Status of mandatory treatment of mentally ill offenders without criminal responsibility in China: Information from 5,262 mandatory treatment judgments.

Background: To avoid public health risks, all governments ensure monitoring and treatment of mentally ill persons if they offend and assess their level of criminal responsibility. The Criminal Procedure Law of the People's Republic of China (2013) instituted special procedures. However, there are few articles in English which explain the implementation of mandatory treatment procedures in China. Methods: We collected 5,262 qualified documents from 2013 to 2021 from the China Judgments Documents Online. We analyzed social demographic characteristics, trial-related information as well as the mandatory treatment-related content, to investigate the mandatory treatment of China's mentally ill offenders without criminal responsibility, from 2013 to 2021. Simple descriptive statistics and chi-square tests were used to compare differences among several types of documents. Results: There was an overall change trend of the number of documents: increasing year by year from 2013 to 2019 after the implementation of the new law, but with sharp decrease in 2020 and 2021 during covid-19 pandemic. From 2013 to 2021, a total of 3,854 people had applications made for mandatory treatment, of whom 3,747 (97.2%) were given mandatory treatment, 107 (2.8%) had applications rejected. "Schizophrenia and other psychotic disorders" was the most common diagnosis in both groups and all offenders receiving mandatory treatment (3,747, 100.0%) were considered to have no criminal responsibility. A total of 1,294 patients had applications made for relief of mandatory treatment, of whom 827 (63.9%) were subsequently approved for relief, 467 (36.1%) were rejected. A total of 118 patients had applications for relief two or more times, and 56 (47.5%) were finally relieved. Conclusion: Our study presents the Chinese model of a criminal mandatory treatment system to the international community which has been in operation since the implementation of the new law. Legislatory changes and covid-19 pandemic can have effect on the number of mandatory treatment cases. Patients, their close relatives and mandatory treatment institutions have the right to apply for relief from mandatory treatment, but the final decision in China is taken by the court.

Role of OAS gene family in COVID-19 induced heart failure.

BACKGROUND: COVID-19, the current global pandemic caused by SARS-CoV-2 infection, can damage the heart and lead to heart failure (HF) and even cardiac death. The 2',5'-oligoadenylate synthetase (OAS) gene family encode interferon (IFN)-induced antiviral proteins which is associated with the antiviral immune responses of COVID-19. While the potential association of OAS gene family with cardiac injury and failure in COVID-19 has not been determined. METHODS: The expression levels and biological functions of OAS gene family in SARS-CoV-2 infected cardiomyocytes dataset (GSE150392) and HF dataset (GSE120852) were determined by comprehensive bioinformatic analysis and experimental validation. The associated microRNAs (miRNAs) were explored from Targetscan and GSE104150. The potential OAS gene family-regulatory chemicals or ingredients were predicted using Comparative Toxicogenomics Database (CTD) and SymMap database. RESULTS: The OAS genes were highly expressed in both SARS-CoV-2 infected cardiomyocytes and failing hearts. The differentially expressed genes (DEGs) in the two datasets were enriched in both cardiovascular disease and COVID-19 related pathways. The miRNAs-target analysis indicated that 10 miRNAs could increase the expression of OAS genes. A variety of chemicals or ingredients were predicted regulating the expression of OAS gene family especially estradiol. CONCLUSION: OAS gene family is an important mediator of HF in COVID-19 and may serve as a potential therapeutic target for cardiac injury and HF in COVID-19.

RPflex: A Coarse-Grained Network Model for RNA Pocket Flexibility Study.

RNA regulates various biological processes, such as gene regulation, RNA splicing, and intracellular signal transduction. RNA's conformational dynamics play crucial roles in performing its diverse functions. Thus, it is essential to explore the flexibility characteristics of RNA, especially pocket flexibility. Here, we propose a computational approach, RPflex, to analyze pocket flexibility using the coarse-grained network model. We first clustered 3154 pockets into 297 groups by similarity calculation based on the coarse-grained lattice model. Then, we introduced the flexibility score to quantify the flexibility by global pocket features. The results show strong correlations between the flexibility scores and root-mean-square fluctuation (RMSF) values, with Pearson correlation coefficients of 0.60, 0.76, and 0.53 in Testing Sets I-III. Considering both flexibility score and network calculations, the Pearson correlation coefficient was increased to 0.71 in flexible pockets on Testing Set IV. The network calculations reveal that the long-range interaction changes contributed most to flexibility. In addition, the hydrogen bonds in the base-base interactions greatly stabilize the RNA structure, while backbone interactions determine RNA folding. The computational analysis of pocket flexibility could facilitate RNA engineering for biological or medical applications.

Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria.

Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/ß-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/ß immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/ß. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/ß-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/ß-dependent antiviral immunity.

Home monitoring of arterial pulse-wave velocity during COVID-19 total or partial lockdown using connected smart scales.

Aims: To investigate the impact of coronavirus disease 2019 lockdown on trajectories of arterial pulse-wave velocity in a large population of users of connected smart scales that provide reliable measurements of pulse-wave velocity. Methods and results: Pulse-wave velocity recordings obtained by Withings Heart Health & Body Composition Wi-Fi Smart Scale users before and during lockdown were analysed. We compared two demonstrative countries: France, where strict lockdown rules were enforced (n = 26 196) and Germany, where lockdown was partial (n = 26 847). Subgroup analysis was conducted in users of activity trackers and home blood pressure monitors. Linear growth curve modelling and trajectory clustering analyses were performed. During lockdown, a significant reduction in vascular stiffness, weight, blood pressure, and physical activity was observed in the overall population. Pulse-wave velocity reduction was greater in France than in Germany, corresponding to 5.2 month reduction in vascular age. In the French population, three clusters of stiffness trajectories were identified: decreasing (21.1%), stable (60.6%), and increasing pulse-wave velocity clusters (18.2%). Decreasing and increasing clusters both had higher pulse-wave velocity and vascular age before lockdown compared with the stable cluster. Only the decreasing cluster showed a significant weight reduction (-400 g), whereas living alone was associated with increasing pulse-wave velocity cluster. No clusters were identified in the German population. Conclusions: During total lockdown in France, a reduction in pulse-wave velocity in a significant proportion of French users of connected smart bathroom scales occurred. The impact on long-term cardiovascular health remains to be established.

Characteristics of COVID-19 (Delta Variant)/HIV Co-infection: A Cross-sectional Study in Henan Province, China.

Background: Since the end of July 2021, SARS-CoV-2 (Delta variant) invaded Henan Province, China, causing a rapid COVID-19 spread in the province. Among them, the clinical features of COVID-19 (Delta Variant)/HIV co-infection have attracted our attention. Methods: We included 12 COVID-19 patients living with HIV (human immunodeficiency virus) from July 30, 2021 to September 17, 2021 in Henan Province, China. Demographic, clinical, laboratory, and computed tomography (CT) imaging data were dynamically collected from first nucleic acid positive to hospital discharge. Laboratory findings included SARS-CoV-2 viral load, HIV viral load, IgM, IgG, cytokines, lymphocyte subpopulation, ferritin, etc. Statistical analyses were performed using IBM SPSS version 26·0 and GraphPad Prism version 9·0. Results: It was founded that the low Ct value persisted for about 21 days, and the viral shedding time (turn negative time) of the patients was 32·36 ± 2·643 days. Furthermore, chest CT imaging revealed that lesions were obviously and rapidly absorbed. It was surprising that IgM levels were statistically higher in patients taking azvudine or convalescent plasma than in patients not taking these drugs (P < 0·001, P = 0·0002, respectively). IgG levels were significantly higher in patients treated with the combined medication of BRII/196 and BRII/198 than in those not treated with these drugs (P = 0·0029). IgM was significantly higher in those with low HIV viral load than those with high HIV viral load (P < 0·001). In addition, as treatment progressed and patients' condition improved, IL-17a showed a decreasing trend. Conclusions: Based on this study, we found that HIV infection might not exacerbate COVID-19 severity. Supplementary Information: The online version contains supplementary material available at 10.1007/s44231-022-00018-z.

