Prenatal ethanol exposure (PEE) is an established risk factor for intrauterine growth retardation. The present study was designed to determine whether PEE can increase the susceptibility of high-fat diet (HFD)-induced metabolic syndrome (MS) in adult offspring in a sex-specific manner, based on a generalized linear model analysis. Pregnant Wistar rats were administered ethanol (4 g/kg.d) from gestational day 11 until term delivery. All offspring were fed either a normal diet or a HFD after weaning and were sacrificed at postnatal week 20, and blood samples were collected. Results showed that PEE reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels but enhanced serum glucose, insulin, insulin resistant index (IRI), triglyceride and total cholesterol (TC) concentrations. Moreover, the analysis showed interactions among PEE, HFD and sex. In the PEE offspring, HFD aggravated the decrease in ACTH and corticosterone levels and further increased serum glucose, insulin, triglyceride and TC levels. The changes of serum ACTH, glucose and IRI levels in the female HFD rats were greater than those in the male HFD rats. Our findings suggest that PEE enhances the susceptibility to MS induced by HFD in a sex-specific manner, which might be primarily associated with the neuroendocrine metabolic programming by PEE.

Rocaglates are a series of structurally complex secondary metabolites with considerable cytotoxicity that have been isolated from plants of the Aglaia genus (Meliaceae). A new rocaglate (aglapervirisin A, 1) and its eight new biosynthetic precursors of rocaglate (aglapervirisins B-J, 2-9) together with five known compounds, were isolated from the leaves of Aglaia perviridis. Their structures were elucidated based on a joint effort of spectroscopic methods [IR, UV, MS, ECD, 1D- and 2D-NMR, HRESIMS], chemical conversion and single-crystal X-ray diffraction. Among these isolates, three (1, 10-11) were silvestrols, a rare subtype rocaglates, exhibiting notable cytotoxicity against four human tumor cell lines, with IC50 values between 8.0 and 15.0 nM. Aglapervirisin A (1) induces cell cycle arrest at the G2/M-phase boundary at concentration 10 nM accompanied by reductions in the expression levels of Cdc2 and Cdc25C in HepG2 cells after 72h co-incubation, and further induces the apoptosis of HepG2 cells at concentrations over 160 nM.

Reintroduction of the threatened red-crowned crane has been unsuccessful. Although gut microbiota correlates with host health, there is little information on gut microbiota of cranes under different conservation strategies. The study examined effects of captivity, artificial breeding and life stage on gut microbiota of red-crown cranes. The gut microbiotas of wild, captive adolescent, captive adult, artificially bred adolescent and artificially bred adult cranes were characterized by next-generation sequencing of 16S rRNA gene amplicons. The gut microbiotas were dominated by three phyla: Firmicutes (62.9%), Proteobacteria (29.9%) and Fusobacteria (9.6%). Bacilli dominated the 'core' community consisting of 198 operational taxonomic units (OTUs). Both captivity and artificial breeding influenced the structures and diversities microbiota of the gut. Especially, wild cranes had distinct compositions of gut microbiota from captive and artificially bred cranes. The greatest alpha diversity was found in captive cranes, while wild cranes had the least. According to the results of ordination analysis, influences of captivity and artificial breeding were greater than that of life stage. Overall, captivity and artificial breeding influenced the gut microbiota, potentially due to changes in diet, vaccination, antibiotics and living conditions. Metagenomics can serve as a supplementary non-invasive screening tool for disease control.

