The Uyghur population has experienced extensive interaction with European and Eastern Asian populations historically. A set of high-resolution genetic markers could be useful to infer the genetic relationships between the Uyghur population and European and Asian populations. In this study we typed 100 unrelated Uyghur males living in southern Xinjiang at 26 Y-STR loci. Using the high-resolution 26 Y-STR loci system, we investigated genetic and phylogenetic relationship between the Uyghur population and 23 reference European or Asian populations. We found that the Uyghur population exhibited a genetic admixture of Eastern Asian and European populations, and had a slightly closer relationship with the selected European populations than the Eastern Asian populations. We also demonstrated that the 26 Y-STR loci system was potentially useful in forensic sciences because it has a large power of discrimination and rarely exhibits common haplotypes. However, ancestry inference of Uyghur samples could be challenging due to the admixed nature of the population.

As a multi-ethnic country, China has some indigenous population groups which vary in culture and social customs, perhaps as a result of geographic isolation and different traditions. However, upon close interactions and intermarriage, admixture of different gene pools among these ethnic groups may occur. In order to gain more insight on the genetic background of X-Chromosome from these ethnic groups, a set of X-markers (18 X-STRs and 16 X-Indels) was genotyped in 5 main ethnic groups of China (HAN, HUI, Uygur, Mongolian, Tibetan). Twenty-three private alleles were detected in HAN, Uygur, Tibetan and Mongolian. Significant differences (p < 0.0001) were all observed for the 3 parameters of heterozygosity (Ho, He and UHe) among the 5 ethnic groups. Highest values of Nei genetic distance were always observed at HUI-Uygur pairwise when analyzed with X-STRs or X-Indels separately and combined. Phylogenetic tree and PCA analyses revealed a clear pattern of population differentiation of HUI and Uygur. However, the HAN, Tibetan and Mongolian ethnic groups were closely clustered. Eighteen X-Indels exhibited in general congruent phylogenetic signal and similar cluster among the 5 ethnic groups compared with 16 X-STRs. Aforementioned results proved the genetic polymorphism and potential of the 34 X-markers in the 5 ethnic groups.

Renal fibrosis, considered to be a common consequence of progressive renal disease, involves glomerulosclerosis and/or tubulointerstitial fibrosis. Currently, research is focused on investigating potential mechanisms to prevent or reverse the damage caused by fibrosis. Under the influence of cytokines, chemokines and other signaling molecules, the cellular interactions that regulate the development of interstitial fibrosis are complex. Epithelial‑mesenchymal transition (EMT) has emerged as an important pathway leading to the generation of matrix‑producing fibroblasts and myofibroblasts in diseased kidneys. The proteomics study compared the protein profiles between the time points of podocyte EMT and tubular cell EMT in a partial unilateral ureteral obstruction (PUUO) model in rats. Proteins isolated from the PUUO group and corresponding sham rat kidney tissues were subjected to 2‑D gel electrophoresis and were then identified by mass spectrometry. In total, 43 proteins with differential expression were identified, which were reported to be involved in the regulation of the cytoskeleton and actin, glucose metabolism, cell apoptosis, mitochondrial energy metabolism, oxidative stress and endoplasmic reticulum stress. Electron transfer flavoprotein, β polypeptide was detected by immunoblot analysis and its mRNA levels were determined in renal tissues. The results demonstrate protein alterations that reflect the pathology of the obstructed kidneys, and thus may aid in understanding the pathogenesis of obstructive nephropathy.

Glioma differentiation therapy is a novel strategy that has been used to induce glioma cells to differentiate into glia-like cells. Although some advances in experimental methods for exploring the molecular mechanisms involved in differentiation therapy have been made, a model-based comprehensive analysis is still needed to understand these differentiation mechanisms and improve the effects of anti-cancer therapeutics. This type of analysis becomes necessary in stochastic cases for two main reasons: stochastic noise inherently exists in signal transduction and phenotypic regulation during targeted therapy and chemotherapy, and the relationship between this noise and drug efficacy in differentiation therapy is largely unknown.