Refinement of SARS-CoV-2 envelope protein structure in a native-like environment by molecular dynamics simulations

COVID-19 has become an unprecedented threat to human health. The SARS-CoV-2 envelope (E) protein plays a critical role in the viral maturation process and pathogenesis. Despite intensive investigation, its structure in physiological conditions remains mysterious: no high-resolution full-length structure is available and only an NMR structure of the transmembrane (TM) region has been determined. Here, we present a refined E protein structure, using molecular dynamics (MD) simulations to investigate its structure and dynamics in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer system. Our initial homology model based upon the SARS-CoV E protein structure is shown to be unstable in the lipid bilayer, and the H3 helices tend to move away from the membrane center to the membrane-water interface. A more stable model was developed by replacing all H3 helices with the fully equilibrated H3 structure sampled in the MD simulations. This refined model exhibited more favorable contacts with lipids and water than the original homology model and induced local membrane curvature, decreasing local lipid order. Interestingly, the pore radius profiles showed that the channel in both homology and refined models remained in a closed state throughout the simulations. We also demonstrated the utility of this structure to develop anti-SARS-CoV-2 drugs by docking a library of FDA-approved, investigational, and experimental drugs to the refined E protein structure, identifying 20 potential channel blockers. This highlights the power of MD simulations to refine low-resolution structures of membrane proteins in a native-like membrane environment, shedding light on the structural features of the E protein and providing a platform for the development of novel antiviral treatments.

Home monitoring of arterial pulse-wave velocity during COVID-19 total or partial lockdown using connected smart scales

Aims To investigate the impact of coronavirus disease 2019 lockdown on trajectories of arterial pulse-wave velocity in a large population of users of connected smart scales that provide reliable measurements of pulse-wave velocity. Methods and results Pulse-wave velocity recordings obtained by Withings Heart Health & Body Composition Wi-Fi Smart Scale users before and during lockdown were analysed. We compared two demonstrative countries: France, where strict lockdown rules were enforced (n = 26 196) and Germany, where lockdown was partial (n = 26 847). Subgroup analysis was conducted in users of activity trackers and home blood pressure monitors. Linear growth curve modelling and trajectory clustering analyses were performed. During lockdown, a significant reduction in vascular stiffness, weight, blood pressure, and physical activity was observed in the overall population. Pulse-wave velocity reduction was greater in France than in Germany, corresponding to 5.2 month reduction in vascular age. In the French population, three clusters of stiffness trajectories were identified: decreasing (21.1%), stable (60.6%), and increasing pulse-wave velocity clusters (18.2%). Decreasing and increasing clusters both had higher pulse-wave velocity and vascular age before lockdown compared with the stable cluster. Only the decreasing cluster showed a significant weight reduction (−400 g), whereas living alone was associated with increasing pulse-wave velocity cluster. No clusters were identified in the German population. Conclusions During total lockdown in France, a reduction in pulse-wave velocity in a significant proportion of French users of connected smart bathroom scales occurred. The impact on long-term cardiovascular health remains to be established. Lay Summary Pulse-wave velocity (PWV) measurements from users of connected smart bathroom scales showed that during the first COVID-19 imposed lockdown in France and Germany, arterial stiffness decreased, with greater improvement in France, where three distinct patterns of PWV progression could be identified. Graphical Graphical During COVID19 total lockdown in 2020 in France, a significant reduction in vascular stiffness, recorded by home smart scales, was observed.

RPpocket: An RNA-Protein Intuitive Database with RNA Pocket Topology Resources.

RNA-protein complexes regulate a variety of biological functions. Thus, it is essential to explore and visualize RNA-protein structural interaction features, especially pocket interactions. In this work, we develop an easy-to-use bioinformatics resource: RPpocket. This database provides RNA-protein complex interactions based on sequence, secondary structure, and pocket topology analysis. We extracted 793 pockets from 74 non-redundant RNA-protein structures. Then, we calculated the binding- and non-binding pocket topological properties and analyzed the binding mechanism of the RNA-protein complex. The results showed that the binding pockets were more extended than the non-binding pockets. We also found that long-range forces were the main interaction for RNA-protein recognition, while short-range forces strengthened and optimized the binding. RPpocket could facilitate RNA-protein engineering for biological or medical applications.

