Search

Aims: Given the reversibility of methylation, biomarkers with discriminating ability are of great interest for targeted therapeutic sites. Materials & methods: Methylation array data of 461 lung adenocarcinoma (LUAD) patients comprising of 458 tumor and 32 LUAD paracancerous samples were compared using partial least squares discrimination analysis and receiver operating characteristics analysis. Results: A six-DNA methylation signature (corresponding to five genes) was found to significantly discriminate normal and LUAD samples. Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment of methylation sites in the Wnt pathway in LUAD compared with controls. Conclusion: This six-DNA methylation signature demonstrated potential as a novel biomarker for diagnosis and therapeutic targets. Further, inhibition of Wnt signaling pathway may be an important step in LUAD progression.

Background A key issue for implementation of CRISPR-Cas9 genome editing for plant trait improvement and gene function analysis is to efficiently deliver the components, including guide RNAs (gRNAs) and Cas9, into plants. Plant virus-based gRNA delivery strategy has proven to be an important tool for genome editing. However, its application in soybean which is an important crop has not been reported yet. ALSV (apple latent spherical virus) is highly infectious virus and could be explored for delivering elements for genome editing. Results To develop a ALSV-based gRNA delivery system, the Cas9-based Csy4-processed ALSV Carry (CCAC) system was developed. In this system, we engineered the soybean-infecting ALSV to carry and deliver gRNA(s). The endoribonuclease Csy4 effectively releases gRNAs that function efficiently in Cas9-mediated genome editing. Genome editing of endogenous phytoene desaturase (PDS) loci and exogenous 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) sequence in Nicotiana. benthamiana (N. benthamiana) through CCAC was confirmed using Sanger sequencing. Furthermore, CCAC-induced mutagenesis in two soybean endogenous GW2 paralogs was detected. Conclusions With the aid of the CCAC system, the target-specific gRNA(s) can be easily manipulated and efficiently delivered into soybean plant cells by viral infection. This is the first virus-based gRNA delivery system for soybean for genome editing and can be used for gene function study and trait improvement.

Symbiosis between soybean (Glycine max) and rhizobia is essential for efficient nitrogen fixation. Rhizobial effectors secreted through the type-III secretion system are key for mediating the interactions between plants and rhizobia, but the molecular mechanism remains largely unknown. Here, our genome-wide association study for nodule number identified G. max Nodule Number Locus 1 (GmNNL1), which encodes a new R protein. GmNNL1 directly interacts with the nodulation outer protein P (NopP) effector from Bradyrhizobium USDA110 to trigger immunity and inhibit nodulation through root hair infection. The insertion of a 179 bp short interspersed nuclear element (SINE)-like transposon into GmNNL1 leads to the loss of function of GmNNL1, enabling bradyrhizobia to successfully nodulate soybeans through the root hair infection route and enhancing nitrogen fixation. Our findings provide important insights into the coevolution of soybean–bradyrhizobia compatibility and offer a way to design new legume–rhizobia interactions for efficient symbiotic nitrogen fixation. Soybean accessions display a variable number of nodules when colonized by rhizobia. The authors identify one locus controlling this trait, a typical TIR–NBS–LRR disease resistance gene called NNL1, and the corresponding bacterial effector called NopP.

Studies on the biomagnification of short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) in terrestrial ecosystems and their bioamplification during metamorphosis in insects and amphibians are scarce. Therefore, this study sought to characterize the occurrence and trophic dynamics of SCCPs and MCCPs in an insect-dominated terrestrial food web in an e-waste recycling site in South China. Median ∑SCCPs and ∑MCCPs concentrations in the organisms ranged from 2200 to 34 000 ng/g lipid weight and from 990 to 19 000 ng/g lipid weight, respectively. The homologue profiles of CPs in the predators were distinct from those in insects, presenting more short chain-high chlorinated congeners (C

Background Paclitaxel (PTX) is one of the widely used chemotherapy drugs in breast cancer (BC) treatment. Unfortunately, the survival rate of metastatic BC patients remains poor due to PTX resistance. Therefore, uncovering the underlying mechanism behind the PTX resistance of BC cells is crucial for BC therapy. Methods The enrichment of circular RNA ATP binding cassette subfamily B member 10 (circ-ABCB10), let-7a-5p and dual specificity phosphatase 7 (DUSP7) was measured by quantitative real time polymerase chain reaction (qRT-PCR) in PTX-resistant and PTX-sensitive BC tissues and cells. Chemoresistance, apoptosis, invasion and autophagy of BC cells were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell invasion assay and Western blot assay, respectively. The binding sites between let-7a-5p and circ-ABCB10 or DUSP7 were predicted by Starbase bioinformatic software, and the combination was confirmed by dual-luciferase reporter assay. The protein expression of DUSP7 was examined by Western blot assay. Murine xenograft model was established to confirm the role of circ-ABCB10 in vivo. Results Circ-ABCB10 depletion promoted the PTX sensitivity and apoptosis while suppressed the invasion and autophagy of PTX-resistant BC cells. Circ-ABCB10 could bind to let-7a-5p in BC cells, and circ-ABCB10 contributed to PTX resistance of BC cells via let-7a-5p. DUSP7 is a direct target of let-7a-5p in BC cells, and the accumulation of DUSP7 reversed the promoting effects of let-7a-5p overexpression on the PTX sensitivity and apoptosis and the inhibitory impact on the invasion and autophagy of PTX-resistant BC cells. Circ-ABCB10 interference suppressed the growth of BC tumors in vivo. Conclusion Circ-ABCB10 mediated PTX resistance, apoptosis, invasion and autophagy of BC cells via let-7a-5p/DUSP7 axis.

Background There are growing number of researches have shown that mesoderm posterior basic helix-loop helix (BHLH) transcription factor 1 (MESP1) plays a crucial role in the development of tumors. However, its expression pattern and function in non-small cell lung cancer (NSCLC) are still unknown. Methods MESP1 expression and biological process were investigated in NSCLC based on bioinformatics analysis. The mRNA or protein expression levels of MESP1 were measured by quantitative real-time PCR (qRT-PCR) and western blot (WB) assay in NSCLC cells and clinical tissue samples. Then, we used small interfering RNA (siRNA) interference to knocking down expression of gene in NSCLC cells. Cell proliferation was performed using cell counting kit-8 (CCK-8), colony forming assay and real-time cell analyzer (RTCA); transwell chambers and RTCA were used to analysis cell migration and invasion. Besides, analyses of the cell cycle progression and apoptosis were measured via BD JAZZ flow cytometric analysis. All the experiments were repeated ≥3 times. And analyses were performed using SPSS software version 21.0 and GraphPad Prism 6.0. P

Brown planthopper (BPH) is one of the most destructive insects affecting rice ( Oryza sativa L.) production. Phenylalanine ammonia-lyase (PAL) is a key enzyme involved in plant defense against pathogens, but the role of PAL in insect resistance is still poorly understood. Here we show that expression of the majority of PALs in rice is significantly induced by BPH feeding. Knockdown of Os PALs significantly reduces BPH resistance, whereas overexpression of OsPAL8 in a susceptible rice cultivar significantly enhances its BPH resistance. We found that OsPALs mediate resistance to BPH by regulating the biosynthesis and accumulation of salicylic acid and lignin. Furthermore, we show that expression of OsPAL6 and OsPAL8 in response to BPH attack is directly up-regulated by OsMYB30, an R2R3 MYB transcription factor. Taken together, our results demonstrate that the phenylpropanoid pathway plays an important role in BPH resistance response, and provide valuable targets for genetic improvement of BPH resistance in rice.

