Some isoquinoline alkaloids from Macleaya cordata (Willd). R. Br. (Bo Luo Hui) exhibited antibacterial, antiparasitic, antitumor, and analgesic effects. The targets of these isoquinoline alkaloids are undefined. This study aims to investigate the compound-target interaction network and potential pharmacological actions of isoquinoline alkaloids of M. cordata by reverse pharmacophore database screening.

Using a culture-independent method that combines CARD-FISH, qPCR and 16S rDNA, we investigated the abundance, community structure and diversity of microbes along a steep thermal gradient (50-90 °C) in the Tengchong Geothermal Field. We found that Bacteria and Archaea abundance changed markedly with temperature changes and that the number of cells was lowest at high temperatures (90.8 °C). Under low-temperature conditions (52.3-74.6 °C), the microbial communities were dominated by Bacteria, which accounted for 60-80% of the total number of cells. At 74.6 °C, Archaea were dominant, and at 90.8 °C, they accounted for more than 90% of the total number of cells. Additionally, the microbial communities at high temperatures (74.6-90.8 °C) were substantially simpler than those at the low-temperature sites. Only a few genera (e.g., bacterial Caldisericum, Thermotoga and Thermoanaerobacter, archaeal Vulcanisaeta and Hyperthermus) often dominated in high-temperature environments. Additionally, a positive correlation between Ammonia-Oxidizing Archaea (AOA) activity and temperature was detected. AOA activity increased from 17 to 52 pmol of NO2(-) per cell d(-1) with a temperature change from 50 to 70 °C.

Socially-conveyed rules and instructions strongly shape expectations and emotions. Yet most neuroscientific studies of learning consider reinforcement history alone, irrespective of knowledge acquired through other means. We examined fear conditioning and reversal in humans to test whether instructed knowledge modulates the neural mechanisms of feedback-driven learning. One group was informed about contingencies and reversals. A second group learned only from reinforcement. We combined quantitative models with functional magnetic resonance imaging and found that instructions induced dissociations in the neural systems of aversive learning. Responses in striatum and orbitofrontal cortex updated with instructions and correlated with prefrontal responses to instructions. Amygdala responses were influenced by reinforcement similarly in both groups and did not update with instructions. Results extend work on instructed reward learning and reveal novel dissociations that have not been observed with punishments or rewards. Findings support theories of specialized threat-detection and may have implications for fear maintenance in anxiety.

Discoid lateral meniscus (DLM) is relatively common in East Asia..Symptomatic discoid lateral meniscus (SDLM) is an important indication for knee arthroscopic surgery. However, studies investigating SDLM are rare. The purpose of this study was to evaluate the clinical characteristics and intra-articular variants of SDLM in a Chinese population.

Due to the proved clinical efficacy, Shuang-Huang-Lian (SHL) has developed a variety of dosage forms. However, the in-depth research on targets and pharmacological mechanisms of SHL preparations was scarce. In the presented study, the bioinformatics approaches were adopted to integrate relevant data and biological information. As a result, a PPI network was built and the common topological parameters were characterized. The results suggested that the PPI network of SHL exhibited a scale-free property and modular architecture. The drug target network of SHL was structured with 21 functional modules. According to certain modules and pharmacological effects distribution, an antitumor effect and potential drug targets were predicted. A biological network which contained 26 subnetworks was constructed to elucidate the antipneumonia mechanism of SHL. We also extracted the subnetwork to explicitly display the pathway where one effective component acts on the pneumonia related targets. In conclusions, a bioinformatics approach was established for exploring the drug targets, pharmacological activity distribution, effective components of SHL, and its mechanism of antipneumonia. Above all, we identified the effective components and disclosed the mechanism of SHL from the view of system.