SARS-CoV-2 productively infects human brain microvascular endothelial cells.

BACKGROUND: The emergence of the novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health emergency. SARS-CoV-2 is highly contagious and has a high mortality rate in severe patients. However, there is very limited information on the effect of SARS-CoV-2 infection on the integrity of the blood-brain barrier (BBB). METHODS: RNA-sequencing profiling was performed to analyze the transcriptomic changes in human brain microvascular endothelial cells (hBMECs) after SARS-CoV-2 infection. Bioinformatic tools were used for differential analysis. Immunofluorescence, real-time quantitative PCR, and Western blotting analysis were used to explore biological phenotypes. RESULTS: A total of 927 differentially expressed genes were identified, 610 of which were significantly upregulated while the remaining 317 were downregulated. We verified the significant induction of cytokines, chemokines, and adhesion molecules in hBMECs by SARS-CoV-2, suggesting an activation of the vascular endothelium in brain. Moreover, we demonstrated that SARS-CoV-2 infection could increase the BBB permeability, by downregulating as well as remodeling the intercellular tight junction proteins. CONCLUSIONS: Our findings demonstrated that SARS-CoV-2 infection can cause BBB dysfunction, providing novel insights into the understanding of SARS-CoV-2 neuropathogenesis. Moreover, this finding shall constitute a new approach for future prevention and treatment of SARS-CoV-2-induced CNS infection.

Pronounced temporal changes in soil microbial community and nitrogen transformation caused by benzalkonium chloride.

As one typical cationic disinfectant, quaternary ammonium compounds (QACs) were approved for surface disinfection in the coronavirus disease 2019 pandemic and then unintentionally or intentionally released into the surrounding environment. Concerningly, it is still unclear how the soil microbial community succession happens and the nitrogen (N) cycling processes alter when exposed to QACs. In this study, one common QAC (benzalkonium chloride (BAC) was selected as the target contaminant, and its effects on the temporal changes in soil microbial community structure and nitrogen transformation processes were determined by qPCR and 16S rRNA sequencing-based methods. The results showed that the aerobic microbial degradation of BAC in the two different soils followed first-order kinetics with a half-life (4.92 vs. 17.33 days) highly dependent on the properties of the soil. BAC activated the abundance of N fixation gene (nifH) and nitrification genes (AOA and AOB) in the soil and inhibited that of denitrification gene (narG). BAC exposure resulted in the decrease of the alpha diversity of soil microbial community and the enrichment of Crenarchaeota and Proteobacteria. This study demonstrates that BAC degradation is accompanied by changes in soil microbial community structure and N transformation capacity.

AT1 Receptors: Their Actions from Hypertension to Cognitive Impairment.

Hypertension is one of the most prevalent cardiovascular disorders worldwide, affecting 1.13 billion people, or 14% of the global population. Hypertension is the single biggest risk factor for cerebrovascular dysfunction. According to the American Heart Association, high blood pressure (BP), especially in middle-aged individuals (~ 40 to 60 years old), is associated with an increased risk of dementia, later in life. Alzheimer's disease and cerebrovascular disease are the two leading causes of dementia, accounting for around 80% of the total cases and usually combining mixed pathologies from both. Little is known regarding how hypertension affects cognitive function, so the impact of its treatment on cognitive impairment has been difficult to assess. The brain renin-angiotensin system (RAS) is essential for BP regulation and overactivity of this system has been established to precede the development and maintenance of hypertension. Angiotensin II (Ang-II), the main peptide within this system, induces vasoconstriction and impairs neuro-vascular coupling by acting on brain Ang-II type 1 receptors (AT1R). In this review, we systemically analyzed the association between RAS and biological mechanisms of cognitive impairment, from the perspective of AT1R located in the central nervous system. Additionally, the possible contribution of brain AT1R to global cognition decline in COVID-19 cases will be discussed as well.

The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-ß are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

Percutaneous Screw Stabilization of Non-Periacetabular Pelvic Lesions Caused by Metastatic Cancer and Multiple Myeloma.

