ABSTRACT
The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant pandemic of coronavirus disease 2019 (COVID-19) has led to over one hundred million confirmed infections, greater than three million deaths, and severe economic and social disruption. Animal models of SARS-CoV-2 are critical tools for the pre-clinical evaluation of antivirals, vaccines, and candidate therapeutics currently under urgent development to curb COVID-19-associated morbidity and mortality. The golden (Syrian) hamster model of SARS-CoV-2 infection recapitulates key characteristics of severe COVID-19, including high-titer viral replication in the upper and lower respiratory tract and the development of pathogenic lesions in the lungs. In this work we examined the influence of the route of exposure, sex, and age on SARS-CoV-2 pathogenesis in golden hamsters. We report that delivery of SARS-CoV-2 primarily to the nasal passages (low-volume intranasal), the upper and lower respiratory tract (high-volume intranasal), or the digestive tract (intragastric) results in comparable viral titers in the lung tissue and similar levels of viral shedding during acute infection. However, low-volume intranasal exposure results in milder weight loss during acute infection while intragastric exposure leads to a diminished capacity to regain body weight following the period of acute illness. Further, we examined both sex and age differences in response to SARS-CoV-2 infection. Male hamsters, and to a greater extent older male hamsters, display an impaired capacity to recover from illness and a delay in viral clearance compared to females. Lastly, route of exposure, sex, and age were found to influence the nature of the host inflammatory cytokine response, but they had a minimal effect on both the quality and durability of the humoral immune response as well as the susceptibility of hamsters to SARS-CoV-2 re-infection. Together, these data indicate that the route of exposure, sex, and age have a meaningful impact SARS-CoV-2 pathogenesis in hamsters and that these variables should be considered when designing pre-clinical challenge studies.
ABSTRACT
Objective To compare the diagnostic value of CT and MRI in the diagnosis of far lateral lumbar disc herniation (FLLDH). Methods The CT and MRI imagine data of 34 patients with FLLDH were retrospectively analyzed and compared. Results The positive rate of CT in diagnosis FLLDH was 88.24%(30/34), and the positive rate of MRI was 94.12%(32/34). There was no statistical difference (P>0.05). There were no statistical differences in the diagnosis of disease region and image representation between CT and MRI (P>0.05). Conclusions There is higher coincidence rate of CT and MRI in the diagnosis of FLLDH, but the two imaging methods have their own advantages and disadvantages. In clinical practice, the two imaging methods can be used to improve the clinical diagnosis rate, and provide a reliable basis for determining the surgical treatment options.
ABSTRACT
Clustered regulatory interspaced short palindromic repeats (CRISPR) found in bacteria and archaea genome that contains multiple short repeats loci, provides acquired immunity against invading foreign DNA via RNA-guided DNA cleavage. The first inkling of this hot new genetic engineering tool turned up in 1987, when a research team observed an oddly repetitive sequence at one end of a bacterial gene. Now three types of CRISPR/Cas system have been identified: types I, II and III. In the type II CRISPR/Cas9 system, short segments of foreign DNA termed 'spacers' are integrated within the CRISPR genomic loci, transcribed and processed into short CRISPR RNA (crRNA). These crRNAs anneal to trans-activating crRNA (tracrRNA) and direct sequence-specific cleavage in that a double-strand break (DSB) is generated by Cas proteins. Based on these findings, various genetic methods, including gene targeting (Gene disruption), gene insertion, gene correction etc., are being designed to manipulate the genomes of different species at specific loci. Compared with zinc finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN), CRISPR/Cas9 is simpler with higher specificity and less toxicity. This review summarizes recent progress, discusses the prospects of CRISPR/Cas9 system, with an emphasis on its structure, principle, applications and potential challenges, and provides a useful reference for researchers who are interested in this new technique.