Esophageal cancer is one of the most prevalent forms of cancer and has a particularly high mortality rate due to early metastasis; however, the underlying mechanisms of its formation and progression remain unclear. The present study performed immunohistochemical analysis and observed that the expression of activating transcription factor 3 (ATF3) was reduced in esophageal squamous cell carcinoma (ESCC) in comparison with non-tumor adjacent tissues. By contrast, inhibitor of DNA binding 1 (ID1) was overexpressed in ESCC tissues, demonstrating an inverse correlation with ATF3 (P<0.01). In ESCC EC109 and KYSE450 cells lines, transfection with an ATF3-overexpression plasmid resulted in the inhibition of cell proliferation, motility and migration, which was associated with the induction of E-cadherin expression and inhibition of cyclin D1 and Twist. Notably, ATF3 exerted an inverse regulatory interaction with ID1. The results of the present study provide additional evidence of the tumor suppressive features of ATF3 and demonstrate a novel mechanism of ATF3-mediated inhibition of cancer metastasis in esophageal cancer.

Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children. There is thus an urgent need to find new treatments to control EV71 infection. In this study, we report potent inhibition of EV71 by a polyene antibiotic Amphotericin B. Amphotericin B profoundly diminished the expression of EV71 RNA and viral proteins in the RD cells and the HEK293 cells. As a result, EV71 production was inhibited by Amphotericin B with an EC50 (50% effective concentration) of 1.75 μM in RD cells and 0.32 μM in 293 cells. In addition to EV71, EV68 was also strongly inhibited by Amphotericin B. Results of mechanistic studies revealed that Amphotericin B targeted the early stage of EV71 infection through impairing the attachment and internalization of EV71 by host cells. As an effective anti-fungi drug, Amphotericin B thus holds the promise of formulating a novel therapeutic to treat EV71 infection.

MiR-98 expression was up-regulated in kidney in response to early diabetic nephropathy in mouse and down-regulated in muscle in type 2 diabetes in human. However, the expression prolife and functional role of miR-98 in human gestational diabetes mellitus (GDM) remained unclear. Here, we investigated its expression and function in placental tissues from GDM patients and the possible molecular mechanisms. The results showed that miR-98 was up-regulated in placentas from GDM patients compared with normal placentas. MiR-98 over-expression increased global DNA methylational level and miR-98 knockdown reduced global DNA methylational level. Further investigation revealed that miR-98 could inhibit Mecp2 expression by binding the 3'-untranslated region (UTR) of methyl CpG binding protein 2 (Mecp2), and then led to the expression dysregulation of canonical transient receptor potential 3 (Trpc3), a glucose uptake related gene. More importantly, in vivo analysis found that the expression level of Mecp2 and Trpc3 in placental tissues from GDM patients, relative to the increase of miR-98, was diminished, especially for GDM patients over the age of 35 years. Collectively, up-regulation of miR-98 in the placental tissues of human GDM is linked to the global DNA methylation via targeting Mecp2, which may imply a novel regulatory mechanism in GDM.

Steroid-induced osteonecrosis of the femoral head (ONFH) is the most common clinical nontraumatic ONFH. Once ONFH occurs, it seriously reduces patients' quality of life. The matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) system was found to play a significant role in the development of ONFH. The aim of this study was to identify the associations between 7 genes selected from the MMP/TIMP system and steroid-induced ONFH.

In southwest China, some maize landraces have long been isolated geographically, and have phenotypes that differ from those of widely grown cultivars. These landraces may harbor rich genetic variation responsible for those phenotypes. Four-row Wax is one such landrace, with four rows of kernels on the cob. We resequenced the genome of Four-row Wax, obtaining 50.46 Gb sequence at 21.87× coverage, then identified and characterized 3,252,194 SNPs, 213,181 short InDels (1-5 bp) and 39,631 structural variations (greater than 5 bp). Of those, 312,511 (9.6%) SNPs were novel compared to the most detailed haplotype map (HapMap) SNP database of maize. Characterization of variations in reported kernel row number (KRN) related genes and KRN QTL regions revealed potential causal mutations in fea2, td1, kn1, and te1. Genome-wide comparisons revealed abundant genetic variations in Four-row Wax, which may be associated with environmental adaptation. The sequence and SNP variations described here enrich genetic resources of maize, and provide guidance into study of seed numbers for crop yield improvement.

