Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Resources curse hypothesis and COP26 target: Mineral and oil resources economies COVID-19 perspective.

In recent times, industrialized economies have focused more on achieving a sustainable environment while maintaining economic prosperity. However, it is clear from the current research that natural resource exploitation and decentralization substantially affect environmental quality. To experimentally validate such data, the current study examines decentralized economies during the previous three decades (1990-2020). This study discovered the existence of long-term cointegration between carbon emissions, economic growth, revenue decentralization, spending decentralization, natural resources, and human capital using panel data econometric techniques. The findings are based on non-parametric techniques, indicating that economic growth and revenue decentralization are the primary barriers to meeting the COP26 objective. Human capital drives down carbon emissions and contributes to meeting the COP26 objective. On the contrary, decentralization of spending and natural resources has a mixed influence on carbon emissions across quantiles. This report recommends investing in human capital, education, and research & development to speed up COP26's target accomplishment.

Weakened humoral and cellular immune response to the inactivated COVID-19 vaccines in Chinese individuals with obesity/overweight.

Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population. However, limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines. In this study, 132 high BMI (Body mass index) (obesity and overweight, BMI ≥ 24 kg/m2) and 82 normal BMI (BMI < 24 kg/m2) participants were enrolled. Adverse events (AEs), Spike receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs), and specific B-cell and T-cell responses were evaluated 21-105 days after full-course inactivated COVID-19 vaccination. The overall incidence of adverse events (AEs) was similar in individuals with and without obesity/overweight. No serious vaccine-related AEs occurred. Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI. Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group. The frequencies of RBD-specific memory B cells (MBCs) and the numbers of spike-specific TNF-α+ spot-forming cells (SFCs) in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight. A similar trend of weakened humoral responses was also observed in individuals with central obesity. Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.

CRISPR‐Cas Biochemistry and CRISPR‐Based Molecular Diagnostics

Polymerase chain reaction (PCR)‐based nucleic acid testing has played a critical role in disease diagnostics, pathogen surveillance, and many more. However, this method requires a long turnaround time, expensive equipment, and trained personnel, limiting its widespread availability and diagnostic capacity. On the other hand, the clustered regularly interspaced short palindromic repeats (CRISPR) technology has recently demonstrated capability for nucleic acid detection with high sensitivity and specificity. CRISPR‐mediated biosensing holds great promise for revolutionizing nucleic acid testing procedures and developing point‐of‐care diagnostics. This review focuses on recent developments in both fundamental CRISPR biochemistry and CRISPR‐based nucleic acid detection techniques. Four ongoing research hotspots in molecular diagnostics‐target preamplification‐free detection, microRNA (miRNA) testing, non‐nucleic‐acid detection, and SARS‐CoV‐2 detection‐are also covered.

Trend and Co-occurrence Network of COVID-19 Symptoms From Large-Scale Social Media Data: Infoveillance Study.

BACKGROUND: For an emergent pandemic, such as COVID-19, the statistics of symptoms based on hospital data may be biased or delayed due to the high proportion of asymptomatic or mild-symptom infections that are not recorded in hospitals. Meanwhile, the difficulty in accessing large-scale clinical data also limits many researchers from conducting timely research. OBJECTIVE: Given the wide coverage and promptness of social media, this study aimed to present an efficient workflow to track and visualize the dynamic characteristics and co-occurrence of symptoms for the COVID-19 pandemic from large-scale and long-term social media data. METHODS: This retrospective study included 471,553,966 COVID-19-related tweets from February 1, 2020, to April 30, 2022. We curated a hierarchical symptom lexicon for social media containing 10 affected organs/systems, 257 symptoms, and 1808 synonyms. The dynamic characteristics of COVID-19 symptoms over time were analyzed from the perspectives of weekly new cases, overall distribution, and temporal prevalence of reported symptoms. The symptom evolutions between virus strains (Delta and Omicron) were investigated by comparing the symptom prevalence during their dominant periods. A co-occurrence symptom network was developed and visualized to investigate inner relationships among symptoms and affected body systems. RESULTS: This study identified 201 COVID-19 symptoms and grouped them into 10 affected body systems. There was a significant correlation between the weekly quantity of self-reported symptoms and new COVID-19 infections (Pearson correlation coefficient=0.8528; P<.001). We also observed a 1-week leading trend (Pearson correlation coefficient=0.8802; P<.001) between them. The frequency of symptoms showed dynamic changes as the pandemic progressed, from typical respiratory symptoms in the early stage to more musculoskeletal and nervous symptoms in the later stages. We identified the difference in symptoms between the Delta and Omicron periods. There were fewer severe symptoms (coma and dyspnea), more flu-like symptoms (throat pain and nasal congestion), and fewer typical COVID symptoms (anosmia and taste altered) in the Omicron period than in the Delta period (all P<.001). Network analysis revealed co-occurrences among symptoms and systems corresponding to specific disease progressions, including palpitations (cardiovascular) and dyspnea (respiratory), and alopecia (musculoskeletal) and impotence (reproductive). CONCLUSIONS: This study identified more and milder COVID-19 symptoms than clinical research and characterized the dynamic symptom evolution based on 400 million tweets over 27 months. The symptom network revealed potential comorbidity risk and prognostic disease progression. These findings demonstrate that the cooperation of social media and a well-designed workflow can depict a holistic picture of pandemic symptoms to complement clinical studies.

