Brain functional network changes associated with psychological symptoms in emergency psychological responding professionals after the first wave of COVID-19 pandemic.

Background: Emergency psychological responding professionals are recruited to help deal with psychological issues as the Corona Virus Disease 2019 (COVID-19) continues. We aimed to study the neural correlates of psychological states in these emergency psychological responding professionals after exposure to COVID-19 related trauma at baseline and after 1-year self-adjustment. Methods: Resting-state functional MRI (rs-fMRI) and multiscale network approaches were utilized to evaluate the functional brain activities in emergency psychological professionals after trauma. Temporal (baseline vs. follow-up) and cross-sectional (emergency psychological professionals vs. healthy controls) differences were studied using appropriate t-tests. The brain functional network correlates of psychological symptoms were explored. Results: At either time-point, significant changes in the ventral attention (VEN) and the default mode network (DMN) were associated with psychological symptoms in emergency psychological professionals. In addition, the emergency psychological professionals whose mental states improved after 1 year demonstrated altered intermodular connectivity strength between several modules in the functional network, mainly linking the DMN, VEN, limbic, and frontoparietal control modules. Conclusion: Brain functional network alterations and their longitudinal changes varied across groups of EPRT with distinctive clinical features. Exposure to emergent trauma does cause psychological professionals to produce DMN and VEN network changes related to psychological symptoms. About 65% of them will gradually adjust mental states, and the network tends to be rebalanced after a year.

Gauging urban resilience in the United States during the COVID-19 pandemic via social network analysis.

Social distancing policies and other restrictive measures have demonstrated efficacy in curbing the spread of the COVID-19 pandemic. However, these interventions have concurrently led to short- and long-term alterations in social connectedness. Comprehending the transformation in intracity social interactions is imperative for facilitating post-pandemic recovery and development. In this research, we employ social network analysis (SNA) to delve into the nuances of urban resilience. Specifically, we constructed intricate networks utilizing human mobility data to represent the impact of social interactions on the structural attributes of social networks while assessing urban resilience by examining the stability features of social connectedness. Our findings disclose a diverse array of responses to social distancing policies regarding social connectedness and varied social reactions across U.S. Metropolitan Statistical Areas (MSAs). Social networks generally exhibited a shift from dense to sparse configurations during restrictive orders, followed by a transition from sparse to dense arrangements upon relaxation of said orders. Furthermore, we analyzed the alterations in social connectedness as demonstrated by network centrality, which can presumably be attributed to the rigidity of policies and the inherent qualities of the examined MSAs. Our findings contribute valuable scientific insights to support informed decision-making for post-pandemic recovery and development initiatives.

Help-Seeking Intentions for Depression and Associated Factors among Chinese Perinatal Women: A Cross-Sectional Study.

A low help-seeking intention for depression is an important reason for the low number of women with perinatal depression who have sought professional help. However, evidence of help-seeking intentions for depression is still lacking in Chinese perinatal women. We aimed to investigate the help-seeking intention for depression and its associated factors among Chinese perinatal women. Participants were recruited from three comprehensive hospitals in Changsha. A total of 874 perinatal women were included in the study. The score for the help-seeking intention for depression in Chinese perinatal women was 3.65 ± 0.79, with about half of participants (58.3%) reporting that they were "likely" and "strongly likely" to seek professional help if they suffered from depression during the perinatal period. Favorable help-seeking attitudes and sufficient knowledge of mental illness help-seeking resources were positively associated with help-seeking intentions for depression. However, self-stigma decreased the help-seeking intention for depression. Chinese perinatal women had relatively positive help-seeking intentions for depression. Reducing the stigma of mental illness and help-seeking, enhancing mental health literacy, and improving attitudes toward professional psychological help-seeking of perinatal women may be the potential key components of interventions to encourage perinatal women to actively seek professional psychological help.

SARS-CoV-2 ORF3a inhibits cGAS-STING-mediated autophagy flux and antiviral function.

Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS-STING-mediated innate immunity is essential for the host defense against viruses. Recent studies have reported that SARS-CoV-2 infection, responsible for the COVID-19 pandemic, triggers cGAS-STING activation. cGAS-STING activation can trigger IRF3-Type I interferon (IFN) and autophagy-mediated antiviral activity. Although viral evasion of STING-triggered IFN-mediated antiviral function has been well studied, studies concerning viral evasion of STING-triggered autophagy-mediated antiviral function are scarce. In the present study, we have discovered that SARS-CoV-2 ORF3a is a unique viral protein that can interact with STING and disrupt the STING-LC3 interaction, thus blocking cGAS-STING-induced autophagy but not IRF3-Type I IFN induction. This novel function of ORF3a, distinct from targeting autophagosome-lysosome fusion, is a selective inhibition of STING-triggered autophagy to facilitate viral replication. We have also found that activation of bat STING can induce autophagy and antiviral activity despite its defect in IFN induction. Furthermore, ORF3a from bat coronaviruses can block bat STING-triggered autophagy and antiviral function. Interestingly, the ability to inhibit STING-induced autophagy appears to be an acquired function of SARS-CoV-2 ORF3a, since SARS-CoV ORF3a lacks this function. Taken together, these discoveries identify ORF3a as a potential target for intervention against COVID-19.

Integration of a hybrid scan approach and in-house high-resolution MS2 spectral database for charactering the multicomponents of Xuebijing Injection

Xuebijing (XBJ) Injection is a reputable patent Chinese medicine widely used to cure sepsis, among the Chinese ″Three Medicines and Three Prescriptions″ solution to fight against COVID-19. We were aimed to achieve the comprehensive multicomponent characterization from the single drugs to traditional Chinese medicine (TCM) formula, by integrating powerful data acquisition and the in-house MS2 spectral database searching. By ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS), a hybrid scan approach (HDMSE-HDDDA) was developed, while the HDMSE data for five component drugs and 56 reference compounds were acquired and processed to establish an in-house MS2 spectral database of XBJ. Good resolution of the XBJ components was accomplished on a Zorbax Eclipse Plus C18 column within 24 min, while a fit-for-purpose HDMSE-HDDDA approach was elaborated in two ionization modes for enhanced MS2 data acquisition. XBJ MS2 spectral library was thus established on the UNIFITM platform involving rich structure-related information for the chemicals from five component drugs. We could identify or tentatively characterize 294 components from XBJ, involving 81 flavonoids, 51 terpenoids, 42 phthalides, 40 organic acids, 13 phenylpropanoids, seven phenanthrenequinones, six alkaloids, and 54 others. In contrast to the application of conventional MS1 library, this newly established strategy could demonstrate superiority in the accuracy of identification results and the characterization of isomers, due to the more restricted filtering/matching criteria. Conclusively, the integration of the HDMSE-HDDDA hybrid scan approach and the in-house MS2 spectral database can favor the efficient and more reliable multicomponent characterization from single drugs to the TCM formula.

Emerging role of the cGAS-STING signaling pathway in autoimmune diseases: Biologic function, mechanisms and clinical prospection.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, as vital component of innate immune system, acts a vital role in distinguishing invasive pathogens and cytosolic DNA. Cytosolic DNA sensor cGAS first binds to cytosolic DNA and catalyzes synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), which is known as the second messenger. Next, cGAMP activates the adaptor protein STING, triggering a molecular chain reaction to stimulate cytokines including interferons (IFNs). Recently, many researches have revealed that the regulatory role of cGAS-STING signaling pathway in autoimmune diseases (AIDs) such as Rheumatoid arthritis (RA), Aicardi Goutières syndrome (AGS) and systemic lupus erythematosus (SLE). Moreover, accumulated evidence have showed inhibition of the cGAS-STING signaling pathway could remarkably suppress the joint swelling and inflammatory cell infiltration in RA mice. Therefore, in this review, we describe the molecular properties, biologic function and mechanisms of the cGAS-STING signaling pathway in AIDs. In addition, potential clinical applications especially selective small molecule inhibitors targeting the cGAS-STING signaling pathway are also discussed.

Immune checkpoint blocking impact and nomogram prediction of COVID-19 inactivated vaccine seroconversion in patients with cancer: a propensity-score matched analysis.

BACKGROUND: Patients with cancer on active immune checkpoint inhibitors therapy were recommended to seek prophylaxis from COVID-19 by vaccination. There have been few reports to date to discuss the impact of progression cell death-1 blockers (PD-1B) on immune or vaccine-related outcomes, and what risk factors that contribute to the serological status remains to be elucidated. The study aims to find the impact of PD-1B on vaccination outcome and investigate other potential risk factors associated with the risk of seroconversion failure. METHODS: Patients with active cancer treatment were retrospectively enrolled to investigate the interaction effects between PD-1B and vaccination. Through propensity score matching of demographic and clinical features, the seroconversion rates and immune/vaccination-related adverse events (irAE and vrAE) were compared in a head-to-head manner. Then, a nomogram predicting the failure risk was developed with variables significant in multivariate regression analysis and validated in an independent cohort. RESULTS: Patients (n=454) receiving either PD-1B or COVID-19 vaccination, or both, were matched into three cohorts (vac+/PD-1B+, vac+/PD-1B-, and vac-/PD-1B+, respectively), with a non-concer control group of 206 participants. 68.1% (94/138), 71.3% (117/164), and 80.5% (166/206) were seropositive in vac+/PD-1B+cohort, vac+/PD-1B- cohort, and non-cancer control group, respectively. None of irAE or vrAE was observed to be escalated in PD-1B treatment except for low-grade rash.The vaccinated patients with cancer had a significantly lower rate of seroconversion rates than healthy control. A nomogram was thus built that encompassed age, pathology, and chemotherapy status to predict the seroconversion failure risk, which was validated in an independent cancer cohort of 196 patients. CONCLUSION: Although patients with cancer had a generally decreased rate of seroconversion as compared with the healthy population, the COVID-19 vaccine was generally well tolerated, and seroconversion was not affected in patients receiving PD-1B. A nomogram predicting failure risk was developed, including age, chemotherapy status, pathology types, and rheumatic comorbidity.

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy.

BACKGROUND: C3 glomerulopathy (C3G) is characterized by the alternative-pathway (AP) hyperactivation induced by nephritic factors or complement gene mutations. Mice deficient in complement factor H (CFH) are a classic C3G model, with kidney disease that requires several months to progress to renal failure. Novel C3G models can further contribute to understanding the mechanism behind this disease and developing therapeutic approaches. METHODS: A novel, rapidly progressing, severe, murine model of C3G was developed by replacing the mouse C3 gene with the human C3 homolog using VelociGene technology. Functional, histologic, molecular, and pharmacologic assays characterize the presentation of renal disease and enable useful pharmacologic interventions in the humanized C3 (C3hu/hu) mice. RESULTS: The C3hu/hu mice exhibit increased morbidity early in life and die by about 5-6 months of age. The C3hu/hu mice display elevated biomarkers of kidney dysfunction, glomerulosclerosis, C3/C5b-9 deposition, and reduced circulating C3 compared with wild-type mice. Administration of a C5-blocking mAb improved survival rate and offered functional and histopathologic benefits. Blockade of AP activation by anti-C3b or CFB mAbs also extended survival and preserved kidney function. CONCLUSIONS: The C3hu/hu mice are a useful model for C3G because they share many pathologic features consistent with the human disease. The C3G phenotype in C3hu/hu mice may originate from a dysregulated interaction of human C3 protein with multiple mouse complement proteins, leading to unregulated C3 activation via AP. The accelerated disease course in C3hu/hu mice may further enable preclinical studies to assess and validate new therapeutics for C3G.

The Therapeutic Effect of Traditional Chinese Medicine on Inflammatory Diseases Caused by Virus, Especially on Those Caused by COVID-19.

Inflammasomes are large multimolecular complexes best recognized because of their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-18 (IL-18) and interleukin-1 ß (IL-1ß). IL-1ß was originally identified as a pro-inflammatory cytokine, capable of inducing local and systemic inflammation as well as a fever response reaction in response to infection or injury. Excessive production of IL-1ß is related to inflammatory and autoimmune diseases. Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterized by excessive inflammatory response. For SARS, there is no correlation between viral load and worsening symptoms. However, there is no specific medicine which is available to treat the disease. As an important part of medical practice, TCM showed an obvious therapeutic effect in SARS-CoV-infected patients. In this article, we summarize the current applications of TCM in the treatment of COVID-19 patients. Herein, we also offer an insight into the underlying mechanisms of the therapeutic effects of TCM, as well as introduce new naturally occurring compounds with anti-coronavirus activity, in order to provide a new and potential drug development strategy for the treatment of COVID-19.

