Associations between serum amino acids and incident type 2 diabetes in Chinese rural adults

Background and aimsSome amino acids (AAs) may be associated with type 2 diabetes (T2DM). This study aimed to determine the associations of individual AAs with the development of T2DM in rural Chinese adults.Methods and resultsA cohort study of 1199 individuals aged 18 years or older was conducted from 2006 to 2008 in a rural community of Deqing, China, a repeated survey was done in 2015 and data linkage with the electronic health records system was performed each year for identifying new T2DM cases. A high-performance liquid chromatography approach was used to measure the baseline serum concentrations of 15 AAs. Cox proportional hazards models were used to examine the associations between AAs and the risk of incident T2DM. A total of 98 new T2DM cases were identified during the follow-up of 12 years on average. Among 15 AAs, proline was associated with an increased risk of incident T2DM after adjusted for age, sex, body mass index, fasting plasma glucose, family history of T2DM, smoking status, alcohol use, and history of hypertension, the adjusted hazard ratio for 1-standard deviation increment was 1.20 (95% confidence interval: 1.00, 1.43). The association tended to be more marked in subjects younger than 60 years and overweight/obese subjects. Among participants without hypertension, proline and phenylalanine were associated with an increased risk of incident T2DM, while aspartic acid was associated with a decreased risk.ConclusionSerum proline was associated with the risk of incident T2DM in rural Chinese adults and might be a potential predictor.     

The motivational process for physical activity in young adults with autism spectrum disorder

Background

Many young adults, specifically those with a diagnosis of autism spectrum disorder (ASD), do not meet the national physical activity (PA) guidelines. One way to address this problem may be to examine the factors that motivate individuals to engage in PA. However, the majority of current literature does not consider the unique characteristics of individuals with ASD, which may influence their motivation.

Statistical Methods for Conditional Survival Analysis

We investigate the survival distribution of the patients who have survived over a certain time period. This is called a conditional survival distribution. In this paper, we show that one-sample estimation, two-sample comparison and regression analysis of conditional survival distributions can be conducted using the regular methods for unconditional survival distributions that are provided by the standard statistical software, such as SAS and SPSS. We conduct extensive simulations to evaluate the finite sample property of these conditional survival analysis methods. We illustrate these methods with real clinical data.     

Cationic liposome co-encapsulation of SMAC mimetic and zVAD using a novel lipid bilayer fusion loaded with MLKL-pDNA for tumour inhibition in vivo

The increase in multidrug resistance among colon cancer cells presents a challenge for the development of effective therapies. Small-molecule analogues of second mitochondria-derived activator of caspase (SMAC) mimetic in association with mixed lineage kinase domain-like protein (MLKL)-pDNA and z-VAD-fmk have shown ideal antitumor effects in colon cancer cells in vitro via induction of RIP3-dependent necroptosis. To achieve synergistic antitumor effects in vivo, liposomes loaded with SMAC mimetic, MLKL-pDNA and z-VAD-fmk have been developed using novel lipid fusion methods to co-localise the molecules of interest within the tumour cells. The co-encapsulation liposome (MLKL-zVAD-BV6-LP) had a high entrapment efficiency of approximately 95% for both zVAD and BV6 and was able to condense MLKL-pDNA very well. The vectors showed good biocompatibility, tumour targeting and small-molecule co-localisation. In a CT26 mouse model, the MLKL-zVAD-BV6-LP exhibited a tumour-suppression rate of over 60% in vivo, which was significantly higher than that of both the null-liposome and coadministration groups. Above all, the co-encapsulation system provided a novel approach to combination tumour therapy.     

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl₄, FeCl₂), whereas Na₂SeO₃ supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.     

CD226 attenuates Treg suppressive capacity via CTLA-4 and TIGIT during EAE

The Cluster of differentiation 226(CD226)/T cell immunoglobulin and immune receptor tyrosine-based inhibitory motif domain (TIGIT) axis plays an important role in the balance of the immune response. A previous study showed that CD226 is involved in CD4+ T cell differentiation and that blocking CD226 may attenuate experimental autoimmune encephalomyelitis (EAE) development. However, the molecular mechanisms underlying this process remain incompletely understood. In this study, it was found that Cd226−/− mice were less susceptible to EAE and that there was less T helper 17(Th17) cell infiltration with higher levels of regulatory cells (Tregs) infiltration in the Cd226−/− EAE mouse central nervous system (CNS) compared with that in the WT EAE mouse CNS. Moreover, the suppressive function of Cd226−/− Tregs was upregulated compared with that of WT Tregs. Furthermore, it was observed that the expression levels of CTLA-4 and TIGIT on Cd226−/− Tregs were higher than those on WT Tregs during EAE in the spleen and CNS. Our results demonstrate a pivotal role for CD226 in attenuating Treg function in EAE that was associated with downregulating the expression levels of CTLA-4 and TIGIT.