Symptom relationships between internet addiction and anxiety across primary and middle school students during the Omicron lockdown.

During the Omicron pandemic, students in Shenzhen took classes at home via the internet, which could lead to internet addiction (IA) symptoms, and anxiety is often considered an important risk factor for IA. There are several different developmental stages within adolescence. However, no studies have explored the interaction between IA and anxiety at the symptom level using a longitudinal design stratified by age. A total of 2744 students completed the questionnaire 50 days after starting the online classes (T1) and 50 days after they returned to school (T2). A cross-lagged panel network model was used to describe the structure of the comorbidity network. With the help of bootstrapping, the Mann-Whitney U test was used to examine the differences between primary school students' and middle school students' networks. The results found that there is a bidirectional interaction between IA and anxiety, and anxiety plays a dominant role. Feeling afraid is the bridge symptom between IA and anxiety. IA did not show developmental stage differences, but anxiety did. These findings extend the model of compensatory internet use and suggest that, when alleviating IA symptoms in adolescents, attention should be given to their possible comorbid anxiety symptoms, especially in middle school students.

Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.

Efficacy and safety of COVID-19 vaccines for patients with spinal tumors receiving denosumab treatment: An initial real-clinical experience study.

Background: Even if COVID-19 vaccine has gradually been adopted in the world, information of side effects and crosstalk in patients with spinal tumors is absent due to the exclusion from clinical research. In this research, we aimed to investigate the efficacy and safety for the patients with spinal tumors treated by denosumab. Methods: In this retrospective research, 400 patients under treatment of denosumab against spinal tumors in real-clinical experience were grouped into two cohorts according to the treatment of COVID-19 vaccine. And linked hospital data, serum samples and unsolicited related adverse events had been collected from January 22nd 2021 to June 1st 2021 respectively. Results: 233 patients of all participants who received regular treatment of denosumab were vaccinated by mRNA or inactivated vaccine. Patients of metastatic disease and primary osseous spinal tumor showed similar distribution in both two groups. Over the study period, within 176 patients tested the status of serologic response of vaccine, 88(81.48%) and 41(87.23%) individuals injected one or two inactivated vaccines had effective antibody against SARS-CoV-2 infections. As 21 patients (85.71%) treated by mRNA vaccine did. Considering of the safety of vaccine, most common systemic adverse events were nausea or vomiting (45 events vs 23events). Interestingly, fewer participants in the vaccine group were statistically recorded in local adverse events than in the placebo group (16 events vs 33 events). Conclusions: Our initial real-clinical experience suggests that COVID-19 vaccines are likely safe and effective in in patients with spinal tumors receiving denosumab treatment.

DeepWare: Imaging Performance Counters With Deep Learning to Detect Ransomware

In the year passed, rarely a month passes without a ransomware incident being published in a newspaper or social media. In addition to the rise in the frequency of ransomware attacks, emerging attacks are very effective as they utilize sophisticated techniques to bypass existing organizational security perimeter. To tackle this issue, this paper presents "DeepWare,” which is a ransomware detection model inspired by deep learning and hardware performance counter (HPC). Different from previous works aiming to check all HPC results returned from a single timing for every running process, DeepWare carries out a simple yet effective concept of " imaging hardware performance counters with deep learning to detect ransomware ,” so as to identify ransomware efficiently and effectively. To be more specific, DeepWare monitors the system-wide change in the distribution of HPC data. By imaging the HPC values and restructuring the conventional CNN model, DeepWare can address HPC's nondeterminism issue by extracting the event-specific and event-wise behavioral features, which allows it to distinguish the ransomware activity from the benign one effectively. The experiment results across ransomware families show that the proposed DeepWare is effective at detecting different classes of ransomware with the 98.6% recall score, which is 84.41%, 60.93%, and 21% improvement over RATAFIA , OC-SVM , and EGB models respectively. DeepWare achieves an average MCC score of 96.8% and nearly zero false-positive rates by using just a 100 ms snapshot of HPC data. This timeliness of DeepWare is critical on the ground that organizations and individuals have the opportunity to take countermeasures in the first stage of the attack. Besides, the experiment conducted on unseen ransomware families such as CoronaVirus, Ryuk, and Dharma demonstrates that DeepWare has excellent potential to be a useful tool for zero-day attack detection.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

SARS-CoV-2: An Updated Review Highlighting Its Evolution and Treatments.

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

High-Efficiency Adsorption of SARS-CoV-2 Spike 1 Protein by Plasma-Modified Porous Polymers

Under the background of the COVID-19 pandemic, this study reports an affordable and easily prepared porous material modified by nanosecond-pulsed discharge plasma, which can adsorb SARS-CoV-2 S1 protein efficiently. Both Western blotting and an enzyme-linked immunosorbent assay were used to detect the adsorption efficiency of SARS-CoV-2 S1 protein. The physical and chemical properties of the modified porous polymer were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. We found that the new type of porous polymer material presented an excellent performance on SARS-CoV-2 S1 protein adsorption, whose adsorption efficiency reached 99.99% in 1 min. Both the physical and chemical characterizations showed that the material has many fresh pores on the material surface and that the surface is implanted with polar functional groups (C-O, C=O, O-C=O and -NH), which gives the material a high chemisorption performance along with an enhanced physical adsorption performance. Notably, the material can be prepared at prices ranging in the tens of dollars per kilogram, which shows that it could have great applications for respiratory virus protection in global epidemic states.

