Effect of E-beam irradiation on the qualitative attributes of shrimp (Penaeus vannamei)

As a non-thermal food processing technology, Electron beam (E-beam) irradiation has been used to enhance microbial safety by deactivating unwanted spoilage and pathogenic microorganisms in food industry. This study evaluated the effects of E-beam irradiation at doses killing SARS-COV-2 on qualities and sensory attributes. The results showed that irradiation caused little effect on the proximate composition, amino acid content, texture, and sensory attributes (P > 0.05). However, E-beam increased TBARS (Thiobarbituric acid reactive substances) and lowered vitamin E content in dose-dependently. Irradiation up to 10 kGy significantly decreased unsaturated fatty acid (UFA) content and inhibited the increase in TVB-N (The total volatile basic nitrogen) while reducing cohesiveness and chewiness (P < 0.05). E-beam irradiation with 7–10 kGy caused greater ΔE values (ΔE > 5) via the significant increase of b*, accompanied by big visual difference in shrimp (P < 0.05). A dose of 4 kGy E-beam irradiation was recommended without altering its physicochemical properties and sensory attributes.

Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients.

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.

Effects of E-beam irradiation on the physicochemical properties of Atlantic cod (Gadus morhua).

Electron beam (E-beam) irradiation can effectively inactivate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cold-chain seafood. This study evaluated the effects of E-beam irradiation at doses killing SARS-CoV-2 on quality indicators of Atlantic cod. The cod samples were exposed to 0, 2, 4, 7, and 10 kGy E-beam irradiation, and nutrition, texture, color, and sensory attributes were investigated. The results showed that E-beam irradiation significantly increased thiobarbituric acid (TBA) value and decreased hardness, chewiness, and a* value of Atlantic cod (P < 0.05). E-beam irradiation with 10 kGy significantly lowered total volatile base nitrogen (TVB-N) and reducing sugar content while increasing moisture and ash content (P < 0.05). A significant color change was observed after irradiation with 2 kGy-7 kGy E-beam (P < 0.05). E-beam irradiation had no effects on sensory attributes (P > 0.05). A dose of 4 kGy was recommended considering the keeping quality in Atlantic cod.

Fast and sensitive detection of SARS-CoV-2 RNA using suboptimal protospacer adjacent motifs for Cas12a.

CRISPR-based assays for the detection of nucleic acids are highly specific, yet they are not fast, sensitive or easy to use. Here we report a one-step fluorescence assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal samples, with a sample-to-answer time of less than 20 minutes and a sensitivity comparable to that of quantitative real-time PCR with reverse transcription (RT-qPCR). The assay uses suboptimal protospacer adjacent motifs, allowing for flexibility in the design of CRISPR RNAs and slowing down the kinetics of Cas12a-mediated collateral cleavage of fluorescent DNA reporters and cis cleavage of substrates, which leads to stronger fluorescence owing to the accumulation of amplicons generated by isothermal recombinase polymerase amplification. In a set of 204 nasopharyngeal samples with RT-qPCR cycle thresholds ranging from 18.1 to 35.8, the assay detected SARS-CoV-2 with a sensitivity of 94.2% and a specificity of 100%, without the need for RNA extraction. Rapid and sensitive assays for nucleic acid testing in one pot that allow for flexibility in assay design may aid the development of reliable point-of-care nucleic acid testing.

Impact of COVID-19 on electricity energy consumption: A quantitative analysis on electricity

In addition to the tremendous loss of life due to coronavirus disease 2019 (COVID-19), the pandemic created challenges for the energy system, as strict confinement measures such as lockdown and social distancing compelled by governments worldwide resulted in a significant reduction in energy demand. In this study, a novel, quantitative and uncomplex method for estimating the energy consumption loss due to the pandemic, which was derived from epidemiological data in the beginning stages, is provided;the method bonds a data-driven prediction (LSTM network) of energy consumption due to COVID-19 to an econometric model (ARDL) so that the long- and short-term impact can be synthesized with adequate statistical validation. The results show that energy loss is statistically correlated with the time-changing effective reproductive number (Rt) of the disease, which can be viewed as quantifying confinement intensity and the severity of the earlier stages of the pandemic. We detected a 1.62% decrease in electricity consumption loss caused by each percent decrease in Rt on average. We verify our method by applying it to Germany and 5 U.S. states with various social features and discuss implications and universality. Our results bridge the knowledge gap between key energy and epidemiological parameters and provide policymakers with a more precise estimate of the pandemic’s impact on electricity demand so that strategies can be formulated to minimize losses caused by similar crises.

