporosis. The p53 signaling pathway was considered to be a key mechanism. Our in vitro results showed that hesperidin partially reversed dexamethasone-induced inhibition of osteogenic differentiation by suppressing the activation of p53, and suggest that hesperidin may be a promising candidate for the treatment against dexamethasone-induced osteoporosis.

Causal Associations Between Circulating Adipokines and Cardiovascular Disease: A Mendelian Randomization Study.

CONTEXT: Observational studies have suggested associations between adipokines and cardiovascular disease (CVD), but the roles of certain adipokines remain controversial, and these associations have not yet been ascertained causally. OBJECTIVE: To investigate whether circulating adipokines causally affect the risk of CVD using 2-sample Mendelian randomization (MR). METHODS: Independent genetic variants strongly associated with adiponectin, resistin, chemerin, and retinol binding protein 4 (RBP4) were selected from public genome-wide association studies. Summary-level statistics for CVD, including coronary artery disease (CAD), myocardial infarction, atrial fibrillation (AF), heart failure (HF), and stroke and its subtypes were collected. The inverse-variance weighted and Wald ratio methods were used for the MR estimates. The MR pleiotropy residual sum and outlier, weighted median, MR-Egger, leave-one-out analysis, MR Steiger, and colocalization analyses were used in the sensitivity analysis. RESULTS: Genetically predicted resistin levels were positively associated with AF risk (odds ratio [OR] 1.09; 95% confidence interval [CI], 1.04-1.13; P = 4.1 × 10-5), which was attenuated to null after adjusting for blood pressure. We observed suggestive associations between higher genetically predicted chemerin levels and an increased risk of CAD (OR 1.27; 95% CI, 1.01-1.60; P = 0.040), higher genetically predicted RBP4 levels and an increased risk of HF (OR 1.14; 95% CI, 1.02-1.27; P = 0.024). There was no causal association between genetically predicted adiponectin levels and CVD risk. CONCLUSIONS: Our findings reveal the causal association between resistin and AF, probably acting through blood pressure, and suggest potential causal associations between chemerin and CAD, RBP4, and HF.