Auricularia auricula-judae is an edible mushroom and a traditional medicine in China as well as the fourth largest cultivated mushroom species in the world. Here for the first time, we present comparative transcriptome analyses of the fruiting bodies of three morphologically distinguishable A. auricula-judae cultivated varieties (Wujin, smooth; Banjin, partially wrinkled; and Quanjin, fully wrinkled) collected from Jilin Province, China. Biological triplicates were performed to determine the expression levels of 13,937 unigenes. Among them, only 13 unigenes were annotated to A. auricula-judae, highlighting the lack of publicly available reference sequences for this economically important species. Principal component analysis (PCA) determined that the gene expression profile of Quanjin was unique when compared to those of Banjin and Wujin. Such relationships were further supported by analyses of annotated and unannotated unigenes, differentially expressed unigenes, gene ontology functions, and the family of peroxidase genes. Using the KEGG database, significant alternations in biological pathways were detected among the three cultivars. This work contributes a large set of A. auricula-judae sequences to public database, establishes the relationships among major cultivars, and provides molecular guidance for breeding and cultivation.

The general transcription factor IID (TFIID) is the first component of the preinitiation complex (PIC) to bind the core promoter of RNA polymerase II transcribed genes. Despite its critical role in protein-encoded gene expression, how TFIID engages promoter DNA remains elusive. We have previously revealed a winged-helix DNA-binding domain in the N-terminal region of the largest TFIID subunit, TAF1. Here, we report the identification of a second DNA-binding module in the C-terminal half of human TAF1, which is encoded by a previously uncharacterized conserved zinc knuckle domain. We show that the TAF1 zinc knuckle aids in the recruit of TFIID to endogenous promoters vital for cellular proliferation. Mutation of the TAF1 zinc knuckle with defects in DNA binding compromises promoter occupancy of TFIID, which leads to a decrease in transcription and cell viability. Together, our studies provide a foundation to understand how TAF1 plays a central role in TFIID promoter binding and regulation of transcription initiation.

Soil microorganisms play a crucial role in the biogeochemical cycling of nutrient elements and maintaining soil health. We aimed to investigate the response of bacteria communities to organic farming over different crops (rice, tea and vegetable) along the middle and lower reaches of the Yangtze River of China. Compared with conventional farming, organic farming significantly increased soil nutrients, soil enzyme activities, and bacterial richness and diversity. A Venn diagram and principal component analysis revealed that the soils with 3 different crops under organic farming have more number and percent of shared OTUs (operational taxonomic units), and shared a highly similar microbial community structure. Under organic farming, several predominant guilds and major bacterial lineages (Rhizobiales, Thiotrichaceae, Micromonosporaceae, Desulfurellaceae and Myxococcales) contributing to nutrient (C, N, S and P) cycling were enriched, whereas the relative abundances of acid and alkali resistant microorganisms (Acidobacteriaceae and Sporolactobacillaceae) were increased under conventional farming practices. Our results indicated that, for all three crops, organic farming have a more stable microflora and the uniformity of the bacterial community structure. Organic agriculture significantly increased the abundance of some nutrition-related bacteria, while reducing some of the abundance of acid and alkali resistant bacteria.

Oilseed rape (Brassica napus L.) is one of the most important oil crops in China as well as worldwide. Branch angle as a plant architecture component trait plays an important role for high density planting and yield performance. In this study, bulked segregant analysis (BSA) combined with next generation sequencing technology was used to fine map QTL for branch angle. A major QTL, designated as branch angle 1 (ba1) was identified on A06 and further validated by Indel marker-based classical QTL mapping in an F2 population. Eighty-two genes were identified in the ba1 region. Among these genes, BnaA0639380D is a homolog of AtYUCCA6. Sequence comparison of BnaA0639380D from small- and big-branch angle oilseed rape lines identified six SNPs and four amino acid variation in the promoter and coding region, respectively. The expression level of BnaA0639380D is significantly higher in the small branch angle line Purler than in the big branch angle line Huyou19, suggesting that the genomic mutations may result in reduced activity of BnaA0639380D in Huyou19. Phytohormone determination showed that the IAA content in Purler was also obviously increased. Taken together, our results suggested BnaA0639380D is a possible candidate gene for branch angle in oilseed rape.

