白细胞端粒长度增长会增加2型糖尿病患者的心血管死亡率

Abstract Aims Leukocyte telomere length (LTL), as a biomarker of biological aging, is associated with the prevalence and complications of diabetes. This study aims to investigate the associations between LTL and all‐cause and cause‐specific mortality in patients with type 2 diabetes. Methods All participants with baseline LTL records were included from the National Health and Nutrition Examination Survey 1999–2002. Death status and its causes were ascertained for National Death Index based on International Classification of Diseases, Tenth Revision code. Cox proportional hazards regression models were established to estimate the hazard ratios (HRs) of LTL associating with all‐cause and cause‐specific mortality. Results The study enrolled 804 diabetic patients with the mean follow‐up of 14.9 ± 2.59 years. There were 367 (45.6%) all‐cause deaths, 80 (10.0%) cardiovascular deaths, and 42 (5.2%) cancer‐related deaths. Longer LTL was associated with reduced all‐cause mortality, whereas this association disappeared after adjusting for other variables. Compared with the lowest tertiles of LTL, the multivariable‐adjusted hazard ratio of cardiovascular mortality was 2.11 (95% confidence interval [CI] 1.31–3.39; p < .05) in the highest tertiles. In terms of cancer mortality, the highest tertile was negatively correlated with the risk of cancer mortality (HR 0.58 [95% CI 0.37, 0.91], p < .05). Conclusion In conclusion, LTL was independently associated with the risk of cardiovascular mortality in patients with type 2 diabetes and was negatively correlated with the risk of cancer mortality. Telomere length may be a predictor of cardiovascular mortality in diabetes

Microstructure evolution and mechanical property of a new multi-component β titanium alloy with ultrahigh strength above 1350 MPa

The microstructure evolution and precipitation behavior of a multi-component β titanium alloy (namely TB17) were investigated through various characterization methods. The results show that with the increase of the solution temperature, the coarse lamellar α phase (αl) and fine secondary α phase (αs) existed in the original as-forged TB17 alloy decrease. At the same time, the molybdenum equivalent value of the β matrix also decreases gradually, leading to the increase of αs phase during the following aging process. For the aged samples, the micro-strain accumulated in the β matrix resulted from phase transformation strain exhibits an increasing trend as the solution treatment temperature rises, highly depending on the volume fraction of αs phase. When the alloy is subjected to a solution treatment at temperature of 805 °C plus aging, it can achieve a good combination of high strength of 1375 MPa and considerable ductility due to mixed microstructure of suitable amount of micro-scale αl and nano-scale αs precipitates. The strength is further improved by increasing the solution temperature (from α+β to β field), which is attributed to higher volume fraction of fine αs precipitates formed during aging that can effectively hinder dislocation slip and induce micro-strain. Morphological features of the fracture surfaces are also discussed against the different microstructural morphologies, revealing the fracture mechanism of TB17 alloy under different heat treatment conditions. The current work could contribute to a better understanding of phase transformation behavior and strengthening mechanism in TB17 alloy

Four new dammarane-type triterpenes derivatives from hydrolyzate of total <i>Gynostemma pentaphyllum</i> saponins and their bioactivities

<p>Phytochemical investigation of hydrolysate of total <i>G. pentaphyllum</i> saponins led to the isolation of four novel triterpenes, Gypensapogenin U (<b>1</b>), Gypensapogenin V (<b>2</b>), Gypensapogenin W (<b>3</b>) and Gypensapogenin X (<b>4</b>). The structures of these compounds were identified by 1D, 2D-NMR and HR-ESI-MS evidences. Additionally, the protective activity of these new compounds against cardiomyocytes injury induced by H₂O₂ and their cytotoxic activity against t-HSC/Cl-6 cells were evaluated.</p

The biogenesis and secretion of exosomes and multivesicular bodies (MVBs): Intercellular shuttles and implications in human diseases

Exosomes carry and transmit signaling molecules used for intercellular communication. The generation and secretion of exosomes is a multistep interlocking process that allows simultaneous control of multiple regulatory sites. Protein molecules, mainly RAB GTPases, cytoskeletal proteins and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE), are specifically regulated in response to pathological conditions such as altered cellular microenvironment, stimulation by pathogenic factors, or gene mutation. This interferes with the smooth functioning of endocytosis, translocation, degradation, docking and fusion processes, leading to changes in the secretion of exosomes. Large numbers of secreted exosomes are disseminated by the flow of body fluids and absorbed by the recipient cells. By transmitting characteristic functional proteins and genetic information produced under disease conditions, exosomes can change the physiological state of the recipient cells and their microenvironment. The microenvironment, in turn, affects the occurrence and development of disease. Therefore, this review will discuss the mechanism by which exosome secretion is regulated in cells following the formation of mature secretory multivesicular bodies (MVBs). The overall aim is to find ways to eliminate disease-derived exosomes at their source, thereby providing an important new basis for the clinical treatment of disease