The present study aimed to evaluate the correlation of integrin α7 (ITGA7) with clinicopathological characteristics and overall survival (OS) in patients with tongue squamous cell carcinoma (TSCC), and to investigate the effect of ITGA7 knockdown on proliferation, apoptosis and stemness of TSCC cells in vitro. ITGA7 expression was measured in tumor tissues and paired adjacent normal tissues from 60 patients with TSCC using immunohistochemistry. ITGA7 expression in human TSCC cell lines and normal oral keratinocytes was measured using quantitative PCR and western blotting. Lentiviruses carrying short hairpin (sh) RNA targeting ITGA7 were used to knockdown its expression in CAL-27 and HSC-4 cells, and then proliferation, apoptosis and stemness were measured. In addition, CAL-27 and HSC-4 cancer stem cells (CSCs) were constructed and their ITGA7 expression was measured. The results demonstrated that ITGA7 was upregulated in the tumor tissues compared with the paired adjacent tissues, and its high expression was correlated with worse pathological grade, N stage, TNM stage and OS. In vitro, ITGA7 expression levels were demonstrated to be increased in the TSCC CAL-27, SCC-9, HSC-4 and SCC-25 cell lines compared to the normal HOK cell line. In CAL-27 and HSC-4 cells, ITGA7 knockdown inhibited cell proliferation, promoted apoptosis, increased CD24 expression, decreased CD44 and CD133 expression, reduced drug resistance to cisplatin and attenuated sphere formation efficiency. Finally, ITGA7 expression levels were greatly elevated in CAL-27 and HSC-4 CSCs compared with parental CAL-27 and HSC-4 cells. In conclusion, ITGA7 knockdown inhibited tumor cell proliferation and stemness in TSCC cells. These findings indicated that ITGA7 might serve as a potential marker for CSCs and may correlate with worse clinical features and prognosis in TSCC.

Soybean (Glycine max [L.] Merr.) is an important source of human dietary protein and vegetable oil. A strong negative correlation between protein and oil contents has hindered efforts to improve soybean seed quality. The metabolic and genetic bases of soybean seed composition remain elusive. We evaluated metabolic diversity in a soybean near-isogenic line (NIL) population derived from parents (JD12 and CMSD) with contrasting seed oil contents. Using GC-TOF/MS, we compared seed primary metabolites of high protein/low oil lines, low protein/high oil lines, and their parents. Principal-components analysis showed that metabolic profiles of all progeny lines could be discriminated based on protein and oil contents. Univariate analysis revealed wide variation and transgressive segregation of metabolites in the population. Twenty-eight annotated metabolites, in particular free asparagine, free 3-cyanoalanine, and L-malic acid, were correlated with seed protein content or seed oil content or seed protein and oil content. These results shed light on the metabolic and genetic basis of soybean seed composition. Keywords: Metabolomics, Seed composition, Protein, Oil, Near-isogenic population

Atopic dermatitis (AD) is a chronic inflammatory skin disease with high morbidity in infants. Several bioactive components of human milk, such as 2′-fucosyllactose (2′-FL) and osteopontin (OPN), are reported to exhibit anti-inflammatory properties. This study determined that oral administration of 2′-FL and OPN significantly attenuated the 2,4-dinitrochlorobenzene (DNCB)-induced AD symptoms in BALB/c mice. 2′-FL and OPN treatment markedly downregulated the serum IgE level and decreased the numbers of mast cells and eosinophils in the dermal tissues from DNCB-sensitized mice. Interestingly, we found that the combination of OPN with 2′-FL produced a great therapeutic effect on AD in mice. Additionally, the result showed that the components suppressed Th2 response, resulting in an attenuated cutaneous inflammatory response. Furthermore, in vitro study validated that 2′-FL and OPN inhibited Th2 cells differentiation. Together, we conclude that 2′-FL and OPN ameliorates DNCB-induced AD-like skin inflammation, and its supplement might help to prevent AD in infants.

Leaf morphology, as a critical measure of plant architecture, has been associated with soybean yield and quality. As yet, conclusive investigations into the genetic basis and biological significance of heteroblasty in soybean remain sparse. To identify and biologically characterize the quantitative trait loci (QTLs) influencing heteroblasty in soybean, 11 traits associated with leaf morphology, seed quality, and grain yield were observed for two recombinant inbred line (RIL) populations grown in two environments. Values of broad-sense heritability (H2) for leaf traits in two RIL populations varied from 0.62 to 0.99. These high heritabilities, taken together with the Kurtosis and Skewness values indicate that the phenotypic variation in leaf morphology observed for both RIL populations are mainly controlled by quantitative traits. The three observed leaf morphology traits exhibited significant correlations (P

Toxoplasma gondii infection during pregnancy can result in adverse pregnancy outcomes. Previously, we have reported that these outcomes are associated with the impaired function of decidual Treg cells; however, the detailed mechanisms involved were unclear. It has been reported that the suppressive capacity of Treg cells is dependent on PD-1 expression. The present study explored the role of decidual PD-1+ Treg cell function in adverse pregnancy outcomes due to T. gondii infection. Toxoplasma gondii-infected pregnant mice were sacrificed on gestational day 14 and their pregnancy outcomes were observed. The expression of PD-1 on decidual Treg cells and expressions of Foxp3, CTLA-4, TGF-β, and IL-10 on decidual PD-1+ and PD-1- Treg cells were determined using flow cytometry. The results showed that the expression of PD-1 on decidual Treg cells was clearly higher in the T. gondii-infected mice than in the normal mice. Meanwhile, the expressions of Foxp3, CTLA-4, TGF-β, and IL-10 on decidual PD-1+ Treg cells were higher in the infected mice than in the normal mice. The expressions were higher in decidual PD1+ Treg cells than in PD-1- Treg cells in the infected mice. However, these expressions on PD-1- Treg cells did not significantly differ between the infected and normal mice. Nonetheless, the absolute percentages of decidual PD-1+ Treg cells decreased significantly in the infected mice compared with those in the normal mice. These results suggest that T. gondii infection mainly influences the function of decidual PD-1+ Treg cells, which would result in an insufficiently immunotolerant microenvironment and consequently in adverse pregnancy outcomes.

Hongliang Li,1,* Xiaopeng Guo,1,* Qiutian Li,2,* Pengzhan Ran,1 Xudong Xiang,3 Yuncang Yuan,1 Tianqi Dong,1 Bei Zhu,1 Lei Wang,1 Fangfang Li,1 Chunyan Yang,1 Dengcai Mu,1 Dan Wang,4 Chunjie Xiao,1 Shangyong Zheng1 1School of Medicine, Yunnan University, Kunming, China; 2Department of Oncology, Kunming General Hospital of Chengdu Military Command, Teaching Hospital of Kunming Medical University, Kunming, China; 3Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China; 4Department of Pharmacy, Kunming General Hospital of Chengdu Military Command, Teaching Hospital of Kunming Medical University, Kunming, China *These authors contributed equally to this work Purpose: Emerging evidence suggests that many differentially expressed long non-coding RNAs (lncRNAs) are involved in tumorigenesis. However, the functional roles of these transcripts and the mechanisms responsible for their deregulation in non-small-cell lung cancer (NSCLC) remain elusive. Here, we identified a novel lncRNA (lncRNA 1308), which was significantly upregulated in NSCLC tissues and investigated its biological function and potential molecular mechanism.Methods: Differences in the lncRNA expression profiles between NSCLC and tumor-adjacent normal tissues were assessed by lncRNA expression microarray analysis. The microRNA in vivo precipitation (miRIP) method was used to identify the targeting microRNAs (miRNAs) on lncRNA 1308, and luciferase reporter assays were performed. Loss-of-function studies were used to explore the effect of lncRNA 1308 on lung carcinogenesis in NSCLC cells.Results: The novel lncRNA 1308 was upregulated in NSCLC tissues and cell lines. By using biotin-labeled lncRNA 1308 for miRIP in NSCLC cells and dual-luciferase reporter assays, the results suggested that miRNA-124 was associated with lncRNA 1308. Furthermore, the expression of a disintegrin and a metalloproteinase 15 (ADAM 15) was downregulated in NSCLC cells when silencing of lncRNA 1308, the target of oncogenic miR-124, inhibits NSCLC cell proliferation and invasion. Conversely, the expression of ADAM 15 was significantly increased, when inhibiting the expression of miR-124, and alleviated cell invasion inhibition.Conclusion: The results suggested that lncRNA 1308 may function as a competing endogenous RNA (ceRNA) for miR-124 to regulate cell invasion through the miR-124/ADAM 15 signaling pathway, indicating that lncRNA 1308 plays an important role in the disease progression of NSCLC. Keywords: lung cancer, lncRNA 1308, miR-124, ADAM 15, competing endogenous RNA

