Cancer-associated fibroblasts refine the classifications of gastric cancer with distinct prognosis and tumor microenvironment characteristics

BackgroundCancer-associated fibroblasts (CAFs) are essential tumoral components of gastric cancer (GC), contributing to the development, therapeutic resistance and immune-suppressive tumor microenvironment (TME) of GC. This study aimed to explore the factors related to matrix CAFs and establish a CAF model to evaluate the prognosis and therapeutic effect of GC.MethodsSample information from the multiply public databases were retrieved. Weighted gene co-expression network analysis was used to identify CAF-related genes. EPIC algorithm was used to construct and verify the model. Machine-learning methods characterized CAF risk. Gene set enrichment analysis was employed to elucidate the underlying mechanism of CAF in the development of GC.ResultsA three-gene (GLT8D2, SPARC and VCAN) prognostic CAF model was established, and patients were markedly divided according to the riskscore of CAF model. The high-risk CAF clusters had significantly worse prognoses and less significant responses to immunotherapy than the low-risk group. Additionally, the CAF risk score was positively associated with CAF infiltration in GC. Moreover, the expression of the three model biomarkers were significantly associated with the CAF infiltration. GSEA revealed significant enrichment of cell adhesion molecules, extracellular matrix receptors and focal adhesions in patients at a high risk of CAF.ConclusionThe CAF signature refines the classifications of GC with distinct prognosis and clinicopathological indicators. The three-gene model could effectively aid in determining the prognosis, drug resistance and immunotherapy efficacy of GC. Thus, this model has promising clinical significance for guiding precise GC anti-CAF therapy combined with immunotherapy

Self‐Assembly of Wireframe DNA Nanostructures from Junction Motifs

Wireframe frameworks have been investigated for the construction of complex nanostructures from a scaffolded DNA origami approach; however, a similar framework is yet to be fully explored in a scaffold‐free “LEGO” approach. Herein, we describe a general design scheme to construct wireframe DNA nanostructures entirely from short synthetic strands. A typical edge of the resulting structures in this study is composed of two parallel duplexes with crossovers on both ends, and three, four, or five edges radiate out from a certain vertex. By using such a self‐assembly scheme, we produced planar lattices and polyhedral objects.Verzweigte Angelegenheit: DNA‐Verzweigungsmotive mit Anordnungen in bestimmten Winkeln wurden entwickelt. Mit ihnen wurden zweidimensionale Drahtgitterstrukturen und dreidimensionale Polyeder konstruiert.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151370/1/ange201906408.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151370/2/ange201906408-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151370/3/ange201906408_am.pd

Self‐Assembly of Wireframe DNA Nanostructures from Junction Motifs

Wireframe frameworks have been investigated for the construction of complex nanostructures from a scaffolded DNA origami approach; however, a similar framework is yet to be fully explored in a scaffold‐free “LEGO” approach. Herein, we describe a general design scheme to construct wireframe DNA nanostructures entirely from short synthetic strands. A typical edge of the resulting structures in this study is composed of two parallel duplexes with crossovers on both ends, and three, four, or five edges radiate out from a certain vertex. By using such a self‐assembly scheme, we produced planar lattices and polyhedral objects.Conjunction junction, what’s your function? Junction motifs of specific angle arrangements are designed. 2D wireframe lattices and 3D wireframe polyhedra are constructed accordingly.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151279/1/anie201906408-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151279/2/anie201906408_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151279/3/anie201906408.pd

pirScan: a webserver to predict piRNA targeting sites and to avoid transgene silencing in C. elegans

pirScan is a web-based tool for identifying C. elegans piRNA-targeting sites within a given mRNA or spliced DNA sequence. The purpose of our tool is to allow C. elegans researchers to predict piRNA targeting sites and to avoid the persistent germline silencing of transgenes that has rendered many constructs unusable. pirScan fulfills this purpose by first enumerating the predicted piRNA-targeting sites present in an input sequence. This prediction can be exported in a tabular or graphical format. Subsequently, pirScan suggests silent mutations that can be introduced to the input sequence that would allow the modified transgene to avoid piRNA targeting. The user can customize the piRNA targeting stringency and the silent mutations that he/she wants to introduce into the sequence. The modified sequences can be re-submitted to be certain that any previously present piRNA-targeting sites are now absent and no new piRNA-targeting sites are accidentally generated. This revised sequence can finally be downloaded as a text file and/or visualized in a graphical format. pirScan is freely available for academic use at http://cosbi4.ee.ncku.edu.tw/pirScan/

Slower-decaying tropical cyclones produce heavier precipitation over China

The post-landfall decay of tropical cyclones (TC) is often closely linked to the magnitude of damage to the environment, properties, and the loss of human lives. Despite growing interest in how climate change affects TC decay, data uncertainties still prevent a consensus on changes in TC decay rates and related precipitation. Here, after strict data-quality control, we show that the rate of decay of TCs after making landfall in China has significantly slowed down by 45% from 1967 to 2018. We find that, except the warmer sea surface temperature, the eastward shift of TC landfall locations also contributes to the slowdown of TC decay over China. That is TCs making landfall in eastern mainland China (EC) decay slower than that in southern mainland China (SC), and the eastward shift of TCs landfall locations causes more TCs landfalling in EC with slower decay rate. TCs making landfall in EC last longer at sea, carry more moisture upon landfall, and have more favorable dynamic and thermodynamic conditions sustaining them after landfall. Observational evidence shows that the decay of TC-induced precipitation amount and intensity within 48 h of landfall is positively related to the decay rate of landfalling TCs. The significant increase in TC-induced precipitation over the long term, due to the slower decay of landfalling TCs, increases flood risks in China’s coastal areas. Our results highlight evidence of a slowdown in TC decay rates at the regional scale. These findings provide scientific support for the need for better flood management and adaptation strategies in coastal areas under the threat of greater TC-induced precipitation

Production of human blood group B antigen epitope conjugated protein in Escherichia coli and utilization of the adsorption blood group B antibody

Additional file 1: Table S1. List of constructed plasmids, strains and primers used in the study. Figure S1. MALDI-TOF detection of MBPmut (a) and MBPmut-OPS (b)

A genome-wide association study of severe asthma exacerbations in Latino children and adolescents

Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups. To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians, and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus (mQTL), expression quantitative trait locus (eQTL), and expression quantitative trait methylation (eQTM) analyses to assess whether the top SNP in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents. In the meta-analysis of GWAS, a SNP in FLJ22447 (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbations (95% confidence interval=1.34 to 1.79, p=6.3×10-9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the FLJ22447 locus, which was in turn associated with increased expression of KCNJ2-AS1 in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10-7). Thus, SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in FLJ22447 and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (KCNJ2-AS1)

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants