The relevance of human parainfluenza viruses (HPIVs) to the epidemiology of acute respiratory infections (ARI) in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs) from hospitalized pediatric patients (age from 1 to 93 months) in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase) sequences of HPIV-3 indicated that three distinct clusters (A,B, and C) were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%-100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China.

In order to supply sufficient microsatellite loci for high-density linkage mapping, whole genome shotgun (WGS) sequences of the common carp (Cyprinus carpio) were assembled and surveyed for microsatellite identification. A total of 79,014 microsatellites were collected which were harbored in 68,827 distinct contig sequences. These microsatellites were characterized in the common carp genome. Information of all microsatellites, including previously published BAC-based microsatellites, was then stored in a MySQL database, and a web-based database interface (http://genomics.cafs.ac.cn/ssrdb) was built for public access and download. A total of 3,110 microsatellites, including 1,845 from WGS and 1,265 from BAC end sequences (BES), were tested and genotyped on a mapping family with 192 individuals. A total of 963 microsatellites markers were validated with polymorphism in the mapping family. They will soon be used for high-density linkage mapping with a vast number of polymorphic SNP markers.

The functional components of bone marrow (i.e., the hematopoietic and stromal populations) and the adjacent bone have traditionally been evaluated incompletely as distinct entities rather than the integrated system. We perturbed this system in vivo using a medically relevant radiation model in the presence or absence of ovarian function to understand integrated tissue interaction.

The transforming growth factor-β (TGF-β) signalling pathway participates in various biological processes. Dysregulation of Smad4, a central cellular transducer of TGF-β signalling, is implicated in a wide range of human diseases and developmental disorders. However, the mechanisms underlying Smad4 dysregulation are not fully understood. Using a functional screening approach based on luciferase reporter assays, we identified 39 microRNAs (miRNAs) as potential regulators of Smad4 from an expression library of 388 human miRNAs. The screening was supported by bioinformatic analysis, as 24 of 39 identified miRNAs were also predicted to target Smad4. MiR-199a, one of the identified miRNAs, was inversely correlated with Smad4 expression in various human cancer cell lines and gastric cancer tissues, and repressed Smad4 expression and blocked canonical TGF-β transcriptional responses in cell lines. These effects were dependent on the presence of a conserved, but not perfect seed paired, miR-199a-binding site in the Smad4 3'-untranslated region (UTR). Overexpression of miR-199a significantly inhibited the ability of TGF-β to induce gastric cancer cell growth arrest and apoptosis in vitro, and promoted anchorage-independent growth in soft agar, suggesting that miR-199a plays an oncogenic role in human gastric tumourigenesis. In conclusion, our functional screening uncovers multiple miRNAs that regulate the cellular responsiveness to TGF-β signalling and reveals important roles of miR-199a in gastric cancer by directly targeting Smad4.

Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II TGFβ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6- induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional TGFβ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.

Homeostasis in adult tissues is maintained by resident stem cells and their progeny. Little is known about the regulation of tissue homeostasis by organ-organ interaction. Here we demonstrate that trachea-derived Decapentaplegic (Dpp), the main bone morphogenetic protein ligand in Drosophila, is essential for adult midgut homeostasis. We show that Dpp signaling is primarily activated in enterocytes (ECs). Depletion of Dpp signaling in ECs results in excess amounts of intestinal stem-cell-like cells and their progeny. Importantly, we find that Dpp is expressed specifically in tracheal cells that reach the intestinal cells through the visceral muscles. Depletion of dpp expression in tracheal cells phenocopies the Dpp loss-of-function defects in ECs. Our data demonstrate that the Drosophila trachea not only exchanges air for bodily needs but also produces a Dpp morphogen essential for neighboring tissue homeostasis. This work will provide important insights into the mechanisms of tissue homeostasis control by interorgan communication.

Polycomb group (PcG) proteins are epigenetic regulators that are essential for stem cell differentiation. Identifying PcG binding profiles is important for understanding the mechanisms of PcG-mediated repression in mammals. We used a mapping-convergence (M-C) algorithm using support vector machine (SVM) technology for genome-wide identification of PcG target genes in human embryonic stem cells. The method combined histone modifications and transcription factor binding motifs, eliminating the need for negative training samples as in traditional SVM. Good prediction accuracy comprising 3-fold cross-validation was obtained. In the analysis of 3133 PcG target genes identified by the model, PcG proteins were observed to suppress gene expression during differentiation. The results suggested that PcG and DNA methylation non-redundantly repress gene expression during differentiation. The genome-wide identification of PcG target genes will aid the further analysis of PcG mechanisms.

