Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail. In this Review, Shi and colleagues summarize the exceptional amount of research that has characterized acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) since this virus has swept around the globe. They discuss what we know so far about the emergence and virology of SARS-CoV-2 and the pathogenesis and treatment of COVID-19.

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Characteristics of SARS-CoV-2 and COVID-19

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.

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SARS and MERS: recent insights into emerging coronaviruses

The use of artificial intelligence, and the deep-learning subtype in particular, has been enabled by the use of labeled big data, along with markedly enhanced computing power and cloud storage, across all sectors. In medicine, this is beginning to have an impact at three levels: for clinicians, predominantly via rapid, accurate image interpretation; for health systems, by improving workflow and the potential for reducing medical errors; and for patients, by enabling them to process their own data to promote health. The current limitations, including bias, privacy and security, and lack of transparency, along with the future directions of these applications will be discussed in this article. Over time, marked improvements in accuracy, productivity, and workflow will likely be actualized, but whether that will be used to improve the patient-doctor relationship or facilitate its erosion remains to be seen.

High-performance medicine: the convergence of human and artificial intelligence

Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty — which affect clinical manifestations, prognosis, and response to treatment — and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials. Inflammageing is a chronic, pro-inflammatory state that develops with age and is a risk factor for cardiovascular disease, comorbidities, frailty, and death. In this Review, Ferrucci and Fabbri discuss whether therapies to modulate inflammageing can reduce the age-related decline in health.

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which are caused by coronaviruses, have attracted substantial attention owing to their high mortality rates and potential to cause epidemics. Yuen and colleagues discuss progress with treatment options for these syndromes, including virus- and host-targeted drugs, and the challenges that need to be overcome in their further development. In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections.

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Coronaviruses - drug discovery and therapeutic options.

Retrospective study: The diagnostic accuracy of conventional forceps biopsy of gastric epithelial compared to endoscopic submucosal dissection (STROBE compliant).

Preliminary screening and functional analysis of circular RNAs associated with hepatic stellate cell activation.

Differential expression of circular RNAs in hepatic tissue in a model of liver fibrosis and functional analysis of their target genes.

p16 Methylation was associated with the development, age, hepatic viruses infection of hepatocellular carcinoma, and p16 expression had a poor survival: A systematic meta-analysis (PRISMA).

BACKGROUND Circular RNAs (circRNAs) are a novel group of RNAs and play essential roles in cancers. However, the expression profiles of circRNAs in human colorectal cancer (CRC) are largely unclear. METHODS The differentially expressed circRNAs, mRNAs, and microRNAs (miRNAs) between CRC tissues and paired adjacent normal tissues were first screened. Then, gene ontology and pathway analyses were performed to predict the possible functions. In addition, we identified the differentially expressed circRNAs in CRC correlated with Kruppel-like factor 4 (KLF4) and validated their expression levels in CRC tissues. Finally, the correlations between hsa_circ_0142527 expression levels and clinicopathological features of patients with CRC were also analyzed. RESULTS After filtered 4735 circRNAs by RNA deep sequencing, 67 differentially expressed circRNAs (fold change >2.0, P < 0.05) were selected. The top two pathways were cell cycle and other glycan degradation. Hsa_circ_0142527 and KLF4 mRNA were significantly lower expressed in CRC tissues in both training and confirm groups and have high positive correlation (r = 0.754). We further found that the expression levels of hsa_circ_0142527 were significantly associated with age (P = 0.004), differentiation (P = 0.008), invasion (P = 0.029), distal metastasis (P = 0.004), TNM stage (P = 0.005), and carcinoembryonic antigen (CEA; P = 0.037). CONCLUSIONS The circRNA expression profile of CRC provided new clues for understanding the occurrence of CRC. Hsa_circ_0142527 may be served as a potential biomarker for the diagnosis of CRC.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcla.22952

Xueyou Lv

Papers

Retrospective study: The diagnostic accuracy of conventional forceps biopsy of gastric epithelial compared to endoscopic submucosal dissection (STROBE compliant).

Preliminary screening and functional analysis of circular RNAs associated with hepatic stellate cell activation.

Differential expression of circular RNAs in hepatic tissue in a model of liver fibrosis and functional analysis of their target genes.

p16 Methylation was associated with the development, age, hepatic viruses infection of hepatocellular carcinoma, and p16 expression had a poor survival: A systematic meta-analysis (PRISMA).

Expression profiles of circular RNAs in human colorectal cancer based on RNA deep sequencing.