The 2019 novel coronavirus (SARS-CoV-2) pandemic has caused a global health emergency. The outbreak of this virus has raised a number of questions: What is SARS-CoV-2? How transmissible is ...SARS-CoV-2? How severely affected are patients infected with SARS-CoV-2? What are the risk factors for viral infection? What are the differences between this novel coronavirus and other coronaviruses? To answer these questions, we performed a comparative study of four pathogenic viruses that primarily attack the respiratory system and may cause death, namely, SARS-CoV-2, severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and influenza A viruses (H1N1 and H3N2 strains). This comparative study provides a critical evaluation of the origin, genomic features, transmission, and pathogenicity of these viruses. Because the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 is ongoing, this evaluation may inform public health administrators and medical experts to aid in curbing the pandemic's progression.
Tumor mutation burden (TMB) has been associated with cancer immunotherapeutic response and cancer prognosis. Although many explorations have revealed that high TMB may yield many neoantigens to ...incite antitumor immune response, a systematic exploration of the correlation between TMB and immune signatures in different cancer types is lacking.
We classified cancer into the lower-TMB subtype and the higher-TMB subtype for each of 32 cancer types based on their somatic mutation data from the Cancer Genome Atlas (TCGA), and compared the expression levels of immune-related genes and gene-sets between both subtypes of cancers in each cancer type. In some cancer types most of the immune signatures analyzed were upregulated in the lower-TMB subtype, while in some other cancer types the immune signatures were prone to be upregulated in the higher-TMB subtype. However, the regulatory T cells, immune cell infiltrate, tumor-infiltrating lymphocytes, and cytokine signatures tended to be upregulated in the lower-TMB subtype, and the cancer-testis antigen (CTA) and pro-inflammatory signatures were inclined to be upregulated in the higher-TMB subtype. Importantly, high TMB was associated with elevated expression of PD-L1 in diverse prevailing cancers. Furthermore, we found that higher TMB was associated with better survival prognosis in numerous cancer types while was associated with worse prognosis in a few cancer types.
High TMB may inhibit immune cell infiltrations while promote CTAs expression and inflammatory response in cancer. In many common cancer types, higher TMB may respond favorably to anti-PD-1/PD-L1 immunotherapy. Our data implicate that higher-TMB patients could gain a more favorable prognosis in diverse cancer types if treated with immunotherapy, otherwise would have a poorer prognosis compared to lower-TMB patients.
Exploring cost-effective and general approaches for highly active and stable bifunctional transition metal phosphide (TMP) electrocatalysts towards overall water splitting is greatly desirable and ...challenging. Herein, a general strategy combining sol–gel and a carbonization-assisted route was proposed to facilely fabricate a series of TMP nanoparticles, including CoP, MoP, FeP, Cu2P, Ni2P, PtP2, FeNiP, CoNiP, and FeCoNiP, coupled in an amorphous carbon matrix with one-step carbon composite formation. The resultant NiFeP@C exhibits excellent activities as a bifunctional electrocatalyst toward oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) with low overpotentials of 260 and 160 mV, respectively, at 10 mA/cm2 in 1 M KOH solution. With the NiFeP@C electrocatalyst as both electrode materials, an integrated electrolyzer can deliver 47.0 mA/cm2 of current density at 1.60 V, better than the assembled Pt/C20∥IrO2 counterpart. The encapsulation of NiFeP nanoparticles in the carbon matrix effectively prevents their corrosion and leads to almost unfading catalytic activities for more than 20 h for either the HER, OER, or overall water splitting, outperforming recently reported bifunctional electrocatalysts. The coexistence of Ni, Fe, P, and C would have synergetic effects to accelerate charge transfer and promote electrocatalytic activity. This universal strategy for TMP-based composites opens up a new avenue to explore TMPs as multifunctional materials for various applications.
Triple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of ...cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed an exhaustive analysis of immunogenic signatures in TNBC based on 2 large-scale breast cancer (BC) genomic data. We compared enrichment levels of 26 immune cell activities and pathways among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features. We found that almost all analyzed immune activities and pathways had significantly higher enrichment levels in TNBC than non-TNBC. Elevated enrichment of these immune activities and pathways was likely to be associated with better survival prognosis in TNBC. This study demonstrated that TNBC likely exhibits the strongest immunogenicity among BC subtypes, and thus warrants the immunotherapeutic option for TNBC.
DNA methylation is considered an essential epigenetic event during leukaemogenesis and the emergence of drug resistance, which is primarily regulated by DNA methyltransferases. DNA ...methyltransferase-1 (DNMT1) is one of the members of DNA methyltransferases, in charge of maintaining established methylation. Recently, DNMT1 is shown to promote malignant events of cancers through the epigenetic and non-epigenetic processes. Increasing studies in solid tumours have identified DNMT1 as a therapeutic target and a regulator of therapy resistance; however, it is unclear whether DNMT1 is a critical regulator in acute myeloid leukaemia (AML) and how it works. In this review, we summarized the recent understanding of DNMT1 in normal haematopoiesis and AML and discussed the possible functions of DNMT1 in promoting the development of AML and predicting the sensitivity of hypomethylation agents to better understand the relationship between DNMT1 and AML and to look for new hope to treat AML patients.