Interferon‐alpha or ‐beta Facilitates SARS‐CoV‐2 Pulmonary Vascular Infection by Inducing ACE2

Severe viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is characterized by a hyperinflammatory state typified by elevated circulating pro‐inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection and subsequent endothelial damage have been described in patients with fatal COVID‐19, the mechanism by which this occurs remains elusive, particularly given that, under naïve conditions, pulmonary endothelial cells demonstrate minimal cell surface expression of the SARS‐CoV‐2 binding receptor ACE2. Herein we describe SARS‐CoV‐2 infection of the pulmonary endothelium in postmortem lung samples from individuals who died of COVID‐19, demonstrating both heterogeneous ACE2 expression and endothelial damage (Figure). In primary endothelial cell cultures, we show that SARS‐CoV‐2 infection is dependent on the induction of ACE2 protein expression and that this process is facilitated by type 1 interferon‐alpha (IFNα) or ‐beta(β) ‐ two of the main anti‐viral cytokines induced in severe SARS‐CoV‐2 infection ‐ but not significantly by other cytokines (including interleukin 6 and interferon g /λ). Our findings suggest that the stereotypical anti‐viral interferon response may paradoxically facilitate the propagation of COVID‐19 from the respiratory epithelium to the vasculature, raising concerns regarding the use of exogenous IFNα/β in the treatment of patients with COVID‐19.

SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.

Deep-dLAMP: Deep Learning-Enabled Polydisperse Emulsion-Based Digital Loop-Mediated Isothermal Amplification.

Digital nucleic acid amplification tests enable absolute quantification of nucleic acids, but the generation of uniform compartments and reading of the fluorescence requires specialized instruments that are costly, limiting their widespread applications. Here, the authors report deep learning-enabled polydisperse emulsion-based digital loop-mediated isothermal amplification (deep-dLAMP) for label-free, low-cost nucleic acid quantification. deep-dLAMP performs LAMP reaction in polydisperse emulsions and uses a deep learning algorithm to segment and determine the occupancy status of each emulsion in images based on precipitated byproducts. The volume and occupancy data of the emulsions are then used to infer the nucleic acid concentration based on the Poisson distribution. deep-dLAMP can accurately predict the sizes and occupancy status of each emulsion and provide accurate measurements of nucleic acid concentrations with a limit of detection of 5.6 copies µl-1 and a dynamic range of 37.2 to 11000 copies µl-1 . In addition, deep-dLAMP shows robust performance under various parameters, such as the vortexing time and image qualities. Leveraging the state-of-the-art deep learning models, deep-dLAMP represents a significant advancement in digital nucleic acid tests by significantly reducing the instrument cost. We envision deep-dLAMP would be readily adopted by biomedical laboratories and be developed into a point-of-care digital nucleic acid test system.

Chromosome-Scale Genome of Masked Palm Civet (Paguma larvata) Shows Genomic Signatures of Its Biological Characteristics and Evolution.

The masked palm civet (Paguma larvata) is a small carnivore with distinct biological characteristics, that likes an omnivorous diet and also serves as a vector of pathogens. Although this species is not an endangered animal, its population is reportedly declining. Since the severe acute respiratory syndrome (SARS) epidemic in 2003, the public has been particularly concerned about this species. Here, we present the first genome of the P. larvata, comprising 22 chromosomes assembled using single-tube long fragment read (stLFR) and Hi-C technologies. The genome length is 2.41 Gb with a scaffold N50 of 105.6 Mb. We identified the 107.13 Mb X chromosome and one 1.34 Mb Y-linked scaffold and validated them by resequencing 45 P. larvata individuals. We predicted 18,340 protein-coding genes, among which 18,333 genes were functionally annotated. Interestingly, several biological pathways related to immune defenses were found to be significantly expanded. Also, more than 40% of the enriched pathways on the positively selected genes (PSGs) were identified to be closely related to immunity and survival. These enriched gene families were inferred to be essential for the P. larvata for defense against the pathogens. However, we did not find a direct genomic basis for its adaptation to omnivorous diet despite multiple attempts of comparative genomic analysis. In addition, we evaluated the susceptibility of the P. larvata to the SARS-CoV-2 by screening the RNA expression of the ACE2 and TMPRSS2/TMPRSS4 genes in 16 organs. Finally, we explored the genome-wide heterozygosity and compared it with other animals to evaluate the population status of this species. Taken together, this chromosome-scale genome of the P. larvata provides a necessary resource and insights for understanding the genetic basis of its biological characteristics, evolution, and disease transmission control.

