Age-atypical brain functional networks in autism spectrum disorder: a normative modeling approach.

BACKGROUND: Despite extensive research into the neural basis of autism spectrum disorder (ASD), the presence of substantial biological and clinical heterogeneity among diagnosed individuals remains a major barrier. Commonly used case‒control designs assume homogeneity among subjects, which limits their ability to identify biological heterogeneity, while normative modeling pinpoints deviations from typical functional network development at individual level. METHODS: Using a world-wide multi-site database known as Autism Brain Imaging Data Exchange, we analyzed individuals with ASD and typically developed (TD) controls (total n = 1218) aged 5-40 years, generating individualized whole-brain network functional connectivity (FC) maps of age-related atypicality in ASD. We then used local polynomial regression to estimate a networkwise normative model of development and explored correlations between ASD symptoms and brain networks. RESULTS: We identified a subset exhibiting highly atypical individual-level FC, exceeding 2 standard deviation from the normative value. We also identified clinically relevant networks (mainly default mode network) at cohort level, since the outlier rates decreased with age in TD participants, but increased in those with autism. Moreover, deviations were linked to severity of repetitive behaviors and social communication symptoms. CONCLUSIONS: Individuals with ASD exhibit distinct, highly individualized trajectories of brain functional network development. In addition, distinct developmental trajectories were observed among ASD and TD individuals, suggesting that it may be challenging to identify true differences in network characteristics by comparing young children with ASD to their TD peers. This study enhances understanding of the biological heterogeneity of the disorder and can inform precision medicine.

Renal and bone side effects of long-term use of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide fumarate in patients with Hepatitis B: a network meta-analysis.

BACKGROUND: Nucleoside analogues are currently applied as a first-line treatment for chronic hepatitis B (CHB) patients. However, the long-term effects of this type of treatment on kidney and bone tissue need to be further investigated. METHODS: We conducted a search of entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) for treatment of CHB patients through October 29, 2023. Side effects of the three drugs were compared. Standardized mean difference (SMD), 95% confidence interval (95%CI), and surface under the cumulative ranking curve (SUCRA) were reported for each outcome. Further subgroup analysis was conducted according to duration of administration. RESULTS: ETV and TAF exhibited less effect on estimated glomerular filtration rate (eGFR) than TDF (SMD = -3.60 (95%CI: -1.94 ~ -5.26) and SMD = -4.27 (95%CI: -2.62 ~ -5.93)). ETV also exhibited less effect on creatinine rise than TAF and TDF (SMD = -0.55 (95%CI: -0.09 ~ -1.01) and SMD = -0.61 (95%CI: -0.15 ~ -1.06)). Moreover, the effect of TAF on bone mineral density (BMD) was less than that of TDF (SMD = -0.02 (95%CI: -0.01 ~ -0.02)). The probabilities of the three drugs changing relevant indicators exhibited similar patterns: eGFR (TDF (100.0%) > ETV (41.2%) > TAF (8.8%)), creatinine (TDF (94.7%) > TAF (54.7%) > ETV (0.6%)), BMD (TDF (79.7%) > ETV (50.6%) > TAF (19.6%)), and blood phosphorus (TDF (90.6%) > TAF (49.8%) > ETV (9.7%)). After 6 and 24 months of treatment, no statistically significant difference in renal function or bone tissue was observed between ETV and TDF. However, greater adverse effects on renal function were observed for TDF than ETV at 60 months compared to 12 months. TDF also exhibited greater adverse effects on bone tissue than ETV at 36 months than at 12 months. CONCLUSIONS: Long-term administration of TDF has resulted in stronger adverse effects than TAF and ETV in regard to both renal function and bone tissue in CHB patients. The effect of TAF on creatinine increase was greater than ETV. The difference in side effects between ETV and TDF was independent of treatment duration.

Amitosis as a strategy of cell division-Insight from the proliferation of Tetrahymena thermophila macronuclei.