With emergence and geographically expanding of antimalarial resistance worldwide, molecular markers are essential tool for surveillance of resistant Plasmodium parasites. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain are shown to be associated with artemisinin (ART) resistance in vivo and in vitro. This study aims to investigate the ART resistance-associated polymorphisms of K13-propeller and PfATPase6 genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea (EG).

Mainstream psychological stress theory claims that it is important to include information on people's ways of coping with work stress when assessing the impact of stressful psychosocial work environments on health. Yet, some widely used respective theoretical models focus exclusively on extrinsic factors. The model of effort-reward imbalance (ERI) differs from them as it explicitly combines information on extrinsic and intrinsic factors in studying workers' health. As a growing number of studies used the ERI model in recent past, we conducted a systematic review of available evidence, with a special focus on the distinct contribution of its intrinsic component, the coping pattern "over-commitment", towards explaining health. Moreover, we explore whether the interaction of intrinsic and extrinsic components exceeds the size of effects on health attributable to single components. Results based on 51 reports document an independent explanatory role of "over-commitment" in explaining workers' health in a majority of studies. However, support in favour of the interaction hypothesis is limited and requires further exploration. In conclusion, the findings of this review support the usefulness of a work stress model that combines extrinsic and intrinsic components in terms of scientific explanation and of designing more comprehensive worksite stress prevention programs.

Next-generation sequencing (NGS) technologies that have advanced rapidly in the past few years possess the potential to classify diseases, decipher the molecular code of related cell processes, identify targets for decision-making on targeted therapy or prevention strategies, and predict clinical treatment response. Thus, NGS is on its way to revolutionize oncology. With the help of NGS, we can draw a finer map for the genetic basis of diseases and can improve our understanding of diagnostic and prognostic applications and therapeutic methods. Despite these advantages and its potential, NGS is facing several critical challenges, including reduction of sequencing cost, enhancement of sequencing quality, improvement of technical simplicity and reliability, and development of semiautomated and integrated analysis workflow. In order to address these challenges, we conducted a literature research and summarized a four-stage NGS workflow for providing a systematic review on NGS-based analysis, explaining the strength and weakness of diverse NGS-based software tools, and elucidating its potential connection to individualized medicine. By presenting this four-stage NGS workflow, we try to provide a minimal structural layout required for NGS data storage and reproducibility.

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate gene expression by post-transcriptional repression of mRNAs. The swimming crab Portunus trituberculatus is one of the most important crustacean species for aquaculture in China. However, to date no miRNAs have been reported to for modulating growth in P. trituberculatus. To investigate miRNAs involved in the growth of this species, we constructed six small RNA libraries for big individuals (BIs) and small individuals (SIs) from a highly inbred family. Six mixed RNA pools of five tissues (eyestalk, gill, heart, hepatopancreas, and muscle) were obtained. By aligning sequencing data with those for known miRNAs, a total of 404 miRNAs, including 339 known and 65 novel miRNAs, were identified from the six libraries. MiR-100 and miR-276a-3p were among the most prominent miRNA species. We identified seven differentially expressed miRNAs between the BIs and SIs, which were validated using real-time PCR. Preliminary analyzes of their putative target genes and GO and KEGG pathway analyzes showed that these differentially expressed miRNAs could play important roles in global transcriptional depression and cell differentiation of P. trituberculatus. This study reveals the first miRNA profile related to the body growth of P. trituberculatus, which would be particularly useful for crab breeding programs.