Key messages
The function of DNA methyltransferase-1 in acute myeloid leukaemia.
DNA methyltransferase-1 predicts the sensitivity of drug and involves the emergence of drug resistance.
Intratumor heterogeneity (ITH) is a biomarker of tumor progression, metastasis, and immune evasion. Previous studies evaluated ITH mostly based on DNA alterations. Here, we developed a new algorithm ...(DEPTH) for quantifying ITH based on mRNA alterations in the tumor. DEPTH scores displayed significant correlations with ITH-associated features (genomic instability, tumor advancement, unfavorable prognosis, immunosuppression, and drug response). Compared to DNA-based ITH scores (EXPANDS, PhyloWGS, MATH, and ABSOLUTE), DEPTH scores had stronger correlations with antitumor immune signatures, cell proliferation, stemness, tumor advancement, survival prognosis, and drug response. Compared to two other mRNA-based ITH scores (tITH and sITH), DEPTH scores showed stronger and more consistent associations with genomic instability, unfavorable tumor phenotypes and clinical features, and drug response. We further validated the reliability and robustness of DEPTH in 50 other datasets. In conclusion, DEPTH may provide new insights into tumor biology and potential clinical implications for cancer prognosis and treatment.
Abstract Currently, the obstacle avoidance control of patrol robots based on intelligent vision lacks professional controller module assistance. Therefore, this paper proposes a design method of ...intelligent controller for obstacle avoidance and navigation of electrical inspection mobile robot based on PLC control. The controller designs a laser range finder to determine the required position of electrical patrol inspection. Use PLC as the core controller, and combine sensors, actuators, communication module and PLC selection module in the process of hardware design to achieve autonomous navigation and obstacle avoidance functions of the robot. Then design the software including the PLC compiler system and the virtual machine module. Based on the above steps, design the control module of obstacle avoidance navigation, which realizes the key link of robot autonomous navigation. The test results show that the controller can successfully avoid obstacles, improve the efficiency and quality of inspection, and achieve accurate and fast obstacle avoidance navigation for the electrical inspection mobile robot.
Because traditional treatment strategies for advanced gastrointestinal (GI) cancers often have a limited therapeutic effect, immunotherapy could be a viable approach for the therapy of advanced GI ...cancers, considering the recent success of immunotherapy in treating various refractory malignancies, including the DNA mismatch repair-deficient GI cancers. However, only a subset of cancer patients currently respond to immunotherapy. Thus, it is important to identify useful biomarkers for predicting cancer immunotherapy response. The tumor suppressor gene
has a high mutation rate in GI cancers and its deficiency is correlated with the microsatellite instability (MSI) genomic feature of cancer. We investigated the correlation between
mutations and tumor immunity using three GI cancer genomics datasets by the bioinformatic approach, and found that diverse antitumor immune signatures were more highly enriched in
-mutated GI cancers than in
-wildtype GI cancers. The elevated immune activity in
-mutated GI cancers was associated with the higher tumor mutation burden and lower tumor aneuploidy level, as well as a higher proportion of MSI cancers in this GI cancer subtype. Moreover, we found that
-mutated GI cancers more highly expressed
than
-wildtype GI cancers. The elevated antitumor immune signatures and
expression could contribute to the more active immunotherapeutic responsiveness and better survival prognosis in
-mutated GI cancers than in
-wildtype GI cancers in the immunotherapy setting, as evidenced in three cancer cohorts receiving immunotherapy. Thus, the
mutation could be a useful biomarker for identifying GI cancer patients responsive to immunotherapy.
Abstract
Background
Gliomas are heterogeneous in the tumor immune microenvironment (TIM). However, a classification of gliomas based on immunogenomic profiling remains lacking.
Methods
We ...hierarchically clustered gliomas based on the enrichment levels of 28 immune cells in the TIM in five datasets and obtained three clusters: immunity-high, immunity-medium, and immunity-low.
Results
Glioblastomas were mainly distributed in immunity-high and immunity-medium, while lower-grade gliomas were distributed in all the three subtypes and predominated in immunity-low. Immunity-low displayed a better survival than other subtypes, indicating a negative correlation between immune infiltration and survival prognosis in gliomas.
IDH
mutations had a negative correlation with glioma immunity. Immunity-high had higher tumor stemness and epithelial-mesenchymal transition scores and included more high-grade tumors than immunity-low, suggesting that elevated immunity is associated with tumor progression in gliomas. Immunity-high had higher tumor mutation burden and more frequent somatic copy number alterations, suggesting a positive association between tumor immunity and genomic instability in gliomas.
Conclusions
The identification of immune-specific glioma subtypes has potential clinical implications for the immunotherapy of gliomas.
PDF
