COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human ...angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.
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•SARS-CoV-2 could infect HFH4-hACE2 mice and cause death•SARS-CoV-2 infection localizes to lungs of mice and causes typical interstitial pneumonia•Pre-exposure to SARS-CoV-2 protects mice from lethal challenge
A SARS-CoV-2 hACE2 transgenic mouse infection model recapitulates a number of infection symptoms and pathology in COVID-19 patients. Pre-exposure to SARS-CoV-2 was able to protect mice from severe pneumonia.
Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats
. ...Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans
. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.
The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a ...mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.
Background and Objective
Periodontitis is a multifactorial disease that can lead to the progressive destruction of dental support tissue. However, the detailed mechanisms and specific biomarkers ...involved in periodontitis remain to be further studied. Recently, long non‐coding RNAs (lncRNAs) have been found to play a more important role than other types of RNAs. In our study, we analysed the expression of lncRNAs in periodontitis by analysing GSE16134.
Material and Methods
We identified highly correlated genes by analysing GSE16134 with weighted gene co‐expression network analysis (WGCNA) and identified 50 hub lncRNAs that were dysregulated. Then, we used the Linear Models for Microarray Data (Limma) package to identify the hub lncRNAs that were differentially expressed (DElncRNAs). The ceRNA co‐expression network data were obtained from several sites, including miRcode, and were used to assess the potential WGCNA function of hub DElncRNAs in periodontitis. Besides, we divided the samples into LBX2‐AS1 high and low expression group by the expression level of LBX2‐AS1 and calculated DEG by Limma package. Furthermore, we performed GO function, KEGG pathway and GSEA enrichment of DEGs.
Results
In the analysis, we identified 50 hub lncRNAs that may play important roles in periodontitis. Then, we used the Limma package to identify 3 hub DElncRNAs (LINC00687, LBX2‐AS1 and LINC01566). We elucidated the potential function of the hub DElncRNA LBX2‐AS1 in periodontitis by constructing a co‐expression network of lncRNA‐miRNA‐mRNA interactions. Totally, 573 DEGs (354 up‐ and 219 downregulated) in periodontitis samples were identified. DEGs were enriched in different GO terms and pathways, such as neutrophil degranulation, neutrophil activation, neutrophil activation involved in immune response, neutrophil‐mediated immunity, antigen processing and presentation, JAK‐STAT signalling pathway, natural killer cell‐mediated cytotoxicity, EGFR tyrosine kinase inhibitor resistance, phosphatidylinositol signalling system and Vascular Endothelial Growth Factor (VEGF) signalling pathway.
Conclusion
In our study, we found that 3 hub DElncRNAs (LINC00687, LBX2‐AS1 and LINC01566) may be involved in the pathogenesis of periodontitis based on WGCNA and Limma analysis. Our study aimed to elucidate the mechanisms involved in periodontitis at the genetic and epigenetic levels by constructing a ceRNA network associated with lncRNA. Besides, identification DEGs of differential LBX2‐AS1 and functional annotation showed that LBX2‐AS1 might be associated with periodontitis.
Chemotherapy‐induced peripheral neuropathy (CIPN) is among the most disabling and frustrating problems for cancer survivors. The neurotoxicity caused by cisplatin varies greatly among patients, and ...few predictors of appearance, duration of symptoms, susceptibility, or severity are available. A deeper understanding of the mechanisms underlying individual differences in status, severity, or sensitivity in response to cisplatin treatment is therefore required. By analyzing the GSE64174 gene expression profile and constructing a weighted gene co‐expression network analysis (WGCNA) network, we screened gene modules and hub genes related to CIPN status, severity and sensitivity. We first identified the transcriptome profile of mouse dorsal root ganglion (DRG) samples and transformed their genes to human DRG counterparts. We then constructed WGCNA gene modules via optimal soft‐threshold power‐identification and module‐preservation analysis. Comprehensive analysis and identification of module hub genes were performed via functional‐enrichment analysis and significant common hub genes were identified, including “Cytoscape_cytoHubba,” “Cytoscape_MCODE,” and “Metascape_MCODE.” Brown, green, and blue modules were selected to represent CIPN sensitivity, status, and severity, respectively, via trait‐module correlational analysis. Additionally, functional enrichment analysis results indicated that these three modules were associated with some crucial biological functions, such as neutrophil migration, chemokine‐mediated signaling pathway, and PI3K‐Akt signaling pathway. We then identified seven common hub genes via three methods, including CXCL10, CCL21, CCR2, CXCR4, TLR4, NPY1R, and GALR2, related to CIPN status, severity and sensitivity. Our results provide possible targets and mechanism insights into the development and progress of CIPN, which can guide further transformation and pre‐clinical research.
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•A new strain of algae was isolated from fresh water.•This novel strain was identified as Desmodesmus sp. by 18s rRNA and ITS1 analysis.•This strain could grow in anaerobic digestion ...wastewater (ADW).•Maximum nutrients removal was observed at 10.0% ADW.•This strain could remove 100% NH4–N, TP and PO4–P, and 75.50% TN at 10.0% ADW.