Acute lung injury (ALI), which is associated with severe acute pancreatitis (SAP), results from damage to the pulmonary microvascular endothelial cells (PMVECs), which in turn leads to high levels of inflammatory cytokines that destroy PMVECs. However, the molecular mechanisms underlying SAP-associated ALI (SAP-ALI) are currently not well understood. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the persistent migration and accumulation of neutrophils and macrophages, which in turn has been associated with the increased permeability of microvascular endothelial cells. Signal transduction via the Janus kinase-2 (JAK2)/signal transducer and activator of transcription-3 (STAT3) transcription factors has been shown to be involved in inflammation. The present study aimed to investigate the expression levels of ICAM-1 and JAK2/STAT3 signaling components in a rat model of SAP-ALI. SAP was induced in the rat model, and dexamethasone (DEX) was administered to the treatment group. Subsequently, ICAM-1, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, JAK2, STAT3 and nuclear factor (NF)-κB mRNA expression levels were determined using reverse transcription-polymerase chain reaction; ICAM-1 protein expression levels were determined using western blotting; and IL-6, IL-8 and TNF-α levels were measured via an enzyme-linked immunosorbent assay. In addition, an immunohistochemical analysis of ICAM-1, NF-κB, JAK2 and STAT3 was conducted, and the protein expression and cell morphology of the lungs in all rats was analyzed. ICAM-1 mRNA and protein expression levels were significantly increased following induction of SAP, and were significantly decreased in the DEX-treated group. Furthermore, treatment with DEX significantly reduced serum expression levels of IL-6, IL-8 and TNF-α and decreased expression levels of NF-κB, JAK2 and STAT3 in the lung tissue, as compared with the untreated SAP group. The present study demonstrated that DEX treatment was able to suppress ICAM-1 mRNA and protein expression in a rat model of SAP-ALI via the inhibition of IL-6 and TNF-α-induced JAK2/STAT3 activation; thus suggesting that DEX treatment may be considered a potential strategy in the treatment of patients with SAP-ALI.

The purpose of the study was to determine the inhibitory effects of Lactobacillus fermentum Suo (LF-Suo) on HCl/ethanol induced gastric injury in ICR (Institute for Cancer Research) mice and explain the mechanism of these effects through the molecular biology activities of LF-Suo. The studied mice were divided into four groups: healthy, injured, LF-Suo-L and LF-Suo-H group. After the LF-Suo intragastric administration, the gastric injury area was reduced compared to the injured group. The serum MOT (motilin), SP (substance P), ET (endothelin) levels of LF-Suo treated mice were lower, and SS (somatostatin), VIP (vasoactive intestinal peptide) levels were higher than the injured group mice. The cytokine IL-6 (interleukin 6), IL-12 (interleukin 12), TNF-α (tumor necrosis factor-α) and IFN-γ (interferon-γ) serum levels were decreased after the LF-Suo treatment. The gastric tissues SOD (superoxide dismutase), GSH-Px (glutathione peroxidase), NO (nitric oxide) and activities of LF-Suo treated mice were increased and MDA (malondialdehyde) activity was decreased compared to the injured group mice. By the RT-PCR assay, LF-Suo raised the occludin, EGF (epidermal growth factor), EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), Fit-1 (fms-like tyrosine kinase-1), IκB-α (inhibitor kappaB-α), nNOS (neuronal nitric oxide synthase), eNOS (endothelial nitric oxide synthase), Mn-SOD, Cu/Zn-SOD, CAT (catalase) mRNA or protein expressions and reduced the COX-2, NF-κB (nuclear factor kappaB), and iNOS (inducible nitric oxide synthase) expressions in gastric tissues compared to the gastric injured group mice. A high concentration (1.0 × 10⁸ CFU/kg b.w.) of LF-Suo treatment showed stronger anti-gastric injury effects compared to a low concentration of (0.5 × 10⁸ CFU/kg b.w.) of LF-Suo treatment. LF-Suo also showed strong survival in pH 3.0 man-made gastric juice and hydrophobic properties. These results indicate that LF-Suo has potential use as probiotics for its gastric injury treatment effects.