BACKGROUND: The pelvis is one of the most common locations for metastatic bone disease. While many of the publications that describe surgical treatments focus on periacetabular lesions (Enneking zone II), there is a lack of investigation into lesions in the non-periacetabular areas (zones I, III, and IV). We recently described a minimally invasive percutaneous screw application for metastatic zone-II lesions with excellent results. In the present study, we aimed to extend this approach to the other pelvic areas. METHODS: Twenty-two consecutive patients with painful non-periacetabular pelvic metastatic cancer were included based on retrospective chart review. There were 16 women and 6 men with an average age of 60 years (range, 36 to 81 years). The most common primary cancers were multiple myeloma (7 cases) and breast (5 cases). The most common locations were the sacrum and the ilium. A pathologic fracture was identified in 15 patients. Most of the lesions were treated with multiple large-diameter screws, except for the isolated zone-III lesions. All of the procedures were completed in a standard operating room without the need for special instruments. Radiation therapy was given to 19 patients; the average dose was 15 Gy. The studied outcomes were pain and functionality as assessed by a visual analog scale (VAS) score and the Eastern Cooperative Oncology Group score (ECOG), respectively. RESULTS: There were no surgical complications and no need for blood transfusion. The average follow-up time was 7 months (range, 0.3 to 34.0 months). Two patients died within 4 weeks of surgery due to COVID-19 infection. There was significant improvement in the postoperative VAS pain score (p < 0.0001) and the ECOG score (p < 0.05) when compared with the preoperative scores. There was no implant failure or revision surgery. Local bone-healing was observed in 12 of 14 patients (86%) who survived for >3 months after surgery. CONCLUSIONS: Percutaneous screw application is safe and effective in the treatment of metastatic non-periacetabular pelvic lesions. Given the simplicity of the technique and the instrumentation and the tolerance for concomitant treatments, this approach is worthy of broader consideration. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Probing the formation, structure and free energy relationships of M protein dimers of SARS-CoV-2.

The M protein of the novel coronavirus 2019 (SARS-CoV-2) is the major structural component of the viral envelope and is also the minimum requirement for virus particle budding. M proteins generally exist as dimers. In virus assembly, they are the main driving force for envelope formation through lateral interactions and interactions with other viral structural proteins that play a central role. We built 100 candidate models and finally analyzed the six most convincing structural features of the SARS-CoV-2 M protein dimer based on long-timescale molecular dynamics (MD) simulations, multiple free energy analyses (potential mean force (PMF) and molecular mechanics Poisson-Boltzmann surface area (MMPBSA)) and principal component analysis (PCA) to obtain the most reasonable structure. The dimer stability was found to depend on the Leu-Ile zipper motif and aromatic amino acids in the transmembrane domain (TMD). Furthermore, the C-terminal domain (CTD) effects were relatively small. These results highlight a model in which there is sufficient binding affinity between the TMDs of M proteins to form dimers through the residues at the interface of the three transmembrane helices (TMHs). This study aims to help find more effective inhibitors of SARS-CoV-2 M dimers and to develop vaccines based on structural information.

Do increased flow rates in displacement ventilation always lead to better results?

Indoor ventilation is essential for a healthy and comfortable living environment. A key issue is to discharge anthropogenic air contamination such as CO\(_2\) gas or, of potentially more direct consequence, airborne respiratory droplets. Here, by employing direct numerical simulations, we study mechanical displacement ventilation with a wide range of ventilation rates \(Q\) from 0.01 to 0.1 m\(

Automatic label-free immunoassay with high sensitivity for rapid detection of SARS-CoV-2 nucleocapsid protein based on chemiluminescent magnetic beads.

