Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on.

Vitellogenin (Vg) is synthesized in the fat body of the female silkworm Bombyx mori and transported to the oocyte as a source of nutrition for embryo development. It is well known that ecdysone regulates physiological, developmental and behavioral events in silkworm. However, it is still not clear how the ecdysone regulates B. mori Vg (BmVg) transcription.

Interferon regulatory factor 4 (IRF4) in mammals is known to be critical in regulation of development and functions of lymphomyeloid cell lineages. Recent studies have demonstrated its involvement in immune responses to bacterial and viral challenges in teleosts. In this study, an IRF4 gene was cloned from Japanese flounder (Paralichthys olivaceus) and its expression in response to polyinosinic:polycytidylic acid [poly(I:C)] and lymphocystis disease virus (LCDV) stimulations was studied in vivo. The cloned gene spans over 5.9 kb, comprises eight exons and seven introns and encodes a putative protein of 456 amino acids. The deduced amino acid sequence possesses a conserved DNA-binding domain (DBD), an IRF-association domain (IAD) and a nuclear localization signal (NLS). Phylogenetic analysis clustered it into the teleost IRF4b clade and, thus, it was named Paralichthys olivaceus (Po)IRF4b. The constitutive expression of PoIRF4b transcripts was detectable in all examined organs, with highest levels found in lymphomyeloid-rich tissues. They were induced by both poly(I:C) and LCDV with a similar inducibility in immune or non-immune organs. Two waves of induced expression of PoIRF4b were observed with the two stimuli during a 7-day time course in the immune organs, with the early-phase induction being stronger. The maximum increases of PoIRF4b transcript levels ranged from 1.3 to 4.0-fold and appeared at day 1-5 post-injection depending on different organs and stimuli. In both stimulation cases, the strongest induction was detected in spleen and the weakest in muscle. These results indicate that PoIRF4b may participate in regulation of immune responses of flounders to both RNA and DNA virus infections.

Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent.

The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20-22 years) who immigrated to the Qinghai-Tibet Plateau (2300-4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits.

Mycoplasma bovis (M. bovis) is a major, but often overlooked, pathogen documented to cause respiratory disease, mastitis, and arthritis in cattle throughout China since 2008. Here, we report the development of a direct competitive enzyme-linked immunosorbent assay (Dc-ELISA) to detect M. bovis antibody.

Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS), lowering blood glucose, free fatty acids (FFA) and triglyceride (TG) levels in several models of dyslipidemia, as well as improving body weight (obesity), insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD) fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. In the HFrD treatment group, NDGA administration by oral gavage decreased plasma levels of TG, glucose, FFA, and insulin, increased hepatic mitochondrial fatty acid oxidation and attenuated hepatic TG accumulation. qRT-PCR measurements indicated that NDGA treatment increased the mRNA expression of key fatty acid transport (L-FABP, CD36), and fatty acid oxidation (ACOX1, CPT-2, and PPARα transcription factor) genes and decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors). Western blot analysis indicated that NDGA administration upregulated hepatic insulin signaling (P-Akt), AMPK activity (P-AMPK), MLYCD, and PPARα protein levels, but decreased SCD1, ACC1 and ACC2 protein content and also inactivated ACC1 activity (increased P-ACC1). These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation.