Cell division is a necessity of life which can be either mitotic or amitotic. While both are fundamental, amitosis is sometimes considered a relic of little importance in biology. Nevertheless, eukaryotes often have polyploid cells, including cancer cells, which may divide amitotically. To understand how amitosis ensures the completion of cell division, we turn to the macronuclei of ciliates. The grand scheme governing the proliferation of the macronuclei of ciliate cells, which involves chromosomal replication and amitosis, is currently unknown, which is crucial for developing population genetics model of ciliate populations. Using a novel model that encompasses a wide range of mechanisms together with experimental data of the composition of mating types at different stages derived from a single karyonide of Tetrahymena thermophila, we show that the chromosomal replication of the macronucleus has a strong head-start effect, with only about five copies of chromosomes replicated at a time and persistent reuse of the chromosomes involved in the early replication. Furthermore the fission of a fully grown macronucleus is non-random with regard to chromosome composition, with a strong tendency to push chromosomes and their replications to the same daughter cell.

Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the development of non-alcoholic fatty liver disease: a cross-sectional study.

BACKGROUND: This study aimed to investigate the correlation of circulating total bilirubin (TB) and UGT1A1 with NAFLD in Chinese Han population. METHODS: 172 adults were enrolled from the Qingdao Municipal Hospital from May 2019 to October 2020. All individuals were examined with MRI-PDFF and divided into no steatosis, mild steatosis, moderate steatosis, and severe steatosis groups according to the MRI-PDFF values. The biochemical indexes and UGT1A1 were measured. RESULTS: There was no significant difference of circulating TB and UGT1A1 levels between NAFLD group and controls. In the moderate steatosis and severe steatosis groups, the circulating TB levels were higher than that in control group (all P < 0.05). In addition, circulating TB levels were weak positively associated with liver fat fraction in NAFLD patients (ρ = 0.205, P = 0.001). There was no significant correlation between circulating UGT1A1 levels with liver fat fraction in patients with NAFLD (ρ = 0.080, P = 0.179), but positively correlation was found in patients with severe steatosis (ρ = 0.305, P = 0.026). CONCLUSIONS: The circulating TB levels were significant high in patients with moderate and severe steatosis. Circulating TB levels were weakly associated with liver fat fraction in patients with NAFLD, and the circulating UGT1A1 levels were positively correlated with liver fat fraction in NAFLD patients with severe steatosis. TRIAL REGISTRATION: ChiCTR, ChiCTR1900022744. Registered 24 April 2019 - Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=38304&htm=4 .

Simultaneous determination of pinoxaden, cloquintocet-mexyl, clodinafop-propargyl ester and its major metabolite in barley products and soil using QuEChERS modified with multi-walled carbon nanotubes coupled with LC-MS/MS.

Herein, a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method with multi-walled carbon nanotube (MWCNT) as a dispersive solid-phase extraction was developed for simultaneous determination of pinoxaden (PXD), cloquintocet-mexyl (CLM), clodinafop-propargyl ester (CPE) and its major metabolite (clodinafop, CP) in barley grass powder, barley grain, and soil using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found that MWCNT as an absorbent could improve the recoveries of the tested analytes, particularly CP, in complex matrices. Under the optimum conditions, the established MWCNT-modified QuEChERS coupled with LC-MS/MS method exhibited excellent linearity (R2 ) of ≥0.9912, low limits of detection (LODs) and quantification (LOQs) of 0.02-0.07 and 0.29-1.26 µg kg-1 , and acceptable recoveries of 80-130% with intra- and inter-day relative standard deviations (RSDs) < 10.5%. No strong matrix effect (ME) has been observed on the respective samples. The method was successfully applied to monitor the tested analytes in the representative field incurred samples. Conclusively, the proposed method is sensitive and reliable and could be used to monitor the residues of PDX, CLM, CPE, and CP in complicated agro-products and soil matrices.

Solidification performances of contaminants by red mud-based cementitious paste filling material and leaching behavior of contaminants in different pH and redox potential environments.

Considering the urgent need for disposal of red mud and the comprehensive treatment of coal mined-out areas, this paper presented red mud-based cementitious paste filling material (RMFM) to achieve the purpose of green filling treatment. However, the solidification performance of alkaline RMFM for contaminants can be affected when in contact with acid goaf water in practice, which may in turn cause secondary pollution to the surroundings. The leaching tests of RMFM under different pH and redox potential (Eh) conditions were designed to investigate the effects of environmental elements on the solidification performance of RMFM, and primarily investigated the treatment effectiveness of RMFM on goaf water. The test results manifest that the acidic and oxidizing environments could damage the hydration products generated by alkali and sulfate activation, thus affecting the solidification performance, while the alkaline and reducing environments could effectively prevent the release of the contaminants by enhancing the degree of alkali activation and inhibiting oxidation acid forming process. In the possible exposure environment, RMFM could effectively stabilize its own pollutants without secondary pollution. In addition, the powder RMFM samples had significant removal effects on heavy metals, the values of Cu, Pb, and As removal efficiency all reached more than 96.15%.

