Significance Thin endometrium is the most common reason for uterine infertility and refractory gynecological diseases due to its complexity in pathogenesis and adverse pregnancy outcomes. Here, we profile cells from normal and thin endometrium at single-cell resolution to investigate the sophisticated alterations in the local microenvironment that occur in thin endometrium. Increased cellular senescence, collagen overdeposition, and significant down-regulation of gene expression related to cell proliferation are observed and confirmed. Moreover, we demonstrate aberrant activation of the SEMA3 pathway accompanied by dampened EGF, PTN, and TWEAK signaling pathways in thin endometrium. These findings aid in understanding the mechanisms of thin endometrium and provide new tools to rejuvenate the atrophic endometrium for female fertility preservation and successful pregnancy.
Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine adhesions (IUAs). Since ΔNp63α is profoundly involved in maintaining the epithelial homeostasis, we hereby focused on its roles in regulating the function and phenotype of endometrial epithelial cells (EECs) in context of endometrial fibrosis. We identified a typical type 2 epithelial-to-mesenchymal transition (EMT) in EECs from IUA patients and this process was induced by the forced expression of ΔNp63α in EECs. In transcriptomic analysis, we found that diverse signaling pathways regulated by ΔNp63α were involved in pro-EMT. We demonstrated that the DUSP4/GSK-3β/SNAI1 pathway was critical in transducing the pro-EMT signals initiated by ΔNp63α, while bFGF reversed ΔNp63α-induced EMT and endometrial fibrosis both in vitro and in vivo by blocking DUSP4/GSK3β/SNAI1 pathway. Taken together, our findings are important to understand the molecular mechanisms of endometrial fibrosis and to provide potential therapeutic targets.
A four-season experiment was carried out in the North China Plain (NCP) to evaluate crop yield and water productivity of winter wheat (Triticum aestivum L.) under sprinkler and surface irrigation. Results show that leaf area index (LAI) of winter wheat was greater and active leaf area lasted for longer in the sprinkler than in the surface irrigated field. Above-ground biomass at harvest was 4~22.1% greater in the sprinkler than in the surface irrigated field, similarly the yield was greater by 11.5~50.9%. The greater yield was mainly due to the greater weight of 1000 kernels in the sprinkler irrigated field. Seasonal crop evapotranspiration (ET) was lower by 4~23%, water productivity (WP) was higher by 18~57% and irrigation water productivity (IWP) was higher by 21~81% in the sprinkler field than in the surface irrigated field. Statistical analysis of four-season data by using a generalized linear model showed that the sprinkler irrigation method significantly increased crop yield, WP and IWP, and significantly decreased crop ET. Crop WP and IWP were also significantly affected by climate conditions and agronomic practices. Therefore, the sprinkler irrigation method was recommended as an efficient and water-saving irrigation method for winter wheat cultivars in the North China Plain. RÉSUMÉUne expérimentation de quatre ans a été réalisée dans la plaine du Nord en Chine pour évaluer le rendement et la productivité de l'eau du blé d'hiver (Triticum aestivum L.) irrigués en gravitaire ou par aspersion. Les résultats d'indice de surface foliaire (LAI) du blé d'hiver montrent que la surface foliaire active est plus importante et dure plus longtemps dans le cas d'irrigation par aspersion. La biomasse aérienne à la récolte était de 4 à 22,1% plus grande dans le cas de l'arrosage par aspersion, de même que le rendement était supérieur de 11,5 à 50,9%. Le meilleur rendement est principalement attribuable à la plus grande fois de 1000 grains. L'évapotranspiration saisonnière (ET) était inférieure de 4 à 23%, la productivité de l'eau (WP) était plus élevée de 18 à 57% et la productivité de l'eau d'irrigation (PTI) a été supérieure de 21 à 81% dans le cas de l'irrigation par aspersion. L'analyse statistique des données des quatre années en utilisant le modèle linéaire généralisé a montré que la méthode d'irrigation par aspersion a augmenté de façon significative le rendement des cultures, WP et IWP, ainsi qu'une diminuation significative d'évaporation des cultures. WP et IWP ont également été significativement affectés par les conditions climatiques et les pratiques agronomiques. Par conséquent, la méthode de l'irrigation par aspersion a été recommandée comme une méthode d'irrigation efficace et d'économie d'eau pour les cultivars de blé d'hiver dans la plaine de Chine du Nord.
Background Frailty increases the adverse outcomes of clinical heart failure; however, the relationship between frailty and stage-B heart failure (SBHF) remains unknown. We aimed to explore the epidemiology and predictive value of frailty in older adults with SBHF. Methods A prospective cohort of SBHF inpatients aged 65 years or older who were hospitalized between September 2018 and February 2019 and were followed up for 6 months were included. SBHF was defined as systolic abnormality, structural abnormality (left ventricular enlargement, left ventricular hypertrophy, wall motion abnormalities, valvular heart disease), or prior myocardial infarction. Frailty was assessed by the Fried frailty phenotype. Multivariable Cox proportional hazards regression was used to explore the independent risk and prognostic factors. Results Data of 443 participants (age: 76.1 ± 6.79 years, LVEF: 62.8 ± 4.92%, men: 225 [50.8%], frailty: 109 [24.6%]) were analyzed. During the 6-month follow-up, 83 (18.7%) older SBHF inpatients experienced all-cause mortality or readmission, and 29 (6.5%) of them developed clinical HF. Frail individuals had a 1.78–fold (95%CI: 1.02–3.10, P = 0.041) higher risk of 6-month mortality or readmission and a 2.83–fold (95%CI 1.24–6.47, P = 0.014) higher risk of developing clinical HF, independent of age, sex, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide level. Conclusions Frailty is common in older SBHF inpatients and should be considered to help identify individuals with an increased risk of mortality or readmission, and developing clinical HF. Trial registration ChiCTR1800017204.
Objective: Our study aimed to explore the association between trimethylamine N-oxide and frailty in older adults with cardiovascular disease. Patients and Methods: This cross-sectional study analyzed a total of 451 people aged 65 years or older who underwent comprehensive geriatric assessments. Frailty status was determined using a frailty index constructed with 48 variables according to the cumulative deficits model. Physical frailty and cognitive frailty were also assessed in detail. Fasting plasma TMAO was measured by mass spectrometry. Results: The proportion of frail subjects was 29.9% (135/451). Plasma TMAO levels were significantly higher in frail patients than in nonfrail individuals (4.04 [2.84-7.01] vs 3.21 [2.13-5.03] µM; p<0.001). Elevated plasma TMAO levels were independently associated with the likelihood of frailty (OR 2.12, 95% CI 1.01-4.38, p=0.046). Dose-response analysis revealed a linear association between the TMAO concentration and the OR for frailty. A 2-unit increase in TMAO was independently correlated with physical frailty (OR 1.23, 95% CI 1.08-1.41, p for trend 0.002) and cognitive frailty (OR 1.21, 95% CI 1.01-1.45, p for trend 0.04). Conclusion: Elevated circulating TMAO levels are independently associated with frailty among older adults with cardiovascular disease.
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