Reliability and validity of the Pittsburgh Sleep Quality Index among frontline COVID-19 health care workers using classical test theory and item response theory.

STUDY OBJECTIVES: The applicability of sleep-related scales to frontline medical staff for the COVID-19 pandemic has not been fully proved, so sleep survey results lack credibility and accuracy, creating difficulties for the guidance and treatment of frontline medical staff with sleep disorders, which is not conducive to the prevention and control of COVID-19. This study sought to analyze the reliability and validity of the Pittsburgh Sleep Quality Index (PSQI) among frontline medical staff fighting the COVID-19 pandemic. METHODS: A network questionnaire survey was used to investigate the PSQI among frontline medical staff who fought COVID-19 in Wuhan, China from March 19 to April 15, 2020. Combined with classical test theory and item response theory, the content validity, internal consistency, construct validity, and other aspects of the PSQI were evaluated. RESULTS: According to classical test theory, content validity, criterion validity, and construct validity of the PSQI were good. But the internal consistency was better after the deletion of the "daytime dysfunction" subscale. With regard to item response theory, difficulty, the differential item function, and the Wright map performed well. CONCLUSIONS: The original PSQI showed acceptable applicability in frontline COVID-19 medical staff, and its characteristics moderately improved after the "daytime dysfunction" subscale was removed. CITATION: Wang L, Wu Y-X, Lin Y-Q, et al. Reliability and validity of the Pittsburgh Sleep Quality Index among frontline COVID-19 health care workers using classical test theory and item response theory. J Clin Sleep Med. 2022;18(2):541-551.

SARS-CoV-2 Membrane Glycoprotein M Triggers Apoptosis With the Assistance of Nucleocapsid Protein N in Cells.

The pandemic of COVID-19 by SARS-CoV-2 has become a global disaster. However, we still don't know how specific SARS-CoV-2-encoded proteins contribute to viral pathogenicity. We found that SARS-CoV-2-encoded membrane glycoprotein M could induce caspase-dependent apoptosis via interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our investigation further revealed that SARS-CoV-2-encoded nucleocapsid protein N could specifically enhance the M-induced apoptosis via interacting with both M and PDK1, therefore strengthening M-mediated attenuation of PDK1-PKB/Akt interaction. Furthermore, when the M-N interaction was disrupted via certain rationally designed peptides, the PDK1-PKB/Akt signaling was restored, and the boosting activity of N on the M-triggered apoptosis was abolished. Overall, our findings uncovered a novel mechanism by which SARS-CoV-2-encoded M triggers apoptosis with the assistance of N, which expands our understanding of the two key proteins of SARS-CoV-2 and sheds light on the pathogenicity of this life-threatening virus.

Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19.

Rationale: Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. Methods: We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were performed to identify molecules specifically altered in COVID-19-children. We also developed a machine learning-based pipeline named inference of biomolecular combinations with minimal bias (iBM) to prioritize proteins and metabolites strongly altered in COVID-19-children, and experimentally validated the predictions. Results: By comparing to the multi-omic data in adults, we identified 44 proteins and 249 metabolites differentially altered in COVID-19-children against healthy children or COVID-19-adults. Further analyses demonstrated that both deteriorative immune response/inflammation processes and protective antioxidant or anti-inflammatory processes were markedly induced in COVID-19-children. Using iBM, we prioritized two combinations that contained 5 proteins and 5 metabolites, respectively, each exhibiting a total area under curve (AUC) value of 100% to accurately distinguish COVID-19-children from healthy children or COVID-19-adults. Further experiments validated that all the 5 proteins were up-regulated upon coronavirus infection. Interestingly, we found that the prioritized metabolites inhibited the expression of pro-inflammatory factors, and two of them, methylmalonic acid (MMA) and mannitol, also suppressed coronaviral replication, implying a protective role of these metabolites in COVID-19-children. Conclusion: The finding of a strong antagonism of deteriorative and protective effects provided new insights on the mechanism and pathogenesis of COVID-19 in children that mostly underwent mild symptoms. The identified metabolites strongly altered in COVID-19-children could serve as potential therapeutic agents of COVID-19.

Risk factors for the mortality of hemodialysis patients with COVID-19: A multicenter study from the overall hemodialysis population in Wuhan.