Establishment, FEM analysis and experimental validation of tooth movement prediction model of orthodontic archwire T-loop.

BACKGROUND: The T-loop has been used clinically to close gap between teeth. And it is a typical orthodontic archwire bending method. However, the design of the T-loop parameters for different patients is based on the clinical experience of the dentists. The variation in dentists' clinical experience is the main reason for inadequate orthodontic treatment, even high incidence of postoperative complications. METHODS: Firstly, the tooth movement prediction model is established based on the analysis of the T-loop structure and the waxy model dynamic resistance. As well as the reverse reconstruction of the complete maxillary 3D model based on the patient CBCT images, the oral biomechanical FEM analysis is completed. A maxillary waxy dental model is manufactured to realize the water-bath measurement experiment in vitro mimicking the oral bio-environment. Thus, the calculated, simulation and experimental data are obtained, as well as obtaining a cloud of total deformation from the simulation analysis. RESULTS: The growth trend of the 11 sets of simulation data is the same as that of the experimental data. And all of them show that the tooth displacement is positively correlated with the cross-sectional size of the archwire, and the clearance distance. As well as the higher Young's modulus of the archwire material, the greater the tooth displacement. And the effect of archwire parameters on tooth displacement derived from simulation and experimental data is consistent with the prediction model. The experimental and calculated data are also compared and analyzed, and the two kinds of data are basically consistent in terms of growth trends and fluctuations, with deviation rates ranging from 2.17 to 10.00%. CONCLUSIONS: This study shows that the accuracy and reliability of the tooth movement prediction model can be verified through the comparative analysis and deviation calculation of the obtained calculated, simulation and experimental data, which can assist dentists to safely and efficiently perform orthodontic treatment on patients. And the FEM analysis can achieve predictability of orthodontic treatment results.

Functional phenomics and genetics of the root economics space in winter wheat using high-throughput phenotyping of respiration and architecture.

The root economics space is a useful framework for plant ecology but is rarely considered for crop ecophysiology. In order to understand root trait integration in winter wheat, we combined functional phenomics with trait economic theory, utilizing genetic variation, high-throughput phenotyping, and multivariate analyses. We phenotyped a diversity panel of 276 genotypes for root respiration and architectural traits using a novel high-throughput method for CO2 flux and the open-source software RhizoVision Explorer to analyze scanned images. We uncovered substantial variation in specific root respiration (SRR) and specific root length (SRL), which were primary indicators of root metabolic and structural costs. Multiple linear regression analysis indicated that lateral root tips had the greatest SRR, and the residuals from this model were used as a new trait. Specific root respiration was negatively correlated with plant mass. Network analysis, using a Gaussian graphical model, identified root weight, SRL, diameter, and SRR as hub traits. Univariate and multivariate genetic analyses identified genetic regions associated with SRR, SRL, and root branching frequency, and proposed gene candidates. Combining functional phenomics and root economics is a promising approach to improving our understanding of crop ecophysiology. We identified root traits and genomic regions that could be harnessed to breed more efficient crops for sustainable agroecosystems.

The clinical characteristics of pediatric inpatients with SARS-CoV-2 infection: A meta-analysis and systematic review.