Developing high yielding cultivars with outstanding quality traits are perpetual objectives throughout crop breeding operations. Confoundingly, both of these breeding objectives typically involve working with complex quantitative traits that can be affected by genetic and environmental factors. Establishing correlations of these complex traits with more easily identifiable and highly heritable traits can simplify breeding processes. In this study, two parental soybean genotypes contrasting in seed hilum size, yield, and seed quality, as well as 175 F9 recombinant inbred lines (RILs) derived from these parents, were grown in 3 years. The h2b of four hilum size, two quality and two yield traits, ranged from 0.72 to 0.87. The four observed hilum size traits exhibited significant correlation (P < 0.05) with most of seed yield and quality traits, as indicated by correlation coefficients varying from -0.35 to 0.42, which suggests that hilum size could be considered as a proxy trait for soybean yield and quality. Interestingly, among 53 significant quantitative trait loci (QTLs) with logarithm of odds (LOD) values ranging from 2.51 to 6.69 and accounting for 6.40–16.10% of genetic variation, three loci encoding hilum size, qSH6.2, qSH8, and qSH10, colocated with QTLs for seed yield and quality traits, demonstrating that genes impacting seed hilum size colocalize in part with genes acting on soybean yield and quality. As a result of the breeding efforts and field observations described in this work, it is reasonable to conclude that optimizing hilum size through selection focused on a few QTLs may be useful for breeding new high yielding soybean varieties with favorable quality characteristics.

Direct conversion of fibroblasts into induced cardiomyocytes (iCMs) holds promising potential to generate functional cardiomyocytes for drug development and clinical applications, especially for direct in situ heart regeneration by delivery of reprogramming genes into adult cardiac fibroblasts in injured hearts. For a decade, many cocktails of transcription factors have been developed to generate iCMs from fibroblasts of different tissues in vitro and some were applied in vivo. Here, we aimed to develop genetic cocktails that induce cardiac reprogramming directly in cultured cardiac fibroblasts isolated from adult mice with myocardial infarction (MICFs), which could be more relevant to heart diseases. We found that the widely used genetic cocktail, Gata4, Mef2c, and Tbx5 (GMT) were inefficient in reprogramming cardiomyocytes from MICFs. In a whole well of a 12-well plate, less than 10 mCherry+ cells (Myh6-reporter transgenic MICFs. By screening 22 candidate transcription factors predicted through analyzing the gene regulatory network of cardiac development, we found that five factors, GMTMS (GMT plus Myocd and Sall4), induced more iCMs expressing the cardiac structural proteins cTnT and cTnI at a frequency of about 22.5 ± 2.7% of the transduced MICFs at day 21 post infection. What is more, GMTMS induced abundant beating cardiomyocytes at day 28 post infection. Specifically, Myocd contributed mainly to inducing the expression of cardiac proteins, while Sall4 accounted for the induction of functional properties, such as contractility. RNA-seq analysis of the iCMs at day 28 post infection revealed that they were reprogrammed to adopt a cardiomyocyte-like gene expression profile. Overall, we show here that Sall4 and Myocd play important roles in cardiac reprogramming from MICFs, providing a cocktail of genetic factors that have potential for further applications in in vivo cardiac reprogramming.

Vertical transmission of Toxoplasma gondii (T. gondii) infection during gestation can result in severe complications such as abortion, congenital malformation, fetal teratogenesis, etc. Immune inhibitory molecule Tim-3 was discovered to be expressed on some decidual immune cells and participates in the maintenance of maternal-fetal tolerance. Dysregulation of Tim-3 expression on decidual NK (dNK) cells was observed in several cases of pregnancy complications, whereas the role of Tim-3 on dNK cells during T. gondii infection remains unclear. In the present study, T. gondii infected Tim-3-/- pregnant mice, and anti-Tim-3 neutralizing antibody treated and infected human dNK cells were successfully established to explore the role of Tim-3 in dysfunction of dNK cells during abnormal pregnancy. Our results illustrated that Tim-3-/- pregnant mice displayed more worse pregnancy outcomes with T. gondii infection compared to infected WT pregnant mice. Also, it demonstrated that Tim-3 expression on dNK cells was significantly down-regulated following T. gondii infection. Data suggested a remarkable activation of dNK cells in Tim-3-/- mice and anti-Tim-3 neutralizing antibody treated and infected groups, with higher ratios of activating receptor NKG2D to inhibitory receptor NKG2A or KIR2DL4, IFN-γ/IL-10, and increased granule production compared with that of the infected group. Mechanism analysis proved that T. gondii-induced Tim-3 down-regulation significantly activated the phosphatidylinositol-3-kinase (PI3K)-AKT and JAK-STAT signaling pathway, by which the GranzymeB, Perforin, IFN-γ, and IL-10 production were further up-regulated. Our research demonstrated that the decrease of Tim-3 on dNK cells caused by T. gondii infection further led to dNK cells function disorder, which finally contributed to the development of abnormal pregnancy outcomes.

Tumor necrosis factor superfamily member 10 (TNFSF10), also known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or Apo-2L, is one of the important members of the TNF superfamily. It is well demonstrated that TNFSF10 preferentially induces a variety of tumor cell apoptosis, and therefore exerts an important role in tumor immune surveillance. However, the function of TNFSF10 in pathogen defense is poorly understood, especially in invertebrates. The blood clam (Tegillarca granosa), an important commercial marine bivalve, plays an important ecological role in the marine ecosystem. The identification of immune genes will provide new perspective for disease control in the blood clam (T. granosa) farming. To better understand the biological function of TNFSF10 protein, the full-length cDNA of TNFSF10 homologous gene of T. granosa (TgTNFSF10) was cloned and identified for the first time, which was found to contain 1239 base pairs and encode 254 amino acids with a molecular weight of 29.5 kDa and a conserved TNF domain in the C-terminal. Quantitative RT-PCR analysis showed that TgTNFSF10 gene was constitutively expressed in all tested tissues, with the highest expression in hemocytes. LPS, Vibrio alginolyticus and Vibrio parahaemolyticus stimulations dramatically increased the expression of TgTNFSF10 in T. granosa (11.47-fold, 3.71-fold and 8.29-fold compared with the control respectively). In vitro experiments showed that recombinant TgTNFSF10 protein strongly inhibited the proliferation of HepG2 cells. Further confocal microscopy and flow cytometry analysis showed that obvious apoptosis occurred in TgTNFSF10-treated hemocytes and HepG2 cells. To sum up, our study demonstrated that TgTNFSF10 had strong apoptosis-inducing activity, which may participate in the innate immune response of T. granosa to pathogen invasion.

