NLRC3 deficiency promotes hypoxia-induced pulmonary hypertension development via IKK/NF-κB p65/HIF-1α pathway.

Hypoxia-induced pulmonary hypertension is a subgroup of type 3 pulmonary hypertension (PH) with the recommended treatment limited to oxygen therapy and lacks potential therapeutic targets. To investigate the role of NLRC3 in hypoxia-induced PH and its potential mechanism, we first collected lung tissues of high-altitude pulmonary hypertension (HAPH) patients. Immunohistochemistry and immunofluorescence showed that NLRC3 was downregulated and was mainly co-localized with the smooth muscle cells of the pulmonary vessels in HAPH patients. Besides, we found that NLRC3 was also expressed in endothelial cells in HAPH patients for the first time. Then, wild type (WT) and NLRC3 knockout (NLRC3-/-) mice were used to construct hypoxia models and primary pulmonary arterial smooth muscle cells (PASMCs) of rats and endothelial cells were cultured for verification. Right heart catheterization and echocardiography suggested that NLRC3 knockout promoted right ventricular systolic pressure (RVSP) up-regulation, right ventricular hypertrophy and fibrosis in hypoxia-induced mice. This study first demonstrated that NLRC3 deficiency promoted hypoxia-stimulated PASMCs proliferation, Human umbilical vein endothelial cells (HUVECs) apoptosis, migration and inflammation through IKK/NF-κB p65/HIF-1α pathway in vitro and in vivo, further promoted vascular remodeling and PH progression, which provided a new target for the treatment of hypoxia-induced PH.

Seasonal variations in water flux compositions controlled by leaf development: isotopic insights at the canopy-atmosphere interface.

Water-stable isotopes provide a valuable tool for tracing plant-water interactions, particularly evapotranspiration (ET) partitioning and leaf water dynamics at the plant-atmosphere interface. However, process-based investigations of plant/leaf development and the associated isotopic dynamics of water fluxes involving isotope enrichment at plant-atmosphere interfaces at the ecosystem scale remain challenging. In this study, in situ isotopic measurements and tracer-aided models were used to study the dynamic interactions between vegetation growth and the isotopic dynamics of water fluxes (ET, soil evaporation, and transpiration) involving isotope enrichment in canopy leaves in a multispecies grassland ecosystem. The day-to-day variations in the isotopic compositions of ET flux were mainly controlled by plant growth, which could be explained by the significant logarithmic relationship determined between the leaf area index and transpiration fraction. Leaf development promoted a significant increase in the isotopic composition of ET and led to a slight decrease in the isotopic composition of water in canopy leaves. The transpiration (evaporation) isoflux acted to increase (decrease) the δ18O of water vapor, and the total isoflux impacts depended on the seasonal tradeoffs between transpiration and evaporation. The isotopic evidence in ET fluxes demonstrates the biotic controls on day-to-day variations in water/energy flux partitioning through transpiration activity. This study emphasizes that stable isotopes of hydrogen and oxygen are effective tools for quantitative evaluations of the hydrological component partitioning of ecosystems and plant-climate interactions.

Weight Loss Using an mHealth App Among Individuals With Obesity in Different Economic Regions of China: Cohort Study.

Background: With the increasing prevalence of obesity, weight loss has become a critical issue in China. Self-managed weight loss through a mobile health (mHealth) app may be a prospective method. However, its practicability in different economic regions of China is unknown. Objective: This study aims to evaluate the effectiveness of self-managed weight loss through an mHealth app among individuals with obesity in different economic regions of China and to demonstrate the feasibility of online self-management for weight loss. Methods: A total of 165,635 Chinese adults who signed up for the mHealth app were included to analyze the body composition characteristics of individuals from different economic regions by χ2 analyses. Furthermore, 2 types of participants with obesity using mHealth monitoring, including 74,611 participants with a BMI ≥24.0 kg/m2 and 22,903 participants with a normal BMI but an excessive percentage of body fat (PBF), were followed for 6 months to explore the weight loss and fat loss effects in different economic regions of China and to find independent predictors associated with weight loss success by 2-tailed Student t test and multivariable logistic regression analysis. Results: There were 32,129 users from low-income regions and 133,506 users from high-income regions. The proportion of users with obesity in low-income regions was higher than in high-income regions, both based on BMI (15,378/32,129, 47.9% vs 59,233/133,506, 44.4%; P<.001) and PBF classification (19,146/32,129, 59.6% vs 72,033/133,506, 54%; P<.001). Follow-up analyses showed that the weight loss effect among participants with overweight or obesity in low-income regions was greater than in high-income regions (mean -4.93, SD 6.41 vs mean -4.71, SD 6.14 kg; P<.001), while there was no significant difference in fat loss (mean -2.06%, SD 3.14% vs mean -2.04%, SD 3.19%; P=.54). In the population with normal-weight obesity, the weight loss (mean -2.42, SD 4.07 vs mean -2.23, SD 4.21 kg; P=.004) and fat loss effects (mean -1.43%, SD 2.73% vs mean -1.27%, SD 2.63%; P<.001) were stronger in high-income regions than in low-income regions. In addition, multivariable logistic regression analyses showed that age, baseline PBF, skeletal muscle rate, and measurement frequency were related to weight loss, whereas gender and baseline body metabolic rate only showed a correlation with weight loss in the population in high-income regions. Conclusions: This study found a high proportion of mHealth app users with obesity in low-income regions. Individuals with overweight and obesity in different economic regions of China experienced significant weight loss and fat loss using an mHealth app. Moreover, individuals in high-income regions paid more attention to body fat and had better fat reduction effects. Therefore, promoting self-monitoring of weight and PBF through an mHealth app could be an important intervention that could be implemented across all regions of China.

