Currently, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread worldwide as an Omicron variant. This variant is a heavily mutated virus and designated as a variant of concern by ...the World Health Organization (WHO). WHO cautioned that the Omicron variant of SARS‐CoV‐2 held a very high risk of infection, reigniting anxieties about the economy's recovery from the 2‐year pandemic. The extensively mutated Omicron variant is likely to spread internationally, posing a high risk of infection surges with serious repercussions in some areas. According to preliminary data, the Omicron variant of SARS‐CoV‐2 has a higher risk of reinfection. On the other hand, whether the current COVID‐19 vaccines could effectively resist the new strain is still under investigation. However, there is very limited information on the current situation of the Omicron variant, such as genomics, transmissibility, efficacy of vaccines, treatment, and management. This review focused on the genomics, transmission, and effectiveness of vaccines against the Omicron variant, which will be helpful for further investigation of a new variant of SARS‐CoV‐2.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variant is a heavily mutated virus and designated as a variant of concern.
This variant may evade vaccine‐induced immunity.
There might have increased risk of SARS‐CoV‐2 reinfection by the Omicron variant.
Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q22;q21), resulting in a PML-RARA fusion that is the master driver of APL. A few cases that cannot be identified with PML-RARA by using ...conventional methods (karyotype analysis, FISH, and RT-PCR) involve abnormal promyelocytes that are fully in accordance with APL in morphology, cytochemistry, and immunophenotype. To explore the mechanisms involved in pathogenesis and recurrence of morphologically diagnosed APL, we performed comprehensive variant analysis by next-generation sequencing in 111 pediatric patients morphologically diagnosed as APL. Structural variant (SV) analysis in 120 DNA samples from both diagnosis and relapse stage identified 95 samples with RARA rearrangement (including 94 with PML-RARA and one with NPM-RARA) and two samples with KMT2A rearrangement. In the eligible 13 RNA samples without any RARA rearrangement at diagnosis, one case each with CPSF6-RARG, NPM1-CCDC28A, and TBC1D15-RAB21 and two cases with a TBL1XR1-RARB fusion were discovered. These uncovered fusion genes strongly suggested their contributions to leukemogenesis as driver alternations and APL phenotype may arise by abnormalities of other members of the nuclear receptor superfamily involved in retinoid signaling (RARB or RARG) or even by mechanisms distinct from the formation of aberrant retinoid receptors. Single-nucleotide variant (SNV) analysis in 77 children (80 samples) with RARA rearrangement showed recurrent alternations of primary APL in FLT3, WT1, USP9X, NRAS, and ARID1A, with a strong potential for involvement in pathogenesis, and WT1 as the only recurrently mutated gene in relapsed APL. WT1, NPM1, NRAS, FLT3, and NSD1 were identified as recurrently mutated in 17 primary samples without RARA rearrangement and WT1, NPM1, TP53, and RARA as recurrently mutated in 9 relapsed samples. The survival of APL with RARA rearrangement is much better than without RARA rearrangement. Thus, patients morphologically diagnosed as APL that cannot be identified as having a RARA rearrangement are more reasonably classified as a subclass of AML other than APL, and individualized treatment should be considered according to the genetic abnormalities.
The polybasic furin cleavage site insertion with four amino acid motifs (PRRA) in spike protein's S1/S2 junction site is important in determining viral infectivity, transmission, and host range. ...However, there is no review so far explaining the effect of the furin cleavage site of the spike protein on SARS‐CoV‐2 replication and pathogenesis in the host and immune responses and vaccination. Therefore, here we specifically focused on genomic evolution and properties of the cleavage site of spike protein in the context of SARS‐CoV‐2 followed by its effect on viral entry, replication, and pathogenesis. We also explored whether the spike protein furin cleavage site affected the host immune responses and SARS‐CoV‐2 vaccination. This review will help to provide novel insights into the effects of polybasic furin cleavage site on the current COVID‐19 pandemic.
Highlights
The genomic evolution and properties of the cleavage site of spike protein in the context of SARS‐CoV‐2 are discussed.
The effects of furin cleavage site of spike protein on viral entry, replication, and pathogenesis are reviewed.
Whether the host immune responses and SARS‐CoV‐2 vaccination are affected by the spike protein furin cleavage site was also discussed.
Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and posttranscriptional ...levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA sequencing data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values. The expression levels of circMAN1A2 were detected by quantitative real‐time PCR, and the correlations of clinical features with circMAN1A2 expression were analyzed by χ2 tests. Receiver operating characteristic curves were used to evaluate the clinical applications of circMAN1A2. The results showed that circMAN1A2 was upregulated in nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer, with areas under the curves of 0.911, 0.779, 0.734, 0.694, and 0.645, respectively, indicating the good diagnostic value of circMAN1A2. Overall, our findings suggested that circMAN1A2 could be a serum biomarker for malignant tumors, providing important insights into diagnostic approaches for malignant tumors. Further studies are needed to elucidate the mechanisms of circMAN1A2 in the pathogenesis of cancer.
We verified that circMAN1A2 was significantly upregulated in the sera of patients with NPC, oral cancer, thyroid cancer, ovarian cancer, and lung cancer and had good clinical diagnostic value. We speculate that circMAN1A2 could be a serum biomarker for malignant cancers and provide effective clues for the early diagnosis of malignant cancers.
Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, ...we design an efficient whole-cell catalyst of hydroxytyrosol in Escherichia coli by de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC of E. coli through structure-guided modeling and directed evolution. Next, we elucidate the structure of the Corynebacterium glutamicum VanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development.
