Square grid pattern with direction-selective surface discharges in dielectric barrier discharge

A new phenomenon that a filament discharged only once instead of twice in a cycle of the applied voltage is observed in a square grid pattern in a dielectric barrier discharge(DBD)with a larger gas gap,which is named intermittent discharge.Its spatiotemporal dynamics and the formation mechanism are studied by the multiple photomultiplier tubes and an intensified charge-coupled device.Corresponding to the positions of spots in the picture with an exposure time of 40 ms,there are some bright spots(discharge spots)and black spots(non-discharged spots)in the instantaneous image with an exposure time of 10μs(a half cycle of the applied voltage).There are at least two bright spots around one black spot and vice versa.The surface discharges(SDS)can be observed between any two adjacent spots.The intensity of the SDSbetween the bright spot and the black spot is 2.5 times greater than that between two adjacent bright spots,which indicates that the SDSare directional-selective.The intermittent discharge with positive(negative)current polarity changes to that with negative(positive)current polarity,after it sustains up to 14 voltage cycles at the longest.The spatial distribution of the electric field component is calculated through COMSOL software to solve the Poisson equation numerically.It is found that the inhomogeneous distribution of surface electric field is caused by the inhomogeneous distribution of wall charges,which leads to direction-selective SDS.The intermittent discharge is formed by the competition between the direction-selective SDSand volume discharges(VDS)in DBD.This is the reason why the intermittent discharge is generated.

Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade

Background:Immune checkpoint blockade(ICB)has revolutionized the treatment of various cancer types.Despite significant preclinical advancements in understanding mechanisms,identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging.Recent evidence,both preclinical and clinical,underscores the pivotal role of the extracellular matrix(ECM)in modulating immune cell infiltration and behaviors.This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy.Methods:We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy.This analysis led to the identification of three distinct immuno-collagenic subtypes predictive of ICB responses.We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas(TCGA)dataset and 1,084 inhouse samples.Additionally,novel therapeutic targets were identified based on these established immuno-collagenic subtypes.Results:Our categorization divided tumors into three subtypes:“soft&hot”(low collagen activity and high immune infiltration),“armored&cold”(high collagen activity and low immune infiltration),and“quiescent”(low collagen activity and immune infiltration).Notably,“soft&hot”tumors exhibited the most robust response to ICB therapy across various cancer types.Mechanistically,inhibiting collagen augmented the response to ICB in preclinical models.Furthermore,these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types.Additionally,an unbiased approach identified B7 homolog 3(B7-H3),an available drug target,as strongly expressed in“armored&cold”tumors,relating with poor prognosis.Conclusion:This study introduces histopathology-based universal immunocollagenic subtypes capable of predicting ICB responses across diverse cancer types.These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

CCGD-ESCC： A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population

Esophageal squamous-cell carcinoma （ESCC） is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies （GWAS） of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma （CCGD-ESCC） database, which contains the associations of 69,593 single nucleotide polymorphisms （SNPs） with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients （survival GWAS） and gene expression （expression quantitative trait loci,eQTL） in 94 ESCC patients. Moreover, this database also provides the associations between8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http：//db.cbi.pku.edu.cn/ccgd/ESCCdb.

VAV2 is required for DNA repair and implicated in cancer radiotherapy resistance

Radiotherapy remains the mainstay for treatment of various types of human cancer;however,the clinical efficacy is often limited by radioresistance,in which the underlying mechanism is largely unknown.Here,using esophageal squamous cell carcinoma(ESCC)as a model,we demonstrate that guanine nucleotide exchange factor 2(VAV2),which is overexpressed in most human cancers,plays an important role in primary and secondary radioresistance.We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation.

A cis-eQTL in NSUN2 promotes esophageal squamous-cell carcinoma progression and radiochemotherapy resistance by mRNA-m^(5)C methylation

Dear Editor,Esophageal squamous cell carcinoma(ESCC)has poor prognosis because of the difficulty in early detection and low sensitivity of advanced disease to radiochemotherapy.1,2 ESCC presents a high proportion of primary resistance to radiochemotherapy,2which may be due to certain individual genetic variations.Expression quantitative trait loci(eQTLs)as proximal and continuous cellular phenotypes have been shown to be helpful to determine how genetic variants may influence phenotype.