The role of landscape evolution in the genetic diversification of a stream fish Sarcocheilichthys parvus from Southern China

Sarcocheilichthys parvus (Cypriniformes: Gobionidae) is a stream fish which is endemic to sub-tropical coastal drainages in southern China, thus offering a valuable model for understanding how genetic divergence arises in stream-adapting freshwater fishes in this region. Using the mitochondrial Cyt b gene, integrative analyses of phylogeny, population demography, and ancestral area and paleo-drainage reconstructions are carried out to explicitly explore the role of landscape evolution in genetic diversification of S. parvus. The time-calibrated phylogeny of S. parvus indicates the splitting of two major lineages (A and B) at ∼3.66 Ma. Lineage A inhabits the Poyang Lake sub-drainage of the middle Yangtze River, Han River and Pearl River, and can be split into two sub-lineages (A-I and A-II), where sub-lineage A-II can be further sub-divided into three infra-sub-lineages (A-IIa, A-IIb and A-IIc). Except for the infra-sub-lineage A-IIc, which is restricted to the Han River and Pearl River, the other sub-lineages and infra-sub-lineages live exclusively in the Poyang Lake sub-drainage. Lineage B lives in the lower Yangtze River, Qiantang River, Jiaojiang River and Ou River, displaying close genetic relationships among the drainages. Rapid population expansion has occurred since the Late Pleistocene. Our findings indicate that the splitting of lineages A and B could be attributed to geographic isolation due to the Zhe–Min Uplift, acting as a biogeographic barrier before the late Early Pleistocene. Furthermore, the strong genetic divergence within Lineage A could be explained by the isolation role of the Nanling Mountains and Poyang Lake acting as an ecological barrier; while the lack of phylogenetic structure within Lineage B may have been the result of paleo-drainage connections or episodic freshwater connections during the eustatic low stand of sea level in the late Middle–Late Pleistocene

Effects of Telbivudine Treatment on the Circulating CD4+ T-Cell Subpopulations in Chronic Hepatitis B Patients

CD4+ T cells serve as master regulators of the adaptive immune response to HBV. However, CD4+ T-cell subsets are heterogeneous, and it remains unknown how the antiviral agents affect the different CD4+ T cell subtypes. To this end, the expressions of signature transcription factors and cytokines of CD4+ T-cell subtypes were examined in hepatitis B patients before and after treatment with telbivudine. Results showed that, upon the rapid HBV copy decrease induced by telbivudine treatment, the frequencies and related cytokines of Th17 and Treg cells were dramatically decreased, while those for Th2 cells were dramatically increased. No obvious changes were observed in Th1 cell frequencies; although, IFN-γ expression was upregulated in response to telbivudine treatment, suggesting another cell source of IFN-γ in CHB patients. Statistical analyses indicated that Th17 and Tr1 (a Treg subtype) cells were the most sensitive subpopulations of the peripheral blood CD4+ T cells to telbivudine treatment over 52 weeks. Thus, Th17 and Tr1 cells may represent a suitable and effective predictor of responsiveness during telbivudine therapy. These findings not only improve our understanding of hepatitis pathogenesis but also can aid in future development of appropriate therapeutic strategies to control viral hepatitis

Prevalence of porcine circovirus-like agent P1 in Jiangsu, China

Recently, we identified a novel porcine circovirus type 2-like agent P1 isolate from swine. The present study represents the first survey of P1 prevalence in swine herds from Jiangsu, China, by using PCR targeting the complete genome of P1. Prevalences of 50% and 19% were found among 6 herds and 248 animals, respectively. The results indicate a high prevalence of P1 in China pig populations

The correlation between admission hyperglycemia and 30-day readmission after hip fracture surgery in geriatric patients: a propensity score-matched study