INTRODUCTION: Maintenance hemodialysis (MHD) patients are highly threatened in the novel coronavirus disease 2019 (COVID-19) pandemic, but evidence of risk factors for mortality in this population is still lacking. METHODS: We followed outcomes of the overall MHD population of Wuhan, including 7154 MHD patients from 65 hemodialysis centers, from January 1 to May 4, 2020. Among them, 130 were diagnosed with COVID-19. The demographic and clinical data of them were collected and compared between survivors and nonsurvivors. RESULTS: Compared to the corresponding period of last year, the all-cause mortality rate of the Wuhan MHD population significantly rose in February, and dropped down in March 2020. Of the 130 COVID-19 cases, 51 (39.2%) were deceased. Advanced age, decreased oxygen saturation, low diastolic blood pressure (DBP) on admission, and complications including acute cardiac injury (HR 5.03 [95% CI 2.21-11.14], p < 0.001), cerebrovascular event (HR 2.80 [95% CI 1.14-6.86], p = 0.025) and acute respiratory distress syndrome (HR 3.50 [95% CI 1.63-7.51], p = 0.001) were identified as independent risk factors for the death of COVID-19. The median virus shedding period of survivors was 25 days, longer than the general population. CONCLUSIONS: Maintenance hemodialysis patients are a highly vulnerable population at increased risk of mortality and prolonged virus shedding period in the ongoing COVID-19 pandemic. Advanced age, decreased oxygen saturation, low DBP on admission, and complications like acute cardiac injury are parameters independently associated with poor prognosis.

Semen quality and windows of susceptibility: A case study during COVID-19 outbreak in China.

BACKGROUND: To evaluate the impact of air pollution exposure on semen quality parameters during COVID-19 outbreak in China, and to identify potential windows of susceptibility for semen quality. METHODS: A retrospective observational study was carried out on 1991 semen samples collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) from 781 sperm donor candidates at University-affiliated Sichuan Provincial Human Sperm Bank. Multivariate mixed-effects regression models were constructed to investigate the relationship between pollution exposure, windows of susceptibility, and semen quality, while controlling for biographic and meteorologic confounders. RESULT(S): The results indicated multiple windows of susceptibility for semen quality, especially sperm motility, due to ambient pollution exposure. Exposure to particulate matters (PM2.5 and PM10), O3 and NO2 during late stages of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO2 appeared to influence semen quality throughout spermatogenesis. CONCLUSION(S): Potential windows of susceptibility for semen quality varied depending on air pollutants. Sperm motility was sensitive to pollution exposure. Findings from current study further elucidate the importance of sensitive periods during spermatogenesis and provide new evidence for the determinants of male fertility.

Plasma metabolomic and lipidomic alterations associated with COVID-19.

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.

SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO.

Coronavirus disease 2019 (COVID-19) is a current global health threat caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that SARS-CoV-2 elicits a dysregulated immune response and a delayed interferon (IFN) expression in patients, which contribute largely to the viral pathogenesis and development of COVID-19. However, underlying mechanisms remain to be elucidated. Here, we report the activation and repression of the innate immune response by SARS-CoV-2. We show that SARS-CoV-2 RNA activates the RIG-I-MAVS-dependent IFN signaling pathway. We further uncover that ORF9b immediately accumulates and antagonizes the antiviral type I IFN response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells. ORF9b targets the nuclear factor κB (NF-κB) essential modulator NEMO and interrupts its K63-linked polyubiquitination upon viral stimulation, thereby inhibiting the canonical IκB kinase alpha (IKKα)/ß/γ-NF-κB signaling and subsequent IFN production. Our findings thus unveil the innate immunosuppression by ORF9b and provide insights into the host-virus interplay during the early stage of SARS-CoV-2 infection.

Reduced Sleep Duration and Sleep Efficiency Were Independently Associated With Frequent Nightmares in Chinese Frontline Medical Workers During the Coronavirus Disease 2019 Outbreak.