Hypertrophic scarring is a common proliferative disorder of dermal fibroblasts characterized by collagen overproduction and excessive deposition of extracellular matrix (ECM). There is no consensus about the best therapeutics to produce complete and permanent improvement of scars with few side effects. To investigate the therapeutic effects of oleanolic acid (OA) on hypertrophic scars and explore the possible mechanism of action involved, a rabbit ear model with hypertrophic scars was established. OA (2.5%, 5%, and 10%) was given once daily to the scars for 28 consecutive days. As a result, OA significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-β(1), MMP-1, TIMP-1, and collagens I and III were notably decreased, and the number of apoptosis cells and mRNA expression of MMP-2, caspase-3, and caspase-9 were markedly increased in the scar tissue. The scar elevation index (SEI) was also evidently reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that OA has the favorable curative effects on formed hypertrophic scars in the rabbit ear model, and the possible mechanism of action is that OA decreases HSFs proliferation and increases HSFs apoptosis by reduction of P311 gene expression and TGF-β(1) production, inhibition of TIMP-1 secretion, enhancement of MMP-2 activity, and subsequently facilitation of degradation of collagen types I and III.

We have previously shown that mouse whole bone marrow cell (BMC) extract results in improvement of cardiac function and decreases scar size in a mouse model of myocardial infarction (MI), in the absence of intact cells. It is not clear if these results are translatable to extracts from human BMC (hBMC) or mononuclear cells (hMNC), which would have significant clinical implications.

Despite great efforts to improve diagnosis and treatment, tuberculosis (TB) remains a major health problem worldwide, especially in developing countries. Lack of concrete immune markers is still the obstacle to properly evaluate active TB. Therefore, identification of more validated biomarkers and phenotypic signatures is imperative. In particular, T cell-related biomarkers are more significant.

This paper examined the National Health Interview Survey (NHIS) 2007 and explored acupuncture users sociodemographics characteristics, reasons and the nature of acupuncture use, and the relationship of such use with conventional medical care. All individuals who completed adults core interviews (N = 23,393) were included. Three subsets of samples (nonuser, former user, and recent user) were used in the analysis performed in Stata. Our findings revealed that ever acupuncture user (including former and recent user) increased from 4.2% to 6.3% of the population, representing 8.19 million and 14.01 million users in 2002 and 2007, respectively. We expected this trend to continue. People not only used acupuncture as a complementary and alternative approach to conventional treatment for a specific health condition, but also used it as a preventive means to promote general health. Effectiveness and safety appeared not to be the main predictors of acupuncture use; rather, awareness, cost, and insurance coverage played a bigger role in decision making.

In silico prediction of genomic long non-coding RNAs (lncRNAs) is prerequisite to the construction and elucidation of non-coding regulatory network. Chromatin modifications marked by chromatin regulators are important epigenetic features, which can be captured by prevailing high-throughput approaches such as ChIP sequencing. We demonstrate that the accuracy of lncRNA predictions can be greatly improved when incorporating high-throughput chromatin modifications over mouse embryonic stem differentiation toward adult Cerebellum by logistic regression with LASSO regularization. The discriminating features include H3K9me3, H3K27ac, H3K4me1, open reading frames and several repeat elements. Importantly, chromatin information is suggested to be complementary to genomic sequence information, highlighting the importance of an integrated model. Applying integrated model, we obtain a list of putative lncRNAs based on uncharacterized fragments from transcriptome assembly. We demonstrate that the putative lncRNAs have regulatory roles in vicinity of known gene loci by expression and Gene Ontology enrichment analysis. We also show that the lncRNA expression specificity can be efficiently modeled by the chromatin data with same developmental stage. The study not only supports the biological hypothesis that chromatin can regulate expression of tissue-specific or developmental stage-specific lncRNAs but also reveals the discriminating features between lncRNA and coding genes, which would guide further lncRNA identifications and characterizations.

Human adipose tissue-derived stem cells (ADSCs) are an attractive multipotent stem cell source with therapeutic applicability across diverse fields for the repair and regeneration of acute and chronically damaged tissues. In recent years, there has been increasing interest in ADSC for tissue engineering applications. However, the mechanisms underlying the regulation of ADSC proliferation are not fully understood. Here we show that 47 transcripts are up-regulated while 23 are down-regulated in ADSC compared to terminally differentiated cells based on global mRNA profiling and microRNA profiling. Among the up-regulated genes, the expression of vascular endothelial growth factor (VEGF) is fine-tuned by miR-199a-5p. Further investigation indicates that VEGF accelerates ADSC proliferation whereas the multipotency of ADSC remains stable in terms of adipogenic, chondrogenic and osteogenic potentials after VEGF treatment, suggesting that VEGF may serve as an excellent supplement for accelerating ADSC proliferation during in vitro expansion.