Millions of people were infected with the coronavirus disease 2019 (COVID-19) all over the world. Data on clinical symptoms of pediatric inpatients with COVID-19 infection were unclear. The aim of study was to investigate the clinical features of pediatric inpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PubMed, EMBASE, and the Cochrane Library were searched to seek for studies providing details on pediatric inpatients with SARS-CoV-2 infection which were published from 1st January to 21st April 2020. Studies with more than five pediatric inpatients were included in our meta-analysis.This study was registered in the PROSPERO database (CRD42020183550). As the results shown, fever (46%) and cough (42%) were the main clinical characters of pediatric inpatients with SARS-CoV-2 infection and the other clinical characters, such as diarrhea, vomiting, nasal congestion, and fatigue account for 10% in pediatric inpatients. The proportion of asymptomatic cases was 0.42 (95% confidence interval [CI]: 0.27-0.59) and severe cases was 0.03 (95% CI: 0.01-0.06). For the laboratory result, leukopenia (21%) and lymphocytosis (22%) were the mainly indicators for pediatric inpatients, followed by high aspartate aminotransferase (19%), lymphopenia (16%), high alanine aminotransferase (15%), high C-reactive protein (17%), leukocytosis (13%), high D-dimer (12%) and high creatine kinase-MB (5%). Regard to chest imaging features, unilateral and bilateral accounts for 22% in pediatric inpatients, respectively. In conclusion, compared with adult inpatients with SARS-CoV-2 infection, the pediatric inpatients had mild clinical characters, lab test indicators, and chest imaging features. More clinical studies focus on the pediatric patients with SARS-CoV-2 infection in other countries should be conducted.

Proportion of NAFLD patients with normal ALT value in overall NAFLD patients: a systematic review and meta-analysis.

BACKGROUND: ALT value is often used to reflect the hepatic inflammation and injury in NAFLD patients, but many studies proved that ALT values were normal in many NAFLD patients. The aim of this study was to identify the summarized proportion of NAFLD patients with normal ALT value in the overall NAFLD patients. METHODS: Electronic databases PubMed, EMBASE, Ovid, and the Cochrane Library were searched for potential studies published from January 1, 2000 to September 30, 2019. Studies that have reported the number of NAFLD or NASH patients with normal and abnormal ALT value were included and analyzed. Abstracts, reviews, case reports, and letters were excluded. RESULTS: A total of 11 studies with 4084 patients were included for assessing the summarized proportion of NAFLD patients with normal ALT in overall NAFLD patients. As the results shown, the summarized proportion of NAFLD patients with normal ALT value in overall NAFLD patients was 25% (95%CI: 20-31%) which was calculated by the random-effects model. The summarized proportion of NASH patients with normal ALT value in overall NASH patients was 19% (95%CI: 13-27%). Subgroup analysis includes region, study type, diagnostic method, and group size were conducted to investigate the resource of heterogeneity in the summarized proportion of NAFLD and NASH patients with normal ALT value. CONCLUSIONS: 25% NAFLD patients and 19% NASH patients possess the normal ALT value in the clinical manifestation. The value of ALT in the clinical diagnosis of NAFLD and NASH remains need be further testified.

MiR-30b-5p regulates the lipid metabolism by targeting PPARGC1A in Huh-7 cell line.

BACKGROUND: MiRNAs are a group of multifunctional non-coding RNAs which play an important role in the various physiological processes including the development of NAFLD. Recent studies have shown that miR-30b-5p tightly associated with the abnormal lipid metabolism in patients with NAFLD, but the detailed mechanism of miR-30b-5p in the lipid metabolism was remain unclear. The aim of this study was to investigate the effect of miR-30b-5p on the lipid metabolism in hepatocellular carcinoma Huh-7 cells. MATERIAL AND METHODS: The correlation of intracellular fat content with the expression of miR-30b-5p in Huh-7 cells and HepG2 cells was investigated by treated cells with different concentrations of FFAs. The effect of miR-30b-5p on the lipid deposition in Huh-7 cells was tested by oil red O staining and TG concentrations measurement. qRT-PCR and western blot were used to investigate the lipid metabolism-related genes PPAR-α, SREBP-1, and GULT1 in miR-30b-5p overexpressed or inhibited Huh-7 cells. Target genes of miR-30b-5p were predicted using starBase, miRDB, and TargetScan databases and verified by qRT-PCR and western blot. RESULTS: The expression of miR-30b-5p was significant decreased in the FFAs treated Huh-7 cells and HepG2 cells. Overexpressing miR-30b-5p in Huh-7 cells decreased the number and size of lipid droplets and intracellular TG concentrations in Huh-7 cells. Expression of fatty acid oxidation related gene PPAR-α was increased and expression of lipid synthesis related gene SREBP-1 was decreased in the miR-30b-5p overexpressed Huh-7 cells. In addition, miR-30b-5p regulates the intracellular lipid metabolism by targeting PPARGC1A. CONCLUSIONS: Overexpression of miR-30b-5p could reduce the intracellular fat deposition in Huh-7 cells, and miR-30b-5p might regulate the intracellular lipid metabolism by targeting the PPARGC1A in Huh-7 cells.

