Renin–angiotensin–aldosterone system (RAAS) inhibitors, including angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are one of the most prescribed antihypertensive medications. Previous studies showed RAAS inhibitors increase the expression of ACE2, a cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which provokes a concern that the use of ACEI and ARB in hypertensive individuals might lead to increased mortality and severity of coronavirus disease 2019 (COVID‐19). To further investigate the effects of ACEI/ARB on COVID‐19 patients, we systematically reviewed relevant studies that met predetermined inclusion criteria in search of PubMed, Embase, Cochrane Library databases, medRxiv, and bioRxiv. The search strategy included clinical data published through October 12, 2020. Twenty‐six studies involving 8104 hypertensive patients in ACEI/ARB‐treated group and 8203 hypertensive patients in non‐ACEI/ARB‐treated group were analyzed. Random‐effects meta‐analysis showed ACEI/ARB treatment was significantly associated with a lower risk of mortality in hypertensive COVID‐19 patients (odds ratio [OR] = 0.624, 95% confidence interval [CI] = 0.457–0.852, p = .003, I2 = 74.3%). Meta‐regression analysis showed that age, gender, study site, Newcastle–Ottawa Scale scores, comorbidities of diabetes, coronary artery disease, chronic kidney disease, or cancer has no significant modulating effect of ACEI/ARB treatment on the mortality of hypertensive COVID‐19 patients (all p > .1). In addition, the ACEI/ARB treatment was associated with a lower risk of ventilatory support (OR = 0.682, 95% CI = 0.475–1.978, p = .037, I2 = 0.0%). In conclusion, these results suggest that ACEI/ARB medications should not be discontinued for hypertensive patients in the context of COVID‐19 pandemic.
Human papillomavirus (HPV) is a causal agent for most cervical cancers. The physical status of the HPV genome in these cancers could be episomal, integrated, or both. HPV integration could serve as a biomarker for clinical diagnosis, treatment, and prognosis. Although whole-genome sequencing by next-generation sequencing (NGS) technologies, such as the Illumina sequencing platform, have been used for detecting integrated HPV genome in cervical cancer, it faces challenges of analyzing long repeats and translocated sequences. In contrast, Oxford nanopore sequencing technology can generate ultra-long reads, which could be a very useful tool for determining HPV genome sequence and its physical status in cervical cancer. As a proof of concept, in this study, we completed whole genome sequencing from a cervical cancer tissue and a CaSki cell line with Oxford Nanopore Technologies. From the cervical cancer tissue, a 7,894 bp-long HPV35 genomic sequence was assembled from 678 reads at 97-fold coverage of HPV genome, sharing 99.96% identity with the HPV sequence obtained by Sanger sequencing. A 7904 bp-long HPV16 genomic sequence was assembled from data generated from the CaSki cell line at 3857-fold coverage, sharing 99.99% identity with the reference genome (NCBI: U89348). Intriguingly, long reads generated by nanopore sequencing directly revealed chimeric cellular–viral sequences and concatemeric genomic sequences, leading to the discovery of 448 unique integration breakpoints in the CaSki cell line and 60 breakpoints in the cervical cancer sample. Taken together, nanopore sequencing is a unique tool to identify HPV sequences and would shed light on the physical status of HPV genome in its associated cancers.
The Oxygen reduction reaction (ORR) plays an important role in fuel cells, but the synthesis of efficient and low-cost catalysts remains challenging. We report the synthesis of ultra-small Mo 2 C nanoparticles with an average size of 1.5 nm embedded in a N-doped holey carbon (NHC) matrix by employing selfassembled macrocycle cucurbit[6]uril (CB[6]) and melamine as carbon precursors. The interaction between Mo precursors and CB[6] effectively prevented the aggregation of Mo 2 C NPs during the pyrolysis procedure. Besides, the holey structural carbon has a larger electrocatalytic activity area and improves mass transfer efficiency and charge transfer rate. The NHC features abundant defective sites and thus effective anchoring and electronic regulation for Mo 2 C nanoparticles. The electrochemical oxygen reduction activity of Mo 2 C/NHC is comparable to that of noble metal Pt/C benchmark catalyst with an initial potential, half-wave potential and limiting current density of 0.95 V, 0.84 V and 5.0 mA cm À 2 , respectively. Mo 2 C/NHC shows a good long-term durability during 25 h chronoamperometry.
Epstein–Barr virus (EBV)‐associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer (GC) distinguished by the presence of the EBV genome and limited viral gene expression within malignant epithelial cells. EBV infection is generally thought to be a relatively late event following atrophic gastritis in carcinogenesis, which implies the heterogeneity of EBVaGC. To facilitate the study of the role of EBV in EBVaGC, we established two EBV‐positive GC cell lines (AGS‐EBV and HGC27‐EBV) with an epitheliotropic EBV strain M81 and characterized viral and cellular gene expression profiles in comparison to SNU719, a naturally derived EBV‐positive GC cell line. Like SNU719, AGS‐EBV and HGC27‐EBV stably maintained their EBV genomes and expressed EBV‐encoded small RNAs and nuclear antigen EBNA1. Comprehensive analysis of the expression of EBV‐encoded miRNAs within the BamHI‐A region rightward transcript region, and the transcripts of EBV latent and lytic genes in cell lines, as well as xenografts, reveals that AGS‐EBV and HGC27‐EBV cells undergo distinct viral expression profiles. A very small fraction of AGS‐EBV and SNU719 cells can spontaneously produce infectious progeny virions, while HGC27‐EBV does not. AGS‐EBV (both M81 and Akata) cells largely mimic SNU719 cells in viral gene expression profiles, and altered cellular functions and pathways perturbed by EBV infection. Phylogenetic analysis of the EBV genome shows both M81 and Akata EBV strains are closely related to clinical EBVaGC isolates. Taken together, these two newly established EBV‐positive GC cell lines can serve as models to further investigate the role of EBV in different contexts of gastric carcinogenesis and identify novel therapeutics against EBVaGC.
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