Unique and complementary suppression of cGAS-STING and RNA sensing- triggered innate immune responses by SARS-CoV-2 proteins.

The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear. In this study, we identified SARS-CoV-2 structural proteins, accessory proteins, and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways. In particular, the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways. Viral accessory protein ORF3a had the unique ability to inhibit STING, but not the RLR response. On the other hand, structural protein N was a unique RLR inhibitor. ORF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-κB signaling. 3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling. Diverse vertebrate STINGs, including those from humans, mice, and chickens, could be inhibited by ORF3a and 3CL of SARS-CoV-2. The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo. Since evasion of host innate immune responses is essential for the survival of all viruses, our study provides insights into the design of therapeutic agents against SARS-CoV-2.

Computational Characterizations of the Interactions Between the Pontacyl Violet 6R and Exoribonuclease as a Potential Drug Target Against SARS-CoV-2.

We report a molecular-docking and virtual-screening-based identification and characterization of interactions of lead molecules with exoribonuclease (ExoN) enzyme in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From previously identified DEDDh/DEEDh subfamily nuclease inhibitors, our results revealed strong binding of pontacyl violet 6R (PV6R) at the catalytic active site of ExoN. The binding was found to be stabilized via two hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations further confirmed the stability of PV6R at the active site showing a shift in ligand to reach a more stabilized binding. Using PV6R as the lead molecule, we employed virtual screening to identify potential molecular candidates that form strong interactions at the ExoN active site. Our study paves ways for evaluating the ExoN as a novel drug target for antiviral treatment against SARS-CoV-2.

New coronavirus-infected pneumonia engulfs Wuhan

A review on new coronavirus-infected pneumonia in Wuhan, China.

Psychological distress and sleep quality of COVID-19 patients in Wuhan, a lockdown city as the epicenter of COVID-19.

The major Corona Virus Disease 2019 (COVID-19) outbreak caused tens of thousands of diagnosed patients quarantined and treated in designated hospitals in Wuhan, the epicenter of the disease in China. Evidence for the psychological problems of COVID-19 patients was limited. Here we report a cross-sectional study of the mental distress and sleep quality of patients in a single center in Wuhan. The study was based on a combined questionnaire of basic questions designed by the study group, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Pittsburgh Sleep Quality Index (PSQI). On Feb 17th and Mar 14th, two groups of patients were recruited respectively in a designated hospital for COVID-19. Univariate analysis and regression models were used to identify predictors for patients' psychological distress and sleep quality. In total, there were 202 participants in our combined sample. The average SAS, SDS, and PSQI score of participants were 44.2, 51.7, and 9.3 respectively. Factors associated with SAS score include gender, subjective evaluation of disease symptoms, and evaluation of medical staffs' attitude. Gender, age, education level, frequency of contacting with family, subjective knowledge level of COVID 19, and evaluation of medical staffs' attitude are associated with participants SDS score. Factors associated with PSQI score are age and subjective evaluation of disease symptoms.

Evaluation of current medical approaches for COVID-19: a systematic review and meta-analysis.

BACKGROUND: Because of the lack of vaccination, it is urgent to find effective antiviral agents for COVID-19 treatment. METHOD: Online databases were searched for articles published before or on 22 June 2020. Studies reporting the effectiveness and safety of antiviral agents for COVID-19 were analysed. RESULTS: A total of 42 studies were included in this analysis. Hydroxychloroquine (HCQ) was not associated with the incidence of death (risk ratio (RR)=1.08; 95% CI 0.81 to 1.44) and severe cases (RR=1.05; 95% CI 0.61 to 1.81). Patients treated with HCQ obtained few benefits with respect to the clearance of viral RNA and were more likely to have adverse reactions. HCQ treatment could shorten the body temperature recovery time (weighted mean difference = -1.04; 95% CI -1.64 to -0.45). Lopinavir/ritonavir (LPV/r) (RR=0.90; 95% CI 0.76 to 1.07) and Arbidol (RR=1.09; 95% CI 0.92 to 1.29) were not associated with the negative conversion rate. Integrative Chinese-Western medicine alleviated clinical symptoms and decreased the incidence of severe cases (RR=0.38; 95% CI 0.25 to 0.59). Remdesivir treatment reduced the 14-day mortality rate of patients with severe COVID-19 (RR=0.64; 95% CI 0.44 to 0.94). Convalescent plasma (CP) tended to increase the negative conversion rate (RR=2.47; 95% CI 1.70 to 3.57). CONCLUSION: HCQ, LPV/r and Arbidol bring little benefit in COVID-19 treatment. Integrative Chinese-Western medicine improved the clinical symptoms of patients with COVID-19. Remdesivir and CP might be the potential treatments for patients with severe COVID-19. However, large-scale clinical randomised trials are needed to validate our conclusions.

