Potential therapeutic targets for COVID-19 complicated with pulmonary hypertension: a bioinformatics and early validation study (preprint)

coronavirus disease(COVID-19)and pulmonary hypertension(PH)are closely correlated. However, the mechanism is still poorly understood.In this article, we analyzed the molecular action network driving the emergence of this event.Two datasets (GSE113439 and GSE147507) from the GEO database were used for the identification of differentially expressed genes (DEGs).Common DEGs were selected by VennDiagram and their enrichment in biological pathways was analyzed. Candidate gene biomarkers were selected using three different machine-learning algorithms (SVM-RFE, LASSO、RF).The diagnostic efficacy of these foundational genes was validated using independent datasets. Eventually, we validated molecular docking and medication prediction. We found 62 common DEGs, including several ones that could be enriched for Immune Response and Inflammation. Two DEGs (SELE and CCL20) could be identified by machine-learning algorithms. They performed well in diagnostic tests on independent datasets. In particular, we observed an upregulation of functions associated with the adaptive immune response, the leukocyte-lymphocyte-driven immunological response, and the proinflammatory response. Moreover, by ssGSEA, natural killer T cells, activated dendritic cells, activated CD4 T cells, neutrophils, and plasmacytoid dendritic cells were correlated with COVID-19 and PH, with SELE and CCL20 showing the strongest correlation with dendritic cells. Potential therapeutic compounds like FENRETI-NIDE were predicted.The findings indicated that ELE and CCL20 were identified as novel diagnostic biomarkers for COVID-19 complicated with PH, and the target of these two key genes, FENRETI-NIDE, was predicted to be a potential therapeutic target, thus providing new insights into the prediction and treatment of COVID-19 complicated with PH in clinical practice.

Exploring the Intersection of Complex Aesthetics and Generative AI for Promoting Cultural Creativity in Rural China after the Post-Pandemic Era (preprint)

This paper explores using generative AI and aesthetics to promote cultural creativity in rural China amidst COVID-19's impact. Through literature reviews, case studies, surveys, and text analysis, it examines art and technology applications in rural contexts and identifies key challenges. The study finds artworks often fail to resonate locally, while reliance on external artists limits sustainability. Hence, nurturing grassroots "artist villagers" through AI is proposed. Our approach involves training machine learning on subjective aesthetics to generate culturally relevant content. Interactive AI media can also boost tourism while preserving heritage. This pioneering research puts forth original perspectives on the intersection of AI and aesthetics to invigorate rural culture. It advocates holistic integration of technology and emphasizes AI's potential as a creative enabler versus replacement. Ultimately, it lays the groundwork for further exploration of leveraging AI innovations to empower rural communities. This timely study contributes to growing interest in emerging technologies to address critical issues facing rural China.

High-intensity vector signals for detecting SARS-CoV-2 RNA using CRISPR/Cas13a couple with stabilized graphene field-effect transistor

False detection of SARS-CoV-2 is detrimental to epidemic prevention and control. The scalar nature of the detected signal and the imperfect target recognition property of developed methods are the root causes of generating false signals. Here, we reported a collaborative system of CRISPR-Cas13a coupling with the stabilized graphene field-effect transistor, providing high-intensity vector signals for detecting SARS-CoV-2. In this collaborative system, SARS-CoV-2 RNA generates a “big subtraction” signal with a right-shifted feature, whereas any untargets cause the left-shifted characteristic signal. Thus, the false detection of SARS-CoV-2 is eliminated. High sensitivity with 0.15 copies/μL was obtained. In addition, the wide concerned instability of the graphene field-effect transistor for biosensing in solution environment was solved by the hydrophobic treatment to its substrate, which should be a milestone in advancing it's engineering application. This collaborative system characterized by the high-intensity vector signal and amazing stability significantly advances the accurate SARS-CoV-2 detection from the aspect of signal nature.

Short-term effects of COVID-19 on risk of traumatic fractures in China: a multi-city study (preprint)

Introduction: Traumatic injury is a leading cause of death and disability worldwide, and fifth most common of in China. Along with the outbreak of COVID-19, strict control measures to restrict people’s movement have been conducted in China. Subsequently, the injury mechanisms and pattern of traumatic fractures changed significantly. This study aimed to investigate the associations between COVID-19 and fracture risk, and provide a targeted reference for the world through China’s experience.Methods: This was a retrospective study of a nationally representative sample of COVID-19 prevalence areas using stratified random sampling. The data of traumatic fracture sustaining patients, including age and sex, fractured sites, mechanism of injury, and concurrent fractures in selected hospitals, were collected from 10 January and 10 July, 2020. The epidemiologic characteristics of traumatic fractures and the associations between COVID-19 and fracture risk were explored using the descriptive epidemiological methods and distribution lag nonlinear model.Results: A total of 67,249 (52.3% males) patients (average age 49.4±19.4 years) with 68,989 fractures were included. The highest proportion of fractures were sustained to the tibia and fibula (14.9%), followed by the femur (13.6%), and ulna and radius (12.5%). Low-energy fractures accounted for 23.3%. With the increase of newly confirmed COVID-19 cases, fracture risk decreased for children, young and middle-aged adults, elderly men, high-energy fracture, and for residents in low and middle-prevalence areas.Conclusion: Fracture risk decreased sharply in all residents except elderly women, low-energy fractures, and in high-prevalence areas when newly confirmed COVID-19 cases increased in China. Primary (home) prevention measures are emphasized to prevent traumatic fractures during the COVID-19 pandemic.