ATP-binding cassette transporter A1 (ABCA1) plays a critical role in maintaining cellular cholesterol homeostasis. The purpose of this study is to identify the molecular mechanism(s) underlying ABCA1 ...epigenetic modification and determine its potential impact on ABCA1 expression in macrophage-derived foam cell formation and atherosclerosis development. DNA methylation induced foam cell formation from macrophages and promoted atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Bioinformatics analyses revealed a large CpG island (CGI) located in the promoter region of ABCA1. Histone methyltransferase enhancer of zeste homolog 2 (EZH2) downregulated ABCA1 mRNA and protein expression in THP-1 and RAW264.7 macrophage-derived foam cells. Pharmacological inhibition of DNA methyltransferase 1 (DNMT1) with 5-Aza-dC or knockdown of DNMT1 prevented the downregulation of macrophage ABCA1 expression, suggesting a role of DNA methylation in ABCA1 expression. Polycomb protein EZH2 induced DNMT1 expression and methyl-CpG-binding protein-2 (MeCP2) recruitment, and stimulated the binding of DNMT1 and MeCP2 to ABCA1 promoter, thereby promoting ABCA1 gene DNA methylation and atherosclerosis. Knockdown of DNMT1 inhibited EZH2-induced downregulation of ABCA1 in macrophages. Conversely, EZH2 overexpression stimulated DNMT1-induced ABCA1 gene promoter methylation and atherosclerosis. EZH2-induced downregulation of ABCA1 gene expression promotes foam cell formation and the development of atherosclerosis by DNA methylation of ABCA1 gene promoter.
More than 20 members of the human cyclin‐dependent kinases (CDKs) family share the feature of being activated by cyclins. CDKs have been involved in diverse biological processes, such as cell cycle, ...transcription, DNA damage response, and apoptosis. If CDKs are not properly regulated, they can cause diseases like cancer. CDKs are Ser/Thr kinases that work with cyclins to control cell cycle progression. Various CDK‐cyclin complexes phosphorylate particular target proteins and drive different cell cycle stages. Accumulating evidence demonstrated that CDKs play an essential role in the cell cycle; however, their roles in antiviral innate immunity are just emerging. This minireview summarizes how CDKs play their roles in antiviral innate immunity. Our goal is to draw attention to the involvement of CDKs in antiviral innate immunity, whether as separate entities or as components of CDK/cyclin complexes that have gotten less attention in the past.
HIGHLIGHTS
1.
Cyclin‐dependent kinases (CDKs) participate in the Toll‐like receptors signaling pathways and regulate antiviral innate immunity
2.
CDKs are involved in the nuclear factor kappa B signaling pathway to regulation antiviral innate immunity
3.
CDKs are involved in antiviral innate immunity by regulating the Janus kinase‐signal transducers and activators of transcription signaling pathway
When RING finger family proteins meet SARS‐CoV‐2 Cai, Chunmei; Tang, Yan‐Dong; Zheng, Chunfu
Journal of medical virology,
July 2022, 2022-Jul, 2022-07-00, 20220701, Volume:
94, Issue:
7
Journal Article
Peer reviewed
The pandemic coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is currently the most formidable challenge to humankind. Understanding the ...complicated virus‐host interplay is crucial for fighting against viral infection. A growing number of studies point to the critical roles of RING (really interesting new gene) finger (RNF) proteins during SARS‐CoV‐2 infection. RNF proteins exert direct antiviral activity by targeting genome and envelope glycoproteins of SARS‐CoV‐2. Additionally, some RNF members serve as potent regulators for antiviral innate immunity and antibody‐dependent neutralization of SARS‐CoV‐2. Notably, SARS‐CoV‐2 also hijacks the RNF proteins‐mediated ubiquitination process to evade host antiviral innate immunity and enhance viral replication. In this mini‐review, we discuss the diverse antiviral mechanisms of RNF proteins and viral immune evasion in an RNF proteins‐dependent manner. Understanding the crosstalk between RNF proteins and SARS‐CoV‐2 infection would help design potential novel targets for COVID‐19 treatment.
Existing commentaries on government responses to COVID-19 have focused on such factors as competent leadership, policy instruments, or cultural dispositions. Yet, few have provided a synthesis that ...examines how these factors relate to each other. This article fills this gap in the debate by comparing COVID-19 responses among five advanced economies in East Asia: Taiwan, Hong Kong, South Korea, Singapore, and Japan. Although agile actions and competence of top leadership are necessary to confront an unprecedented crisis, they are by themselves insufficient. Equally critical is whether a society has the necessary institutional infrastructure in place when a crisis strikes. Policy instruments are more likely to succeed when existing institutional infrastructure supports their administration and implementation. For an instrument to generate enduring impact, it must be compatible with a polity’s underlying culture; instruments that accommodate the underlying cultural orientations are more likely to elicit public cooperation and voluntary compliance over time. Policy instruments must also address equity issues by reaching marginalized groups across all layers of the population. Progress in emergency management may be visible in mainstream society but masking brewing problems among marginalized groups. A comparison across the five advanced economies in East Asia yields several implications for comparative research and policy.
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), since its outbreak in December 2019, has been capable of continuing the pandemic by mutating itself into different variants. Mass ...vaccinations, antibiotic treatment therapy, herd immunity, and preventive measures have reduced the disease's severity from the emerging variants. However, the virus is undergoing recombination among the current two variants: Delta and Omicron, resulting in a new variant, informally known as “Deltacron,” which was controversial as it might be a product of lab contamination between Omicron and Delta samples. However, the proclamation was proved wrong, and the experts are putting more effort into better understanding the variant's epidemiological characteristics to control potential outbreaks. This review has discussed the potential mutations in the novel variant and prospective risk factors and therapeutic options in the context of this new variant. This study could be used as a guide for implementing appropriate controls in a sudden outbreak of this new variant.
PDF