CRISPR-Cas Biochemistry and CRISPR-Based Molecular Diagnostics.

Polymerase chain reaction (PCR)-based nucleic acid testing has played a critical role in disease diagnostics, pathogen surveillance, and many more. However, this method requires a long turnaround time, expensive equipment, and trained personnel, limiting its widespread availability and diagnostic capacity. On the other hand, the clustered regularly interspaced short palindromic repeats (CRISPR) technology has recently demonstrated capability for nucleic acid detection with high sensitivity and specificity. CRISPR-mediated biosensing holds great promise for revolutionizing nucleic acid testing procedures and developing point-of-care diagnostics. This review focuses on recent developments in both fundamental CRISPR biochemistry and CRISPR-based nucleic acid detection techniques. Four ongoing research hotspots in molecular diagnostics-target preamplification-free detection, microRNA (miRNA) testing, non-nucleic-acid detection, and SARS-CoV-2 detection-are also covered.

Research status and development trend of extracorporeal membrane oxygenation based on bibliometrics.

Background: Using bibliometric method to analyze the research status and development trend of extracorporeal membrane oxygenation (ECMO), we aim to provide clinicians, scientists, and stakeholders with the most up-to-date and comprehensive overview of ECMO research. Materials and methods: Using Excel and VOSviewer, the literature on ECMO was systematically analyzed regarding publication trends, journal source, foundation, countries, institutions, core authors, research hotspots, and market distribution. Results: There were five important time nodes in the research process of ECMO, including the success of the first ECMO operation, the establishment of ELSO, and the outbreak of influenza A/H1N1 and COVID-19. The R&D centers of ECMO were the United States, Germany, Japan, and Italy, and the attention to ECMO was gradually increasing in China. The products most used in the literature were from Maquet, Medtronic, and LivaNova. Medicine enterprises attached great importance to the funding of ECMO research. In recent years, the literature has mainly focused on the following aspects: the treatment of ARDS, the prevention of coagulation system-related complications, the application in neonatal and pediatric patients, mechanical circulatory support for cardiogenic shock, and ECPR and ECMO during the COVID-19 pandemic. Conclusion: The frequent epidemic occurrence of viral pneumonia and the technical advancement of ECMO in recent years have caused an increase in clinical applications. The hot spots of ECMO research are shown in the treatment of ARDS, mechanical circulatory support for cardiogenic shock, and the application during the COVID-19 pandemic.

Engineered LwaCas13a with enhanced collateral activity for nucleic acid detection.