Clinical features and outcomes of seven patients with COVID-19 in a family cluster.

BACKGROUND: The family cluster is one of most important modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission throughout China, and more details are needed about how family clusters cause the spread of coronavirus disease 2019 (COVID-19). CASE PRESENTATION: We retrospectively reviewed 7 confirmed cases from one family cluster. Both clinical features and laboratory examination results were described. Patient 1 had been in close contact with someone who was later confirmed to have COVID-19 in Wuhan City before he returned back to his hometown. He had dinner with 6 other members in his family. All the persons developed COVID-19 successively except for one older woman who neither had dinner with them nor shared a sleeping room with her husband. Six patients had mild or moderate COVID-19 but one older man with underlying diseases progressed into the severe type. After general and symptomatic treatments, all the patients recovered. CONCLUSIONS: In a family cluster, having dinner together may be an important mode for the transmission of SARS-CoV-2. In this setting, most cases are mild with a favorable prognosis, while elderly patients with underlying diseases may progress into the severe type. For someone who has close contact with a confirmed case, 14-day isolation is necessary to contain virus transmission.

Multistage CT features of coronavirus disease 2019. / 2019å† çŠ¶ç— æ¯’ç— å¤šé˜¶æ®µCT影像学特征.

OBJECTIVES: To determine imaging features of coronavirus disease 2019 (COVID-19) in different stages, and to provide foundations for early diagnosis and treatment. METHODS: CT image data of 187 COVID-19 patients were analyzed in the period of hospitalization. CT scanning was performed on admission and repeated every 3 days. The improvement time of clinical symptoms and the image changes of follow-up CT were statistically analyzed. RESULTS: All 187 patients' nucleic acid test were positive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The early CT images of lung in 187 cases (100%) showed multiple patchy and ground-glass opacities with fine mesh and consolidation shade, which mainly distributed in pulmonary band or under the pleura. In the progressive stage, the pulmonary lesions in 146 cases (78.1%) were mainly consolidation, accompanied by air bronchogram, thickening of blood vessels, and interstitial changes. Severe pulmonary CT images in 15 cases (8%) showed diffuse lesions in both lungs, displaying consolidation, or "white lung". The CT imaging features in 185 cases (98.9%) at the absorptive period showed that the lesions diminished and fibrogenesis. The imaging features of 6 times of lung CT examination in one case showed continuous progress. The original lesion in one case was obviously absorbed, but new lesions appeared under the pleura of both lungs at the third review of CT scanning. The changes of CT imaging lesions during follow-up were significantly different in different clinical symptoms improvement time (P< 0.01). CONCLUSIONS: Images of COVID-19 in various stages have special characteristics. The change of clinical symptoms is synchronous with the change of reexamination CT. Follow-up CT can reflect the trend of clinical changes. Repeat CT examination plays an important role in the early clinical diagnosis and the evaluation for the therapeutic effect on COVID-19 patient.

Classroom Study of Online Education Experiment in China under Epidemic Control Situation

In year 2020, in response to unexpected Coronavirus, the Chinese Ministry of Education put forward the requirements of ＂classes suspended but teaching won't stop, classes suspended but learning won't stop＂. The ＂Learning Revolution＂ in education has been furtherpromoted. With the strong support and cooperation of the government, radio and television stations, network companies and parents, 200 million students in China achieved home-based classes.