Soybean [Glycine max (L.) Merr.] is a crop of great interest worldwide. Exploring molecular approaches to increase yield genetic gain has been one of the main challenges for soybean breeders and geneticists. Agronomic traits such as maturity, plant height, and seed weight have been found to contribute to yield. In this study, a total of 250 soybean accessions were genotyped with 10,259 high-quality SNPs postulated from genotyping by sequencing (GBS) and evaluated for grain yield, maturity, plant height, and seed weight over three years. A genome-wide association study (GWAS) was performed using a Bayesian Information and Linkage Disequilibrium Iteratively Nested Keyway (BLINK) model. Genomic selection (GS) was evaluated using a ridge regression best linear unbiased predictor (rrBLUP) model. The results revealed that 20, 31, 37, and 23 SNPs were significantly associated with maturity, plant height, seed weight, and yield, respectively; Many SNPs were mapped to previously described maturity and plant height loci (E2,E4, andDt1) and a new plant height locus was mapped to chromosome 20. Candidate genes were found in the vicinity of the two SNPs with the highest significant levels associated with yield, maturity, plant height, seed weight, respectively. A 11.5-Mb region of chromosome 10 was associated with both yield and seed weight. Overall, the accuracy of GS was dependent on the trait, year, and population structure, and high accuracy indicates that these agronomic traits can be selected in molecular breeding through GS. The SNP markers identified in this study can be used to improve yield and agronomic traits through the marker-assisted selection and GS in breeding programs.

Microbiota especially Bifidobacterium play an important role in adjusting and maintaining homeostatic balance within the infant intestine. The aim of this study was to elucidate the relationship between maternal and infant gut microbiota and identify the Bifidobacterium species that may transfer from mother to infant over the first 42 days of the infant’s life. Nineteen mother-infant-pair fecal samples were collected and the diversity and composition of the total bacterial and Bifidobacterium communities were analyzed via 16S rDNA and bifidobacterial groEL gene high throughput sequencing. The results revealed that the relative abundance of Bifidobacterium was significantly higher in the infant gut while Parabacteroides, Blautia, Coprococcus, Lachnospira and Faecalibacterium were at lower relative abundance in 7-day and 42-day infant fecal samples compared to the maternal samples. The maternal gut has more B. pseudocatenulatum. In the infant group, B. breve and B. dentium relative abundance increased while B. animalis subsp. lactis decreased from days 7 to 42. Additionally, B. longum subsp. longum isolated from FGZ16 and FGZ35 may have transferred from mother to infant and colonized the infant gut. The results of the current study provide insight toward the infant gut microbiota composition and structure during the first 42 days and may help guide Bifidobacterium supplementation strategies in mothers and infants.

Diuron, a commonly used herbicide and antifouling biocide, has been frequently detected in seawater. The effects of diuron on fish behaviour are currently poorly understood. Herein, the marine medaka (Oryzias melastigma) was continuously exposed to environmentally realistic levels of diuron from the fertilised egg stage to the adult stage. Behavioural evaluation of adult marine medaka indicated that exposure to diuron increased anxiety in the light-dark test and increased predator avoidance. In addition, diuron exposure significantly reduced aggression, social interaction, shoaling, and learning and memory ability. However, only negligible variations in foraging behaviour and in behaviour in the novel tank test were observed. Marine medaka chronically exposed to diuron also showed decreased levels of dopamine in the brain, and changes were observed in the transcription of genes related to dopamine synthesis, degradation and receptors. Exposure to 5000 ng/L diuron caused significant downregulation of the expression of the genes of tyrosine hydroxylase and monoamine oxidase and significantly upregulated the expression of the genes of the D5 dopaminergic receptor. The relative expression of the D4 dopaminergic receptor was significantly upregulated in the 50, 500 and 5000 ng/L diuron-treated groups. These findings highlight the significant neurotoxic effects of diuron and the extent to which this may involve the dopaminergic system of the brain. More broadly, this study reveals the ecological risk associated with environmentally realistic levels of diuron in marine animals.

Cyanobacterial harmful algal blooms (CyanoHABs) bring economic loss, damage aquatic ecosystems, and produce cyanobacterial toxins that threaten human health. Algicidal bacteria as pathogens can expediate the decline of CyanoHABs. In this study, a Streptomyces globisporus strain (designated G9), isolated from soil near a eutrophic pond, showed high algicidal activity against Microcystis aeruginosa. Experimental results show that G9 preyed on Microcystis through cell-to-cell contact: (1) the hyphae of G9 killed cyanobacterial cells by twining around them, while cells beyond the reach of G9 hyphae were in normal shapes; (2) No algicides were detectable in the supernatant of G9 cultures or G9-Microcystis cocultures. The algicidal ratio of G9 to M. aeruginosa reached 96.7% after 6 days. G9 selectively killed the tested cyanobacterial strains, while it had only minor impacts on the growth of tested Chlorophyceae. Differential gene expression studies show that G9 affected the expression of key genes of M. aeruginosa involved in photosynthesis, microcystin synthesis and cellular emergency responses. Further, the microcystin-LR content decreased gradually with G9 treatment. As the first reported Streptomyces sp. with algicidal (predation) activity requiring cell-to-cell contact with target prey, G9 is a good candidate for the exploration of additional cyanobacteria-bacteria interactions and the development of novel strategies to control CyanoHABs.

Introduction: As a gaseous me dilator, hydrogen sulfide (H2S) has many physiological effects and pathological effects in atherosclerosis. In recent years, many exogenous H2S donors have been synthesized to study atherosclerosis diseases. Methods: Proglumide-(5-(4-Hydroxyphenyl)-3H-1, 2-dithiole-3-thione) (P-A) was synthesized as a H2S donor. The protective effect and mechanism of P-A on HUVEC that injured by ox-LDL was detected. Results: The HUEVCs was affected by 100μmol/L P-A for 24 hours, the release of H2S was the largest. After 100μmol/L P-A acted on HUVEC damage model for 12h, the cell proliferation activity was the best. The results showed that P-A can down regulate the expression of p-NF-кBp65 protein and reduce the amount of TNF-α and IL-6 and promote the formation of IL-10 by inhibiting the NF-кB pathway, and also induce the expression of superoxide dismutase (SOD) to protect HUVEC from ox-LDL injury. P-A can also regulate JAK/STAT pathway to reduce the expression of p-JAK2 protein and reduce the production of IL-6 and TNF-α. Conclusion: P-A has protective effect on HUVEC injured by ox-LDL, and the protective mechanism is related to the regulation of JAK/STAT pathway and NF-кB pathway.

BackgroundCultivated soybean (Glycine max) is an important source for protein and oil. Each soybean strain has its own genetic diversity, and the availability of more soybean genomes may enhance comparative genomic analysis of soybean.ResultsIn this study, we constructed a high-quality de novo assembly of an elite soybean cultivar Jidou 17 (JD17) with high contiguity, completeness, and accuracy. We annotated 59,629 gene models and reconstructed 235,109 high-quality full-length transcripts. We have molecularly characterized the genotypes of some important agronomic traits of JD17 by taking advantage of these newly established genomic resources.ConclusionsWe reported a high-quality genome and annotations of a wide range of cultivars, and used them to analyze the genotypes of genes related to important agronomic traits of soybean in JD17. We have demonstrated that high-quality genome assembly can serve as a valuable reference for soybean genomics and breeding research community.

Soluble epoxide hydrolase (sEH) is responsible for rapid degradation of 14, 15-EET, which is one of the isomers of EETs and plays an important role in cardiovascular diseases. In this study, we investigated the mechanism by which sEH inhibitor AUDA played an anti-inflammatory effect in HCAECs. Our results indicated that AUDA treatment promoted PPARγ expression, while knockdown of PPARγ blocked the cell growth and STAT1 expression inhibition induced by 100 μmol/L AUDA in HCAECs. AUDA also inhibited the overexpression of TNF-α, IL-1 β, and MMP-9 induced by KD sera in HCAECs. Moreover, 30 blood samples from children with Kawasaki disease (KD) were collected with 30 healthy children as the control group. QPCR and ELISA assays were used to detect the level of 14, 15-EET, TNF-α, IL-1β, and MMP-9. We found that the level of 14, 15-EET was higher in peripheral blood of children with KD compared with healthy controls (P < 0.05). In comparison to KD children with non-coronary artery lesion (nCAL), the level of 14, 15-EET was higher in peripheral blood of KD children with coronary artery lesion (CAL) (P < 0.05). Compared with healthy control group, the expression levels of TNF-α, IL-1β, and MMP-9 in patients with KD were significantly up-regulated. Compared with nCAL KD children, the expression levels of TNF-α, IL-1β, and MMP-9 in CAL children were abnormally high (P < 0.05). Our study indicated that AUDA played an anti-inflammatory effect in HCAECs through PPARγ/STAT1 signaling pathway, and 14, 15-EET is up-regulated in children with KD, suggesting that 14, 15-EET involved in the progression of KD.