Growth, Antigenicity, and Immunogenicity of SARS-CoV-2 Spike Variants Revealed by a Live rVSV-SARS-CoV-2 Virus.

SARS-CoV-2 is an emerging coronavirus threatening human health and the economy worldwide. As an RNA virus, variants emerge during the pandemic and potentially influence the efficacy of the anti-viral drugs and vaccines. Eight spike variants harboring highly recurrent mutations were selected and introduced into a replication-competent recombinant VSV in place of the original G protein (rVSV-SARS-CoV-2). The resulting mutant viruses displayed similar growth curves in vitro as the wild-type virus and could be neutralized by sera from convalescent COVID-19 patients. Several variants, especially Beta strain, showed resistance to human neutralizing monoclonal antibodies targeting the receptor-binding domain (RBD). A single dose of rVSV-SARS-CoV-2 Beta variant could elicit enhanced and broad-spectrum neutralizing antibody responses in human ACE2 knock-in mice and golden Syrian hamsters, while other mutants generated antibody levels comparable to the wild-type. Therefore, our results will be of value to the development of next-generation vaccines and therapeutic antibodies.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

Recent Advances on Drugs and Vaccines for COVID-19.

The current situation of Coronavirus Disease 2019 (COVID-19) worldwide is still very severe. Presently, many breakthroughs have been accomplished in the research and development of drugs for the treatment of COVID-19, especially vaccines; however, some of the so-called COVID-19-specific drugs highlighted in the early stage failed to achieve the expected curative effect. There is no antiviral therapy available, by stimulating protective immunity vaccine is the best choice for the future management of infection. Therefore, we aimed to identify the latest developments in the research and development of these drugs and vaccines and provide a reference for the prevention and treatment of COVID-19.

The trans-omics landscape of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.

The State of Emergency in Public Health and the Exceptional Regulations in Administrative Law

It is a great shock to the legal system by COVID-19 or the spread of so-called severe acute respiratory syndrome coronavirus, which made it hard to react. Even though there might be some general principles for emergency in the Administrative Law, they belong to individual administrative cases. Moreover, the regulation for emergency in Constitution depends on the political decision of the decision-maker. Therefore, it is necessary to give the administrative agencies the possibility for the discretion in the field of the general theory of Administrative Law and of Public Health concerning to emergency due to the pandemic. The review of the norm-interpretating should be loose as well. Meanwhile, in order to avoid abusing rights, an regular examination on its validity and rationality should also be performed. Besides, administrative discretion should be made from the consensus decision by specialists.

Research progress on coronavirus S proteins and their receptors.

Coronaviruses are a large family of important pathogens that cause human and animal diseases. At the end of 2019, a pneumonia epidemic caused by a novel coronavirus brought attention to coronaviruses. Exploring the interaction between the virus and its receptor will be helpful in developing preventive vaccines and therapeutic drugs. The coronavirus spike protein (S) plays an important role in both binding to receptors on host cells and fusion of the viral membrane with the host cell membrane. This review introduces the structure and function of the S protein and its receptor, focusing on the binding mode and binding region of both.

When Zombies Invade Taiwan - Current Status and Future Challenges of Facebook Fake Accounts and Disinformation

社群平台假訊息、假帳號已是全球關注之議題。近期有研究發現，來自社群媒體的假訊息、假帳號的肆虐可能對台灣的民主社會帶來負面的衝擊。鑑於臺灣具有獨特的地緣政治性，特定勢力可能藉由問題帳號針對特定事件來散播假訊息，並試圖影響臺灣的政治環境。為探索假訊息在社群媒體的活動狀況，本研究以臺灣2020年總統選舉及新冠肺炎疫情為對象，觀測各種問題帳號在高聲量臉書貼文中的分布、留言情形。此外，本研究也透過焦點團體訪談，探討我國當前假訊息之現況、困境，並提出相關政策建議。最後，本研究認為網路主管機關的成立、對網站平台的課責、法令與策略的調整、強化政府假訊息闢謠之效能，以及持續關注未來假訊息的變化，是遏止危害性言論的必要之舉。 The spreading of disinformation by fake accounts on social media has become an issue of global concern. Recent studies have found that the roaming of fake messages and fake accounts from social media may have a negative impact on Taiwan's democratic society. Given Taiwan's unique geopolitical nature, certain forces may try to influence Taiwan's political environment by spreading fake messages through zombie accounts targeting specific events. This study examines the distribution of questionable accounts and messages in high-volume Facebook posts in the context of Taiwan's 2020 presidential election and the COVID-19 epidemic. In addition, focus group interviews were conducted to explore the current situation of disinformation and provide relative policy suggestions. Finally, this study argues that the establishment of a specific internet authority, the accountability of the social media platform, the adjustment of acts and strategies, the strengthening of the government's effectiveness in refuting fake messages, and the focusing on future changes in disinformation are necessary to counter the rampant spread of disinformation on social media.