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Socioeconomic status (SES) has been linked to mortality rates, with family income being a quantifiable marker of SES. However, the precise association between the family income-to-poverty ratio (PIR) and all-cause mortality in adults aged 40 and older remains unclear. A cross-sectional study was conducted using data from NHANES III, including 20,497 individuals. The PIR was used to assess financial status, and various demographic, lifestyle, and clinical factors were considered. Mortality data were collected from the NHANES III linked mortality file. The study revealed a non-linear association between PIR and all-cause mortality. The piecewise Cox proportional hazards regression model showed an inflection point at PIR 3.5. Below this threshold, the hazard ratio (HR) for all-cause mortality was 0.85 (95% CI 0.79–0.91), while above 3.5, the HR decreased to 0.66 (95% CI 0.57–0.76). Participants with lower income had a higher probability of all-cause mortality, with middle-income and high-income groups showing lower multivariate-adjusted HRs compared to the low-income group. This study provides evidence of a non-linear association between PIR and all-cause mortality in adults aged 40 and older, with an inflection point at PIR 3.5. These findings emphasize the importance of considering the non-linear relationship between family income and mortality when addressing socioeconomic health disparities. [ABSTRACT FROM AUTHOR]

Hypermethylation of CpG islands in the promoter region of tumor suppressor genes (TSGs) and their subsequent silencing is thought to be one of the main mechanisms of carcinogenesis. MBD2b enrichment coupled with a NimbleGen array was applied to examine the genome-wide CpG island methylation profile of hepatocellular carcinoma (HCC). Hypermethylated DNA of 58 pairs of HCC and adjacent tissue samples was enriched and hybridized in the same array. Aberrant hypermethylated peaks of HCC and adjacent tissues were screened and annotated after data processing using NimbleScan2.5 and our newly developed Weighting and Scoring (WAS) method, respectively. Validation using bisulfite sequencing of randomly selected ANKRD45, APC, CDX1, HOXD3, PTGER and TUBB6 genes demonstrated significant hypermethylation modification in HCC samples, consistent with the array data. [ABSTRACT FROM AUTHOR]

Eukaryotic elongation factor 1 alpha (eEF1A) is an essential component of the translational apparatus. In the present study, eEF1A1b was isolated from the Nile tilapia. Real-time PCR and Western blot revealed that eEF1A1b was expressed highly in the testis from 90 dah (days after hatching) onwards. In situ hybridization and immunohistochemistry analyses showed that eEF1A1b was highly expressed in the spermatogonia of the testis. CRISPR/Cas9 mediated mutation of eEF1A1b resulted in spermatogenesis arrest and infertility in the F0 XY fish. Consistently, heterozygous mutation of eEF1A1b (eEF1A1b+/−) resulted in an absence of spermatocytes at 90 dah, very few spermatocytes, spermatids and spermatozoa at 180 dah, and decreased Cyp11b2 and serum 11-ketotestosterone level at both stages. Further examination of the fertilization capacity of the sperm indicated that the eEF1A1b+/− XY fish were infertile due to abnormal spermiogenesis. Transcriptomic analyses of the eEF1A1b+/− testis from 180 dah XY fish revealed that key elements involved in spermatogenesis, steroidogenesis and sperm motility were significantly down-regulated compared with the control XY. Transgenic overexpression of eEF1A1b rescued the spermatogenesis arrest phenotype of the eEF1A1b+/− testis. Taken together, our data suggested that eEF1A1b is crucial for spermatogenesis and male fertility in the Nile tilapia. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) threw lights on heart failure treatment, however, parts of patients showed nonresponse to CRT. Unfortunately, it lacks effective parameters to predict CRT non-response. In present study, we try to seek effective electro-echocardiographic predictors on CRT non-response. This is a retrospective study to review a total of 227 patients of dyssynchronous heart failure underwent CRT implantation. Logistic analysis was performed between CRT responders and CRT non-responders. The primary outcome was the occurrence of improved left ventricular ejection fraction 1 year after CRT implantation. We concluded that LVEDV > 255 mL (OR = 2.236; 95% CI, 1.016-4.923) rather than LVESV > 160 mL (OR = 1.18; 95% CI, 0.544-2.56) and TpTe/QTc > 0.203 (OR = 5.206; 95% CI, 1.89-14.34) significantly predicted CRT non-response. Oppositely, S wave > 5.7 cm/s (OR = 0.242; 95% CI, 0.089-0.657), E/A > 1 (OR = 0.211; 95% CI, 0.079-0.566), E'/A' > 1 (OR = 0.054; 95% CI, 0.017-0.172), CLBBB (OR = 0.141; 95% CI, 0.048-0.409), and QRS duration >160 ms (OR = 0.52; 95% CI, 0.305-0.922) surprisingly predicted low-probability of CRT non-response. [ABSTRACT FROM AUTHOR]

Chronic obstructive sleep apnea (OSA) may promote the development of atrial fibrillation (AF) by inducing atrial electrical and structural remodeling as well as autonomic nerve hyperinnervation. Here, we investigated the roles of metoprolol in regulation of atrial remodeling induced by chronic OSA. A canine model of chronic OSA was established by stopping the ventilator and closing the airway for 4 h/day every other day for 12 weeks, while metoprolol (5 mg·kg-1·day-1) was continuously administered. Using that model, we observed that increases in sympathetic sprouting and atrial structural remodeling were sharply inhibited by metoprolol. Moreover, metoprolol dramatically inhibited the impairment of atrial energy metabolism by activating the Sirt1-AMPK pathway. In vitro, metoprolol significantly activated the Sirt1-AMPK pathway in intermittent hypoxic and isoproterenol-treated HL-1 cells, and the effect was abolished by the coadministration of EX-527, an inhibitor of Sirt1 activation. In summary, metoprolol protects against chronic OSA-induced atrial remodeling. Our results suggest a new and feasible treatment strategy for AF induced by OSA.

Patency of the ductus arteriosus (DA) is crucial for both fetal circulation and patients with DA-dependent congenital heart diseases (CHD). The Na + /Ca 2+ exchanger 1 (NCX1) protein has been shown to play a key role in the regulation of vascular tone and is elevated in DA-dependent CHD. This current study was conducted to investigate the mechanisms underpinning the role of NCX1 in DA patency. Our data showed NCX1 expression was up-regulated in the DA of fetal mice. Up-regulation of NCX1 expression resulted in a concomitant decrease in cytosolic Ca 2+ levels in human DA smooth muscle cells (DASMCs) and an inhibition of the proliferation and migration capacities of human DASMCs. Furthermore, treatment of DASMCs with KB-R7943, which can reduce Ca 2+ influx, resulted in the inhibition of both cell proliferation and migration. These findings indicate that NCX1 may play a role in maintaining patent DA not only by preventing DA functional closure through reducing cytosolic Ca 2+ level in DASMC but also by delaying the anatomical closure process. The latter delay is facilitated by the down-regulation of human DASMC proliferation and migration. It is also likely that a reduction in cytosolic Ca 2+ levels inhibits the proliferation and migration capacities of human DASMCs in vitro.