Background The plant chloroplast is essential for photosynthesis and other cellular processes, but an understanding of the biological mechanisms of plant chloroplast development are incomplete. Results A new temperature-sensitive white stripe leaf 9(wsl9) rice mutant is described. The mutant develops white stripes during early leaf development, but becomes green after the three-leaf stage under field conditions. The wsl9 mutant was albinic when grown at low temperature. Gene mapping of the WSL9 locus, together with complementation tests indicated that WSL9 encodes a novel protein with an HNH domain. WSL9 was expressed in various tissues. Under low temperature, the wsl9 mutation caused defects in splicing of rpl2, but increased the editing efficiency of rpoB. Expression levels of plastid genome-encoded genes, which are transcribed by plastid-coded RNA polymerase (PEP), chloroplast development genes and photosynthesis-related genes were altered in the wsl9 mutant. Conclusion WSL9 encodes an HNH endonuclease domain-containing protein that is essential for early chloroplast development. Our study provides opportunities for further research on regulatory mechanisms of chloroplast development in rice.

We reported that DGS1 plays a positive role in regulating grain size in rice and was regulated by OsBZR1. Grain size is an important agronomic trait that contributes to grain yield. However, the underlying molecular mechanisms that determine final grain size are still largely unknown. We isolated a rice mutant showing reduced grain size in a 60Co-irradiated variety Nanjing 35 population. We named the mutant decreased grain size1 (dgs1). Map-based cloning and subsequent transgenic CRISPR and complementation assays indicated that a mutation had occurred in LOC_Os03g49900 and that the DGS1 allele regulated grain size. DGS1 encodes a protein with a 7-transmembrane domain and C3HC4 type RING domain. It was widely expressed, especially in young tissues. DGS1 is a membrane-located protein. OsBZR1 (BRASSINAZOLE-RESISTANT1), a core transcription activator of BR signaling, also plays a positive role in grain size. We provided preliminary evidence that OsBZR1 can bind to the DGS1 promoter to activate expression of DGS1.

Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. This study was mainly aimed at investigating the effects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in serum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyze LDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42 mg/g DW) and isoquercitrin (4.60 mg/g DW) were the main constituents of ACE using HPLC analysis. Furthermore, ACE reduced the levels of TC, TG, LDL-C, and MDA, and increased HDL levels and elevated SOD activity both in serum and liver in hyperlipidemic SD rats (p < .05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and the lipid and foam cells of the aortic arch of the rats in ACE group were markedly ameliorated. WB results showed that ACE promoted the degradation of HMGCR and increased LDLR expression in liver (p < .05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR. PRACTICAL APPLICATIONS: Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, during atherosclerosis development, hyperlipidemia is an important risk factor. To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the side effects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statin lipid-lowering agent.

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction has been recognized as an important early event in atherosclerosis. G-protein-coupled receptor 40 (GPR40) is a cell surface...

1AbstractProtected areas are central to meeting biodiversity conservation goals, but measuring their effectiveness is challenging. We address this challenge by using DNA from leech-ingested bloodmeals to estimate vertebrate occupancies across the 677 km2 Ailaoshan reserve in Yunnan, China. 163 park rangers collected 30,468 leeches from 172 patrol areas. We identified 86 vertebrate species, including amphibians, mammals, birds, and squamates. Multi-species occupancy modelling showed that species richness increased with elevation and distance to reserve edge, including the distributions of most of the large mammals (e.g. sambar, black bear, serow, tufted deer). The exceptions were the three domestic mammal species (cows, sheep, goats) and muntjak deer, which were more common at lower elevations. eDNA-estimated vertebrate occupancies are Granular, Repeatable, Auditable, Direct, Efficient, and Simple-to-understand measures that can be used to assess conservation effectiveness and thus to improve the contributions that protected areas make to achieving global biodiversity goals.

Characterization of the molecular factors regulating early embryonic development and their functional mechanisms is critical for understanding the causes of early pregnancy loss in monotocous species (cattle, human). We previously characterized a stage specific functional role of follistatin, a TGF-beta superfamily binding protein, in promoting early embryonic development in cattle. The mechanism by which follistatin mediates this embryotropic effect is not precisely known as follistatin actions in cattle embryos are independent of its classically known activin inhibition activity. Apart from activin, follistatin is known to bind and modulate the activity of the bone morphogenetic proteins (BMPs), which signal through SMAD1/5 pathway and regulate several aspects of early embryogenesis in other mammalian species. Present study was designed to characterize the activity and functional requirement of BMP signaling during bovine early embryonic development and to investigate if follistatin involves BMP signaling for its stage specific embryotropic actions. Immunostaining and western blot analysis demonstrated that SMAD1/5 signaling is activated after embryonic genome activation in bovine embryos. However, days 1–3 follistatin treatment reduced the abundance of phosphorylated SMAD1/5 in cultured embryos. Inhibition of active SMAD1/5 signaling (8–16 cell to blastocyst) using pharmacological inhibitors and/or lentiviral-mediated inhibitory SMAD6 overexpression showed that SMAD1/5 signaling is required for blastocyst production, first cell lineage determination as well as mRNA and protein regulation of TE (CDX2) cell markers. SMAD1/5 signaling was also found to be essential for embryotropic actions of follistatin during days 4–7 but not days 1–3 of embryo development suggesting a role for follistatin in regulation of SMAD1/5 signaling in bovine embryos.

Seed dormancy is closely related to pre-harvest sprouting resistance. Both plant hormone abscisic acid (ABA) and DELAY OF GERMINATION 1 (DOG1) protein are key regulators of seed dormancy. Their relationship is well reported in Arabidopsis, but little is known in rice. Here, we show that a quantitative trait locus, qSd-1-1 contributes significantly to seed dormancy differences between the strongly dormant indica variety N22 and non-dormant japonica variety Nanjing35. It encodes a DOG1-like protein named OsDOG1L-3 with homology to Arabidopsis DOG1. There were evident promoter and expression differences in OsDOG1L-3 between N22 and Nanjing35, and overexpression or introduction of the N22 OsDOG1L-3 allele in Nanjing35 enhanced its seed dormancy. OsDOG1L-3 expression was positively correlated with seed dormancy and induced by ABA. OsbZIP75 and OsbZIP78 bound directly with the promoter of OsDOG1L-3 to induce its expression. Overexpression of OsbZIP75 increased OsDOG1L-3 protein abundance and promoted seed dormancy. OsDOG1L-3 upregulated expression of ABA-related genes and increased ABA content. We propose that the N22 OsDOG1L-3 allele is a candidate gene for the seed dormancy in QTL qSd-1-1, and that it participates in the ABA pathway to establish seed dormancy in rice.