InDels are short-length polymorphisms characterized by low mutation rates, high inter-population diversity, short amplicon strategy and simplicity of laboratory analysis. This work describes the developmental validation of an X-InDels panel amplifying 18 bi-allelic markers and Amelogenin in one single PCR system. Developmental validation indicated that this novel panel was reproducible, accurate, sensitive and robust for forensic application. Sensitivity testing of the panel was such that a full profile was obtainable even with 125 pg of human DNA with intra-locus balance above 70%. Specificity testing was demonstrated by the lack of cross-reactivity with a variety of commonly encountered animal species and microorganisms. For the stability testing in cases of PCR inhibition, full profiles have been obtained with hematin (≤1000 μM) and humic acid (≤150 ng/μL). For the forensic investigation of the 18 X-InDels in the HAN population of China, no locus deviated from the Hardy-Weinberg equilibrium and linkage disequilibrium. Since they are independent from each other, the CDPfemale was 0.999999726 and CDPmale was 0.999934223. The forensic parameters suggested that this X-Indel panel is polymorphic and informative, which provides valuable X-linked information for deficient relationship cases where autosomal markers are uninformative.

Chotosan (CTS, Diaoteng San), a Kampo medicine (ie Chinese medicine) formula, is reportedly effective in the treatment of patients with cerebral ischemic insults. This study aims to evaluate the therapeutic potential of CTS in cognitive deficits and investigates the effects and molecular mechanism(s) of CTS on learning and memory deficits and emotional abnormality in an animal aging model, namely 20-week-old senescence-accelerated prone mice (SAMP8), with and without a transient ischemic insult (T2VO).

Ubiquitin modification of cellular proteins commonly targets them for proteosomal degradation, but can also convey non-proteolytic functions. Over the past years, advances in experimental approaches have helped uncover the extensive involvement of ubiquitination in protein regulation. However, our understanding of the dynamics of the ubiquitination-related networks have lagged behind. A common regulatory theme for many E3 ligases is the ability to self-catalyse their own ubiquitination without involving external E3 ligating enzymes. Here, the authors have explored computational models of both proteolytic and non-proteolytic auto-ubiquitination of E3 ligases and characterised the dynamic properties of these regulatory motifs. Remarkably, in both cases auto-ubiquitination coupled with multi-step de-ubiquitination process can bring about sustained oscillatory behaviour. In addition, the same basic wiring structures can trigger bistable switches of activity and excitable firing of the dynamic responses of the ubiquitinated E3 ligase. Bifurcation analysis allows one to derive parametric conditions that govern these dynamics. They also show that these complex non-linear behaviours persist for a more detailed mechanistic description that involves the E1 and E2 enzymes. Their work therefore provides new insights into the dynamic features of auto-ubiquitination in different cellular contexts.

Although PIWI-interacting RNAs (piRNAs) have recently been linked to human diseases, their roles and functions in malignancies remain unclear. This study aimed to investigate the significance of some piRNAs in colorectal cancer (CRC). Methods: We first analyzed the expression profile of piRNAs in CRC using the TCGA and GEO databases. The top 20 highly expressed piRNAs were selected and tested in our CRC tumor and non-tumor tissue samples. We then examined the relevance of the significantly differentially expressed piRNA to the CRC outcomes in 218 patients receiving postoperative chemotherapy and 317 patients receiving neoadjuvant chemotherapy. A series of biochemical and molecular biological assays were conducted to elucidate the functional mechanism of a piRNA of interest in CRC. Furthermore, experiments with mice xenografts were performed to evaluate the therapeutic effect of an inhibitor specific to the piRNA. Results: We found that among the examined 20 piRNAs, only piRNA-54265 was overexpressed in CRC compared with non-tumor tissues and higher levels in tumor or in serum were significantly associated with poor survival in patients. Functional assays demonstrated that piRNA-54265 binds PIWIL2 protein and this is necessary for the formation of PIWIL2/STAT3/phosphorylated-SRC (p-SRC) complex, which activates STAT3 signaling and promotes proliferation, metastasis and chemoresistance of CRC cells. Treatment with a piRNA-54265 inhibitor significantly suppressed the growth and metastasis of implanted tumors in mice. Conclusion: These results indicate that piRNA-54265 is an oncogenic RNA in CRC and thus might be a therapeutic target.

