Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

The peripheral blood of healthy or ketosis dairy cows was collected,and CD4+T cells were isolated.The expressions of lipid synthesis related proteins fatty acid synthase(FASN),acetyl coenzyme A carboxylase 1(ACC1),cluster of differentiation 36(CD36)and store-operated calcium entry(SOCE)related proteins ORAIl,ORAI2,ORAI3,STIM1,STIM2 were detected by Western blot.IL-17 cells were detected by flow cytometry.CD4+T cells were isolated from the spleen of 1-day-old calves and cultured in vitro.Cells were treated and divided into control(Ctrl)group,si-lenced CD36(siCD36)group,stearic acid(SA)group,and SA+siCD36 group.Cells in the Ctrl and SA groups were transfected with 75 pmol/L negative control siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h;Cells in the siCD36 group and SA+siCD36 group were transfected with 75 pmol/L CD36 siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h in the SA+siCD36 group.The protein expression of FASN,CD36,ACC1,ORAI1,ORAI2,ORAI3,STIM1 and STIM2 was detected by Western blot,and IL-17 cells were detected by flow cytometry.The results showed that the expression of IL-17 in peripheral blood CD4+T cells of ketosis dairy cows was significantly increased compared to that of healthy cows(P＜0.01).Additionally,the protein level of FASN,CD36,STIM1(P＜0.05),and ACC1,ORAI2,ORAI3,STIM2(P＜0.01)were up-regulated.Compared with the Ctrl group,the protein expression levels of CD36,ACC1 and ORAI3(P＜0.05)were up-regulated in the SA group,as well as the protein expression of FASN and STIM1(P＜0.01).Additionally,the expression of IL-17 was significantly increased(P＜0.05).Compared with the SA group,there was a decrease in the protein expression of STIM1,ORAI1(P＜0.05)and CD36,ACC1,FASN,ORAI2(P＜0.01)in the siCD36+SA group,as well as IL-17(P＜0.05).These results suggest that SA can promote the expression of IL-17 in CD4+T cells in ketosis cows by regulating fatty acid synthesis and activating SOCE channels through CD36.

The peripheral blood of healthy or ketosis dairy cows was collected,and CD4+T cells were isolated.The expressions of lipid synthesis related proteins fatty acid synthase(FASN),acetyl coenzyme A carboxylase 1(ACC1),cluster of differentiation 36(CD36)and store-operated calcium entry(SOCE)related proteins ORAIl,ORAI2,ORAI3,STIM1,STIM2 were detected by Western blot.IL-17 cells were detected by flow cytometry.CD4+T cells were isolated from the spleen of 1-day-old calves and cultured in vitro.Cells were treated and divided into control(Ctrl)group,si-lenced CD36(siCD36)group,stearic acid(SA)group,and SA+siCD36 group.Cells in the Ctrl and SA groups were transfected with 75 pmol/L negative control siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h;Cells in the siCD36 group and SA+siCD36 group were transfected with 75 pmol/L CD36 siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h in the SA+siCD36 group.The protein expression of FASN,CD36,ACC1,ORAI1,ORAI2,ORAI3,STIM1 and STIM2 was detected by Western blot,and IL-17 cells were detected by flow cytometry.The results showed that the expression of IL-17 in peripheral blood CD4+T cells of ketosis dairy cows was significantly increased compared to that of healthy cows(P＜0.01).Additionally,the protein level of FASN,CD36,STIM1(P＜0.05),and ACC1,ORAI2,ORAI3,STIM2(P＜0.01)were up-regulated.Compared with the Ctrl group,the protein expression levels of CD36,ACC1 and ORAI3(P＜0.05)were up-regulated in the SA group,as well as the protein expression of FASN and STIM1(P＜0.01).Additionally,the expression of IL-17 was significantly increased(P＜0.05).Compared with the SA group,there was a decrease in the protein expression of STIM1,ORAI1(P＜0.05)and CD36,ACC1,FASN,ORAI2(P＜0.01)in the siCD36+SA group,as well as IL-17(P＜0.05).These results suggest that SA can promote the expression of IL-17 in CD4+T cells in ketosis cows by regulating fatty acid synthesis and activating SOCE channels through CD36.