The overall process of polyhydroxyalkanoates (PHA) production in a mixed culture fed by thermophilic fermented valerate-dominant sludge hydrolysate with high-level soluble organics (proteins and carbohydrates) and nutrients (nitrogen and phosphorus) was investigated in this study. The valerate-dominant hydrolysate was fed to enrich a PHA culture with an increasing concentration, and the enriched culture displayed a strong PHA-producing capacity under feast-famine conditions. Valerate in the feedstock was preferentially utilized over acetate and butyrate, and its uptake correlated with the production of 3-hydroxyvalerate (3HV) and 3-hydroxy-2-methylvalerate (3H2MV). The maximum PHA content (42.31%) was highest to date in a mixed culture with complex feedstock, and the PHA consisted of 3-hydroxybutyrate (3HB), 3HV, 3H2MV at 68.4, 23.7, 7.9 mmol C%. PHA production was inhibited when the nutrients exceeded a certain limit. Microbial analysis revealed that valerate-dominant feedstock caused Delftia (53%) to become the prevailing group over other PHA-producing bacteria. For long-term operation, 75% of the biomass at the end of feast phase was collected for PHA recovery, and the entire process exhibited a potential to produce 5 g PHA from 1 kg sludge. These findings indicate that the complex valerate-dominant sludge hydrolysate can be used to stably produce PHA containing high 3HV and 3H2MV.

The effect of lipid lowering on the incidence of deep venous thrombosis (DVT) is controversial. The purpose of this study was to determine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice. Pcsk9 deficient (pcsk9 -/-) and wild-type (WT) littermates underwent partial inferior vena cava (IVC) ligation to induce venous thrombosis. 48 hours following IVC ligation, IVC thrombosis was evident in 60% of WT mice and 25% of pcsk9 -/- mice (p < 0.05). Analysis of IVC thrombosis revealed greater thrombus weight, length, myeloid cell recruitment, and more neutrophil extracellular trap formation (NETs) in WT compared to pcsk9 -/- mice. Intravital microscopy performed two hours following partial IVC ligation revealed that leukocyte firm attachment was increased in WT mice compared to mice undergoing a sham operation, however leukocyte attachment was reduced in pcsk9 -/- mice compared to WT mice. In conclusion, deficiency of PCSK9 is associated with protection from venous thrombosis. This protection is associated with reduced leukocyte recruitment and NET formation at the site of thrombosis.

We previously demonstrated thatprenatal caffeine exposure (PCE) suppressed fetal adrenal steroidogenesis and resulted in developmental programming changes in offspring rats. However, whether these changes play a role in adrenal corticosterone synthesis under high-fat diet (HFD) and unpredictable chronic stress (UCS) remains unknown. In present study, rat model was established by PCE (120 mg/kg.d), and male offspring were provided normal diet or HFD after weaning. At postnatal week 21, several rats fed HFD were exposed to UCS for 3 weeks and sacrificed. The results showed that compared with the corresponding control group, the serum corticosterone levels and adrenal steroid synthetase expression of the PCE offspring without UCS were reduced. Moreover, the glucocorticoid (GC)-activation system was inhibited, and insulin-like growth factor 1 (IGF1) signaling pathway expression was increased. With UCS exposure in the PCE offspring, serum corticosterone levels and adrenal steroid synthetase expression were increased, the activity of GC-activation system was enhanced, and adrenal IGF1 signaling pathway expression was decreased. Based on these findings, PCE induced adrenal hypersensitivity in adult male offspring rats, as shown by the reduced corticosterone levels under HFD conditions but significantly enhanced corticosterone levels with UCS, in which GC-IGF1 axis programming alteration may play an important role.

Airway epithelial cell-derived thymic stromal lymphopoietin (TSLP) and IL-33 can enhance lung-resident group 2 innate lymphoid cells (ILC2s), and they play an important role in the development of allergic diseases. This study tests the hypothesis that Der f 31 (Dermatophagoides farinae-31), an allergen, modulates airway epithelial cell functions and increases the frequency of lung ILC2s. Our previous research identified cofilin (Der f 31) as a novel allergen. In this study, we found that recombinant Der f 31 (r-Der f 31) upregulated the expression of co-stimulatory molecules in DCs and promoted Th2-skewed polarization. The levels of TSLP and IL-33 in epithelial cells were upregulated by r-Der f 31 via the activation of Toll-like receptor 2. Furthermore, in in vivo studies, r-Der f 31 induced eosinophil-like airway allergy and increased the number of lung-resident ILC2s. In summary, Der f 31 can modulate the functions of airway epithelial cells and increase levels of lung-resident ILC2s.