Association between nonalcoholic fatty liver disease and extrahepatic cancers: a systematic review and meta-analysis.

BACKGROUND: NAFLD is tightly associated with various diseases such as diabetes, cardiovascular disease, kidney disease, and cancer. Previous studies had investigated the association between NAFLD and various extrahepatic cancers, but the available data to date is not conclusive. The aim of this study was to investigate the association between NAFLD and various extrahepatic cancers comprehensively. METHODS: Searches were conducted of various electronic databases (PubMed, EMBASE, Medline, and the Cochrane Library) to identify observational studies published between 1996 and January 2020 which investigated the association between NAFLD and extrahepatic cancers. The pooled OR/HR/IRR of the association between NAFLD and various extrahepatic cancers were analyzed. RESULTS: A total of 26 studies were included to investigate the association between NAFLD and various extrahepatic cancers. As the results shown, the pooled OR values of the risk of colorectal cancer and adenomas in patients with NAFLD were 1.72 (95%CI: 1.40-2.11) and 1.37 (95%CI: 1.29-1.46), respectively. The pooled OR values of the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in patients with NAFLD were 2.46 (95%CI: 1.77-3.44) and 2.24 (95%CI: 1.58-3.17), respectively. The pooled OR value of the risk of breast cancer in patients with NAFLD was 1.69 (95%CI: 1.44-1.99). In addition, NAFLD was also tightly associatied with the risk of gastric cancer, pancreatic cancer, prostate cancer, and esophageal cancer. CONCLUSIONS: NAFLD could significantly increase the development risk of colorectal adenomas and cancer, intrahepatic and extrahepatic cholangiocarcinoma, breast, gastric, pancreatic, prostate, and esophageal cancer. NAFLD could be considered as one of the influencing factors during the clinical diagnosis and treatment for the extrahepatic cancers.

[Analysis of gene expression of Tetrahymena thermophila treated with Panax japonicas].

Panax japonicus is a traditional Chinese medicine,and its principle components have shown certain pharmacological activities for cell damage,aging and cell apoptosis. In order to clarify the pharmacological mechanism and involved metabolic pathways of P. japonicas,the gene expression of Tetrahymena thermophila under P. japonicus treatment was analyzed through high-throughput transcriptome sequencing in this study. Based on the transcriptome analysis,3 544 differentially expressed genes were identified in control group,of which 1 945 genes showed up-regulated expression and 1 599 genes showed down-regulated expression. Under P. japonicas treatment in the experiment group,3 312 differentially expressed genes were screened,of which 1 `493 genes showed up-regulated expression and 1 819 genes showed down-regulated expression. GO enrichment analysis indicated that in control group,the genes in the cells in a series of fundamental biological process were down-regulated,such as DNA replication and protein synthesis; while the signal transduction process and fatty acids oxidizing process were enriched. Whereas in the experiment group,down-regulated genes were mainly enriched in oxidation-reduction,cofactor metabolic process and vitamin metabolic process; up-regulated genes were enriched in signal transduction process and protein modification process. In the analysis using KEGG database,cell cycle pathway was enhanced and autophagy pathway was inhibited under the condition of P. japonicas treatment. Real-time quantitative polymerase chain reaction( RT-qPCR) was used to detect the expression differences between 6 up-regulated and 4 down-regulated genes in related metabolic pathways. The RT-q PCR results and RNA-Seq data were highly correlated and consistent with each other. This study could provide important direction and basis for further study on the mechanism of cell growth regulation with the treatment of P. japonica.

A Verticillium dahliae Extracellular Cutinase Modulates Plant Immune Responses.