PurposeThis study aimed to investigate the association between admission hyperglycemia and 30-day readmission after hip fracture surgery in geriatric patients.MethodsThis retrospective study included 1253 geriatric hip fracture patients. Patients were categorized into normoglycemia(<6.10 mmol/L) and hyperglycemia groups(≥6.10 mmol/L) based on admission blood glucose. We performed multivariable logistic regression analyses and propensity score matching (PSM) to estimate adjusted odds ratios and 95% confidence intervals for 30-day readmission, controlling for potential confounding factors. An analysis of the dose-dependent association between admission blood glucose and the probability of 30-day readmission was performed. Additional subgroup analysis was conducted to examine the impact of other factors on the relationship between admission blood glucose and 30-day readmission.ResultsPatients with hyperglycemia had higher 30-day readmission rates than normoglycemic patients before (19.1% vs 9.7%, p<0.001) and after PSM (18.1% vs 12.3%, p=0.035). Admission hyperglycemia was an independent predictor of increased 30-day readmission risk, with an adjusted odds ratio of 1.57 (95% CI 1.08-2.29, p=0.019) after multivariable regression and 1.57 (95% CI 1.03-2.39, p=0.036) after PSM. A dose-response relationship was observed between higher glucose levels and increased readmission risk.ConclusionAdmission hyperglycemia is an independent risk factor for 30-day readmission after hip fracture surgery in the elderly. Routine glucose testing upon admission and perioperative glycemic control may help reduce short-term readmissions in this vulnerable population

Identifying a Universal Activity Descriptor and a Unifying Mechanism Concept on Perovskite Oxides for Green Hydrogen Production

Producing indispensable hydrogen and oxygen for social development via water electrolysis shows more prospects than other technologies. Although electrocatalysts have been explored for centuries, a universal activity descriptor for both hydrogen-evolution reaction (HER) and oxygen-evolution reaction (OER) is not yet developed. Moreover, a unifying concept is not yet established to simultaneously understand HER/OER mechanisms. Here, the relationships between HER/OER activities in three common electrolytes and over ten representative material properties on 12 3d-metal-based model oxides are rationally bridged through statistical methodologies. The orbital charge-transfer energy (Δ) can serve as an ideal universal descriptor, where a neither too large nor too small Δ (≈1 eV) with optimal electron-cloud density around Fermi level affords the best activities, fulfilling Sabatier's principle. Systematic experiments and computations unravel that pristine oxide with Δ ≈ 1 eV possesses metal-like high-valence configurations and active lattice-oxygen sites to help adsorb key protons in HER and induce lattice-oxygen participation in the OER, respectively. After reactions, partially generated metals in the HER and high-valence hydroxides in the OER dominate proton adsorption and couple with pristine lattice-oxygen activation, respectively. These can be successfully rationalized by the unifying orbital charge-transfer theory. This work provides the foundation of rational material design and mechanism understanding for many potential applications

Targeting cavity-creating p53 cancer mutations with small-molecule stabilizers: the Y220X paradigm

We have previously shown that the thermolabile, cavity-creating p53 cancer mutant Y220C can be reactivated by small-molecule stabilizers. In our ongoing efforts to unearth druggable variants of the p53 mutome, we have now analyzed the effects of other cancer-associated mutations at codon 220 on the structure, stability and dynamics of the p53 DNA-binding domain (DBD). We found that the oncogenic Y220H, Y220N and Y220S mutations are also highly destabilizing, suggesting that they are largely unfolded under physiological conditions. A high-resolution crystal structure of the Y220S mutant DBD revealed a mutation-induced surface crevice similar to that of Y220C, whereas the corresponding pocket’s accessibility to small molecules was blocked in the structure of the Y220H mutant. Accordingly, a series of carbazole-based small molecules, designed for stabilizing the Y220C mutant, also bound to and stabilized the folded state of the Y220S mutant, albeit with varying affinities due to structural differences in the binding pocket of the two mutants. Some of the compounds also bound to and stabilized the Y220N mutant, but not the Y220H mutant. Our data validate the Y220S and Y220N mutant as druggable targets and provide a framework for the design of Y220S or Y220N-specific compounds as well as compounds with dual Y220C/Y220S specificity for use in personalized cancer therap

Associations of IL-4, IL-4R, and IL-13 Gene Polymorphisms in Coal Workers' Pneumoconiosis in China: A Case-Control Study

Background: The IL-4, IL-4 receptor (IL4R), and IL-13 genes are crucial immune factors and may influence the course of various diseases. In the present study, we investigated the association between the potential functional polymorphisms in IL-4, IL-4R, and IL-13 and coal workers ’ pneumoconiosis (CWP) risk in a Chinese population. Methods: Six polymorphisms (C-590T in IL-4, Ile50Val, Ser478Pro, and Gln551Arg in IL-4R, C-1055T and Arg130Gln in IL-13) were genotyped and analyzed in a case-control study of 556 CWP and 541 control subjects. Results: Our results revealed that the IL-4 CT/CC genotypes were associated with a significantly decreased risk of CWP (odd

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(−5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity