Association of sleep duration with sarcopenic obesity in multi-ethnic older adults: findings from the WCHAT Study.

OBJECTIVE: Sarcopenic obesity is a prevalent geriatric syndrome, characterized by concurrence of sarcopenia and obesity. Sleep duration is linked to both obesity and sarcopenia. However, little was known regarding the association of sleep duration with sarcopenic obesity. In this study, we aimed to examine the association of sleep duration with sarcopenic obesity in multi-ethnic community-dwelling older adults. METHODS: Sarcopenia was defined according to the criteria established by Asian Working Group for Sarcopenia (AWGS) 2019. Obesity was defined as body fat percentage above the 60th percentile specified by sex. Sarcopenic obesity was defined as concurrence of obesity and sarcopenia. Sleep duration was collected by a self-reported questionnaire and was further divided into 5 groups: "<6 h", "6-7 h", "7-8 h", "8-9 h" (reference group) and "≥9 h" (long sleep). Logistic regressions were adopted to examine the association. RESULTS: 2256 multi-ethnic adults aged 60 and over from the West China Health and Aging Trend (WCHAT) study were involved for present study. Overall, 6.25% of the participants were classified as sarcopenic obesity. In the fully adjusted model, long sleep duration (≥ 9 h) was significantly associated with sarcopenic obesity compared with reference group (OR = 1.81, 95%CI = 1.10-2.98, P = 0.019). However, in subgroup analysis, this association can only be observed in male (OR 1.98, 95% CI = 1.02-3.87, P = 0.043) not in female (OR = 1.83, 95%CI = 0.85-3.94, P = 0.118). Regarding ethnic difference, Han older adults with long sleep duration (≥ 9 h) presented increased risk of sarcopenic obesity while ethnic minorities did not. CONCLUSION: This study disclosed that long sleep duration significantly increased the risk of sarcopenic obesity among older adults. And our findings highlight the critical role of assessing sleep duration to identify individuals at risk of sarcopenic obesity.

Evaluation of the Risk Prediction Tools for Patients With Coronavirus Disease 2019 in Wuhan, China: A Single-Centered, Retrospective, Observational Study.

OBJECTIVES: To evaluate and compare the efficacy of National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment on predicting in-hospital death in patients with coronavirus disease 2019. DESIGN: A retrospective, observational study. SETTING: Single center, West Campus of Wuhan Union hospital-a temporary center to manage critically ill patients with coronavirus disease 2019. PATIENTS: A total of 673 consecutive adult patients with coronavirus disease 2019 between January 30, 2020, and March 14, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demography, comorbidities, vital signs, mental status, oxygen saturation, and use of supplemental oxygen at admission to the ward were collected from medical records and used to score National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment. Total number of patients was 673 (51% male) and median (interquartile range) age was 61 years (50-69 yr). One-hundred twenty-one patients died (18%). For predicting in-hospital death, the area under the receiver operating characteristics (95% CI) for National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment were 0.882 (0.847-0.916), 0.880 (0.845-0.914), 0.839 (0.800-0.879), 0.766 (0.718-0.814), and 0.694 (0.641-0.746), respectively. Among the parameters of National Early Warning Score, the oxygen saturation score was found to be the most significant predictor of in-hospital death. The area under the receiver operating characteristic (95% CI) for oxygen saturation score was 0.875 (0.834-0.916). CONCLUSIONS: In this single-center study, the discrimination of National Early Warning Score/National Early Warning Score 2 for predicting mortality in patients with coronavirus disease 2019 admitted to the ward was found to be superior to Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment. Peripheral oxygen saturation could independently predict in-hospital death in these patients. Further validation of our finding in multiple settings is needed to determine its applicability for coronavirus disease 2019.

Stem cell competition driven by the Axin2-p53 axis controls brain size during murine development.