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 13 (Cas13) has been rapidly developed for nucleic-acid-based diagnostics by using its characteristic collateral activity. Despite the recent progress in optimizing the Cas13 system for the detection of nucleic acids, engineering Cas13 protein with enhanced collateral activity has been challenging, mostly because of its complex structural dynamics. Here we successfully employed a novel strategy to engineer the Leptotrichia wadei (Lwa)Cas13a by inserting different RNA-binding domains into a unique active-site-proximal loop within its higher eukaryotes and prokaryotes nucleotide-binding domain. Two LwaCas13a variants showed enhanced collateral activity and improved sensitivity over the wild type in various buffer conditions. By combining with an electrochemical method, our variants detected the SARS-CoV-2 genome at attomolar concentrations from both inactive viral and unextracted clinical samples, without target preamplification. Our engineered LwaCas13a enzymes with enhanced collateral activity are ready to be integrated into other Cas13a-based platforms for ultrasensitive detection of nucleic acids.

Multiscale Correlation Analysis of Sino-US Corn Futures Markets and the Impact of International Crude Oil Price: A New Perspective from the Multifractal Method

Based on the multifractal method, this paper studies the dynamic characteristics of the cross-correlation between Sino-US corn futures markets after 2020 in the context of a series of exogenous shocks, and the impact of international crude oil prices on this relationship. We find that the cross-correlation significantly strengthened after 2020 at multi-time scales, but its uncertainty and complexity reduced. Besides, shocks of the crude oil market increase the cross-correlation at multi-time scales, which notably weakened after 2020. This suggests the Chinese government's interventions and regulations on the domestic grain market were effective.

Unlocking G-Quadruplexes as Targets and Tools against COVID-19.

The applicability of G-quadruplexes (G4s) as antiviral targets, therapeutic agents and diagnostic tools for coronavirus disease 2019 (COVID-19) is currently being evaluated, which has drawn the extensive attention of the scientific community. During the COVID-19 pandemic, research in this field is rapidly accumulating. In this review, we summarize the latest achievements and breakthroughs in the use of G4s as antiviral targets, therapeutic agents and diagnostic tools for COVID-19, particularly using G4 ligands. Finally, strength and weakness regarding G4s in anti-SARS-CoV-2 field are highlighted for prospective future projects.

Forecasting Tourist Arrivals for Hainan Island in China with Decomposed Broad Learning before the COVID-19 Pandemic.

This study proposes a decomposed broad learning model to improve the forecasting accuracy for tourism arrivals on Hainan Island in China. With decomposed broad learning, we predicted monthly tourist arrivals from 12 countries to Hainan Island. We compared the actual tourist arrivals to Hainan from the US with the predicted tourist arrivals using three models (FEWT-BL: fuzzy entropy empirical wavelet transform-based broad learning; BL: broad Learning; BPNN: back propagation neural network). The results indicated that US foreigners had the most arrivals in 12 countries, and FEWT-BL had the best performance in forecasting tourism arrivals. In conclusion, we establish a unique model for accurate tourism forecasting that can facilitate decision-making in tourism management, especially at turning points in time.

Adenovirus-mediated Over-Expression of FcγRIIB Attenuates Pulmonary Inflammation and Fibrosis.

Progressive fibrosing interstitial lung diseases (PF-ILDs) result in high mortality and lack effective therapies. The pathogenesis of PF-ILDs involves macrophages driving inflammation and irreversible fibrosis. Fc-gamma receptors (FcγRs) regulate macrophages and inflammation, but their roles in PF-ILDs remain unclear. We characterized the expression of FcγRs and found up-regulated FcγRIIB in human and mouse lungs following exposure to silica. FcγRIIB deficiency aggravated lung dysfunction, inflammation and fibrosis in silica-exposed mice. Using single-cell transcriptomics and in vitro experiments, FcγRIIB was found in alveolar macrophages, where it regulated the expression of fibrosis-related genes Spp1 and Ctss. In mice with macrophage-specific over-expression of FcγRIIB, and in mice treated with adenovirus by intra-tracheal instillation to up-regulate FcγRIIB, silica-induced functional and histological changes were ameliorated. Our data from three genetic models and a therapeutic model suggest that FcγRIIB plays a protective role that can be enhanced by adenoviral over-expression, representing a potential therapeutic strategy for PF-ILDs.

Gas Chromatography-Mass Spectrometry Technology: Application in the Study of Inflammatory Mechanism in COVID-19 Patients.