OBJECTIVES: Nightmares were related to emotion and behavioral problems and also emerged as one of the core features of post-traumatic stress disorder (PTSD). Our study aimed to investigate the associations of frequent nightmares with sleep duration and sleep efficiency among frontline medical workers in Wuhan during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: A total of 528 health-care workers from the province of Fujian providing medical aid in Wuhan completed the online questionnaires. There were 114 doctors and 414 nurses. The age, sex, marital status, and work situation were recorded. A battery of scales including the Pittsburgh Sleep Quality Index (PSQI) and the 12-item General Health Questionnaire (GHQ-12) were used to evaluate subjects' sleep and general mental health. Frequent nightmares were defined as the response of at least once a week in the item of "nightmare" of PSQI. RESULTS: Frequent nightmares were found in 27.3% of subjects. The frequent nightmare group had a higher score of PSQI-sleep duration and PSQI-habitual sleep efficiency (frequent nightmares vs. non-frequent nightmares: PSQI-sleep duration, 1.08 ± 0.97 vs. 0.74 ± 0.85, P < 0.001; PSQI-habitual sleep efficiency, 1.08 ± 1.10 vs. 0.62 ± 0.88, P < 0.001). Reduced sleep duration and reduced sleep efficiency were independently associated with frequent nightmares after adjustment for age, sex, poor mental health, and regular sleeping medication use (reduced sleep duration: OR = 1.96, 95% CI = 1.07-3.58, P = 0.029; reduced sleep efficiency: OR = 2.17, 95% CI = 1.09-4.32, P = 0.027). Subjects with both reduced sleep duration and sleep efficiency were also associated with frequent nightmares (OR = 2.70, 95% CI = 1.57-4.65, P < 0.001). CONCLUSION: The present study found that sleep duration and sleep efficiency were both independently associated with frequent nightmares among frontline medical workers in Wuhan during the COVID-19 pandemic. We should pay attention to nightmares and even the ensuing PTSD symptoms among subjects with reduced sleep duration or sleep efficiency facing potential traumatic exposure.

Effective virus-neutralizing activities in antisera from the first wave of survivors of severe COVID-19.

The coronavirus disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst public health crisis in a century. However, knowledge about the dynamics of antibody responses in patients with COVID-19 is still poorly understood. In this study, we performed a serological study with serum specimens collected at the acute and the convalescent phases from 104 patients with severe COVID-19 who were part of the first wave of COVID-19 cases in Wuhan, China. Our findings revealed that neutralizing antibodies to SARS-CoV-2 are persistent for at least 6 months in patients with severe COVID-19, despite that IgG levels against the receptor binding domain (RBD) and nucleocapsid protein (N) IgG declined from the acute to the convalescent phase. Moreover, we demonstrate that the level of RBD-IgG is capable of correlating with SARS-CoV-2-neutralizing activities in COVID-19 serum. In summary, our findings identify the magnitude, functionality, and longevity of antibody responses in patients with COVID-19, which sheds light on the humoral immune response to COVID-19 and would be beneficial for developing vaccines.

Imaging Mass Cytometric Analysis of Postmortem Tissues Reveals Dysregulated Immune Cell and Cytokine Responses in Multiple Organs of COVID-19 Patients.

SARS-coronavirus-2-induced immune dysregulation and inflammatory responses are involved in the pathogenesis of coronavirus disease-2019 (COVID-19). However, very little is known about immune cell and cytokine alterations in specific organs of COVID-19 patients. Here, we evaluated immune cells and cytokines in postmortem tissues, i.e., lungs, intestine, liver, kidneys, and spleen of three patients with COVID-19. Imaging mass cytometry revealed monocyte, macrophage, and dendritic cell (DC) infiltration in the lung, intestine, kidney, and liver tissues. Moreover, in patients with COVID-19, natural killer T cells infiltrated the liver, lungs, and intestine, whereas B cells infiltrated the kidneys, lungs, and intestine. CD11b+ macrophages and CD11c+ DCs also infiltrated the lungs and intestine, a phenomenon that was accompanied by overproduction of the immunosuppressive cytokine interleukin (IL)-10. However, CD11b+ macrophages and CD11c+ DCs in the lungs or intestine of COVID-19 patients did not express human leukocyte antigen DR isotype. In contrast, tumor necrosis factor (TNF)-α expression was higher in the lungs, intestine, liver, and kidneys, but not in the spleen, of all COVID-19 patients (compared to levels in controls). Collectively, these findings suggested that IL-10 and TNF-α as immunosuppressive and pro-inflammatory agents, respectively,-might be prognostic and could serve as therapeutic targets for COVID-19.

SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts.

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. SARS-coronavirus-2 (SARS-CoV-2), the causative pathogen of COVID-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals.