Serum klotho as a novel biomarker for metabolic syndrome: findings from a large national cohort

BackgroundMetabolic syndrome is a cluster of metabolic abnormalities that significantly increase the risk of cardiovascular disease and mortality. The identification of novel biomarkers associated with mortality in patients with metabolic syndrome could facilitate early risk stratification and targeted interventions.MethodsWe conducted a large prospective cohort study using data from five cycles (2009-2016) of the National Health and Nutrition Examination Survey (NHANES) database, including a total of 40,439 participants. Logistic regression analysis was used to assess the association between serum klotho protein levels and metabolic syndrome, while Cox regression analysis was employed to examine the correlation between serum klotho levels and all-cause mortality. Mortality data were updated until December 31, 2019.ResultsAfter adjusting for demographic and socioeconomic confounders, the logistic regression model demonstrated that higher serum klotho levels were significantly associated with a decreased prevalence of metabolic syndrome (OR [95% CI] Highest vs. lowest quartile: 0.84 [0.70-0.99], P=0.038). In the Cox regression model, elevated klotho levels were found to significantly reduce the risk of all-cause mortality among individuals with metabolic syndrome (HR [95% CI] Highest vs. lowest quartile: 0.68 [0.51-0.90], P=0.006).ConclusionSerum klotho levels were found to be inversely associated with the prevalence of metabolic syndrome, independent of potential confounding factors such as demographics, socioeconomic status, and lifestyle factors. Furthermore, higher klotho levels strongly indicated a lower risk of all-cause mortality in individuals with metabolic syndrome

Ignored Opinions: Villager-Satisfaction-Based Evaluation Method of Tourism Village Development—A Case Study of Two Villages in China

The neglect of endogenous strength is one of the reasons for the lack of sustainability in mountainous rural development and tourism development in China at present. How to incorporate the opinions of villagers in the tourism development process led by the government and other external entities is the main focus of this article. Based on the fieldwork of two typical mountainous villages and a previous rural development evaluation method, this article proposes the villager-satisfaction-based evaluation method for tourism village development, covering rural settlement construction, village esthetics, and economic and social development. “Villager satisfaction” is a crucial indicator obtained by objectifying the subjective opinions of villagers. Finally, the evaluation method was applied in the form of a questionnaire in two villages. The experimental results are correlated with the tourism development patterns of the two villages, verifying the feasibility and effectiveness of the evaluation method. It is expected that this evaluation method will become an effective communication medium between non-professional villagers and the professional tourism development process, thereby promoting the sustainable development of rural areas in the future

Association between the CASC16 rs4784227 polymorphism and breast cancer risk and prognosis in a northeast Chinese Han population

Background Breast cancer (BC) poses a serious threat to women worldwide. This research was designed to explore the association between the rs4784227 polymorphism of cancer susceptibility candidate gene 16 (CASC16) and BC susceptibility and prognosis, aiming to provide further information for the early detection of BC and to accelerate comprehensive cancer management. Methods A total of 1,733 subjects were recruited for this case-control study, of which 828 are BC patients and 905 are healthy individuals. The relevance between SNP rs4784227 and BC risk in diverse genetic models was analyzed by using the SNPStats analysis program and was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) using the binary logistic regression model. Pearson’s χ2 test was used to determine the correlation between the polymorphism and clinical characteristics of BC patients. Additionally, univariate survival analysis was performed by the Kaplan-Meier method and log-rank test, and multivariate survival analysis was performed by Cox regression. Results SNP rs4784227 was significantly associated with susceptibility to BC in the dominant model (CT/TT versus CC, OR = 1.237, 95% CI = 1.012–1.513, P = 0.038). The minor allele of SNP rs4784227 was significantly linked to an increased risk of BC (OR = 1.197, 95% CI = 1.022–1.401, P = 0.026). In addition, the rs4784227 polymorphism of CASC16 was associated with perineural invasion (P = 0.030), menstrual status (P = 0.016) and histological grade (P = 0.001, P = 0.003, P = 0.025; respectively) of BC patients. There was no significant association between the genotypes of rs4784227 and disease-free survival (DFS) or overall survival (OS) of breast cancer patients (P > 0.05). Conclusions The rs4784227 polymorphism of CASC16 may affect susceptibility to breast cancer and is associated with perineural invasion, menstrual status and histological grade in BC patients. Additionally, our results could not confirm that this polymorphism was related to breast cancer prognosis