SARS-CoV-2 infection in the human body induces a severe storm of inflammatory factors. However, its specific mechanism is still not clear. Gas chromatography-mass spectrometry (GC-MS) technology is expected to explain the possible mechanism of the disease by detecting differential metabolites. 15 COVID-19 patients and healthy controls were included in this study. Immune indicators such as hs CRP and cytokines were detected to reflect the level of inflammation in patients with COVID-19. The distribution of lymphocytes and subpopulations in peripheral whole blood were detected using flow cytometry to assess the immune function of COVID-19 patients. The expression of differential metabolites in serum was analyzed using GC-MS non-targeted metabolomics. The results showed that hs CRP, IL-5/6/8/10 and IFN-α in the serum of COVID-19 patients increased to varying degrees, and CD3/4/8+ T lymphocytes decreased. Additionally, 53 metabolites in the serum of COVID-19 patients were up regulated, 18 metabolites were down regulated, and 8 metabolites remained unchanged. Increased Cholesterol, Lactic Acid and 1-Monopalmitin may be the mechanism that causes excessive inflammation in COVID-19 patients. The increase of D-Allose may be involved in the process of lymphocyte decrease. In conclusion, the significance of our study is to reveal the possible mechanism of inflammatory response in patients with COVID-19 from the perspective of metabolomics. This provided a new idea for the treatment of COVID-19.

Dual-Gene-Controlled Rolling Circle Amplification Strategy for SARS-CoV-2 Analysis.

The development of sensitive, accurate, and conveniently operated methods for the simultaneous assay of two nucleic acids is promising while still challenging. In this work, by using two genes (the N gene and RdRp gene) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as examples, we have designed an ingenious dual-gene-controlled rolling circle amplification (RCA) strategy to propose an accurate and sensitive electrochemical method. Specifically, the coexistence of the two target genes can trigger the RCA reaction to generate a number of repeated G-quadruplex (G4)-forming sequences. These sequences then switch into G4/hemin complexes with redox activity after the incubation of hemin, which can catalyze the TMB/H2O2 substrates to produce significantly enhanced current responses. Experimental results reveal that the proposed method exhibits satisfying feasibility and analytical performance, enabling the sensitive detection of SARS-CoV-2 in the range of 0.1-5000 pM, with the detection limit of 57 fM. Meanwhile, because only the simultaneous existence of the two target genes can effectively trigger the downstream amplification reaction, this method can effectively avoid false-positives and ensure specificity as well as accuracy. Furthermore, our method can distinguish the COVID-19 samples from healthy people, and the outcomes show a satisfying agreement with the results of RT-PCR, manifesting that our label-free dual-gene-controlled RCA strategy exhibits great possibility in clinical application.

Microfluidics for nano-drug delivery systems: From fundamentals to industrialization

In recent years, owing to the miniaturization of the fluidic environment, microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems (NDDSs) production processes. Compared with traditional methods, microfluidics improves the controllability and uniformity of NDDSs. The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs, including particle size, distribution and morphology, resulting in narrow particle size distribution and high drug-loading capacity. The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up. In this review, we provide a comprehensive summary of microfluidics-based NDDSs, including the fundamentals of microfluidics, microfluidic synthesis of NDDSs, and their industrialization. The challenges of microfluidics-based NDDSs in the current status and the prospects for future development are also discussed. We believe that this review will provide good guidance for microfluidics-based NDDSs.

Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process.

Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. Drug repurposing is a therapeutic strategy used in treatments for newly emerging and re-emerging infectious diseases. It has recently been shown that the voltage-dependent Ca2+ channel Cav1.2 is critical for influenza A virus entry, providing a potential target for antiviral strategies. Nisoldipine, a selective Ca2+ channel inhibitor, is commonly used in the treatment of hypertension. Here, we assessed the antiviral potential of nisoldipine against the influenza A virus and explored the mechanism of action of this compound. We found that nisoldipine treatment could potently inhibit infection with multiple influenza A virus strains. Mechanistic studies further revealed that nisoldipine impaired the internalization of the influenza virus into host cells. Overall, our findings demonstrate that nisoldipine exerts antiviral effects against influenza A virus infection and could serve as a lead compound in the design and development of new antivirals.