Spatiotemporal Patterns of the Omicron Wave of COVID-19 in the United States.

COVID-19 has undergone multiple mutations, with the Omicron variant proving to be highly contagious and rapidly spreading across many countries. The United States was severely hit by the Omicron variant. However, it was still unclear how Omicron transferred across the United States. Here, we collected daily COVID-19 cases and deaths in each county from 1 December 2021 to 28 February 2022 as the Omicron wave. We adopted space-time scan statistics, the Hoover index, and trajectories of the epicenter to quantify spatiotemporal patterns of the Omicron wave of COVID-19. The results showed that the highest and earliest cluster was located in the Northeast. The Hoover index for both cases and deaths exhibited phases of rapid decline, slow decline, and relative stability, indicating a rapid spread of the Omicron wave across the country. The Hoover index for deaths was consistently higher than that for cases. The epicenter of cases and deaths shifted from the west to the east, then southwest. Nevertheless, cases were more widespread than deaths, with a lag in mortality data. This study uncovers the spatiotemporal patterns of Omicron transmission in the United States, and its underlying mechanisms deserve further exploration.

Artemisinin Alleviates Intestinal Inflammation and Metabolic Disturbance in Ulcerative Colitis Rats Induced by DSS.

Objective: This study is aimed to reveal the possible mechanisms of artemisinin in the treatment of ulcerative colitis (UC) through bioinformatics analysis and experimental verification in UC model rats. Methods: Firstly, we searched two microarray data of the Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) between UC samples and normal samples. Then, we selected DEGs for gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The acute UC model of rats was established by using 3.5% dextran sulfate sodium (DSS) for 10 days to verify the core pathway. Finally, we evaluated the therapeutic effect of artemisinin at the molecular level and used metabonomics to study the endogenous metabolites in the rat serum. Results: We screened in the GEO database and selected two eligible microarray datasets, GSE36807 and GSE9452. We performed GO function and KEGG pathway enrichment analyses of DEGs and found that these DEGs were mainly enriched in the inflammatory response, immune response, and IL-17 and NF-κB signaling pathways. Finally, we verified the IL-17 signaling pathway and key cytokines, and ELISA and immunohistochemical results showed that artemisinin could downregulate the expression of proinflammatory cytokines such as IL-1ß and IL-17 in the IL-17 signaling pathway and upregulate the expression of the anti-inflammatory cytokine PPAR-γ. Metabolomics analysis showed that 33 differential metabolites were identified in the artemisinin group (AG) compared to the model group (MG). Differential metabolites were mainly involved in alanine, aspartate, and glutamate metabolism and synthesis and degradation of ketone bodies. Conclusion: In this study, we found that artemisinin can significantly inhibit the inflammatory response in UC rats and regulate metabolites and related metabolic pathways. This study provides a foundation for further research on the mechanism of artemisinin in the treatment of UC.

Receptor tyrosine kinase inhibitors block proliferation of TGEV mainly through p38 mitogen-activated protein kinase pathways.

Emerging coronaviruses (CoVs) primarily cause severe gastroenteric or respiratory diseases in humans and animals, and no approved therapeutics are currently available. Here, A9, a receptor tyrosine kinase inhibitor (RTKI) of the tyrphostin class, is identified as a robust inhibitor of transmissible gastroenteritis virus (TGEV) infection in cell-based assays. Moreover, A9 exhibited potent antiviral activity against the replication of various CoVs, including murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV) and feline infectious peritonitis virus (FIPV). We further performed a comparative phosphoproteomic analysis to investigate the mechanism of action of A9 against TGEV infection in vitro. We specifically identified p38 and JNK1, which are the downstream molecules of receptor tyrosine kinases (RTKs) required for efficient TGEV replication, as A9 targets through plaque assays, qRT-PCR and Western blotting assays. p38 and JNK1 inhibitors and RNA interference further showed that the inhibitory activity of A9 against TGEV infection was mainly mediated by the p38 mitogen-activated protein kinase (MAPK) signaling pathway. All these findings indicated that the RTKI A9 directly inhibits TGEV replication and that its inhibitory activity against TGEV replication mainly occurs by targeting p38, which provides vital clues to the design of novel drugs against CoVs.

Magnifying endoscopy with narrow-band imaging to assist the linear stapler closure of the pharynx during total laryngectomy.

OBJECTIVE: This study aimed to present a novel technique for stapler-assisted laryngectomy under direct visualization using a videoendoscope with narrow-band imaging (NBI-endoscopy). METHODS: A case series of five consecutive patients were treated with stapler-assisted total laryngectomy from December 2014 to March 2016. The technique involved monitoring the stapler closure of laryngopharyngeal cavity under NBI-endoscopic vision, triple checking of neo-pharynx cavity by an endoscopic view inside and transillumination verification outside, air leakage test, and guiding the insertion of feeding tube under direct visualization. The main evaluation of this study was pharyngocutaneous fistula, surgical margin, and oral feeding time. RESULTS: All the patients healed well without a pharyngocutaneous fistula. The mean of surgical time, oral feeding, and hospitalization time were 40 min, 6 days, and 8 days, respectively. CONCLUSION: This study demonstrated a technique simple to learn and associated with decreased complication rates, which could be safe and efficient for stapler-assisted laryngectomy.