Cell competition acts as a quality-control mechanism that eliminates cells less fit than their neighbors to optimize organ development. Whether and how competitive interactions occur between neural progenitor cells (NPCs) in the developing brain remains unknown. Here, we show that endogenous cell competition occurs and intrinsically correlates with the Axin2 expression level during normal brain development. Induction of genetic mosaicism predisposes Axin2-deficient NPCs to behave as "losers" in mice and undergo apoptotic elimination, but homogeneous ablation of Axin2 does not promote cell death. Mechanistically, Axin2 suppresses the p53 signaling pathway at the post-transcriptional level to maintain cell fitness, and Axin2-deficient cell elimination requires p53-dependent signaling. Furthermore, mosaic Trp53 deletion confers a "winner" status to p53-deficient cells that outcompete their neighbors. Conditional loss of both Axin2 and Trp53 increases cortical area and thickness, suggesting that the Axin2-p53 axis may coordinate to survey cell fitness, regulate natural cell competition, and optimize brain size during neurodevelopment.

High-throughput novel microsatellite marker of faba bean via next generation sequencing.

BACKGROUND: Faba bean (Vicia faba L.) is an important food legume crop, grown for human consumption globally including in China, Turkey, Egypt and Ethiopia. Although genetic gain has been made through conventional selection and breeding efforts, this could be substantially improved through the application of molecular methods. For this, a set of reliable molecular markers representative of the entire genome is required. RESULTS: A library with 125,559 putative SSR sequences was constructed and characterized for repeat type and length from a mixed genome of 247 spring and winter sown faba bean genotypes using 454 sequencing. A suit of 28,503 primer pair sequences were designed and 150 were randomly selected for validation. Of these, 94 produced reproducible amplicons that were polymorphic among 32 faba bean genotypes selected from diverse geographical locations. The number of alleles per locus ranged from 2 to 8, the expected heterozygocities ranged from 0.0000 to 1.0000, and the observed heterozygosities ranged from 0.0908 to 0.8410. The validation by UPGMA cluster analysis of 32 genotypes based on Nei's genetic distance, showed high quality and effectiveness of those novel SSR markers developed via next generation sequencing technology. CONCLUSIONS: Large scale SSR marker development was successfully achieved using next generation sequencing of the V. faba genome. These novel markers are valuable for constructing genetic linkage maps, future QTL mapping, and marker-assisted trait selection in faba bean breeding efforts.

Genetic diversity and relationship of global faba bean (Vicia faba L.) germplasm revealed by ISSR markers.

Genetic diversity and relationships of 802 faba bean (Vicia faba L.) landraces and varieties from different geographical locations of China and abroad were examined using ISSR markers. A total of 212 repeatable amplified bands were generated with 11 ISSR primers, of which 209 were polymorphic. Accessions from North China showed highest genetic diversity, while accessions from central China showed low level of diversity. Chinese spring faba bean germplasm was clearly separated from Chinese winter faba bean, based on principal component analysis and UPGMA clustering analysis. Winter accessions from Zhejiang (East China), Jiangxi (East China), Sichuan (Southwest China) and Guizhou (Southwest China) were quite distinct to that from other provinces in China. Great differentiation between Chinese accessions and those from rest of the world was shown with a UPGMA dendrogram. AMOVA analyses demonstrated large variation and differentiation within and among groups of accessions from China. As a continental geographic group, accessions from Europe were genetically closer to those from North Africa. Based on ISSR data, grouping results of accessions from Asia, Europe and Africa were obviously associated with their geographical origin. The overall results indicated that the genetic relationship of faba bean germplasm was closely associated with their geographical origin and their ecological habit.

Development of 161 novel EST-SSR markers from Lathyrus sativus (Fabaceae).

PREMISE OF THE STUDY: Expressed sequence tag (ESTs)-derived microsatellite markers were developed in Lathyrus sativus by screening the National Center for Biotechnology Information (NCBI) database. The usefulness of these novel markers was validated for size polymorphism among grasspea accessions. • METHODS AND RESULTS: Three hundred EST-simple sequence repeat (SSR) primer pairs were identified and loci characterized for size polymorphism among 24 grasspea accessions from worldwide sources. Among them 139 SSR loci produced no PCR product, 117 SSR loci were monomorphic, and 44 SSR loci were polymorphic. The mean number of alleles per locus ranged from two to 11. The observed heterozygosity and expected heterozygosity ranged from 0.000 to 1.000 and 0.042 to 0.836, respectively. • CONCLUSIONS: These novel markers will be useful and convenient to study genetic mapping and molecular breeding in grasspea.