Cutinases have been implicated as important enzymes during the process of fungal infection of aerial plant organs. The function of cutinases in the disease cycle of fungal pathogens that invade plants through the roots has been less studied. Here, functional analysis of 13 cutinase (carbohydrate esterase family 5 domain-containing) genes (VdCUTs) in the highly virulent vascular wilt pathogen Verticillium dahliae Vd991 was performed. Significant sequence divergence in cutinase family members was observed in the genome of V. dahliae Vd991. Functional analyses demonstrated that only VdCUT11, as purified protein, induced cell death and triggered defense responses in Nicotiana benthamiana, cotton, and tomato plants. Virus-induced gene silencing showed that VdCUT11 induces plant defense responses in Nicotiana benthamania in a BAK1 and SOBIR-dependent manner. Furthermore, coinfiltration assays revealed that the carbohydrate-binding module family 1 protein (VdCBM1) suppressed VdCUT11-induced cell death and other defense responses in N. benthamiana. Targeted deletion of VdCUT11 in V. dahliae significantly compromised virulence on cotton plants. The cutinase VdCUT11 is an important secreted enzyme and virulence factor that elicits plant defense responses in the absence of VdCBM1.

SNARE-Encoding Genes VdSec22 and VdSso1 Mediate Protein Secretion Required for Full Virulence in Verticillium dahliae.

Proteins that mediate cellular and subcellular membrane fusion are key factors in vesicular trafficking in all eukaryotic cells, including the secretion and transport of plant pathogen virulence factors. In this study, we identified vesicle-fusion components that included 22 soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), four Sec1/Munc18 (SM) family proteins, and 10 Rab GTPases encoded in the genome of the vascular wilt pathogen Verticillium dahliae Vd991. Targeted deletion of two SNARE-encoding genes in V. dahliae, VdSec22 and VdSso1, significantly reduced virulence of both mutants on cotton, relative to the wild-type Vd991 strain. Comparative analyses of the secreted protein content (exoproteome) revealed that many enzymes involved in carbohydrate hydrolysis were regulated by VdSec22 or VdSso1. Consistent with a role of these enzymes in plant cell-wall degradation, pectin, cellulose, and xylan utilization were reduced in the VdSec22 or VdSso1 mutant strains along with a loss of exoproteome cytotoxic activity on cotton leaves. Comparisons with a pathogenicity-related exoproteome revealed that several known virulence factors were not regulated by VdSec22 or VdSso1, but some of the proteins regulated by VdSec22 or VdSso1 displayed different characteristics, including the lack of a typical signal peptide, suggesting that V. dahliae employs more than one secretory route to transport proteins to extracellular sites during infection.

Comparative genomics reveals cotton-specific virulence factors in flexible genomic regions in Verticillium dahliae and evidence of horizontal gene transfer from Fusarium.

Verticillium dahliae isolates are most virulent on the host from which they were originally isolated. Mechanisms underlying these dominant host adaptations are currently unknown. We sequenced the genome of V. dahliae Vd991, which is highly virulent on its original host, cotton, and performed comparisons with the reference genomes of JR2 (from tomato) and VdLs.17 (from lettuce). Pathogenicity-related factor prediction, orthology and multigene family classification, transcriptome analyses, phylogenetic analyses, and pathogenicity experiments were performed. The Vd991 genome harbored several exclusive, lineage-specific (LS) genes within LS regions (LSRs). Deletion mutants of the seven genes within one LSR (G-LSR2) in Vd991 were less virulent only on cotton. Integration of G-LSR2 genes individually into JR2 and VdLs.17 resulted in significantly enhanced virulence on cotton but did not affect virulence on tomato or lettuce. Transcription levels of the seven LS genes in Vd991 were higher during the early stages of cotton infection, as compared with other hosts. Phylogenetic analyses suggested that G-LSR2 was acquired from Fusarium oxysporum f. sp. vasinfectum through horizontal gene transfer. Our results provide evidence that horizontal gene transfer from Fusarium to Vd991 contributed significantly to its adaptation to cotton and may represent a significant mechanism in the evolution of an asexual plant pathogen.

Genome-wide association study discovered candidate genes of Verticillium wilt resistance in upland cotton (Gossypium hirsutum L.).