Objective To explore the application of quantitative EEG(QEEG)trends in the assessment of the state of brain function in patients with severe stenosis of the internal carotid artery and its predictive value for the risk of acute occlusion in the short term.Methods The clinical and imaging data of a case of severe left internal carotid stenosis were retrospectively analyzed,and QEEG trends were used for evaluating the state of brain function.Results It showed that rhythmicity spectrogram,amplitude-integrated EEG,fast Fourier transformation spectrogram and fast Fourier transform power spectrum in QEEG trends could quickly and visually display theta activity and amplitude at the side of severe internal carotid artery stenosis continued to increase compared with the healthy side hemisphere.Acute occlusion of the left internal carotid artery and large artery atherosclerotic cerebral infarction occurred in the patient after 3 days.Conclusion As a supplement to neuroimaging examination,QEEG trends may be helpful for rapidly diagnosing brain function damage in the early stage of patients with severe internal carotid artery stenosis who are under the ischemic attack state,and even have potential predictive values for patients with acute occlusion in the short term.

Objective:To elucidate the phenomenon that epileptic seizure occurs in patients with epilepsy without definite diagnosis when driving a motor vehicle and its hazards.Methods:From January 2020 to June 2022, 7 epileptic patients who experienced traffic accidents caused by seizures were selected from the First Affiliated Hospital of Soochow University, and their demographic data, traffic accident related data and epilepsy diagnosis and treatment data were summarized and analyzed.Results:A total of 7 adult patients with epilepsy were collected, including 6 males, 4 of whom had been driving for more than 10 years. Among them, 1 patient drove a bus, and the other 6 patients drove private cars. Totally 5/7 of the accidents resulted in personal injury, and 3/7 of the accidents resulted in personal death. In 5 patients, video electroencephalogram showed interictal epileptiform discharges. In 2 patients, the imaging findings suggested the presence of cerebral cortical lesions that may lead to seizures. In terms of the form of seizure, 3 patients′ seizure type was focal to bilateral tonic-clonic, and the other 4 patients were very probable to be focal impaired awareness seizure.Conclusions:Undiagnosed epileptic seizures lead to traffic accidents, endanger patients and public safety, which need to attract attention from both doctors and patients, as well as the whole society.

Objective To analyze the types and epidemiological characteristics of influenza virus in Xi'an during 2009 to 2017.Methods A total of 21 856 samples of throat swabs from patients with influenza like illness ( ILI) were collected from 5 national influenza sentinel surveillance hospitals from August 2009 to December 2017.Influenza virus nucleic acid was detected by real-time fluorescence quantitative PCR and virus types were confirmed , chick-embryo cells or Madin-Darby canine kidney (MDCK) cells were used to isolate influenza virus.SPSS 18.0 software was used for data analysis.Results The positive detection rate of influenza virus was 16.19%(3 539/21 856), the seasonal influenza A virus subtypes including H1, H3, the new type H1and H7 accounted for 62.39%(2 208/3 539), influenza B virus subtypes including Victoria , Yamagata and unclassified type B accounted for 37.50%( 1 327/3 539), and the mixed influenza virus infection accounted for 0.11%(4/3 539).The positive rate of influenza virus detected in different years was significantly different ( χ2＝357.651, P ＜0.01).During January to March the major influenza A viruses accounted for 49.07%(947/1 930), influenza B viruses accounted for 50.93%(983/1 930); during October to December , the influenza A viruses accounted for 78.07%( 1 061/1 359 ), and influenza B viruses accounted for 21.93%( 298/1 359 ); there was significant difference in composition of type A virus and type B virus between different seasons ( χ2＝ 550.06, P＜0.05).The positive detection rate of influenza virus in patients with ILI of age groups 0-3 years,＞3-7 years,＞7-13 years,＞13-18 years,＞18-24 years,＞24-60 years and ＞60 years were 12.61%, 19.41%, 19.66%, 22.98%, 14.91%, 13.50% and 12.84%, respectively ( χ2＝202.52, P＜0.05).Conclusion Influenza A virus is common in Xi'an,winter and spring are the peak seasons for influenza epidemics.It is recommended for susceptible people to take influenza vaccination .