Epacromius coerulipes (Ivanov) is one of the most widely distributed locusts. To date, the main methods to kill locusts still rely on chemical controls, which can result in the selection of locusts with resistance to chemical pesticides. Butene-fipronil is a new pesticide that was discovered by the structural modification of fipronil. This pesticide has been used to control various agricultural pests and has become an important pesticide product to control pests that exhibit resistance to other pesticides, including locusts. To extend its useful half-life, studies of the initiation and progression of resistance to this pesticide are needed. Herein, two E. coerulipes strains, a pesticide-sensitive (PS) and a pesticide-resistant (PR) strain, were chosen to undergo de novo assembly by paired-end transcriptome Illumina sequencing. Overall, 63,033 unigenes were detected; the average gene length was 772 bp and the N50 was 1,589 bp. Among these unigenes, ∼ 25,132 (39.87% of the total) could be identified as known proteins in bioinformatic databases from national centers. A comparison of the PR and PS strains revealed that 2,568 genes were differentially expressed, including 1,646 and 922 genes that were up- and down-regulated, respectively. According to the Gene Ontology (GO) database, among biological processes the metabolic process group was the largest group (6,900 genes, 22.47%) and contained a high frequency of differentially expressed genes (544 genes, 27.54%). According to the Clusters of Orthologous Groups (COG) categories, 28 genes, representing 2.98% of all genes, belonged to the group of genes involved in the biosynthesis, transportation, and catabolism of secondary metabolites. The differentially expressed genes that we identified are involved in 50 metabolic pathways. Among these pathways, the metabolism pathway was the most represented. After enrichment analysis of differential gene expression pathways, six pathways--ribosome; starch, and sucrose metabolism; ascorbate and aldarate metabolism; drug metabolism-cytochrome P450; metabolism of xenobiotics by cytochrome P450; and glutathione metabolism--showed a high degree of enrichment. Among these pathways, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, and glutathione metabolism have been associated with pesticide metabolism. Furthermore, 316 unigenes in the E. coerulipes transcriptome encode detoxifying enzymes and 76 unigenes encode target proteins of pesticides. Among these genes, 23 genes that encode detoxifying enzymes in the resistance group were found to be up-regulated. The transcriptome sequencing results of E. coerulipes established a genomics database of E. coerulipes for the first time. This study also establishes a molecular basis for gene function analysis of E. coerulipes Moreover, it provides a theoretical resource for mechanistic studies on pesticide resistance through the screening and investigation of resistance genes.

The interactions between viruses and cellular autophagy have been widely reported. On the one hand, autophagy is an important innate immune response against viral infection. On the other hand, some viruses exploit the autophagy pathway for their survival and proliferation in host cells. Vaccinia virus is a member of the family of Poxviridae which includes the smallpox virus. The biogenesis of vaccinia envelopes, including the core envelope of the immature virus (IV), is not fully understood. In this study we investigated the possible interaction between vaccinia virus and the autophagy membrane biogenesis machinery. Massive LC3 lipidation was observed in mouse fibroblast cells upon vaccinia virus infection. Surprisingly, the vaccinia virus induced LC3 lipidation was shown to be independent of ATG5 and ATG7, as the atg5 and atg7 null mouse embryonic fibroblasts (MEFs) exhibited the same high levels of LC3 lipidation as compared with the wild-type MEFs. Mass spectrometry and immunoblotting analyses revealed that the viral infection led to the direct conjugation of ATG3, which is the E2-like enzyme required for LC3-phosphoethanonamine conjugation, to ATG12, which is a component of the E3-like ATG12–ATG5-ATG16 complex for LC3 lipidation. Consistently, ATG3 was shown to be required for the vaccinia virus induced LC3 lipidation. Strikingly, despite the high levels of LC3 lipidation, subsequent electron microscopy showed that vaccinia virus-infected cells were devoid of autophagosomes, either in normal growth medium or upon serum and amino acid deprivation. In addition, no autophagy flux was observed in virus-infected cells. We further demonstrated that neither ATG3 nor LC3 lipidation is crucial for viral membrane biogenesis or viral proliferation and infection. Together, these results indicated that vaccinia virus does not exploit the cellular autophagic membrane biogenesis machinery for their viral membrane production. Moreover, this study demonstrated that vaccinia virus instead actively disrupts the cellular autophagy through a novel molecular mechanism that is associated with aberrant LC3 lipidation and a direct conjugation between ATG12 and ATG3.

Gossypium barbadense (Sea Island, Egyptian or Pima cotton) cotton has high fiber quality, however, few studies have investigated the genetic basis of its traits using molecular markers. Genome complexity reduction approaches such as genotyping-by-sequencing have been utilized to develop abundant markers for the construction of high-density genetic maps to locate quantitative trait loci (QTLs).