Endothelial TET2 regulates the white adipose browning and metabolism via fatty acid oxidation in obesity.

Obesity is a complex metabolic disorder, manifesting as excessive accumulation of body fat. Ten-Eleven Translocation-2 (TET2) has garnered significant attention in the context of obesity due to its crucial role in epigenetic regulation and metabolic homeostasis. In this study, we aimed to investigate the effect of endothelial TET2 on obesity and explore the potential mechanism. We generated endothelial cell-specific TET2 deficiency mice and investigated endothelial TET2 using transcriptomic and epigenomic analyses. We determined the downregulation of endothelial TET2 in white adipose tissues. Furthermore, we identified that endothelial TET2 loss aggravated high-fat diet-induced obesity by inhibiting vascularization and thus suppressing white adipose tissue browning. Mechanistically, endothelial TET2 modulates obesity by engaging in endothelial fatty acid oxidation and angiocrine-mediated secretion of bone morphogenetic protein 4 (BMP4), in which nuclear factor-erythroid 2-related factor 2 (NRF2) serves as a key mediator. Our study reveals that endothelial TET2 regulates white adipose tissue browning by interacting with NRF2 to facilitate fatty acid oxidation and lipolysis in adipocytes.

Self-managed weight loss by smart body fat scales ameliorates obesity-related body composition during the COVID-19 pandemic: A follow-up study in Chinese population.

Background: Since 2020, longer stay-at-home time in response to the coronavirus disease 2019 (COVID-19) pandemic has changed the weight-related behaviors of Chinese population. Objectives: To explore the demographic and basic characteristics of body fat scale users and to investigate the changes in obesity-related body composition of overweight and obese users during COVID-19. Further, we analyzed the factors associated with successful weight loss and improved body composition changes in overweight and obese people. Methods: The study included 107,419 Chinese adults registered in the smart app connecting to the body fat scale in 2020 to describe the demographic characteristics of body fat scale users by Unpaired Student's t-test and Chi-Square test. Subsequently, overweight and obese participants with body mass index (BMI) of more than 24 kg/m2 were screened to investigate the independent factors associated with effective weight loss and improved body composition changes by multivariable logistic regression analyses. Results: During the pandemic, the number of body fat scale users increased markedly compared with pre-pandemic. Over half of the participants were women and with normal baseline BMI. Based on BMI classification, multivariable logistic regressions showed that age, gender, measurement frequency classification, baseline BMI, visceral adipose index and skeletal muscle rate were associated with weight loss and fat loss in the overweight and obese population, with the high-frequency measurement being the most important factor for effective weight and fat loss. In the population with normal BMI obesity, younger age was the most significant factor for effective fat loss. Conclusion: During the COVID-19 pandemic, participation in self-monitored weight loss increased markedly compared with pre-pandemic, and women accounted for the majority. We found that many overweight and obese participants achieved weight loss goals by smart body fat scales, and the effectiveness of weight and fat loss was greater in obese participants than in overweight participants, both based on BMI and PBF classification. In addition, promoting the usage of smart body fat scales could contribute to more effective weight and fat loss in the overweight and obese population based on BMI classification. However, in the population with normal BMI obesity, young subjects might be easier to successfully lose fat compared with the elder. Digital self-management by smart body fat scales could become a promising approach for the obese population with high BMI to lose weight and keep healthy.

Stable carbon isotope as a signal index for monitoring grassland degradation.

Grassland degradation due to overgrazing is common in many areas of the world. This study analyzed the potential of the stable carbon isotope (δ(13)C) value as a structural microcosmic index to monitor processes of grassland degradation. The δ(13)C values of plant leaves, roots and soils in non-grazed (NG) and over-grazed (OG) grassland were measured from samples collected from the seven types of grassland in China. We found that the leaf δ(13)C values of palatable species (δ(13)Cleaf) and root δ(13)C values (δ(13)Croot) in OG grasslands were reduced compared with those from NG grasslands. Furthermore, the δ(13)Cleaf and δ(13)Csoil were positive correlation with elevation and latitude, δ(13)Croot was negative correlation with them at high altitude (3000~5000m), and δ(13)Croot and δ(13)Csoil were negative correlation with them at low altitude (0~2000m), respectively. Consequently, tracing of the δ(13)C variations in grassland ecosystem can provide a powerful tool to evaluate the degree of grassland degradation.