Image_1_Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level.tif

BackgroundGlioblastoma (GBM), with its high recurrence and mortality rates, makes it the deadliest neurological malignancy. Oxidative phosphorylation is a highly active cellular pathway in GBM, and NFYB is a tumor-associated transcription factor. Both are related to mitochondrial function, but studies on their relationship with GBM at the single-cell level are still scarce.MethodsWe re-analyzed the single-cell profiles of GBM from patients with different subtypes by single-cell transcriptomic analysis and further subdivided the large population of Glioma cells into different subpopulations, explored the interrelationships and active pathways among cell stages and clinical subtypes of the populations, and investigated the relationship between the transcription factor NFYB of the key subpopulations and GBM, searching for the prognostic genes of GBM related to NFYB, and verified by experiments.ResultsGlioma cells and their C5 subpopulation had the highest percentage of G2M staging and rGBM, which we hypothesized might be related to the higher dividing and proliferating ability of both Glioma and C5 subpopulations. Oxidative phosphorylation pathway activity is elevated in both the Glioma and C5 subgroup, and NFYB is a key transcription factor for the C5 subgroup, suggesting its possible involvement in GBM proliferation and recurrence, and its close association with mitochondrial function. We also identified 13 prognostic genes associated with NFYB, of which MEM60 may cause GBM patients to have a poor prognosis by promoting GBM proliferation and drug resistance. Knockdown of the NFYB was found to contribute to the inhibition of proliferation, invasion, and migration of GBM cells.ConclusionThese findings help to elucidate the key mechanisms of mitochondrial function in GBM progression and recurrence, and to establish a new prognostic model and therapeutic target based on NFYB.</p

Influence of ultrasonic vibration on percussion drilling performance for millisecond pulsed Nd:YAG laser

The ultrasonic vibration-assisted laser drilling is a recently emerging/growing new technique, especially in laser drilling. Differently from the previous work reported, this paper proposed to use the ultrasonic vibration (25 kHz) for assisting the millisecond pulsed Nd:YAG laser percussion drilling process to improve the drilling performance. Through comparing the drilled microholes without/using ultrasonic assistance, the influence of ultrasonic vibration on the drilled blind hole morphology/geometry, the hole wall surface roughness, the recast layer microstructure, and the hardness distribution of the heat affected zone for the drilled microhole was analyzed by altering laser pulse energy and/or laser pulse number. It was shown that the ultrasonic vibration incorporated into the laser drilling process might enhance the drilling efficiency in terms of the increase of hole depth and width. However, the drilled hole taper might be decreased via using ultrasonic assistance. Moreover, the ultrasonic vibration might clean the inner hole wall surface, and the microhole morphology/geometry could be improved through using ultrasonic assistance, resulting in a relatively clean and better-profiled hole wall with less defects and smaller taper due to the contribution of ultrasonic assistance. In addition, it was indicated that ultrasonic vibration might also improve the microhole heat affected zone hardness and reduce the inner hole wall surface roughness

A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1

Abstract Background Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, little is known about the mechanisms underlying the activation of this proto-oncogene in tumors. Results Immunohistochemical staining showed that FLI1 is aberrantly overexpressed in advanced stage and metastatic breast cancers. Using a CRISPR Cas9-guided immunoprecipitation assay, we identify a circular RNA in the FLI1 promoter chromatin complex, consisting of FLI1 exons 4-2-3, referred to as FECR1.Overexpression of FECR1 enhances invasiveness of MDA-MB231 breast cancer cells. Notably, FECR1 utilizes a positive feedback mechanism to activate FLI1 by inducing DNA hypomethylation in CpG islands of the promoter. FECR1 binds to the FLI1 promoter in cis and recruits TET1, a demethylase that is actively involved in DNA demethylation. FECR1 also binds to and downregulates in trans DNMT1, a methyltransferase that is essential for the maintenance of DNA methylation. Conclusions These data suggest that FECR1 circular RNA acts as an upstream regulator to control breast cancer tumor growth by coordinating the regulation of DNA methylating and demethylating enzymes. Thus, FLI1 drives tumor metastasis not only through the canonical oncoprotein pathway, but also by using epigenetic mechanisms mediated by its exonic circular RNA