RNA alternative splicing (AS) is an important post-transcriptional mechanism enabling single genes to produce multiple proteins. It has been well demonstrated that viruses deploy host AS machinery for viral protein productions. However, knowledge on viral AS is limited to a few disease-causing viruses in model species. Here we report a novel approach to characterizing viral AS using whole transcriptome dataset from host species. Two insect transcriptomes (Acheta domesticus and Planococcus citri) generated in the 1,000 Insect Transcriptome Evolution (1KITE) project were used as a proof of concept using the new pipeline. Two closely related densoviruses (Acheta domesticus densovirus, AdDNV, and Planococcus citri densovirus, PcDNV, Ambidensovirus, Densovirinae, Parvoviridae) were detected and analyzed for AS patterns. The results suggested that although the two viruses shared major AS features, dramatic AS divergences were observed. Detailed analysis of the splicing junctions showed clusters of AS events occurred in two regions of the virus genome, demonstrating that transcriptome analysis could gain valuable insights into viral splicing. When applied to large-scale transcriptomics projects with diverse taxonomic sampling, our new method is expected to rapidly expand our knowledge on RNA splicing mechanisms for a wide range of viruses.

Our previous studies revealed that many proteins in addition to the known allergens of D. farinae have not been fully characterized. We observed that Pplase did not respond to serum collected from patients sensitized to D. farinae. In a mouse model, Pplase significantly enhanced airway hyperresponsiveness (AHR) and Th2 responses induced by ovalbumin (OVA) compared with mice treated with OVA alone. Moreover, exposure to Pplase significantly increased the expression of IRF4, CD80, CD83, MHCII and TNF-α in DC2.4 cells, which was abolished in the presence of a TLR4 inhibitor. In vitro T cell polarization experiments revealed that Pplase alone could not induce T cell polarization but enhanced T cell polarization together with OVA. In addition, transfer of Pplase-primed bone marrow-derived DCs (BMDCs) to naïve mice enhanced AHR and Th2 immune responses in mice sensitized to OVA. In conclusion, Pplase is not an allergen of D. farinae but can activate DC cells to facilitate OVA-induced allergic responses.

With the discovery of magnetoreceptor mechanisms in animals, it materialized the novel applications of controlling cell and animal behaviors using magnetic fields. T cells have shown to be sensitive to magnetic fields. Here, we reported that exposure to moderate SMFs (static magnetic fields) led to increased granule and cytokine secretion as well as ATP production and mitochondrial respiration from CD8+ T cells. These effects were inhibited by knocking down the Uqcrb and Ndufs6 genes of mitochondrial respiratory chain, whose transcriptions were regulated by candidate magnetoreceptor genes Isca1 and Cry1/Cry2. SMF exposure also promoted CD8+ T cell granule and cytokine secretion and repressed tumor growth in vivo. SMFs enhanced CD8+ T cell cytotoxicity, and the adoptive transfer into tumor-bearing mice resulted in enhanced antitumor effects. Collectively, our study suggests that moderate SMFs enhance CD8+ T cell cytotoxicity by promoting mitochondrial respiration and promoted the antitumor function of CD8+ T cells.