Strategies for COVID-19 test in laboratory

Early and rapid laboratory test of Corona Virus Disease 2019(COVID-19) is crucial to the treatment of viral infection and monitoring of prognosis and is one of the most important means to improve the therapeutic effects. The traditional nucleic acid test based on polymerase chain reaction(PCR) and the protein test based on immune reaction are the main approaches for early and rapid tests. Each technique has its own advantages and disadvantages due to the limitations of the methodologies. Nonspecific laboratory indexes also have important value in the clinical diagnosis and treatment of patients with COVID-19. The approaches and strategies for COVID-19 test were explored in detail by focusing on nucleic acid, protein and routine laboratory indexes, and the joint detection of nucleic acid, protein and serological indexes is expected to be an important mean for clinical diagnosis of infectious diseases.

Sequential ER stress and inflammatory responses are induced by SARS-CoV-2 ORF3 through ERphagy (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have resulted in a number of severe cases of COVID-19 and deaths worldwide. However, knowledge of SARS-CoV-2 infection, diseases and therapy remains limited, underlining the urgency of fundamental studies and drug development. Studies have shown that induction of autophagy and hijacking of autophagic machinery are essential for infection and replication of SARS-CoV-2; however, the mechanism of this manipulation and function of autophagy during SARS-CoV-2 infection remain unclear. In the present study, we identified ORF3 as an inducer of autophagy and revealed that ORF3 localizes to the ER and induces FAM134B-related ERphagy through the HMGB1-Beclin1 pathway. As a consequence, ORF3 induces ER stress and inflammatory responses through ERphagy and sensitizes cells to ER stress-induced cell death, suggesting that SARS-CoV-2 ORF3 hijacks ERphagy and then harms ER homeostasis to induce inflammatory responses through excessive ER stress. These findings reveal a sequential induction of ERphagy, ER stress and acute inflammatory responses during SARS-CoV-2 infection and provide therapeutic potential for ERphagy and ER stress-related drugs for COVID-19 treatment and prevention. ImportanceSARS-CoV-2 infection and replication require autophagosome-like double-membrane vacuoles. Inhibition of autophagy suppresses viral replication, indicating the essential role of autophagy in SARS-CoV-2 infection. However, how SARS-CoV-2 hijacks autophagy and the function of autophagy in the disease progression remain unknown. Here, we reveal that SARS-CoV-2 ORF3 induces ERphagy and consequently induces ER stress to trigger acute inflammatory responses and enhance sensitivity to ER stress-induced apoptosis. Our studies uncover ERphagy-induced inflammatory responses during SARS-CoV-2 infection and provide a promising therapeutic approach for treating SARS-CoV-2 infection and inflammatory responses in COVID-19 by manipulating autophagy and ER stress.

Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2 (preprint)

Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKK, subsequently leading to IRF3 and NF-{kappa}B phosphorylation. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral agents indicates that SARS-CoV-2 escapes from antiviral immune responses via an unknown mechanism. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses. It downregulates the expression of type I IFNs, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and impairing its K63-linked polyubiquitination. Our findings reveal that NSP8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.

Coagulopathy in patients with Coronavirus Disease 2019 (COVID-19): A systematic review and meta-analysis (preprint)

Patients with COVID-19 frequently manifest coagulation abnormalities and thrombotic events. In this meta-analysis, we aimed to explore the role of coagulopathy on the severity differences in patients with COVID-19. We conducted systematic literature search via Pubmed, Embase, Cochrane, WanFang Database, CNKI, and medRxiv from December 1, 2019 to May 1, 2020, to identify all original studies that reports on coagulation parameters (D-dimer, PLT, PT, APTT, and FIB) during COVID-19 infection. Thereafter, we compared the coagulation parameters between less severe and more severe cases. All Statistical analyses were performed via Stata14.0 software. A total of 3,952 confirmed COVID-19 infected patients were included from 25 studies. Patients with severe COVID-19 infection exhibited significantly higher levels of D-dimer, PT, and FIB (SMD 0.83, 95% CI: 0.70-0.97, I2 56.9%; SMD 0.39, 95% CI: 0.14-0.64, I2 77.9%; SMD 0.35, 95% CI: 0.17-0.53, I2 42.4% respectively). However, difference in PLT and APTT levels between less severe and more severe patients was not statistically significant (SMD-0.26, 95% CI: -0.56-0.05, I2 82.2%; SMD-0.14,95% CI: -0.45-0.18, I2 75.5% respectively) This meta-analysis revealed coagulopathy is associated with the severity of COVID-19. Notably, D-dimer, PT, and FIB are the dominant parameters that should be considered in evaluating coagulopathy in COVID-19 patients.