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A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence SummaryNeutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.
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The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1x106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.
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The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be confirmed. Therefore, we herein used a SARS-CoV-2 spike (S) protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed plasma membrane fusion capacity superior to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. We then generated a series of lipopeptides and found that the EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than that of EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, potently inhibiting replication of 4 live human coronaviruses, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by currently circulating SARS-CoV-2 and emerging SARSr-CoVs.
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Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Kochs postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.
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A novel solid-phase extraction (SPE) adsorbent for simultaneous extraction of atrazine (ATZ) and its metabolites, deisopropylatrazine (DIA) and deethylatrazine (DEA) from environmental water samples was prepared. Polyacrylonitrile nanofibers (PAN NFs) mat was prepared via electrospinning, and was further functionalized to obtain polypyrrole modified polyacrylonitrile nanofibers (PPy-PAN NFs) mat, hydrazine modified polyacrylonitrile nanofibers (NH2-PAN NFs) mat and carboxyl modified polyacrylonitrile (COOH-PAN NFs) mat. The results showed that the adsorption capacity of COOH-PAN NFs mat was better than other three NFs mats in both static (2.0 mg/g) and dynamic (0.19 mg/g) experiments. Meanwhile, the runoff ratios of COOH-PAN NFs mat were the lowest (less than 30.0%) in the adsorption of three analytes, especially for high polar analytes, which showed that the hydrogen bond between carboxyl groups and analytes was the main interactive force. A combination of mat-based SPE and high performance liquid chromatography-diode array detection was further established for determination of 3 analytes in environmental water samples. The recoveries were 81.4%-120.3% and the limits of detection were 0.12 ng/mL for DIA, 0.09 ng/mL for DEA and ATZ, respectively.
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Type 2 innate lymphoid cells ( ILC2s) are recently identified members of the innate lymphoid cell ( ILC) family. These cells are capable of producing Th2-type cytokines such as IL-5 and IL-13 in response to epithelial cell-derived cytokines IL-25 and IL-33 and play critical roles in allergic diseases such as bronchial asthma. Further investigations on ILC2s will enhance the better understanding of type 2 immune responses and may provide new strategies for the treatment of allergic asthma. In this review, we fo-cus on the origin, location and biological function of ILC2s as well as their possible roles in the pathogenesis of bronchial asthma.
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Nanofibers have been considered as a potential kind of sorbent for solid phase extraction, accordingly nanofiber-based solid phase extraction ( Nanofibers based solid phase extraction, NFs-SPE ) becomes a popular research point of sample pretreatment technique. This article reviewed in and abroad research status of practical application in food, environmental and biological sample preparation based on nanofibers mat, and proposed that there was a dual “structure”-“activity” relationship between target adsorption efficiency and the two structures ( nanometer morphological structure and molecular structure ) of nanofibers, which would be the key breakthrough to explore adsorption mechanism.
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Tumor metastasis, the main characteristic of malignance tumor, is the primary cause of death for most cancer patients.The initiation of tumor metastasis involves complex signaling pathway within tumor cell and microenvironment, mediating primary tumor metastasis, invasion, survival and arrest in the blood circulation, and progressive growth at the distant site.The most research on the mechanism of tumor metastais will help understand the metastasis process, and identify promising molecular targets for cancer clinical diagnosis and treatment.