Hierarchical deployment of Tbx3 dictates the identity of hypothalamic KNDy neurons to control puberty onset.

The neuroendocrine system consists of a heterogeneous collection of neuropeptidergic neurons in the brain, among which hypothalamic KNDy neurons represent an indispensable cell subtype controlling puberty onset. Although neural progenitors and neuronal precursors along the cell lineage hierarchy adopt a cascade diversification strategy to generate hypothalamic neuronal heterogeneity, the cellular logic operating within the lineage to specify a subtype of neuroendocrine neurons remains unclear. As human genetic studies have recently established a link between TBX3 mutations and delayed puberty onset, we systematically studied Tbx3-derived neuronal lineage and Tbx3-dependent neuronal specification and found that Tbx3 hierarchically established and maintained the identity of KNDy neurons for triggering puberty. Apart from the well-established lineage-dependent fate determination, we uncovered rules of interlineage interaction and intralineage retention operating through neuronal differentiation in the absence of Tbx3. Moreover, we revealed that human TBX3 mutations disturbed the phase separation of encoded proteins and impaired transcriptional regulation of key neuropeptides, providing a pathological mechanism underlying TBX3-associated puberty disorders.

Cascade diversification directs generation of neuronal diversity in the hypothalamus.

The hypothalamus contains an astounding heterogeneity of neurons that regulate endocrine, autonomic, and behavioral functions. However, its molecular developmental trajectory and origin of neuronal diversity remain unclear. Here, we profile the transcriptome of 43,261 cells derived from Rax+ hypothalamic neuroepithelium to map the developmental landscape of the mouse hypothalamus and trajectory of radial glial cells (RGCs), intermediate progenitor cells (IPCs), nascent neurons, and peptidergic neurons. We show that RGCs adopt a conserved strategy for multipotential differentiation but generate Ascl1+ and Neurog2+ IPCs. Ascl1+ IPCs differ from their telencephalic counterpart by displaying fate bifurcation, and postmitotic nascent neurons resolve into multiple peptidergic neuronal subtypes. Clonal analysis further demonstrates that single RGCs can produce multiple neuronal subtypes. Our study reveals that multiple cell types along the lineage hierarchy contribute to fate diversification of hypothalamic neurons in a stepwise fashion, suggesting a cascade diversification model that deconstructs the origin of neuronal diversity.

Effect of methylprednisolone in severe and critical COVID-19: Analysis of 102 cases.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has brought great challenges to public health. Aggravation of COVID-19 is closely related to the secondary systemic inflammatory response. Glucocorticoids are used to control severe diseases caused by the cytokine storm, owing to their anti-inflammatory effects. However, glucocorticoids are a double-edged sword, as the use of large doses has the potential risk of secondary infection and long-term serious complications, and may prolong virus clearance time. Nonetheless, the risks and benefits of glucocorticoid adjuvant therapy for COVID-19 are inconclusive. AIM: To determine the effect of methylprednisolone in severe and critically ill patients with COVID-19. METHODS: This single-center retrospective study included 102 adult COVID-19 patients admitted to a ward of a designated hospital in Wuhan, Hubei Province from January to March 2020. All patients received general symptomatic treatment and organ function support, and were given different respiratory support measures according to their conditions. In case of deterioration, considering the hyperinflammatory state of the patients, methylprednisolone was intravenously administered at 0.75-1.5 mg/kg/d, usually for less than 14 d. Patient vital signs and oxygenation were closely monitored, in combination with imaging and routine blood tests such as C-reactive protein, biochemical indicators (liver and kidney function, myocardial enzymes, electrolytes, etc.), and coagulation function. Patient clinical outcomes were discharge or death. RESULTS: A total of 102 severe and critically ill COVID-19 patients were included in this study. They were divided into treatment (69, 67.6%) and control groups (33, 32.4%) according to methylprednisolone use. Comparison of baseline data between the two groups showed that the treatment group patients had higher aspartic acid aminotransferase, globulin, hydroxybutyrate dehydrogenase, and lactate dehydrogenase. There was no significant difference in other baseline data between the two groups. With regard to prognosis, 29 (78.4%) patients in the treatment group died as opposed to 40 (61.5%) in the control group. The mortality was higher in the treatment group than in the control group; however, according to the log-rank test and the Kaplan-Meier survival curve, the difference in mortality between both groups was insignificant (P = 0.655). The COX regression equation was used to correct the variables with differences, and the results showed that methylprednisolone treatment did not improve prognosis. CONCLUSION: Methylprednisolone treatment does not improve prognosis in severe and critical COVID-19 patients.