The CYP17A1 gene encodes cytochrome P450c17α, an enzyme that catalyzes the formation of sex hormones, which have been linked to the pathogenesis of Alzheimer's disease (AD). An association between the CYP17A1 rs743572 single nucleotide polymorphism (SNP) and AD has been reported; however, the findings are controversial. In the present study, we investigated the association between rs743572 and another SNP, rs3824755, and AD risk in a Chinese Han population (n=207 patients and 239 controls), and their interaction with the apolipoprotein E (APOE) e4 allele. We found that the C allele and GC+CC genotypes of rs3824755 conferred protection against AD only in APOE e4 carriers. Both rs3824755 and rs743572 polymorphisms showed interactions with APOE e4. The C allele and GC+CC genotypes of rs3824755 acted as protective factors that decreased the risk of APOE e4 in AD. The CYP17A1 rs743572G allele and AG+GG genotypes were found to be potential risk factors that act synergetically with APOE e4. Moreover, the CA and GG haplotypes were protective and conferred a slight risk, respectively, in APOE e4 carriers. These results indicate that CYP17A1 rs3824755 and rs743572 are associated with AD in the Chinese Han population and act in combination with APOE e4.

In the present study, we constructed a lentivirus, FIV-CMV-GFP-miR-7-3, containing the microRNA-7-3 gene and the green fluorescent protein gene, and used it to transfect human glioma U251 cells. Fluorescence microscopy showed that 80% of U251 cells expressed green fluorescence. Real-time reverse transcription PCR showed that microRNA-7-3 RNA expression in U251 cells was significantly increased. Proliferation was slowed in transfected U251 cells, and most cells were in the G1 phase of the cell cycle. In addition, the expression of the serine/threonine protein kinase 2 was decreased. Results suggested that transfection with a lentivirus carrying microRNA-7-3 can effectively suppress epidermal growth factor receptor pathway activity in U251 cells, arrest cell cycle transition from G1 phase to S phase and inhibit glioma cell growth.

To overcome the increasing resistance of pathogens to existing antibiotics the 10×'20 Initiative declared the urgent need for a global commitment to develop 10 new antimicrobial drugs by the year 2020. Naturally occurring animal antibiotics are an obvious place to start. The recently sequenced genomes of mammals that are divergent from human and mouse, including the tammar wallaby and the platypus, provide an opportunity to discover novel antimicrobials. Marsupials and monotremes are ideal potential sources of new antimicrobials because they give birth to underdeveloped immunologically naïve young that develop outside the sterile confines of a uterus in harsh pathogen-laden environments. While their adaptive immune system develops innate immune factors produced either by the mother or by the young must play a key role in protecting the immune-compromised young. In this study we focus on the cathelicidins, a key family of antimicrobial peptide genes.

Fructose-based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) is a novel antitumor agent and belongs to glycosylated spiro-heterocyclic oxadiazole scaffold derivative. This research first reported a simple, specific, sensitive and stable high performance liquid chromatography-ultraviolet detector (HPLC-UV) method for the quantitative determination of GLB in plasma. In this method, the chromatographic separation was achieved with a reversed phase C18 column. The calibration curve for GLB was linear at 300 nm. The lower limit of quantification was 10 ng/mL. The precision, accuracy and stability of the method were validated adequately. This method was successfully applied to the pharmacokinetic study in rats for detection of GLB after oral administration. Moreover, the structures of parent compound GLB and its two major metabolites M1 and M2 were identified in plasma using an ultra performance liquid chromatography-electrospray ionization-quadrupole-time of flight- mass spectrometry (UPLC-ESI-QTOF-MS) method. Our results indicated that the di-hydroxylation (M1) and hydroxylation (M2) of GLB are the major metabolites. In conclusion, the present study provided valuable information on an analytical method for the determination of GLB and its metabolites in rats, can be used to support further developing of this antitumor agent.