BackgroundSoybean [Glycine max (L.) Merr.] is a legume of great interest worldwide. Enhancing genetic gain for agronomic traits via molecular approaches has been long considered as the main task for soybean breeders and geneticists. The objectives of this study were to conduct a genome-wide association study (GWAS) for these traits and identify SNP markers associated with the four traits, and to assess genomic selection (GS) accuracy.Results A total of 250 soybean accessions were evaluated for maturity, plant height, seed weight, and yield over three years. This panel was genotyped with a total of 10,259 high quality SNPs postulated from genotyping by sequencing (GBS). Population structure was inferred using STRUCTURE 2.3.4, GWAS was performed using a Bayesian Information and Linkage Disequilibrium Iteratively Nested Keyway (BLINK) model, and GS was evaluated using a ridge regression best linear unbiased predictor (rrBLUP) model. The results revealed that: a total of 20, 31, 37, 31, and 23 SNPs were significantly associated with the average 3-year data for maturity, plant height, seed weight, and yield, respectively; some significant SNPs were mapped into previously described loci (E2, E4, and Dt1) affecting maturity and plant height in soybean and a new locus mapped on chromosome 20 was significantly associated with plant height; Glyma.10g228900, Glyma.19g200800, Glyma.09g196700, and Glyma.09g038300 were candidate genes found in the vicinity of the top or the second best SNP (if no annotated genes found close the top one) for maturity, plant height, seed weight, and yield, respectively; a 11.5-Mb region of chromosome 10 was associated with both seed weight and yield; and GS accuracy was trait-, year-, and population structure-dependent.Conclusions The SNP markers identified from this study for plant height, maturity, seed weight and yield can be used to improve the four agronomic traits in soybean through marker-assisted selection (MAS) and GS in breeding programs. After validation, the candidate genes can be transferred to new cultivars using the linked SNP markers through MAS. The high GS accuracy has confirmed that the four agronomic traits can be selected in molecular breeding through GS.

Background: Breakthroughs have been made in cancer immunotherapy using antibodies against immune checkpoints. But successful immune checkpoint blockade (ICB) responses only occur in a fraction of people, and we have no idea which patients will be the lucky one before treatment. Picking out the effective population accurately can improve the cure rate significantly. We set out to design a novel immunophenotyping approaches for kidney renal clear cell carcinoma (KIRC) based on the tumor immune microenvironment(TIME), which target to distinguish immunotherapy responders. Methods: Five hundred and thirty KIRC samples from The Cancer Genome Atlas (TCGA) were analyzed as the training cohort. Non-negative matrix factorization (NMF) was used to extract immune-related features from complex tumor bulks. We associated the expression patterns with a series of immune-related gene signatures and clinicopathological features. GSE73731 and GSE40435 validation datasets were analyzed to further confirm our findings. Findings: We found that almost 40% of KIRC patients in the training cohort (209/530) were designated as the Immune Class with a high enrichment score for inflammatory response, cytolytic activity, and CD8 T cells (all P

BACKGROUND Ghrelin is a novel peptide with abundant cardioprotective effects. The miR-208 family, consisting of cardiac-specifically expressed microRNAs, are not only involved in hypertrophy and fibrosis, but are also closely related with myocyte apoptosis. This study explored the role of the miR-208 family in the protective effect of ghrelin on angiotensin II (Ang II)-induced apoptosis. MATERIAL AND METHODS H9c2 cells were exposed to Ang II with or without ghrelin. Cell viability was detected by MTT assay and the percentage of apoptotic cells was confirmed by flow cytometry. miRNAs expression levels were measured by qRT-PCR. Then, cells transfected with miR-208 negative control, mimics, and inhibitors were treated with Ang II and ghrelin, followed by flow cytometry. PCR array was performed to explore the pathways affected by miR-208. RESULTS The miR-208 level was reduced in Ang II-treated H9c2 cells, accompanied with increased cell apoptosis, which were both reversed by ghrelin administration. Flow cytometry revealed that miR-208 inhibitors clearly upregulated the apoptotic percentage, whereas miR-208 mimics showed the opposite effects in the Ang II group. miR-208a further alleviated apoptosis when treated with ghrelin. miR-208 mainly affected caspase, inflammatory-related genes, and several signaling pathways. CONCLUSIONS We provide new evidence that the miR-208 family is regulated by Ang II and ghrelin. Overexpression of miR-208 family alleviated Ang II-induced cell apoptosis and miR-208a assisted in the protective effect of ghrelin. Several apoptosis pathways affected by miR-208 family were found. These findings suggest the pathogenesis of cardiomyocyte apoptosis and the protective mechanism of ghrelin.

A Toxoplasma gondii infection during pregnancy can result in spontaneous abortion, preterm labor, or congenital fetal defects. The decidual immune system plays a critical role in regulating the immune micro-environment and in the induction of immune tolerance. To better understand the factors that mediate the decidual immune response associated with the T. gondii infection, a large-scale study employing TMT proteomics was conducted to characterize the differential decidual immune proteomes from infected and uninfected human decidual immune cells samples. The decidual immune cells from 105 human voluntary abortion tissues were purified, and of the 5510 unique proteins identified, 181 proteins were found to be differentially abundant (1.2-fold cutoff, p 0.05) in the T. gondii-infected decidual immune cells. 11 proteins of 181 differentially expressed proteins associated with trophoblast invasion, placental development, intrauterine fetal growth, and immune tolerance were verified using a quantitative real-time polymerase chain reaction and western blotting. This systematic analysis for the proteomics of decidual immune cells identified a broad range of immune factors in human decidual immune cells, shedding a new insight into the decidual immune molecular mechanism for abnormal pregnancy outcomes associated with T. gondii infection.

Soybean is a major source of protein for human consumption and animal feed. Releasing new cultivars with high nutritional value is one of the major goals in soybean breeding. To achieve this goal, genome-wide association studies of seed amino acid contents were conducted based on 249 soybean accessions from China, US, Japan, and South Korea. The accessions were evaluated for 15 amino acids and genotyped by sequencing. Significant genetic variation was observed for amino acids among the accessions. Among the 231 single nucleotide polymorphisms (SNPs) significantly associated with variations in amino acid contents, fifteen SNPs localized near 14 candidate genes involving in amino acid metabolism. The amino acids were classified into two groups with five in one group and seven amino acids in the other. Correlation coefficients among the amino acids within each group were high and positive, but the correlation coefficients of amino acids between the two groups were negative. Twenty-five SNP markers associated with multiple amino acids can be used to simultaneously improve multi-amino acid concentration in soybean. Genomic selection analysis of amino acid concentration showed that selection efficiency of amino acids based on the markers significantly associated with all 15 amino acids was higher than that based on random markers or markers only associated with individual amino acid. The identified markers could facilitate selection of soybean varieties with improved seed quality. Hebei Province Natural Science Foundation for Distinguished Young Scholars [C2014301035]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31100880]; Key Project of the Natural Science Foundation of Hebei Province [C2012301020] The authors would like to thank Prof. Lijuan Qiu (Chinese Academy of Agricultural Sciences) for providing seeds of 249 soybean accessions. This study was supported by the Hebei Province Natural Science Foundation for Distinguished Young Scholars (C2014301035), National Natural Science Foundation of China (31100880), and Key Project of the Natural Science Foundation of Hebei Province (C2012301020).

Background Identification of the quantitative trait locus (QTL) underlying salt tolerance is a prerequisite for marker-assisted selection in the salt-tolerant breeding process. Methods In this study, the recombinant inbred lines derived from the salt-tolerant elite soybean cultivar ‘Jidou 12’ and the salt-sensitive elite cultivar ‘Ji NF 58’ were used to identify the QTL associated with salt tolerance, using both salt tolerance rating (STR) and leaf chlorophyll content (SPAD) as indicators. Results A major salt-tolerant QTL, which was flanked by SSR markers GMABAB and Barcsoyssr_03_1421 on chromosome 3, was identified based on single-marker regression, single trait composite interval mapping, and multiple interval mapping analysis. For STR, the LOD ranged from 19.8 to 20.1; R2 ranged from 44.3 to 44.7%; and the additive effect ranged from 0.876 to 0.885 among the three mapping methods. For SPAD, the LOD ranged from 10.6 to 11.0; R2 ranged from 27.0 to 27.6%; and the additive effect ranged from 1.634 to 1.679 among the three mapping methods. Conclusions In this study, a major QTL conditioning salt tolerance on chromosome 3 was identified. The DNA markers closely associated with the QTLs might be useful in marker-assisted selection for soybean salt tolerance improvement in Huanghuaihai, China. Electronic supplementary material The online version of this article (10.1186/s13104-018-3202-3) contains supplementary material, which is available to authorized users.

