Chronic exercise improves renal AT1 and ETB receptor functions via modulating GRK4 expression in obese Zucker rats.

BACKGROUND: Physical activity has profound benefits on health, especially in patients with cardiovascular and metabolic disease. Exercise training can reduce oxidative stress, improve renal function, and thus lower blood pressure. However, the effect of exercise training on angiotensin II type 1 receptors (AT1R) and endothelin subtype B receptors (ETBR)-mediated diuresis and natriuresis in obese Zucker rats is unclear. METHODS: Lean and obese Zucker rats were exercised or placed on a nonmoving treadmill for 8 weeks. Blood pressure was measured by tail-cuff plethysmography, and functions of AT1R and ETBR in the kidney were measured by natriuresis, respectively. RESULTS: Our data showed that exercise training improved glucose and lipid metabolism, renal function and sodium excretion in obese Zucker rats, accompanied by decreased oxidative stress and GRK4 expression in obese Zucker rats. Moreover, exercise training reduced the Candesartan-induced an increase in diuresis and natriuresis and increased ETBR agonists (BQ3020)-mediated diuresis and natriuresis in obese Zucker rats, which were associated with decreased renal AT1R expression and ETBR phosphorylation levels. CONCLUSIONS: The results demonstrate that exercise training lowers blood pressure via improving renal AT1R and ETBR function through modulating GRK4 expression in Obese Zucker Rats and provides potentially effective targets for obesity-related hypertension.

Characterization and phylogenetic analysis of the complete chloroplast genome of Asterothamnus centraliasiaticus Novopokr. (Asteraceae: Asterothamnus).

Asterothamnus centraliasiaticus Novopokr., a species of perennial deciduous semi-shrub within the family Asteraceae, has excellent medical, economic, ecological and genetic value. In this study, the chloroplast genome of A. centraliasiaticus was first assembled using Illumina HiSeq2500 sequences. The results indicate that the complete cp genome of A. centraliasiaticus is 152,205 bp in length, and comprises a pair of inverted repeat (IR) regions of 25,031 bp each, a large single-copy (LSC) region of 83,956 bp and a small single-copy (SSC) region of 18,187 bp. The GC content of A. centraliasiaticus is 37.3%. A total of 130 genes were successfully annotated containing 85 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes. The maximum likelihood (ML) phylogenetic analysis based on the complete chloroplast genome data highly supported that A. centraliasiaticus was close to Aster lavandulifolius. These results will provide significant genetic information for the germplasm protection and reasonable development.

The m6A demethylase FTO targets POLQ to promote ccRCC cell proliferation and genome stability maintenance.

BACKGROUND AND AIM: As the first identified m6A demethylase, FTO has been implicated in the progression of various cancers. However, the specific mechanism of FTO in clear cell renal cell carcinoma (ccRCC) remains incompletely understood. In this study, we aimed to explore the potential molecular mechanisms influencing the progression of ccRCC. METHODS: We initially assessed the expression of FTO in tumor and adjacent tissues using TCGA database, RT-qPCR, and Western blot. We then conducted CCK-8, cell cycle analysis, and colony formation assay to investigate the impact of FTO on ccRCC cell proliferation. MeRIP-seq and RNA-seq were employed to identify potential downstream targets of FTO in ccRCC, and these findings were further validated through dual-luciferase reporter assays and MeRIP-qPCR. Then, DNA damage and cell death were assessed separately through gammaH2AX immunofluorescence detection and the LIVE/DEAD Fixable Dead Cell Stain assay, respectively. Subsequently, we identified downstream pathways influenced by FTO's regulation of POLQ through TCGA database analysis and GSEA enrichment analysis. Validation was carried out through Western blot. RESULTS: FTO is highly expressed in ccRCC tissues and cell lines. Furthermore, ROC curve demonstrates that FTO contributes to the diagnosis of ccRCC. FTO modulates m6A modification, consequently influencing the expression of POLQ, thus facilitating cell proliferation and maintaining genome stability in ccRCC. CONCLUSION: FTO could potentially serve as a diagnostic marker for ccRCC. FTO promotes the progression of ccRCC by regulating m6A modification, making the inhibition of FTO a potential novel therapeutic strategy in ccRCC.

Geographical patterns and environmental influencing factors of variations in Asterothamnus centraliasiaticus seed traits on Qinghai-Tibetan plateau.

Introduction: Seed traits related to recruitment directly affect plant fitness and persistence. Understanding the key patterns and influencing factors of seed trait variations is conducive to assessing plant colonization and habitat selection. However, the variation patterns of the critical seed traits of shrub species are usually underrepresented and disregarded despite their vital role in alpine desert ecosystems. Methods: This study gathered seeds from 21 Asterothamnus centraliasiaticus populations across the Qinghai-Tibetan Plateau, analyzing geographical patterns of seed traits to identify external environmental influences. Additionally, it explored how seed morphology and nutrients affect germination stress tolerance, elucidating direct and indirect factors shaping seed trait variations. Results: The results present substantial intraspecific variations in the seed traits of A. centraliasiaticus. Seed traits except seed length-to-width ratio (LWR) all vary significantly with geographic gradients. In addition, the direct and indirect effects of climatic variables and soil nutrients on seed traits were verified in this study. Climate mainly influences seed nutrients, and soil nutrients significantly affect seed morphology and seed nutrients. Furthermore, climate directly impacts seed germination drought tolerance index (GDTI) and germination saline-alkali tolerance index (GSTI). Seed germination cold tolerance index (GCTI) is influenced by climate and soil nutrients (mostly SOC). GDTI and GSTI are prominently influenced by seed morphology (largely the seed thousand-grain weight (TGW)), and GCTI is evidently affected by seed nutrients (mainly the content of soluble protein (CSP)). Discussion: The findings of this study amply explain seed trait variation patterns of shrubs in alpine desert ecosystems, possessing significant importance for understanding the mechanism of shrub adaptation to alpine desert ecosystems, predicting the outcomes of environmental change, and informing conservation efforts. This study can be a valuable reference for managing alpine desert ecosystems on the Qinghai-Tibetan Plateau.