Accurate and efficient early diagnosis is crucial for the control of COVID-19 pandemic. However, methods that can balance sensitivity, high throughput, detection speed and automation simultaneously are still scarce. Here, we report an automatic label-free chemiluminescence immunoassay (CLIA) for rapid SARS-CoV-2 nucleocapsid protein (NP) detection with high sensitivity and throughput. N-(4-aminobutyl)-N-ethylisoluminol and Co2+ dual-functionalized chemiluminescent magnetic beads (dfCL-MB) were first applied to the detection of protein by a novel and simple strategy. Sulphydryl polyethylene glycol was coated on the surface of dfCL-MB so as to assemble dfCL-MB and antibody conjugated gold nanoparticles through Au-S bond. Considering the high-risk application scenarios, the immunosensor was integrated with an automatic chemiluminescence analyzer so that the whole testing procedure could be carried out automatically without manual operation. A linear correlation between CL intensities and the logarithm of NP concentration was obtained in the range of 0.1-10,000 pg/mL with a detection limit of 21 fg/mL. The whole process cost 25 min and the sample compartment can bear 24 samples simultaneously. The spiked human serum samples and serum samples from COVID-19 patients were determined with satisfactory recoveries of 91.1-109.4%, suggesting that the proposed label-free CLIA is of great potential for SARS-CoV-2 NP detection in practice.

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-ß. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-ß do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

Depression, Anxiety, and Suicidal Ideation in Chinese University Students During the COVID-19 Pandemic.

Coronavirus disease-2019 (COVID-19) pandemic has seriously threatened the global public health security and caused a series of mental health problem. Current research focuses mainly on mental health status and related factors in the COVID-19 pandemic among Chinese university students. Data from 11133 participants was obtained through an online survey. The Patient Health Question-9 (PHQ-9) was used to assess depressive symptoms, the Social Support Rate Scale (SSRS) was used to assess social support. We also used 7-item Generalized Anxiety Disorder Scale (GAD-7) to assess anxiety symptoms. Totally, 37.0% of the subjects were experiencing depressive symptoms, 24.9% anxiety symptoms, 20.9% comorbid depressive and anxiety symptoms, and 7.3% suicidal ideation. Multivariable logistic regression analysis revealed an increased presence of mental health problems in female students, graduate students, and those with personal COVID-19 exposure. Awareness of COVID-19, living with family were protective factors that reduced anxiety and depression symptoms. In addition, male, personal COVID-19 exposure, depressive and anxiety symptoms were risk factors for suicidal ideation. Social support, COVID-19 preventive and control measures, prediction of COVID-19 trends, living with family and graduate students are protective factors for reducing suicidal ideation.

A one-step, one-pot CRISPR nucleic acid detection platform (CRISPR-top): Application for the diagnosis of COVID-19.

The existing CRISPR-mediated diagnostic tests require a two-step procedure (DNA or RNA amplification followed by CRISPR-mediated sequence-specific detection) for nucleic acid detection, which increases complexity and the risk of sample cross-contamination. Here, we report a new CRISPR-mediated test, called CRISPR-top (CRISPR-mediated testing in one-pot), which integrates simultaneous target pre-amplification with CRISPR/cas12b-mediated detection into a one-pot reaction mixture, performed at a constant temperature. The novel CRISPR-top assay was applied to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19 (coronavirus disease 2019). COVID-19 CRISPR-top targets the ORF1ab (opening reading frame 1a/b) and NP (nucleoprotein) genes of SARS-CoV-2, and operates at 59 °C for 40 min with minimal instrument. The COVID-19 CRISPR-top assay can return results within 60-min and is easily interpreted by visual fluorescence or lateral flow readouts. The analytical limit of detection (LoD) for COVID-19 CRISPR-top is 10 copies (for each detection target) per reaction with no cross-reactivity observed from non-SARS-CoV-2 templates. Among clinically collected non-COVID-19 samples, the assay's specificity was 100% (80/80 oropharynx swab samples). Among 52 COVID-19 positive clinical samples collected, the COVID-19 CRISPR-top assay yielded 38 (73.1%) positive results using fluorescence readout and 35 (67.3%) positive results with lateral-flow readout. These diagnostic results were similar to those obtained using RT-PCR (34 positive (65.4%)). These data indicate that COVID-19 CRISPR-top is a simple, rapid, accurate and highly sensitive method for SARS-CoV-2 detection which can be used in the clinic, field laboratories and primary care facilities in resource-challenged settings.