Identification of genomic features associated with immunotherapy response in gastrointestinal cancers

Gastrointestinal(GI) cancers prevail and account for an extremely high number of cancer deaths worldwide. The traditional treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapy, have a limited therapeutic effect for advanced GI cancers. Recently, immunotherapy has shown promise in treating various refractory malignancies, including the GI cancers with mismatch repair deficiency(dMMR) or microsatellite instability(MSI). Thus,immunotherapy could be a promising treatment approach for GI cancers.Unfortunately, only a small proportion of GI cancer patients currently respond to immunotherapy. Therefore, it is important to discover predictive biomarkers for stratifying GI cancer patients response to immunotherapy. Certain genomic features, such as dMMR/MSI, tumor mutation burden(TMB), and tumor aneuploidy have been associated with tumor immunity and im-munotherapy response and may serve as predictive biomarkers for cancer immunotherapy. In this review, we examined the correlations between tumor immunity and three genomic features: dMMR/MSI, TMB, and tumor aneuploidy. We also explored their correlations using The Cancer Genome Atlas data and confirmed that the dMMR/MSI status, high TMB, and low tumor aneuploidy are associated with elevated tumor immunity in GI cancers. To improve the immunotherapeutic potential in GI cancers, more genetic or genomic features associated with tumor immune response need to be identified. Furthermore, it is worth exploring the combination of different immunotherapeutic methods and the combination of immunotherapy with other therapeutic approaches for cancer therapy.

Immunological classification of hepatitis B virus-positive hepatocellular carcinoma by transcriptome analysis

BACKGROUND Hepatitis B virus(HBV)infection is a major factor responsible for HBV+hepatocellular carcinoma(HCC).AIM An immunological classification of HBV+HCC may provide both biological insights and clinical implications for this disease.METHODS Based on the enrichment of 23 immune signatures,we identified two immunespecific subtypes(Imm-H and Imm-L)of HBV+HCC by unsupervised clustering.We showed that this subtyping method was reproducible and predictable by analyzing three different datasets.RESULTS Compared to Imm-L,Imm-H displayed stronger immunity,more stromal components,lower tumor purity,lower stemness and intratumor heterogeneity,lower-level copy number alterations,higher global methylation level,and better overall and disease-free survival prognosis.Besides immune-related pathways,stromal pathways(ECM receptor interaction,focal adhesion,and regulation of actin cytoskeleton)and neuro-related pathways(neuroactive ligand-receptor interaction,and prion diseases)were more highly enriched in Imm-H than in Imm-L.We identified nine proteins differentially expressed between Imm-H and Imm-L,of which MYH11,PDCD4,Dvl3,and Syk were upregulated in Imm-H,while PCNA,Acetyl-a-Tubulin-Lys40,ER-α_pS118,Cyclin E2,andβ-Catenin were upregulated in Imm-L.CONCLUSION Our data suggest that“hot”tumors have a better prognosis than“cold”tumors in HBV+HCC and that“hot”tumors respond better to immunotherapy.

Angiotensin-converting enzyme 2 connects COVID-19 with cancer and cancer immunotherapy

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than two million deaths.Underlying diseases,including cancer,are high-risk factors for severe COVID-19 outcomes.Angiotensin-converting enzyme 2(ACE2),as a SARS-CoV-2 host cell receptor,plays a crucial role in SARS-CoV-2 invading human cells.ACE2 also has significant associations with cancer.Recent studies showed that ACE2 was inversely correlated with the activities of multiple oncogenic pathways and tumor progression phenotypes,and was positively correlated with antitumor immune response and survival prognosis in diverse cancers,suggesting a potential protective role of ACE2 in cancer progression.Positive expression of ACE2 is also correlated with programmed death-ligand 1(PD-L1)in cancer.The positive associations of ACE2 expression with antitumor immune signatures and PD-L1 expression indicate that ACE2 expression is a positive predictor for the response to immune checkpoint inhibitors(ICIs).This was evidenced in multiple cancer cohorts treated with ICIs.Thus,ACE2 may build potential connections between COVID-19 and cancer and cancer immunotherapy.The potential connections suggest that ACE2 inhibitors may not be a good option for treating COVID-19 patients with cancer,particularly in cancer patients who are receiving immunotherapy.Furthermore,the relationships between ACE2,COVID-19,and cancer are worth confirming by more experimental and clinical data,considering that many cancer patients are at high risk for COVID-19.

地下调蓄隧道系统气团释放诱发的井喷特性研究

地下调蓄隧道系统是解决城市调蓄能力不足和防止内涝的重要工程,井喷现象是系统内发生的一种严重水力事故,气团释放诱发的井喷特性研究对调蓄隧道系统的安全运行有着重要意义。该文采用实验和数值模拟相结合的方法,对气团运移及释放过程中的水气两相运动进行了深入研究,结果表明,气团释放诱发的井喷气泡形态类似于经典的泰勒气泡,但其上升速度显著大于泰勒气泡速度,且有加速上升的趋势;调蓄隧道系统中,气泡压力与水柱重力之间存在一个动态平衡过程,气泡压力水头与水柱高度差决定了井喷的强度,其大小随着井隧直径比的增大而快速减小,当井隧直径比等于0.8时,气泡压力水头与水柱高度差已接近于0,此时气团释放不会引发井喷。

Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues

Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this virus have markedly distinct disease severity.This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.

Effects of surface roughness on overflow discharge of embankment weirs

A numerical study was performed on the embankment weir overflows with various surface roughness and tailwater submergence, to better understand the effects of weir roughness on discharge performances under the free and submerged conditions. The variation of flow regime is captured, from the free overflow, submerged hydraulic jump, to surface flow with increasing tailwater depth. A roughness factor is introduced to reflect the reduction in discharge caused by weir roughness. The roughness factor decreases with the roughness height, and it also depends on the tailwater depth, highlighting various relations of the roughness factor with the roughness height between different flow regimes, which is linear for the free overflow and submerged hydraulic jump while exponential for the surface flow. Accordingly, the effects of weir roughness on overflow discharge appear nonnegligible for the significant roughness height and the surface flow regime occurring under considerable tailwater submergence. The established empirical expressions of discharge coefficient and submergence and roughness factors make it possible to predict the discharge over embankment weirs considering both tailwater submergence and surface roughness.