A case of POEMS syndrome comprising of a complicated diagnostic procedure: Case report.

RATIONALE: This article presents the case of a patient with recurrent chronic diarrhea and cachexia who was misdiagnosed, followed by a literature review to summarize the reasons for misdiagnosis of POEMS syndrome and the treatment strategies. PATIENT CONCERNS: The diagnosis and treatment of this patient suggest that with the improvement of M-protein detection levels, the diagnosis of patients with low M-protein levels, such as those with POEMS syndrome, has been greatly aided. DIAGNOSES: POEMS syndrome requires polyneuropathy and monoclonal plasma cell proliferation as mandatory diagnostic criteria. Therefore, patients presenting with polyneuropathy should routinely undergo M-protein testing and consider the possibility of POEMS syndrome. INTERVENTIONS: The patient, in this case, was treated primarily with relatively conservative immunomodulatory agents. OUTCOMES: During follow-up after treatment, the patient's diarrhea and malnutrition showed significant improvement. LESSONS SUBSECTIONS: POEMS syndrome has low clinical specificity and a high rate of misdiagnosis. However, once a definitive diagnosis is made, the treatment outcome is favorable.

The optimized Maxent model reveals the pattern of distribution and changes in the suitable cultivation areas for Reaumuria songarica being driven by climate change.

Reaumuria songarica, a drought-resistant shrub, is widely distributed and plays a crucial role in the northern deserts of China. It is a key species for desert rehabilitation and afforestation efforts. Using the Maxent model to predict suitable planting areas for R. songarica is an important strategy for combating desertification. With 184 occurrence points of R. songarica and 13 environmental variables, the optimized Maxent model has identified the main limiting factors for its distribution. Distribution patterns and variation trends of R. songarica were projected for current and future climates (2030s, 2050s, 2070s, and 2090s) and different scenarios (ssp_126, ssp_370, and ssp_585). Results show that setting parameters to RM (regulation multiplier) = 4 and FC (feature combination) = LQHPT yields a model with good accuracy and high reliability. Currently, R. songarica is primarily suitable for desert control in eight provinces and autonomous regions, including Inner Mongolia, Xinjiang, Qinghai, and Ningxia. The total suitable planting area is 148.80 × 104 km2, representing 15.45% of China's land area. Precipitation (Precipitation of the wettest month, Precipitation of the warmest quarter, and Annual precipitation) and Ultraviolet-B seasonality are the primary environmental factors limiting the growth and distribution of R. songarica. Mean temperature of the warmest quarter is the primary factor driving changes in the distribution of suitable areas for R. songarica under future climate scenarios. In future climate scenarios, the suitable planting area of R. songarica will shrink, and the distribution center will shift towards higher latitude, potentially indicate further desertification. The area of highly suitable habitat has increased, while moderately and less suitable habitat areas have decreased. Increased precipitation within R. songarica's water tolerance range is favorable for its growth and reproduction. With changes in the suitable cultivation area for R. songarica, priority should be given to exploring and utilizing its germplasm resources. Introduction and cultivation can be conducted in expanding regions, while scientifically effective measures should be implemented to protect germplasm resources in contracting regions. The findings of this study provide a theoretical basis for addressing desertification resulting from climate change and offer practical insights for the development, utilization, introduction, and cultivation of R. songarica germplasm resources.

METTL3 facilitates renal cell carcinoma progression by PLOD2 m6A-methylation under prolonged hypoxia.

N6-methyladenosine (m6A) is the most prevalent reversible modification in eukaryotic mRNA, and it plays a critical role in tumor progression. The purpose of this study was to investigate the function and regulatory mechanisms of the methyltransferase METTL3 in renal cell carcinoma (RCC). METTL3 expression was upregulated and predicted a poor prognosis in patients with advanced RCC. METTL3 facilitated the proliferation, migration, and invasion of RCC cells, depending on its methylase activity. METTL3 positively regulated the expression of PLOD2, and both genes were triggered under prolonged hypoxia. Mechanistically, hypoxia-induced the binding of HIF-1α to the METTL3 promoter, which enhanced its transcriptional activity. METTL3-mediated m6A modifications of PLOD2 mRNA at 3'UTR region, promoting the translation of PLOD2 protein. Furthermore, silencing METTL3 impaired RCC progression in vitro. In vivo, administration of highly potent and selective METTL3 inhibitor STM2457 showed anti-tumor effects, whereas AAV9-mediated re-transduction of PLOD2 largely abolished the above phenomenon in a subcutaneous mouse model. These findings reveal that hypoxia and HIF-driven METTL3 transcription promote RCC progression by increasing PLOD2 expression in an m6A-dependent manner, suggesting that METTL3 may serve as a novel pharmaceutical intervention for RCC.