In comparison to severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 appears to be more contagious [1], and coronavirus disease 2019 (COVID-19) patients demonstrate varied clinical manifestations distinct from those seen in patients with SARS-CoV and Middle East respiratory syndrome coronavirus infections [2]. Collective results from the clinical and epidemiological observations suggest a distinct viral-host interaction in COVID-19 patients. Profiling of the antibody response during SARS-CoV-2 infection may help improve our understanding of the viral-host interaction and the immunopathological mechanisms of the disease. Studies on humoral responses to infections have been mainly geared toward the production of high-affinity IgG antibodies that efficiently resolve an infection. It has been well recognised, however, that humoral immune response to infection can be a double-edged sword that either serves as a protective mechanism to resolve the infection or aggravates the tissue injury, e.g. the IgG response causes fatal acute lung injury by skewing the inflammation-resolving response in SARS-CoV [3]. In the case of respiratory infection, while IgM and IgG isotypes have been the primary emphasis in characterising immunity, mucosal and systemic IgA responses that may play a critical role in the disease pathogenesis have received much less attention. This study was designed to better understand the timing and patterns of humoral immune responses to SARS-CoV-2 in a cohort of COVID-19 patients and evaluate their relationship with the disease course and severity. 37 patients with COVID-19, with a mean±SD age of 52.3±16.3 years, were enrolled in this study. The enrolled COVID-19 patients consisted of 25 (67.6%) males and 12 (32.4%) females. All patients tested positive for viral nucleic acid of SARS-CoV-2 (Real-Time Fluorescent RT-PCR Kit; BGI, Shenzhen, China). According to the "Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection" published by the National Health Commission of China, the enrolled COVID-19 patients were categorised into two groups: 20 (54.1%) severe cases and 17 (46.0%) nonsevere cases [4]. The nonsevere group included patients with mild and moderate symptoms who were also required to be admitted to hospital by the COVID-19 control policy in China. The severe group included severe and critically ill patients. Mild patients did not demonstrate abnormal computed tomography (CT) imaging. Moderate patients had fever and/or classical respiratory symptoms, and typical CT images of viral pneumonia. Severe patients met at least one of following additional conditions: 1) shortness of breath with a respiratory rate ⩾30 times•min −1 ; 2) oxygen saturation measured by pulse oximetry (resting state) of ⩽93%; or 3) arterial oxygen tension/inspiratory oxygen tension of ⩽300 mmHg. Critically ill patients met at least one of the extra following conditions in addition to the COVID-19 diagnosis: 1) respiratory failure that required mechanical ventilation; 2) shock; or 3) mu...

Laboratory diagnosis of acute infection of hepatitis E virus (HEV) is commonly based on the detection of HEV RNA, IgM and/or rising IgG levels. However, the profile of these markers when the patients present have not been well determined. To clarify the extent of misdiagnosed sporadic hepatitis E in the initial laboratory detection, serial sera of 271 sporadic acute hepatitis cases were collected, detected and the dynamics of each acute marker during the illness course were analyzed. 91 confirmed cases of hepatitis E were identified based on the presentation of HEV RNA, IgM or at least 4 fold rising of IgG levels. 21 (23.1%) hepatitis E cases were false negative for the viral RNA and 40 (44.0%) for rising IgG, because occurrence of these markers were confined to acute phase of infection and viremia had already subsided and antibody level peaked when these patients presented. IgM was detected in 82 (90.1%) cases. It is the most prevalent of the three markers, because the antibody persisted until early convalescence. Nine cases negative for IgM were positive for rising IgG and one was also positive for the viral RNA; all of these nine cases showed high avid IgG in their acute phase sera, which indicated re-infection. In summary, it is not practicable to determine the true occurrence of sporadic hepatitis E. Nevertheless, it could be closely approximated by approach using a combination of all three acute markers.

FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs in human cancers remain largely unknown. Aberrant expression and activation of Nrf2 often correlate with chemoresistance and poor prognosis. Here, we report that FoxO3 directs the basal transcription of Kelch-like ECH-associated protein 1 (Keap1), an adaptor protein that bridges Nrf2 to Cul3 for degradation. FoxO3 depletion resulted in Keap1 downregulation, thereby activating Nrf2 signaling. We further demonstrated that inhibition of the FoxO3-Keap1 axis accounts for Nrf2 induction and activation induced by constitutively active AKT signaling or tumor necrosis factor a treatment. Unlike previous findings, FoxO3 silencing led to decreased reactive oxygen species production, therefore protecting cells from oxidative stress-induced killing in an Nrf2-dependent manner. Importantly, FoxO3 deficiency strongly potentiated tumor formation in nude mice and rendered cholangiocarcinoma xenografts resistant to cisplatin-induced cell death by activating Nrf2. Additionally, we found that clinical cholangiocarcinoma samples displayed FoxO3-Keap1 down-regulation and Nrf2 hyperactivation, underscoring the essential roles of these proteins in cholangiocarcinoma development. Conclusion: Our results unravel a unique mechanism underlying the tumor suppressor function of

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