Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor.

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

Inhibition of PEDV viral entry upon blocking N-glycan elaboration.

Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to the global swine industry, demanding a thorough understanding of its cellular invasion mechanism for effective interventions. This study meticulously investigates the impact of O- and N-linked glycans on PEDV proteins and host cell interaction, shedding light on their influence on the virus's invasion process. Utilizing CRISPR-Cas9 technology to inhibit cell surface O- and N-linked glycan synthesis demonstrated no discernible impact on virus infection. However, progeny PEDV strains lacking these glycans exhibited a minor effect of O-linked glycans on virus infection. Conversely, a notable 40% reduction in infectivity was observed when the virus surface lacked N-linked glycans, emphasizing their pivotal role in facilitating virus recognition and binding to host cells. Additionally, inhibition studies utilizing kifunensine, a natural glycosidase I inhibitor, reaffirmed the significant role of N-linked glycans in virus infection. Inhibiting N-linked glycan synthesis with kifunensine substantially decreased virus entry into cells and potentially influenced spike protein expression. Assessment of the stability and recovery potential of N-linked glycan-deficient strains underscored the critical importance of N-glycans at various stages of the virus lifecycle. In vivo experiments infecting piglets with N-glycan-deficient strains exhibited milder clinical symptoms, reduced virus excretion, and less severe pathological lesions compared to conventional strains. These findings offer promising translational applications, proposing N-glycosylation inhibitors as potential therapeutic interventions against PEDV. The utilization of these inhibitors might mitigate virus invasion and disease transmission, providing avenues for effective antiviral strategies and vaccine development. Nonetheless, further research is warranted to elucidate the precise mechanisms of N-linked glycans in PEDV infection for comprehensive clinical applications.

Robot-assisted technique vs conventional freehand technique in spine surgery: A meta-analysis.

BACKGROUND: The impact of robot-assisted techniques versus conventional freehand techniques in terms of the accuracy of pedicle screw placement remains conflicting. This meta-analysis was performed to evaluate this relationship. METHODS: A systematic literature search up to July 2020 was performed and 15 studies were detected with 6041 pedicle screw placements with 2748 of them were using robot-assisted techniques and 3293 were conventional freehand techniques. They reported relationships between robot-assisted techniques and conventional freehand techniques in pedicle screw placement. Odds ratio (OR) or Mean differences (MD) with 95% confidence intervals (CIs) was calculated comparing the robot-assisted techniques to conventional freehand techniques in pedicle screw placement risks using the dichotomous and continuous method with a random or fixed-effect model. RESULTS: Robot-assisted techniques had a significantly higher screw position grade A in Gertzbein-Robbins classification of the screw placement accuracy (OR, 2.43; 95% CI, 1.66-3.54, P < .001); shorter postoperative stay (MD, -0.67; 95% CI, -1.16 to -0.19, P < .001); lower intraoperative blood loss (MD, -91.64; 95% CI, -152.44 to -30.83, P = .003); fewer intraoperative radiation dose (MD, -23.52; 95% CI, -40.12 to -6.0.93, P = .005); and low proximal facet violations (MD, 0.08; 95% CI, 0.03-0.20, P < .001) compared with conventional freehand techniques. However, no significant difference was found between robot-assisted techniques and conventional freehand techniques in surgical time (OR, 11.71; 95% CI, 03.27-26.70, P = .13); visual analogue scale scores (MD, -0.15; 95% CI, -0.54 to 0.23, P = .44); and Oswestry disability index scores (MD, 0.21; 95% CI, -5.09-5.51, P = .94). CONCLUSIONS: The extent of the improvement with robot-assisted techniques in screw position grade A in Gertzbein-Robbins classification of the screw placement accuracy, postoperative stay, intraoperative blood loss, intraoperative radiation dose, and proximal facet violations was significantly better than conventional freehand techniques. This relationship forces us to recommend robot-assisted techniques for pedicle screw placement to avoid any possible negative postoperative results.