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The multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus. Here, the authors show that GalNAc-T3 and T7 regulate furin cleavage of the SARS-CoV-2 spike protein via O-glycosylation. This influences viral assembly and infection, highlighting glycosylation as a host defense mechanism. [ABSTRACT FROM AUTHOR]

Microchromosome maintenance (MCM) proteins are a number of nuclear proteins with significant roles in the development of cancer by influencing the process of cellular DNA replication. Of the MCM protein family, MCM10 is a crucial member that maintains the stability and extension of DNA replication forks during DNA replication and is significantly overexpressed in a variety of cancer tissues, regulating the biological behaviour of cancer cells. But little is understood about MCM10’s functional role and regulatory mechanisms in a range of malignancies. We investigate the impact of MCM10 in human cancers by analyzing data from databases like the Gene Expression Profiling Interaction Analysis (GEPIA2), Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA), among others. Possible relationships between MCM10 and clinical staging, diagnosis, prognosis, Mutation burden (TMB), microsatellite instability (MSI), immunological checkpoints, DNA methylation, and tumor stemness were identified. The findings demonstrated that MCM10 expression was elevated in the majority of cancer types and was connected to tumor dryness, immunocytic infiltration, immunological checkpoints, TMB and MSI. Functional enrichment analysis in multiple tumors also identified possible pathways of MCM10 involvement in tumorigenesis. We also discovered promising MCM10-targeting chemotherapeutic drugs. In conclusion, MCM10 may be a desirable pan-cancer biomarker and offer fresh perspectives on cancer therapy. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a primary malignant bone tumor with no effective treatment. Apoptosis, one of the programmed cell death, is any pathological form of cell death mediated by intracellular processes. Under the pathological state, the de-regulated regulation of apoptosis can disrupt the balance between cell proliferation and death, causing osteosarcoma proliferation and metastasis. As carcinogenic or tumor suppressor factors, microRNAs (miRNAs) regulate apoptosis of osteosarcoma cells by regulating apoptosis-related genes and apoptosis-related signaling pathways, such as mitochondrial apoptosis pathway, death receptor pathway, and endoplasmic reticulum pathway. Meanwhile as these abnormal miRNAs can be stored and transported by exosomes, detecting exosomes can be seen an effective method to diagnose osteosarcoma in the early stage. This review provides the current knowledge of miRNAs and their target genes related to the apoptosis of osteosarcoma, summarizes abnormal expression and regulation of miRNAs and signaling pathways in osteosarcoma and prospects the detection of exosome as a method for early diagnosis of osteosarcoma. [ABSTRACT FROM AUTHOR]

The buds of I Z. striolatum i were collected in August of 2019 from Guizhou Province of P. R. China and were authenticated by Dr. Daopeng Tan (Pharmacognosy), an associate professor of Zunyi Medical University. In the present study, our further chemical investigation into the constituents of the buds of I Z. striolatum, i nine compounds were isolated and identified previously from this plant. The EtOAc extract (60 g) was subjected to a series of chromatographic methods, such as column chromatography using silica gel (200-300 or 300-400 mesh) and Sephadex LH-20, and yielded compounds B 1-9 b . The buds of I Z. striolatum i contain abundant protein, polysaccharides, amino acids, and trace elements, and serve as a delicious vegetable with high nutritional value [[3]]. [Extracted from the article]

Background: Hydrogen/potassium ATPase β (ATP4B) is a proton pump acting an essential role in gastric acid secretion. This study aimed to investigate the diagnostic performance of ATP4B and its biological role in tumor progression in gastric cancer. Methods: The correlations between ATP4B expression level and clinicopathologic parameters, as well as the relevance of ATP4B expression with overall survival were assessed. The functional roles of ATP4B in gastric cancer were verified by gain- and loss-of-function cell models and tumor xenograft models. The possible downstream effects of ATP4B were analyzed by iTRAQ-based quantitative proteomics analysis. Results: A dramatic decrease in ATP4B was associated with malignant transformation in gastric mucosa lesions and correlated with poor differentiation. Restoration of ATP4B expression in gastric cancer cells significantly suppressed cell proliferation, cell viability, migration, invasion, tumorigenicity and induced apoptosis, whereas ATP4B silencing exerted the opposite effects. Mechanistically, we found a quality control on mitochondrial metabolism and functions in ATP4B-overexpression GC cells. Conclusions: Our data suggest that decreasing ATP4B is an indicator for gastric mucosa malignant transformation and GC aggressive phenotype and it plays an inhibitory role in gastric cancer as a tumor suppressor via regulating mitochondrial metabolism and apoptosis pathway. [ABSTRACT FROM AUTHOR]

Background and Aims: Endoscopic submucosal dissection (ESD) is a prolonged procedure with serious adverse events. The clip with line traction method was reported to improve ESD. However, there was no comparison with conventional ESD especially for trainees. We report here on the feasibility and efficacy of traction using dental floss with endoscopic clip to facilitate ESD versus conventional method for ESD trainees.Methods: Twenty simulated gastric lesions, paired with location and size, were created in porcine stomachs using a standard template. After a circular incision was made, submucosal dissection (control, n = 10) was performed with standard ESD, while the study (clip, n = 10) was performed with traction using dental floss and endoclip. Primary outcome was speed of submucosal dissection. Secondary outcome included frequency of submucosal injection and adverse event.Results: Compared with controls, median procedure time was significantly shorter in the clip group (5.6 ± 1.1 vs. 13.6 ± 2.5 min, P = 0.003), with a significantly faster submucosal dissection time (1.8 ± 0.3 vs. 0.6 ± 0.1 cm(2)/min, P = 0.001) and less frequent submucosal injection (5.7 ± 0.6 vs. 8.5 ± 1.0 times, P = 0.024). There were no perforations in either group, but less adverse events (bleeding and injury to muscularis propria) in the clip group (1 vs. 7, P = 0.068, α = 0.1).Conclusions: Traction provided by dental floss and endoclip improves visualization of the submucosal layer during ESD. It allows a faster and safer gastric ESD especially among trainees in the early learning phase. [ABSTRACT FROM AUTHOR]