Verticillium wilt (VW), caused by infection by Verticillium dahliae, is considered one of the most yield-limiting diseases in cotton. To examine the genetic architecture of cotton VW resistance, we performed a genome-wide association study (GWAS) using a panel of 299 accessions and 85 630 single nucleotide polymorphisms (SNPs) detected using the specific-locus amplified fragment sequencing (SLAF-seq) approach. Trait-SNP association analysis detected a total of 17 significant SNPs at P < 1.17 × 10-5 (P = 1/85 630, -log10 P = 4.93); the peaks of SNPs associated with VW resistance on A10 were continuous and common in three environments (RDIG2015, RDIF2015 and RDIF2016). Haplotype block structure analysis predicted 22 candidate genes for VW resistance based on A10_99672586 with a minimum P-value (-log10 P = 6.21). One of these genes (CG02) was near the significant SNP A10_99672586 (0.26 Mb), located in a 372-kb haplotype block, and its Arabidopsis AT3G25510 homologues contain TIR-NBS-LRR domains that may be involved in disease resistance response. Real-time quantitative PCR and virus-induced gene silencing (VIGS) analysis showed that CG02 was specific to up-regulation in the resistant (R) genotype Zhongzhimian2 (ZZM2) and that silenced plants were more susceptible to V. dahliae. These results indicate that CG02 is likely the candidate gene for resistance against V. dahliae in cotton. The identified locus or gene may serve as a promising target for genetic engineering and selection for improving resistance to VW in cotton.

Genome-wide analysis of the gene families of resistance gene analogues in cotton and their response to Verticillium wilt.

BACKGROUND: Gossypium raimondii is a Verticillium wilt-resistant cotton species whose genome encodes numerous disease resistance genes that play important roles in the defence against pathogens. However, the characteristics of resistance gene analogues (RGAs) and Verticillium dahliae response loci (VdRLs) have not been investigated on a global scale. In this study, the characteristics of RGA genes were systematically analysed using bioinformatics-driven methods. Moreover, the potential VdRLs involved in the defence response to Verticillium wilt were identified by RNA-seq and correlations with known resistance QTLs. RESULTS: The G. raimondii genome encodes 1004 RGA genes, and most of these genes cluster in homology groups based on high levels of similarity. Interestingly, nearly half of the RGA genes occurred in 26 RGA-gene-rich clusters (Rgrcs). The homology analysis showed that sequence exchanges and tandem duplications frequently occurred within Rgrcs, and segmental duplications took place among the different Rgrcs. An RNA-seq analysis showed that the RGA genes play roles in cotton defence responses, forming 26 VdRLs inside in the Rgrcs after being inoculated with V. dahliae. A correlation analysis found that 12 VdRLs were adjacent to the known Verticillium wilt resistance QTLs, and that 5 were rich in NB-ARC domain-containing disease resistance genes. CONCLUSIONS: The cotton genome contains numerous RGA genes, and nearly half of them are located in clusters, which evolved by sequence exchanges, tandem duplications and segmental duplications. In the Rgrcs, 26 loci were induced by the V. dahliae inoculation, and 12 are in the vicinity of known Verticillium wilt resistance QTLs.

IKKß/NF-κB mediated the low doses of bisphenol A induced migration of cervical cancer cells.

Cervical cancer is considered as the second most common female malignant disease. There is an urgent need to illustrate risk factors which can trigger the motility of cervical cancer cells. Our present study revealed that nanomolar concentration of bisphenol A (BPA) significantly promoted the in vitro migration and invasion of cervical cancer HeLa, SiHa, and C-33A cells. Further, BPA treatment increased the expression of metalloproteinase-9 (MMP-9) and fibronectin (FN) in both HeLa and SiHa cells, while did not obviously change the expression of MMP-2, vimentin (Vim) or N-Cadherin (N-Cad). BAY 11-7082, the inhibitor of NF-κB, significantly abolished BPA induced up regulation of FN and MMP-9 in cervical cancer cells. While the inhibitors of PKA (H89), ERK1/2 (PD 98059), EGFR (AG1478), or PI3K/Akt (LY294002) had no effect on the expression of either FN or MMP-9. BPA treatment rapidly increased the phosphorylation of both IκBα and p65, stimulated nuclear translocation, and up regulated the promoter activities of NF-κB. The BPA induced up regulation of MMP-9 and FN and activation of NF-κB were mediated by phosphorylation of IKKß via PKC signals. Collectively, our study found for the first time that BPA stimulated the cervical cancer migration via IKK-ß/NF-κB signals.