Transition protein 2 (TNP2) participates in removing nucleohistones and the initial condensation of spermatid nucleus during spermiogenesis. This study investigated the relationship between the variants of the bovine TNP2 gene and the semen quality traits of Chinese Holstein bulls. We detected three single nucleotide polymorphisms (SNPs) of the TNP2 gene in 392 Chinese Holstein bulls, namely, g.269 G>A (exon 1), g.480 C>T (intron 1), and g.1536 C>T (3'-UTR). Association analysis showed that the semen quality traits of the Chinese Holstein bulls was significantly affected by the three SNPs. The bulls with the haplotypic combinations H6H4, H6H6, and H6H8 had higher initial semen motility than those with the H7H8 and H8H4 haplotypic combinations (P<0.05). SNPs in the microRNA (miRNA) binding region of the TNP2 gene 3'-UTR may have contributed to the phenotypic differences. The phenotypic differences are caused by the altered expression of the miRNAs and their targets. Bioinformatics analysis predicted that the g.1536 C>T site in the TNP2 3'-UTR is located in the bta-miR-154 binding region. The quantitative real-time polymerase chain reaction results showed that the TNP2 mRNA relative expression in bulls with the CT and CC genotypes was significantly higher than those with the TT genotype (P<0.05) in the g.1536 C>T site. The luciferase assay also indicated that bta-miR-154 directly targets TNP2 in a murine Leydig cell tumor cell line. The SNP g.1536 C>T in the TNP2 3'-UTR, which altered the binding of TNP2 with bta-miR-154, was found to be associated with the semen quality traits of Chinese Holstein bulls.

Osteoporosis is a serious health problem worldwide. MicroRNA is a post-transcriptional regulator of gene expression by either promoting mRNA degradation or interfering with mRNA translation of specific target genes. It plays a significant role in the pathogenesis of osteoporosis. Here, we first demonstrated that miR-106b (miR-106b-5p) negatively regulated osteogenic differentiation of mesenchymal stem cells in vitro. Then, we found that miR-106b expression increased in C57BL/6 mice with glucocorticoid-induced osteoporosis (GIOP), and that silencing of miR-106b signaling protected mice against GIOP through promoting bone formation and inhibiting bone resorption. At last, we showed that miR-106b inhibited osteoblastic differentiation and bone formation partly through directly targeting bone morphogenetic protein 2 (BMP2) both in vitro and in the GIOP model. Together, our findings have identified the role and mechanism of miR-106b in negatively regulating osteogenesis. Inhibition of miR-106b might be a potential new strategy for treating osteoporosis and bone defects.

Thiopurines are widely used as anticancer and immunosuppressive agents. However, life-threatening myelotoxicity has been noticed and largely explained by genetic variations, including NUDT15 polymorphisms (e.g., rs116855232). In this study, we conduct a meta-analysis to investigate the impact of rs116855232 on thiopurines-induced myelotoxicity susceptibility (1752 patients from 7 independent cohorts), as well as on thiopurines intolerance dose (2745 patients from 13 cohorts). Variant allele of rs116855232 contributes 7.86-fold (P < 0.00001, 95% CI: 6.13-10.08) higher risk to develop leucopenia with high specificity (91.74%) and sensitivity (43.19%), and lower thiopurines intolerance dose (P < 0.00001). Through bioinformatics prediction, amino acid changes induced by genetic variants are considered to reduce the stability, and break an α helix of NUDT15, which is part of the thiopurine binding pocket. Additionally, we conduct an expression quantitative trait loci (eQTL) analysis for NUDT15, and find a promoter-located eQTL signal (rs554405994), which may act as a potential marker to predict thiopurines-induced myelotoxicity. In conclusion, genetic polymorphisms in NUDT15 are strongly associated with adverse drug reaction (ADR) of thiopurines, although more evidences are needed to determine values of all functional NUDT15 polymorphisms for clinical regimen, rs116855232 should be considered as a highly credible pharmacogenetic indicator for thiopurines using espcially is Asians.