Genotyping-by-Sequencing (GBS) is a low-cost, high-throughput genotyping method that relies on restriction enzymes to reduce genome complexity. GBS is being widely used for various genetic and breeding applications. In the present study, 2240 individuals from eight maize populations, including two association populations (AM), backcross first generation (BC1), BC1F2, F2, double haploid (DH), intermated B73 × Mo17 (IBM), and a recombinant inbred line (RIL) population, were genotyped using GBS. A total of 955,120 of raw data for SNPs was obtained for each individual, with an average genotyping error of 0.70%. The rate of missing genotypic data for these SNPs was related to the level of multiplex sequencing: ~ 25% missing data for 96-plex and ~ 55% for 384-plex. Imputation can greatly reduce the rate of missing genotypes to 12.65% and 3.72% for AM populations and bi-parental populations, respectively, although it increases total genotyping error. For analysis of genetic diversity and linkage mapping, unimputed data with a low rate of genotyping error is beneficial, whereas, for association mapping, imputed data would result in higher marker density and would improve map resolution. Because imputation does not influence the prediction accuracy, both unimputed and imputed data can be used for genomic prediction. In summary, GBS is a versatile and efficient SNP discovery approach for homozygous materials and can be effectively applied for various purposes in maize genetics and breeding.

Genetic factors were identified to be associated with the development of idiopathic pulmonary fibrosis (IPF). We aimed to investigate associations between mucin 5B (MUC5B) and telomerase reverse transcriptase (TERT) polymorphisms and telomere length (TL) with honeycombing extent and survival in a Chinese IPF cohort. Seventy-nine patients diagnosed with IPF were enrolled. The honeycombing extents in high resolution CT scan (HRCT) were quantitatively scored and defined as mild (<10%), moderate (10-50%), and severe (>50%) upon the honeycombing extents involving the total lung. We tested five single-nucleotide polymorphisms [rs35705950, rs868903 in MUC5B, rs2736100, rs2853676 in TERT and rs1881984 in Telomerase RNA Gene (TERC) and TLs in peripheral blood leucocytes, and evaluated their associations with radiographic extent and survival in IPF. The minor allele frequencies (MAF) were significantly greater for MUC5B rs868903 (P = 0.042) and TERT rs2853676 (P = 0.041) in IPF than those in healthy controls. CT/CC genotype of MUC5B rs868903 (p = 0.045) and short TLs (p = 0.035) were correlated with the more extensive honeycombing opacities in HRCT. After adjustment for age, sex, and smoking status, MUC5B rs868903 polymorphism was the significant gene risk factors for reduced survival (p = 0.044) in IPF. MUC5B promoter rs868903 polymorphism and TLs were associated with radiographic extent and survival in a Chinese IPF cohort. These findings suggested a genetic clue for exploring the underlying molecular basis and pathogenesis of IPF.

The application of straw and biochar can effectively improve soil quality, but whether such application impacts paddy soil bacterial community development remains to be clarified. Herein, the impacts of three different field amendment strategies were assessed including control (CK) treatment, rice straw (RS) application (9000 kg ha-1), and biochar (BC) application (3150 kg ha-1). Soil samples were collected at five different stages of rice growth, and the bacterial communities therein were characterized via high-throughput 16S rDNA sequencing. The results of these analyses revealed that soil bacterial communities were dominated by three microbial groups (Chloroflexi, Proteobacteria and Acidobacteria). Compared with the CK samples, Chloroflexi, Actinobacteria, Nitrospirae and Gemmatimonadetes levels were dominated phyla in the RS treatment, and Acidobacteria, Actinobacteria, Nitrospirae and Patescibacteria were dominated phyla in the BC treatment. Compared with the RS samples, Chloroflexi, Acidobacteria, Actinobacteria, and Verrucomicrobia levels were increased, however, Proteobacteria, Gemmatimonadetes, Nitrospirae, and Firmicute levels were decreased in the BC samples. Rhizosphere soil bacterial diversity rose significantly following RS and BC amendment, and principal component analyses confirmed that there were significant differences in soil bacterial community composition among treatment groups when comparing all stages of rice growth other than the ripening stage. Relative to the CK treatment, Gemmatimonadaceae, Sphingomonadaceae, Thiovulaceae, Burkholderiaceae, and Clostridiaceae-1 families were dominant following the RS application, while Thiovulaceae and uncultured-bacterium-o-C0119 were dominant following the BC application. These findings suggest that RS and BC application can improve microbial diversity and richness in paddy rice soil in Northeast China.

