Bacillus megaterium BMJBN02 induces the resistance of grapevine against downy mildew

Grape downy mildew caused by Plasmopara viticola is one of the most destructive diseases of grapes. All grape cultivars are susceptible to P. viticola. However, the resistance of grape plants could be induced in plant defense with some help of microbes. In this study, Bacillus megaterium BMJBN02 obtained from farmland soil was shown to regulate the resistance of grapevine against downy mildew. The salicylic acid (SA) content and the expression of pathogenesis-related (PR) genes of grapes under different treatments were examined using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and reverse transcription- quantitative polymerase chain reaction (RT-qPCR), and it was found that SA content and the expression of PR genes could play a role in regulating the resistance of grapevine against downy mildew. The five-year plot experiment showed that the resistance effectiveness of isolate BMJBN02 was approximately equal to that of 0.1 % nicotinyl morpholine (commercial fungicide). Therefore, this study provides a valuable candidate method that uses B. megaterium BMJBN02 by regulating the resistance of grape against downy mildew for quality and yield of grape in commercial productivity

Genomic heterogeneity of multiple synchronous lung cancer

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

S100A4 Mediates Endometrial Cancer Invasion and is a Target of TGF-β1 Signaling

The molecular mechanisms of endometrial cancer invasion are poorly understood. S100A4, also known as FSP1 (fibroblast specific protein 1), has long been known to be a molecular marker of fibrosis in a variety of different fibrotic diseases of the lungs, liver, kidney, and heart. We demonstrate here that increased expression of S100A4 is associated with advanced stage endometrial cancer and decreased recurrence free survival. To verify the essential role of S100A4 in invasiveness of endometrial cancer, S100A4 expression was down-regulated by RNAi in HEC-1A cells, which resulted in undetectable S100A4 protein and significantly decreased migration and invasion. Due to the established connection between TGF-β1 and S100A4 induction in experimental models of kidney and liver fibrosis, we next examined whether TGF-β1 could also regulate S100A4 in endometrial cancer cells. TGF-β1 stimulated endometrial cancer cell migration and invasion with a concomitant increase in S100A4 protein. Induction of S100A4 was associated with the activation of Smads. TGF -β1 mediated endometrial cancer cell motility was inhibited by S100A4 siRNA. In aggregate, these results suggest that S100A4 is a critical mediator of invasion in endometrial cancer and is upregulated by the TGF-β1 signaling pathway. These results also suggest that endometrial cancer cell invasion and fibrosis share common molecular mechanisms

Survival times of HIV/AIDS in different AIDS Diagnostic and Treatment Guidelines from 2006 to 2020 in Liuzhou, China

Abstract Background To compare the survival rates of four timing of treatment initiation for people living with HIV/AIDS provided in China in 2006, 2011, 2015, and 2018, and to investigate the factors impacting survival time. Methods A people living with HIV/AIDS retrospective cohort study was in Liuzhou City from April 2006 to December 2020. The information was obtained from the National Comprehensive AIDS Prevention and Control Information System. Life tables and the Kaplan–Meier method were used to calculate participant survival rates and time. The univariate and multivariate Cox regression models were used to investigate the factors related to survival. Results 18,543 participants were included in this study. In four periods, the 1-year survival rates were 81%, 87%, 95%, and 95%. The 2-year survival rates were 76%, 85%, 93%, and 94%. The 3-year survival rates were 73%, 84%, 92%, and 94%. Results of multivariate Cox regression showed that sex, age of HIV diagnosis, ethnicity, household registration, occupation, marital status, the timing of treatment, education level, route of HIV transmission, whether receiving antiretroviral therapy (ART), and the count of CD4+T cells at baseline (count of CD4+T cells at HIV diagnosis) were factors that are significantly correlated with mortality caused by HIV infection. Conclusions With the Guidelines updated from 2006 to 2020, the 1-, 2-, and 3-year survival rates of people living with HIV/AIDS in four periods tended to increase. The timing of treatment initiation of the updated edition of the AIDS Diagnostic and Treatment Guidelines (Guidelines) significantly prolonged the survival time of people living with HIV/AIDS