The environmental risk of potentially toxic metals in tailing soils is of universal concern. We conducted a 3-month pot experiment to research the distribution and variations of potentially toxic metals (PTMs), and the translocation and accumulation capability of these metals (Cr, Ni, Mn, Cu, Zu) in natural plants for three Fe/Mg tailing soils (serpentine-type, olivine-type and magnetite-type) with growth of a grass plant-Imperata cylindrica. We used comparative analysis, regression analysis and correlation analysis to process relevant experimental data. Results showed the rhizosphere tailing soils decreased from 3.70% to 16.8%, compared to the bulk soils, after growth of Imperata cylindrica, and the acid soluble fraction of Mn, Cu and Zn increased significantly. Cu and Zn were more bioavailable than other PTMs, especially for serpentine-type tailing soils. Linear regression analysis indicated that non-residual fractions showed different effects on metal concentrations of Imperata cylindrica. The non-residual metal fractions of serpentine-type and olivine-type tailing soils showed better correlations with metal concentrations in grass plants than those of magnetite-type tailing soils. We found that the chemical compositions of tailing soils showed remarkable effects on Ni and Mn compared with other elements, especially Mg and Al. Overall, the grass plant can alter the metal distribution, enhance metal bioavailability and promote land use of Fe/Mg tailing soils.

The pedunculopontine nucleus (PPN) shows altered electrophysiological and anatomic characteristics in Parkinson's disease (PD), but little is known about the effect of 6-hydroxydopamine (6-OHDA) lesion and levodopa (L-DOPA) therapy on the relationship between spike and local field potential (LFP) activities in the PPN and motor cortex. Aiming to investigate this, synchronous spike and LFP signals in the PPN and primary motor cortex (M1) were recorded. The spike-LFP relationship was evaluated using coherence analysis, phase-lock and spike-field coherence (SFC). The results suggested that 6-OHDA lesion had a significant effect on the spike-LFP relationship between the PPN and M1 in rats under a rest or locomotion state. The significantly altered frequency bands varied across different neuron types and animal activity states. In addition, the altered coherence values between PPN spike and M1 LFP were refractory to long-term L-DOPA therapy although all other changes could be reversed by this drug treatment. All results provided evidence of the spike-LFP relationship between the PPN and M1 in PD, revealing some network mechanisms of the cortico-basal ganglia circuitry and PPN, which might be an underlying candidate for PD pathophysiology and therapy.

Osteoarthritis (OA) is an aging-related chronic degenerative disease characterized by the degradation of chondrocyte extracellular matrix (ECM). Previous studies have suggested that microRNAs (miRNAs) are associated with OA, but the role of miR-146b in OA remains unclear. The aim of this study was to determine the role of miR-146b in OA progression. The effect of miR-146b on ECM degradation were studied in mouse chondrocytes transfected with miRNA and treated with IL-1β. Cell viability and the expression levels of proteolytic enzymes in the transfected cells were assessed by real-time RT-PCR, ELISA and Western blots. We found downregulation of miR-146b expression in chondrocytes dramatically inhibited IL-1β-induced caspase activation and proteolytic enzyme expression via influencing its targeted Alpha-2-macroglobulin (A2M). Luciferase reporter assays confirmed that A2M mRNA was negatively regulated by miR-146b in chondrocytes. Intra-articular injection of antago-miR-146b against miR-146b effectively protected mice from the progression of DMM-induced osteoarthritis by inhibiting cartilage proteoglycan degradation. Our study indicates that miR-146b plays a critical role in the progression of injury-induced osteoarthritis by directly targeting A2M expression to elevate the proteolytic enzyme production and stimulate chondrocytes apoptosis, and miR-146b as well as A2M could be therapeutic targets.

We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a Chinese neonate with mastocytosis carrying heterozygous mutation (c.2447A > T (p.D816V)) in KIT gene by episomal vector (EV) reprogramming system. This iPSC line carrying KIT gene mutation, was free of exogenous gene, showed a normal karyotype, expressed pluripotency markers and exhibited differentiation potential.

Carbamoyl phosphate synthetase I (CPS1) deficiency (CPS1D), is a rare autosomal recessive disorder, characterized by life-threatening hyperammonemia. In this study, we presented the detailed clinical features and genetic analysis of two patients with neonatal-onset CPS1D carrying two compound heterozygous variants of c.1631C > T (p.T544M)/c.1981G > T (p.G661C), and c.2896G > T (p.E966X)/c622-3C > G in CPS1 gene, individually. Out of them, three variants are novel, unreported including a missense (c.1981G > T, p.G661C), a nonsense (c.2896G > T, p.E966X), and a splicing change of c.622-3C > G. We reviewed all available publications regarding CPS1 mutations, and in total 264 different variants have been reported, with majority of 157 (59.5%) missense, followed by 35 (13.2%) small deletions. This study expanded the mutational spectrum of CPS1. Moreover, our cases and review further support the idea that most (≥90%) of the mutations were "private" and only ∼10% recurred in unrelated families.