Prognostic and predictive markers are needed to predict the clinical outcomes of patients with advanced colorectal cancer (CRC) who receive standard first-line treatments. We performed a prospective cohort study in advanced CRC patients to identify a miRNA signature that could predict the benefit of receiving first-line chemotherapy for these patients. Twenty-one paired tumours and adjacent normal tissues were collected from advanced CRC patients and analysed by miRNA microarrays. Between tumour and normal tissues, 33 miRNAs were differentially expressed and was confirmed by qRT-PCR from another group of 67 patients from a prospective cohort study. A two-miRNA-based signature was obtained using the LASSO Cox regression model based on the association between the expression of each miRNA and the PFS of individual patients. Internal and external validation cohorts, including 40 and 44 patients with advanced CRC, respectively, were performed to prove the prognostic and predictive value of this signature. A signature was built based on two miRNAs, miR-125b-2-3p and miR-933. CRC patients were classified into low- and high-risk groups for disease progression based on this tool. The patients with low risk scores generally had better PFS than those with high risk scores. In the training set, the median PFS in the low- and high-risk groups were 12.00 and 7.40 months, respectively. In the internal validation set, the median PFS in the low- and high-risk groups were 9.90 and 5.10 months, respectively. In the external validation set, the median PFS in the low- and high-risk groups were 9.90 and 6.40 months, respectively. Furthermore, we detected miR-125b-2-3p associated with CRC cell sensitivity to first-line chemotherapy. Our two-miRNA-based signature was a reliable prognostic and predictive tool for tumour progression in patients with advanced CRC, and might be able to predict the benefit of receiving standard first-line chemotherapy in CRC.

Temporal relationships between the time to appropriate antibiotic therapy and outcomes are not well described.

Ophthalmoplegia is a disease that affects many people every year and is caused by reasons, such as cavernous sinus lesion, intracranial aneurysm, diabetes, and trauma. Acupuncture has been widely used to treat ophthalmological diseases especially ophthalmoplegia in China. Many clinical trials indicate that acupuncture may promote the recovery of extraocular muscles in ophthalmoplegia patients. We aim to conduct a meta-analysis to evaluate the efficacy and safety of acupuncture for ophthalmoplegia.

The arginine vasopressin (AVP) system has been postulated to play a role in glucose homeostasis, insulin resistance, and diabetes mellitus in human and animal studies. The aim of this study was to evaluate the role of plasma copeptin in Chinese patients with type 2 diabetes mellitus (T2DM) with and without diabetic retinopathy (DR).

Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unclear. In this study, hyperhomocysteinemia was induced in apolipoprotein E-deficient mice with 1.7% methionine. Pathological changes in the olfactory bulb were observed through hematoxylin-eosin and Pischingert staining. Cell apoptosis in the olfactory bulb was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Transmission electron microscopy revealed an abnormal ultrastructure of neurons. Furthermore, immunoreactivity and expression of the hairy enhancer of the split 1 (Hes1) and Hes5 were measured using immunohistochemistry, immunofluorescence, and western blot assay. Our results revealed no significant structural abnormality in the olfactory bulb of hyperhomocysteinemic mice. However, the number of TUNEL-positive cells increased in the olfactory bulb, lipofuscin and vacuolization were visible in mitochondria, and the expression of Hes1 and Hes5 decreased. These findings confirm that hyperhomocysteinemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression.

Morels, a group of the world's most prized edible and medicinal mushrooms, are of very important economic and scientific value. Here, we review recent research progress in the genus Morchella, and focus on its taxonomy, species diversity and distribution, ecological diversity, phylogeny and biogeography, artificial cultivation, and genome. We also discuss the potential issues remaining in the current research and suggest some future directions for study.