Predictive value of serum cystatin C for risk of mortality in severe and critically ill patients with COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. COVID-19 is clinically categorized into mild, moderate, severe, and critical illness. Acute kidney injury is an independent risk factor for poor prognosis in patients with. Serum cystatin C (sCys C) is considered a more sensitive biomarker for early renal insufficiency than conventional indicators of renal function. Early detection of risk factors that affect the prognosis of severe and critically ill patients while using active and effective treatment measures is very important and can effectively reduce the potential mortality rate. AIM: To determine the predictive value of sCys C for the prognosis of patients with COVID-19. METHODS: The clinical data of 101 severe and critically ill patients with COVID-19 at a designated hospital in Wuhan, Hubei Province, China were analyzed retrospectively. According to the clinical outcome, the patients were divided into a discharge group (64 cases) and a death group (37 cases). The general information, underlying diseases, and laboratory examination indexes of the two groups were compared. Multivariate Cox regression was used to explore the relationship between sCys C and prognosis. The receiver operating characteristic (ROC) curve was used to demonstrate the sensitivity and specificity of sCys C and its optimal cut-off value for predicting death. RESULTS: There were significant differences in age, sCys C, creatinine, C-reactive protein, serum albumin, creatine kinase-MB, alkaline phosphatase, lactate dehydrogenase, neutrophil count, and lymphocyte count between the two groups (P < 0.001). Multivariate logistic regression analysis showed that sCys C was an independent risk factor for death in patients with COVID-19 (Odds ratio = 1.812, 95% confidence interval [CI]: 1.300-2.527, P < 0.001). The area under the ROC curve was 0.755 (95%CI: 1.300-2.527), the cut-off value was 0.80, the specificity was 0.562, and the sensitivity was 0.865. CONCLUSION: sCys C is an independent risk factor for death in patients with COVID-19. Patients with a sCys C level of 0.80 mg/L or greater are at a high risk of death.

Frailty and Rejuvenation with Stem Cells: Therapeutic Opportunities and Clinical Challenges.

Frailty, one appealing target for improving successful aging of the elderly population, is a common clinical syndrome based on the accumulation of multisystemic function declines and the increase in susceptibility to stressors during biological aging. The age-dependent senescence, the frailty-related stem cell depletion, chronic inflammation, imbalance of immune homeostasis, and the reduction of multipotent stem cells collectively suggest the rational hypothesis that it is possible to (partially) cure frailty with stem cells. This systematic review has included all of the human trials of stem cell therapy for frailty from the main electronic databases and printed materials and screened the closely related reviews themed on the mechanisms of aging, frailty, and stem cells, to provide more insights in stem cell strategies for frailty, one promising method to recover health from a frail status. To date, a total of four trials about this subject have been registered on clinicaltrials.gov. The use of mesenchymal stem cells (MSCs), doses of 100 million cells, single peripheral intravenous infusion, follow-up periods of 6-12 months, and a focus primarily on safety and secondarily on efficacy are common characteristics of these studies. We conclude that intravenous infusion of allogenic MSCs is safe, well tolerated, and preliminarily effective clinically. More preclinical experiments and clinical trials are warranted to precisely elucidate the mechanism, safety, and efficacy of frailty stem cell therapy.