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

The aim of the present study was to explore the miRNA-Gene regulatory mechanism in chronic lymphocytic leukemia (CLL), and identify new targets for the therapy of CLL. The miRNA expression dataset GSE62137 and mRNA expression dataset GSE22529 were downloaded from National Center of Biotechnology Information Gene Expression Omnibus database. In CLL samples compared with normal B cell samples, differentially expressed miRNAs (DEMs) were identified via the GEO2R instrument of GEO and differentially expressed genes (DEGs) were obtained via the limma package of R. Functional enrichment analysis of the DEGs was performed via the Database for Annotation, Visualization and Integrated Discovery. The targets of the DEMs were identified based on the miRNAWalk platform. The overlaps between the DEGs and the targets of the DEMs were selected, and the miRNA-Gene regulatory network was constructed based on the overlaps and the corresponding DEMs. A total of 63 DEMs and 504 DEGs were identified in CLL samples compared with normal B cell samples. Eleven enriched functional clusters of the DEGs were obtained. 405 miRNA-Gene regulatory pairs were identified. The miRNA-Gene regulatory pairs contained 351 target genes of the DEMs, including 9 overlaps with the DEGs. A miRNA-Gene regulatory network was constructed. Bioinformatics methods could help us develop a better understanding of the molecular mechanism of CLL. MiRNAs may play a critical role in regulating the process of CLL. They may affect CLL by regulating the processes of immunoreactivity and protein degradation. Genes such as Neurogenic Locus Notch Homolog Protein 2, PR/SET domain 4 and A-kinase anchoring protein 12 may be their regulating targets in CLL.

Induced pluripotent stem cell (iPSC) line (SDQLCHi012-A) was generated from peripheral blood mononuclear cells of an 11-month-old male who was diagnosed as inflammatory bowel disease-28 caused by compound heterozygote for IL10RA mutations (c.188 + 1G > A and c.301C > T). Non-integrating episomal vectors coding OCT4, SOX2, KLF4, BCL-XL and MYC were used for reprogramming. The established iPSC line contained the same mutations identified in the patient, showed a normal karyotype, differentiation potential in vitro and expressed pluripotency markers.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the accumulation of triglycerides and associated with obesity, hyperlipidemia and insulin resistance. Currently, there is no therapy for NAFLD. Emerging evidences suggest that the inhibition of liver X receptor (LXR) activity may be a potential therapy for hepatic steatosis. Here, we identified that sophoricoside is a selective antagonist of LXRβ. Sophoricoside protected against obesity and glucose tolerance, and inhibited lipid accumulation in the liver of high-fat diet-induced obesity (DIO) mice and methionine and choline-deficient diet-induced nonalcoholic steatohepatitis mice. Furthermore, sophoricoside inhibited malondialdehyde, and increased superoxide dismutase and glutathione in the liver of the mice. In HepG2 cells, pretreatment with sophoricoside rescued GSH concentration decrease induced by H2 O2 treatment. Our data suggest that sophoricoside is a novel LXRβ selective antagonist and may improve glucose and lipid dysfunction, and attenuate lipid accumulation in the liver of DIO mice via anti-oxidant properties, which may be developed as a therapy for NAFLD.

Given that the population of Chinese college and university graduates has become larger and larger year by year since 1999, the problem of individual graduate's employment and workplace adaptability has captured widespread social concern and interest from both scholars and practitioners. Initial work role behavior is essential to an individual graduate's successful adaptation to the workplace and sustainable career development as a new employee. Based on social cognition theory, sense-making theory, and regulatory focus theory, we argue that the individual graduate's zero-sum construal of workplace success is a key factor influencing his or her initial workplace adaptability, which not only directly augments initial work role behavior but also elicits the new employee's inclination toward prevention focus, which in turn enhances initial work role behavior in the context of China's present steady economic development. Moreover, the individual graduate's average pay level moderates the mediating effect of prevention focus, such that the higher the average pay level is, the stronger the positive effect of zero-sum construal on initial work role behavior via prevention focus becomes. Two-stage survey data from 258 Chinese university graduates who have already entered organizations as full-time employees and their direct supervisors provided evidence consistent with our hypothesized first-stage moderated mediation model. Implications, limitations, and future research suggestions are also discussed.