Dyslipidemia is one of the known risk factors for cardiovascular disease, and its prevalence is increasing worldwide. At present, the study of dyslipidemia has gradually shifted from simple environmental or genetic factors to environment-gene interactions. In order to further explore the etiology and mechanism of dyslipidemia, we used occupational stress(OS) and LYPLAL1, APOC3 and SOD2 gene as research variables to explore their association with dyslipidemia.Here we used a case-control study to include Han workers from a coal mining enterprise in China to determine the association between study variables and dyslipidemia. Monofactor analysis showed that smoking, drinking, physical activity level, DASH diet score, sleep quality, BMI, hypertension, hyperuricemia, shift work, OS were significantly different between the two groups (P < 0.05). In the APOC3 rs2854116 dominant model, patients with CT/CC genotype had a higher risk of dyslipidemia than those with TT genotype. In SOD2 rs4880 recessive model, patients with GG genotype had a lower risk of dyslipidemia than those with AA/AG genotype, and the difference was statistically significant. We found that rs12137855 and OS, rs2854116 and OS, rs4880 and OS had joint effects, but no interaction based on the multiplication and addition model was found (Pinteraction > 0.05). GMDR model showed that the rs12137855-rs2854116-rs4880-OS four-factor model had the highest cross-validation consistency and training-validation accuracy (P < 0.05), suggesting that there was a high-order interaction between them associated with dyslipidemia. We found that dyslipidemia in coal miners was related to OS and genetic factors. Through this study, we revealed the dual regulation of environmental factors and genetic factors on dyslipidemia. At the same time, this study provides clues for understanding the etiology and mechanism of dyslipidemia.

Motion sensitivity impairment in Alzheimer's disease (AD) is often characterized as elevated coherence threshold. An alternative way to measure motion sensitivity is the direction threshold, i.e., the minimal angle of motion direction that can be discriminated. So far, it is less clear whether and how the direction threshold is altered in AD. Here we asked a group of AD patients and two control groups of healthy participants (young and elderly adults) to judge their perceived heading direction based on a field of optic flow stimuli simulating a forward translation in the environment. We manipulated the heading direction and the coherence of the optic flow independently and measured the direction and coherence thresholds from each participant. We found that the direction threshold increased significantly in AD patients as compared to healthy controls, like the coherence threshold. Yet, the elevation in the direction threshold was less pronounced than the coherence threshold. Moreover, the magnitudes of the direction and coherence thresholds in AD patients were not correlated. Our results suggest that coherence and direction impairments are two distinct forms of motion deficits in AD patients which might be associated with independent neural mechanisms.

Fenton-like system formed in a natural soil environment deemed to be significant in the aging process of biochar. Aged biochars have distinct physico-chemical and surface properties compared to non-aged biochar. The aged biochar proved to be useful soil amendment due to its improved elements contents and surface properties. The biochar aging process resulted in increased surface area and pore volume, as well as carbon and oxygen-containing functional groups (such as C=O, -COOH, O-C=O etc.) on its surface, which were also associated with the adsorption behavior of 2,4,6-trichlorophenol (2,4,6-TCP). The biochar aging increased the adsorption capacity of 2,4,6-TCP, which was maximum at pH 3.0. The 2,4,6-TCP adsorption capacity of aged-bush biochar (ABB) and aged-peanut shell biochar (APB) was increased by 1.0-11.0% and 7.4-38.8%, respectively compared with bush biochar (BB) and peanut shell biochar (PB) at the same initial concentration of 2,4,6-TCP. All biochars had similar 2,4,6-TCP desorption rates ranging from 33.2 to 73.3% at different sorption temperatures and times. The desorbed components were mainly 2,4,6-TCP and other degraded components, which were low in concentration with small molecule substance. The results indicated that the aged-biochar could be effective for the long-term remediation of naturally organic polluted soils.