Anaerobic digestion wastewater (ADW), which contains large amount of nitrogen and phosphorus, particularly high concentration of ammonium, might lead to severely environmental pollution. A new unicellular green microalgae species from a wetland at the Olympic Forest Park, Beijing, China was screened based on its growth rates and nutrients removal capability under ADW. Results of 18s rDNA and ITS1 analysis indicated that this strain have a close relationship with Desmodesmus sp., named as EJ9-6. Desmodesmus sp. EJ9-6 could remove 100% NH4–N (68.691mg/L), TP (4.565mg/L) and PO4–P (4.053mg/L), and 75.50% TN (84.236mg/L) at 10.0% ADW, which the highest biomass production was 0.412g/L after 14d cultivation. Maximum nutrients removal was observed at 10.0% ADW with daily removal rates of TN, NH4–N, TP and PO4–P at 4.542, 5.284, 0.326 and 0.290mg/L/d, respectively.
To compare the new zero-profile (Zero-P) fusion cage with regular cage and plate (CP) in the treatment of anterior cervical single-level cervical degenerative diseases.
Patients operated from January ...2013 to August 2018 were enrolled. They were divided into the Zero-P group (n = 74 cases) and CP groups (n = 116 cases). Follow-up assessment was at 1, 3, 12, and 24 months after surgery, including the incidence of dysphagia, visual analogue scale (VAS) score, Japanese orthopaedic association (JOA)score, C2-C7 Cobb angle, intervertebral disc height (IDH) and adjacent joint degeneration.
The operation time and blood loss of patients in Zero-P group were less than those in the CP group, and there was no difference in hospitalization time. All 190 patients were followed up for 24 to 72 months, with an average of 35.29 months. In terms of clinical outcomes, vas and JOA scores of the two groups were significantly improved at one month and the last follow-up. The incidence of dysphagia in the Zero-P group was lower than that in the CP group. On radiological effects, Cobb angle and IDH showed significant correction in both groups, but the degeneration rate of adjacent joints in the Zero-P group was lower than the CP group.
In ACDF, the clinical and radiological results of Zero-P and CP devices are satisfactory, but Zero-P cage may be superior in operation time, blood loss, the incidence of dysphagia and adjacent joint degeneration.
Following acute infection, individuals COVID-19 may still shed SARS-CoV-2 RNA. However, limited information is available regarding the active shedding period or whether infectious virus is also shed. ...Here, we monitored the clinical characteristics and virological features of 38 patients with COVID-19 (long-term carriers) who recovered from the acute disease, but still shed viral RNA for over 3 months. The median carrying history of the long-term carriers was 92 days after the first admission, and the longest carrying history was 118 days. Negative-positive viral RNA-shedding fluctuations were observed. Long-term carriers were mostly elderly people with a history of mild infection. Infectious SARS-CoV-2 was isolated from the sputum, where high level viral RNA was found. All nine full-length genomes of samples obtained in March-April 2020 matched early viral clades circulating in January-February 2020, suggesting that these patients persistently carried SARS-CoV-2 and were not re-infected. IgM and IgG antibodies and neutralizing-antibody profiles were similar between long-term carriers and recovered patients with similar disease courses. In summary, although patients with COVID-19 generated neutralizing antibodies, they may still shed infectious SARS-CoV-2 for over 3 months. These data imply that patients should be monitored after discharge to control future outbreaks.
Severe respiratory disease coronavirus-2 (SARS-CoV-2) has been the most devastating disease COVID-19 in the century. One of the unsolved scientific questions of SARS-CoV-2 is the animal origin of ...this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbour highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). This study identified a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities with SARS-CoV-2 in the conserved ORF1b region, it only shows less than 77.6% nucleotide identity to all known SARSr-CoVs at the genome level, thus forming a distinct lineage in the Sarbecovirus phylogenetic tree. We found that the RaTG15 receptor-binding domain (RBD) can bind to ACE2 from Rhinolophus affinis, Malayan pangolin, and use it as an entry receptor, except for ACE2 from humans. However, it contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we showed that none of the known viruses in bat SARSr-CoV-2 lineage discovered uses human ACE2 as efficiently as the pangolin-derived SARSr-CoV-2 or some viruses in the SARSr-CoV-1 lineage. Therefore, further systematic and longitudinal studies in bats are needed to prevent future spillover events caused by SARSr-CoVs or to understand the origin of SARS-CoV-2 better.
From July 2019 to January 2020, 70 women with AMA who had chosen selective caesarean section in the Third Affiliated Hospital of Nanchang University and 65 non-pregnant women who had undergone ...selective surgery in our hospital were both included in the study (The inclusion and exclusion criteria are detailed in the supplementary materials). ...it can be concluded that CSA cannot be predicted by a single variable nor can the size of CSA be judged by a single index, such as the length of gestation week or fasting time. ...this study is a single center study, the number of cases included is limited, and multi center, large sample data are needed to verify this result. ...future research should indicate whether the new fasting guidelines are also applicable to women with AMA.Funding No external funding.Declaration of Competing Interest The authors have no interests to disclose with the matter.Appendix A Supplementary data Supplementary dataImage 1Appendix A Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jclinane.2021.110270.
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