Cyprodinil, one of the main pyrimidinamine fungicides, has been used to control fungal diseases in plants and vegetables worldwide. Previous studies have investigated the influences of cyprodinil on the developmental and reproductive toxicity of fish. However, it remains unknown whether it affects fish behaviors and the underlying mechanisms. In our current study, zebrafish, an ideal model animal for behavioral studies, were exposed to cyprodinil from fertilization to 240 days postfertilization at 0.1 μg/L (environmentally relevant concentration) and 1, 10 μg/L. Firstly, we observed that aggressive behavior of zebrafish was significantly enhanced after exposure to 0.1–10 μg/L cyprodinil and antipredator behavior was decreased after exposure. Cyprodinil exposure altered the adrenocorticotropic hormone and cortisol levels, which regulate cortisol homeostasis and were significantly reduced in all exposure groups (0.1–10 μg/L). In addition, most of the key genes in the hypothalamic–pituitary–interrenal gland axis, such as corticotropin-releasing hormone and melanocortin 2 receptor, were downregulated significantly in all exposure groups, which was consistent with the hormone levels. In addition, in the hypothalamus, the number of apoptotic cells increased in a dose-dependent manner in the cyprodinil exposure groups. Moreover, these changes were potentially responsible for the increased aggression of zebrafish during the mirror-like aggressive test and for the reduced antipredator behavior during the predator avoidance test. Overall, the data provided herein further our understanding of cyprodinil toxicity and can be used to assess the ecological effects of cyprodinil on the induction of abnormal behaviors at the environmental level.

International audience; China has recently announced a reform of forestry policy, with a major goal being to transform from plantation to heterogeneous forests, which have higher resistance to pests and disease and house more biodiversity. One driver of reform is increased intensity and frequency of pest-induced tree-dieback events. To inform management, we ask what effects these events have on insect biodiversity in Pinus yunnanensis monocultures in Yunnan province, the province with one of the highest proportions of forest cover in China. We sampled aerial arthropods (mostly insect) biodiversity along gradients of Pinus yunnanensis dieback severity using Malaise traps and used metabarcoding to characterise the insect community. We used MS-GDM ('multi-site generalized dissimilarity modelling of zeta diversity'), zeta-decline analysis, and iNEXT ('Interpolation and extrapolation for species diversity') to assess community change as functions of forest-structure covariates. Metabarcoding of Malaisetrapped insects reveals that bark-beetle induced forest dieback does not result in detectable differences in species diversity but does result in compositional change, with the biggest turnover occurring between 0% and infested-0%-open-canopy forests and 20%-infested-20%-open-canopy forests. Zeta-decline analysis found that the insect community in low-infestation forests is characterized by a stochastic assembly, while in highinfestation forests, the community structure is consistent with niche assembly. Our results thus suggest that bark-beetle dieback mimics natural forest-gap dynamics, consistent with the interpretation of bark beetles as a keystone species in European conifer forests, where it has been proposed that forest heterogeneity can be created efficiently by allowing natural disturbances, including bark-beetle outbreaks, to proceed naturally, without being mitigated by deadwood removal and dense replanting. In Yunnan's situation, and given predicted increases in bark-beetle dieback severity and frequency, this strategy should probably be supplemented with anthropogenic treatments, such as deadwood enhancement and planting of multiple tree species, to accelerate the succession of plantations into heterogeneous forests.

X. sorbifolia can be used as both food material and medicinal plant. In this study, ultrasound-assisted extraction (UAE) was firstly used to optimize the extraction process of total polyphenols from X. sorbifolia husks. Ultrasonic time, ultrasonic temperature, ratio of solvent to material and volume fraction of ethanol were investigated and optimized by orthogonal experiments. Then, High Performance Liquid Chromatography (HPLC) was applied to analyze the polyphenols of the extract under the optimal extraction process. The optimized results for UAE was 40 min of ultrasonic time, 40 ℃ of ultrasonic temperature, 100:1 mL/g of solvent to material ratio and 60% aqueous ethanol. Under the optimal extraction process, the total polyphenol content (TPC) of the extract was 23.16 mg GAE/g DW. Furthermore, the most abundant polyphenols in X. sorbifolia husks extract, such as gallic acid, protocatechuic acid, epicatechin, myricetin-3-O-β-D-rutinoside, rutin and quercetin, were analysed using HPLC. In addition, UAE extract showed antioxidant activity in a concentration-dependent manner. Accordingly, X. sorbifolia husks can be used as a rich source of natural antioxidants. To sum up, these results provided a solid chemical basis underlying the future research and application of Xanthoceras sorbifolia husks.

In this work, an integrated strategy of fermentation and separation was developed to improve nisin production. During fermentation, the acidification of fermentation liquid would hinder the synthesis and maturation of nisin inside strain cells. First, Saccharomyces cerevisiae (S. cerevisiae) was co-cultivated with Lactococcus lactis subsp. lactis (L. lactis) to overcome above obstacle. Experimental results indicated that lactose could be used as the substrate carbon source of co-cultivation fermentation. When inoculation ratio of L. lactis and S. cerevisiae was 102:1, nisin titer and ethanol concentration in the fermentation liquid were 3436.3 ± 171.8 IU/mL and 5.9 ± 0.2 mg/mL, respectively. Subsequently, glucose (500 g/L) was supplied into the culture at 24 h for further increasing nisin yield through the quorum sensing of microorganisms. Foam fractionation was used to recover nisin from fermentation liquid. Under the conditions of volumetric air flow rate 40 mL/min, pore diameter of gas distributor 180 μm and initial coupling time of fermentation and foam fractionation after sugar supplementation 9 h, enrichment ratio and recovery percentage of nisin reached 5.8 ± 0.2 and 63.1 ± 2.8%, respectively. Through integrating pervaporation after sugar supplementation for 9 h, permeate concentration and recovery percentage of bioethanol were 367.2 ± 16.5 mg/mL and 76.2 ± 3.4%, respectively. The total nisin titer was 4593.2 ± 206.6 IU/mL.

Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. In this study, we aim to demonstrate that cyclic nucleotide phosphodiesterase 1A (PDE1A), a Ca2+/calmodulin-stimulating PDE family member, plays a critical role in the induction of fibrosis and angiogenesis in the lung.To induce pulmonary damage, adult male SD rats were treated with bleomycin in a dose of 6 mg/kg body weight by a single intratracheal instillation. For in vivo silencing of PDE1A in rat lung, a nonspecific control siRNA or PDE1A-specific siRNA was used to treat rat through nasal instillation. Human normal pulmonary fibroblasts MRC-5 and hFL1 and rat lung fibroblasts were used as in vitro model. Immunohistochemistry and immunoflurescence staining were performed to detect PDE1A and α-SMA expression. Reverse transcription-qPCR was performed to detect microRNA and mRNA expression. In vitro wound healing assay was performed to detect pulmonary fibroblasts'mortality ability.In vitro studies showed that PDE1A can stimulate lung fibroblasts to undergo myofibroblastic changes. This led to the identification of miR-541-5p as one of the miRNA candidates associated with bleomycin response. We found that miR-541-5p expression is downregulated in TGF-β-treated lung fibroblasts and the rat pulmonary fibrosis model. Overexpression of miR-541-5p in lung fibroblasts inhibited mortality of human lung fibroblasts.MiR-541-5p is a key effector in lung fibroblastsby by regulating PDE1A expression at protein translation level and its overexpression is protective against bleomycin-induced lung fibrosis.