Long non-coding RNA (lncRNA) plays an important role in many important biological processes and has attracted widespread attention. Although the precise functions and mechanisms for most lncRNAs are still unknown, we are certain that lncRNAs usually perform their functions by interacting with the corresponding RNA- binding proteins. For example, lncRNA-protein interactions play an important role in post transcriptional gene regulation, such as splicing, translation, signaling, and advances in complex diseases. However, experimental verification of lncRNA-protein interactions prediction is time-consuming and laborious. In this work, we propose a computational method, named IRWNRLPI, to find the potential associations between lncRNAs and proteins. IRWNRLPI integrates two algorithms, random walk and neighborhood regularized logistic matrix factorization, which can optimize a lot more than using an algorithm alone. Moreover, the method is semi-supervised and does not require negative samples. Based on the leave-one-out cross validation, we obtain the AUC of 0.9150 and the AUPR of 0.7138, demonstrating its reliable performance. In addition, by means of case study in the "Mus musculus," many lncRNA-protein interactions which are predicted by our method can be successfully confirmed by experiments. This suggests that IRWNRLPI will be a useful bioinformatics resource in biomedical research.

Individuals' peak bone mineral density (BMD) achieved and maintained at ages 20-40 years is the most powerful predictor of low bone mass and osteoporotic fractures later in life. The aim of this study was to identify metabolomic factors associated with peak BMD variation in US Caucasian women.

Animal venoms are considered as one of the most important sources for drug development. Deinagkistrodon acutus is famous for its toxicity to the human hematological system and envenomed patients develop a coagulation disorder with the symptoms of hemorrhage and microthrombi formation. The purpose of this study was to separate antiplatelet peptides from D. acutus venom using a combination of an ultrafiltration technique and reversed-phase high performance liquid chromatography (HPLC), which was guided by monitoring antiplatelet aggregation bioactivity. A novel octa-peptide named DAA-8 was found. This peptide inhibited protease-activated receptor1 (PAR-1) agonist (SFLLRN-NH₂) induced platelet aggregation and it also inhibited platelet aggregation induced by thrombin, ADP, and collagen. Furthermore, DAA-8 showed significant antithrombotic activity and resulted in a slightly increased bleeding risk in vivo. This is the first report of a peptide derived from snake venom, which inhibited PAR-1 agonist-induced platelet aggregation. This peptide may provide a template to design a new PAR-1 inhibitor.

Tumor, is one of the major reason for human death, due to its widespread occurrence. Betulinic acid derivatives have attracted considerable attention as cancer chemopreventive agents and also as cancer therapeutics. Many of its derivatives inhibit the growth of human cancer cell lines by triggering apoptosis. With this background, we planned to synthesize a series of betulinic acid derivatives to assess their antiproliferation efficacy on human cancer cell lines.

Diabetes is one of the risk factors for cognitive deficits such as Alzheimer's disease. To obtain a better understanding of the anti-dementia effect of chotosan (CTS), a Kampo formula, we investigated its effects on cognitive and emotional deficits of type 2 diabetic db/db mice and putative mechanism(s) underlying the effects.

Starting from publicly-accessible datasets, we have utilized comparative and phylogenetic genome analyses to characterize the evolution of the human MAGE gene family. Our characterization of genomic structures in representative genomes of primates, rodents, carnivora, and macroscelidea indicates that both Type I and Type II MAGE genes have undergone lineage-specific evolution. The restricted expression pattern in germ cells of Type I MAGE orthologs is observed throughout evolutionary history. Unlike Type II MAGEs that have conserved promoter sequences, Type I MAGEs lack promoter conservation, suggesting that epigenetic regulation is a central mechanism for controlling their expression. Codon analysis shows that Type I but not Type II MAGE genes have been under positive selection. The combination of genomic and expression analysis suggests that Type 1 MAGE promoters and genes continue to evolve in the hominin lineage, perhaps towards functional diversification or acquiring additional specific functions, and that selection pressure at codon level is associated with expression spectrum.