Background. This study compared outcomes of abdominal lifting and compression cardiopulmonary resuscitation (ALP-CPR) with standard CPR (STD-CPR). Materials and Methods. Patients with cardiac arrest seen from April to December 2014 were randomized to receive standard CPR or ALP-CPR performed with a novel abdominal lifting/compression device. The primary outcome was return of spontaneous circulation (ROSC). Results. Patients were randomized to receive ALP-CPR (n = 40) and STD-CPR (n = 43), and the groups had similar baseline characteristics. After CPR, 9 (22.5%) and 7 (16.3%) patients in the ALP-CPR and STD-CPR groups, respectively, obtained ROSC. At 60 minutes after ROSC, 7 (77.8%) and 2 (28.6%) patients, respectively, in the ALP-CPR and STD-CPR groups survived (P = 0.049). Patients in the ALP-CPR group had a significantly higher heart rate and lower mean arterial pressure (MAP) than those in the STD-CPR group (heart rate: 106.8 versus 79.0, P < 0.001; MAP: 60.0 versus 67.3 mm Hg, P = 0.003). The posttreatment PCO2 was significantly lower in ALP-CPR group than in STD-CPR group (52.33 versus 58.81, P = 0.009). PO2 was significantly increased after ALP-CPR (45.15 to 60.68, P < 0.001), but it was not changed after STD-CPR. PO2 after CPR was significantly higher in the ALP-CPR group (60.68 versus 44.47, P < 0.001). There were no differences between genders and for patients who are > 65 or ≤ 65 years of age. Conclusions. The abdominal lifting and compression cardiopulmonary resuscitation device used in this study is associated with a higher survival rate after ROSC than standard CPR.

Lichong Shengsui Yin (LCSSY) is an effective and classic compound prescription of Traditional Chinese Medicines (TCMs) used for the treatment of ovarian cancer. To investigate its pharmacodynamic basis for treating ovarian cancer, the multi-dimensional spectrum-effect relationship was determined. Four compositions (I to IV) were obtained by extracting LCSSY successively with supercritical CO₂ fluid extraction, 75% ethanol reflux extraction, and the water extraction-ethanol precipitation method. Nine samples for pharmacological evaluation and fingerprint analysis were prepared by changing the content of the four compositions. The specific proportions of the four compositions were designed according to a four-factor, three-level L₉(3⁴) orthogonal test. The pharmacological evaluation included in vitro tumor inhibition experiments and the survival extension rate in tumor-bearing nude mice. The fingerprint analyzed by chromatographic condition I (high-performance liquid chromatography-photodiode array detec tor，HPLC-PDA) identified 19 common peaks. High-performance liquid chromatography-photodiode array detector-Evaporative Light-scattering Detector (HPLC-PDA-ELSD )hyphenated techniques were used to compensate for the use of a single detector, and the fingerprint analyzed by chromatographic condition II identified 28 common peaks in PDA and 23 common peaks in ELSD. Furthermore, multiple statistical analyses were utilized to calculate the relationships between the peaks and the pharmacological results. The union of the regression and the correlation analysis results were the peaks of X₅, X₉, X11, X12, X16, X18, Y₅, Y₈, Y12, Y14, Y20, Z₄, Z₅, Z₆, and Z₈. The intersection of the regression and the correlation analysis results were the peaks of X11, X12, X16, X18, Y₅, Y12, and Z₅. The correlated peaks were assigned by comparing the fingerprints with the negative control samples and reference standard samples, and identifying the structure using high-performance liquid chromatography-mass spectrometry detector(HPLC-MS). The results suggested that the pharmacodynamic basis of LCSSY on anti-ovarian cancer activities were germacrone, furandiene, β-elemene, calycosin-7-glucoside, ononin, epimedin B, icariin, ginsenoside Rc, astragaloside, ginsenoside Rd, astragaloside II, and some unknown components.

Hemotropic mycoplasmas (hemoplasmas) are emerging zoonotic pathogens with a worldwide distribution that can cause mild to severe hemolytic anemia, icterus, ill-thrift, infertility, and poor weight gain. However, understanding of the molecular epidemiology of hemoplasmas (Mycoplasma ovis and 'Candidatus Mycoplasma haemovis') is limited in sheep and goats, and the hemoplasma strain/species/variant 'Candidatus M. haemovis' was poorly studied throughout the world and had never been detected in China until now. Thus, the aim of the present study was to determine the molecular prevalence of hemoplasmas, including M. ovis and 'Candidatus M. haemovis' in sheep and goats from seven provinces and one autonomous region of China.

This cross sectional investigation included 12,966 subjects with hypertension, a cohort of the China Stroke Primary Prevention Trial (CSPPT), a randomized, multicenter clinical trial. This study aimed to explore the correlation between serum uric acid (SUA) concentration and hypertensive retinopathy in hypertensive adults.