Accumulating studies showed that microRNAs are maintaining a variety of important biological processes but the underlying mechanism in proliferation and tumourigenicity is unclear. In this study we show that miR-342 expression in bone marrow and patients' sera of childhood acute myeloid leukemia (AML) was both significantly higher than those in the corresponding normal controls. Functional assays demonstrated that forced expression of miR-342 significantly suppresses AML cell proliferation and G1/S transition of leukemia cells. Mechanistically, bioinformatics prediction and luciferase reporter assay identified N-a-acetyltransferase 10 protein (Naa10p) as a direct molecular target of miR-342, Naa10p siRNA significantly repressed cell proliferation and increased cell apoptosis. In conclusion, our study confirmed that miR-342/Naa10p plays key roles in AML progression, providing insights into underlying mechanisms of AML pathogenesis and also a potential therapeutic target for this malignancy.

Soybean mosaic virus (SMV) is a major pathogen causing yield loss. Developing soybean plants tolerant or resistant to SMV is important for mitigating the adverse effects of the viral infection. However, most studies have focused on the resistance to normal SMV strains. Thus, investigations of the resistance or tolerance to the novel recombinant SMV strain have been limited. To address the threat of the recombinant SMV, two soybean parent genotypes with contrasting reactions to the recombinant SMV and 211 F9:11 recombinant inbred lines were evaluated under artificial inoculation conditions. The JD12 plants are resistant to the recombinant SMV, whereas HT is highly tolerant, but still susceptible. Genetic analyses suggested that the resistance of JD12 is controlled by a single dominant gene and the tolerance is a quantitative trait. The QTL mapping results revealed one QTL (qTsmv-13) for resistance and two QTLs (qTsmv-2 and qTsmv-3) for tolerance. A comparison between known resistance genes and the QTLs identified in this study suggested that qTsmv-13 and qTsmv-2 may correspond to Rsv1 and Rsv4, respectively, whereas qTsmv-3 represents a newly identified QTL for SMV tolerance. We further delimited qTsmv-3 to an interval of approximately 86 kb with a map-based cloning strategy. Only two of five candidate genes, Glyma.03G00550 and Glyma.03G00570, varied between the parents. Additionally, Glyma.03G00550, which is a multidrug and toxic compound extrusion transporter gene, is the likely candidate gene for qTsmv-3. In summary, our research opens a new avenue for formulating strategies to breed soybean varieties tolerant to SMV.

Vertical transmission of the intracellular parasite Toxoplasma gondii (T. gondii) can lead to devastating consequences during gestation. Tim-3, a negative immune regulator, is constitutively expressed on decidual macrophages, but its specific role during T. gondii infection has not yet been explored. In the present study, we discovered that Tim-3 plays an important role in the abnormal pregnancy due to T. gondii infection using Tim-3−/− pregnant mice and anti-Tim-3 neutralizing antibody treated human decidual macrophages. The results showed that abnormal pregnancy outcomes were more prevalent in Tim-3−/− infected pregnant mice than in wild-type infected pregnant mice. Tim-3 expression in decidual macrophages was significantly down-regulated after T. gondii infection both in vitro and in vivo. Tim-3 down-regulation by T.gondii infection could strengthen M1 activation and weaken M2 tolerance by changing the M1 and M2 membrane molecule expression, arginine metabolic enzymes synthesis, and cytokine secretion profiles of decidual macrophages. Moreover, Tim-3 down-regulation by T.gondii infection led to PI3K-AKT phosphorylation inhibition, downstream transcription factor C/EBPβ expression, and SOCS1 activation, which resulted in enzymes synthesis regulation and cytokines secretion. Our study demonstrates that Tim-3 plays an indispensable role in the adverse pregnancy outcomes caused by T. gondii infection.

The use of sterility is common in plants and multiple loci for hybrid sterility have been identified in crops such as rice. In soybean, fine-mapping and research on the molecular mechanism of male sterility is limited. Here, we identified a male-sterile soybean line, which produces larger, abnormal pollen grains that stain poorly with I2-KI. In an inheritance test, all F1 plants were fertile and the F2 and F2:3 populations conformed with the expected segregation ratio of 3:1 (fertility:sterility) (p = 0.82) and showed a 1:2:0 ratio of homozygous fertile: heterozygous fertile: homozygous sterile genotypes (p = 0.73), suggesting that the sterility was controlled by a single recessive gene (designated “mst-M”). Bulked segregant analysis showed that almost all single-nucleotide polymorphisms (SNPs; 95.92%) were distributed on chromosome 13 and 868 SNPs (95.81%) were distributed in the physical region of Chromosome 13.21877872 to Chromosome 13.22862641. Genetic mapping revealed that mst-M was flanked by W1 and dCAPS-1 with genetic distances of 0.6 cM and 1.8 cM, respectively. The order of the consensus markers and known sterility genes was: Satt146 - (5.0 cM) - st5 - (2.5 cM) - Satt030 - (15.3 cM) - ms6 - (5.0 cM) - Satt149 - (39.5 cM) - W1 - (0.6 cM) - mst-M - (14.1 cM) - Satt516 (7.5 cM) - ms1 - (16.3 cM) - Satt595. These results suggest that mst-M is a newly identified male-sterility gene, which represents an alternative genetic resource for developing a hybrid seed production system for soybean.

The summer soybeans (Glycine max (L.) Merr.) in Hebei Province, China, which have adapted to different environments, show extraordinarily rich genetic diversity and extensive species variation. The objectives of this study were to analyze the population structure of summer soybean using simple sequence repeat (SSR) markers and to identify the SSR markers associated with specific traits. A set of 135 SSR markers was used to analyze 50 soybean cultivars, of which 47 cultivars were from 10 breeding institutions in Hebei Province and three cultivars were introductions from the United States. Software tools, the TASSEL, DARwin, and STRUCTURE, were used to analyze linkage disequilibrium (LD) and genetic structure. In addition, an association analysis between the molecular markers and the phenotypic values of 15 agronomic and quality traits was performed. The yield-related agronomic traits included plant height, bottom pod height, effective branch number, number of nodes on main stem, pod number per plan...

Highlight The rice SLG gene, functioning as homomers, plays essential roles in regulating grain size and leaf angle via modulation of brassinosteroid homeostasis., Grain size and leaf angle are two important traits determining grain yield in rice. However, the mechanisms regulating the two traits remain largely unknown. Here, we characterized a rice gain-of-function mutant, slender grain Dominant (slg-D), which exhibited longer and narrower grains and larger leaf angles, similar to plants with elevated brassinosteroid (BR) levels or strengthened BR signaling. The increased cell length is responsible for the mutant phenotypes in slg-D. We demonstrated that the phenotype of slg-D is caused by enhanced expression of SLG, a BAHD acyltransferase-like protein gene. SLG is preferentially expressed in young panicles and lamina joints, implying its role in controlling cell growth in those two tissues. slg-D was restored to wild type by treatment with brassinazole, an inhibitor of BR biosynthesis. Overexpression of SLG in d11-2 (deficient in BR synthesis) and d61-1 (deficient in BR signaling) did not change the existing phenotypes. The slg-D plants had elevated BR contents and, accordingly, expression of BR-related genes was changed in a manner similar to BR treatment. Moreover, SLG RNAi plants displayed mild BR-deficient phenotypes including shorter grains, smaller leaf angles, and compact semi-dwarf plant types. The in vitro biochemical assays and transgenic approaches collectively demonstrated that SLG functions as homomers. Taken together, we conclude that SLG is an important regulator in BR homeostasis and that manipulation of SLG expression to an optimal level may provide a way to develop an ideal plant type.