Comprehensive analysis of m6A RNA methylation regulators in esophageal carcinoma.

Background: N6-methyladenosine (m6A) is the most pervasive modification of RNA methylation in eukaryotic cells. m6A modification plays a pivotal role in tumorigenesis and progression in many types of cancers. Until now, the role of m6A modification in esophageal carcinoma (ESCA) has remained obscure. The aim of the study was to construct and validate prognostic signatures based on m6A regulators for ESCA. Methods: Transcriptomic data, somatic mutations and clinical information were obtained from The Cancer Genome Atlas (TCGA). Copy number variations were obtained from the UCSC (University of California, Santa Cruz) Xena database. We curated 21 m6A regulators and performed consensus clustering analysis to quantify the m6A modification pattern. Results: Of the 184 patients, 23 (12.5%) were genetically altered in m6A regulators, with the highest frequency of mutations in ZC3H13 and LRPPRC. We constructed a m6A score system to investigate the prognosis of ESCA. The m6A score was closely related to immune cell infiltration in the tumor immune microenvironment. Patients with a high m6A score had an unfavorable prognosis. The combination of tumor mutation burden and m6A score would improve the prognostic value. Conclusions: Our study established and validated a strong prognostic signature based on m6A regulators. This can be used to accurately predict the prognosis of ESCA.

Preparation and characterization of nanobodies targeting SARS-CoV-2 papain-like protease.

Coronavirus Papain-like protease (PLpro) mediates the cleavage of viral polyproteins and assists the virus escaping from innate immune response. Thus, PLpro is an attractive target for the development of broad-spectrum drugs as it has a conserved structure across different coronaviruses. In this study, we purified SARS-CoV-2 PLpro as an immune antigen, constructed a nanobody phage display library, and identified a set of nanobodies with high affinity for SARS-CoV-2. In addition, enzyme activity experiments demonstrated that two nanobodies had a significant inhibitory effect on the PLpro. These nanobodies should therefore be investigated as candidates for the treatment of coronaviruses.

TOMM34 serves as a candidate therapeutic target associated with immune cell infiltration in colon cancer.

Background: Colon cancer represents one of the most pervasive digestive malignancies worldwide. Translocase of the outer mitochondrial membrane 34 (TOMM34) is considered an oncogene and is implicated in tumor proliferation. However, the correlation between TOMM34 and immune cell infiltration in colon cancer has not been investigated. Materials and methods: Based on multiple open online databases, we performed integrated bioinformatics analysis of TOMM34 to evaluate the prognostic value of TOMM34 and its correlation with immune cell infiltration. Results: TOMM34 gene and protein expression levels were elevated in tumor tissues compared with normal tissues. Survival analysis revealed that upregulation of TOMM34 was significantly associated with poorer survival time in colon cancer. High TOMM34 expression was dramatically related to low levels of B cells, CD8+ T cells, neutrophils, dendritic cells, PD-1, PD-L1 and CTLA-4. Conclusions: Our results confirmed that high expression of TOMM34 in tumor tissue correlates with immune cell infiltration and worse prognosis in colon cancer patients. TOMM34 may serve as a potential prognostic biomarker for colon cancer diagnosis and prognosis prediction.