OSov: An Interactive Web Server to Evaluate Prognostic Biomarkers for Ovarian Cancer

Ovarian cancer is one of the most aggressive and highly lethal gynecological cancers. The purpose of our study is to build a free prognostic web server to help researchers discover potential prognostic biomarkers by integrating gene expression profiling data and clinical follow-up information of ovarian cancer. We construct a prognostic web server OSov (Online consensus Survival analysis for Ovarian cancer) based on RNA expression profiles. OSov is a user-friendly web server which could present a Kaplan–Meier plot, forest plot, nomogram and survival summary table of queried genes in each individual cohort to evaluate the prognostic potency of each queried gene. To assess the performance of OSov web server, 163 previously published prognostic biomarkers of ovarian cancer were tested and 72% of them had their prognostic values confirmed in OSov. It is a free and valuable prognostic web server to screen and assess survival-associated biomarkers for ovarian cancer

Efficacy of Transarterial Chemoembolization Combined with Molecular Targeted Agents for Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis

Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) is the mainstay treatment for unresectable hepatocellular carcinoma (uHCC). However, studies investigating different combinations of agents have shown inconsistent results. Here, we used network meta-analysis (NMA) to compare different agents across 41 studies (36 cohort studies and five RCTs) in 11,540 patients. Multiple RCTs and cohort studies were searched to evaluate TACE combined with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and tumor response. NMA used a random-effects consistency model to pool evidence from direct and indirect comparisons. Hazard ratio (HR) and relative risks (RR) with 95% confidence intervals (CI) were analyzed. Further, heterogeneity and publication bias analyses were performed and agents were ranked. TACE plus lenvatinib provided the maximal OS (Rank probability: 0.7559), PFS (Rank probability: 0.8595), CR (Rank probability: 0.4179), and DCR (Rank probability: 0.3857). TACE plus anlotinib demonstrated the highest PR (p = 0.62649) and ORR (p = 0.51158). SD was more often associated with TACE plus sorafenib (Rank probability: 0.601685). TACE plus lenvatinib provides optimal treatment for uHCC based on the highest ranking of OS, PFS, and DCR rates. However, given the lack of statistically significant OS benefit, shared decision making should include other TKIs as acceptable alternatives

Convolutional neural network applied to preoperative venous-phase CT images predicts risk category in patients with gastric gastrointestinal stromal tumors

Abstract Objective The risk category of gastric gastrointestinal stromal tumors (GISTs) are closely related to the surgical method, the scope of resection, and the need for preoperative chemotherapy. We aimed to develop and validate convolutional neural network (CNN) models based on preoperative venous-phase CT images to predict the risk category of gastric GISTs. Method A total of 425 patients pathologically diagnosed with gastric GISTs at the authors’ medical centers between January 2012 and July 2021 were split into a training set (154, 84, and 59 with very low/low, intermediate, and high-risk, respectively) and a validation set (67, 35, and 26, respectively). Three CNN models were constructed by obtaining the upper and lower 1, 4, and 7 layers of the maximum tumour mask slice based on venous-phase CT Images and models of CNN_layer3, CNN_layer9, and CNN_layer15 established, respectively. The area under the receiver operating characteristics curve (AUROC) and the Obuchowski index were calculated to compare the diagnostic performance of the CNN models. Results In the validation set, CNN_layer3, CNN_layer9, and CNN_layer15 had AUROCs of 0.89, 0.90, and 0.90, respectively, for low-risk gastric GISTs; 0.82, 0.83, and 0.83 for intermediate-risk gastric GISTs; and 0.86, 0.86, and 0.85 for high-risk gastric GISTs. In the validation dataset, CNN_layer3 (Obuchowski index, 0.871) provided similar performance than CNN_layer9 and CNN_layer15 (Obuchowski index, 0.875 and 0.873, respectively) in prediction of the gastric GIST risk category (All P >.05). Conclusions The CNN based on preoperative venous-phase CT images showed good performance for predicting the risk category of gastric GISTs