TBtools: An Integrative Toolkit Developed for Interactive Analyses of Big Biological Data.

After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

https://www.pnas.org/content/pnas/117/20/10970.full.pdf

Effective treatment of severe COVID-19 patients with tocilizumab.

FASTA and FASTQ are basic and ubiquitous formats for storing nucleotide and protein sequences. Common manipulations of FASTA/Q file include converting, searching, filtering, deduplication, splitting, shuffling, and sampling. Existing tools only implement some of these manipulations, and not particularly efficiently, and some are only available for certain operating systems. Furthermore, the complicated installation process of required packages and running environments can render these programs less user friendly. This paper describes a cross-platform ultrafast comprehensive toolkit for FASTA/Q processing. SeqKit provides executable binary files for all major operating systems, including Windows, Linux, and Mac OSX, and can be directly used without any dependencies or pre-configurations. SeqKit demonstrates competitive performance in execution time and memory usage compared to similar tools. The efficiency and usability of SeqKit enable researchers to rapidly accomplish common FASTA/Q file manipulations. SeqKit is open source and available on Github at https://github.com/shenwei356/seqkit.

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SeqKit: A Cross-Platform and Ultrafast Toolkit for FASTA/Q File Manipulation.

As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID-19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute-phase reactants, and serum biochemistry in COVID-19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals. In the majority of the patients, a 1-week, self-limiting viral respiratory disease typically occurs, which ends with the development of neutralizing antiviral T cell and antibody immunity. The IgM-, IgA-, and IgG-type virus-specific antibodies levels are important measurements to predict population immunity against this disease and whether cross-reactivity with other coronaviruses is taking place. High viral load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID-19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome, and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine-secreting cells with innate and adaptive immune mechanisms both of which contribute to a poor prognosis. Elevated levels of acute-phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome, and novel approaches to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.

/pdf/immune-response-to-sars-cov-2-and-mechanisms-of-ornvi6jkta.pdf

Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19.

The rapid development of high-throughput sequencing (HTS) techniques has led biology into the big-data era. Data analyses using various bioinformatics tools rely on programming and command-line environments, which are challenging and time-consuming for most wet-lab biologists. Here, we present TBtools (a Toolkit for Biologists integrating various biological data handling tools), a stand-alone software with a user-friendly interface. The toolkit incorporates over 100 functions, which are designed to meet the increasing demand for big-data analyses, ranging from bulk sequence processing to interactive data visualization. A wide variety of graphs can be prepared in TBtools, with a new plotting engine (“JIGplot”) developed to maximum their interactive ability, which allows quick point-and-click modification to almost every graphic feature. TBtools is a platform-independent software that can be run under all operating systems with Java Runtime Environment 1.6 or newer. It is freely available to non-commercial users at https://github.com/CJ-Chen/TBtools/releases.

/pdf/tbtools-an-integrative-toolkit-developed-for-interactive-365f4nv0la.pdf

TBtools - an integrative toolkit developed for interactive analyses of big biological data

Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response.

DNA methylation is a key factor in the pathogenesis of gene expression diseases or malignancies. Thus, it has become a significant biomarker for the diagnosis and prognosis of these diseases. In this paper, we designed an ultrasensitive and specific electrochemical biosensor for DNA methylation detection. The platform consisted of stem–loop–tetrahedron composite DNA probes anchoring at a Au nanoparticle-coated gold electrode, a restriction enzyme digestion of HpaII, and signal amplification procedures including electrodeposition of Au nanoparticles, hybridization chain reaction, and horseradish peroxidase enzymatic catalysis. Under optimal conditions, the design showed a broad dynamic range from 1 aM to 1 pM and a detection limit of about 0.93 aM. The approach also showed ideal specificity, repeatability, and stability. The recovery test demonstrated that the design is a promising platform for DNA methylation detection under clinical circumstances and could meet the need for cancer diagnosis.

Electrochemical Biosensor for DNA Methylation Detection through Hybridization Chain-Amplified Reaction Coupled with a Tetrahedral DNA Nanostructure.

Malfunctioned gap junctional intercellular communication (GJIC) has been thought associated with malignant transformation of normal cells. However, the role of GJIC-related proteins such as connexins in sustaining the malignant behavior of cancer stem cells remains unclear. In this study, we obtained tumorspheres formed by glioma stem cells (GSCs) and adherent GSCs and then examined their GJIC. All GSCs showed reduced GJIC, and differentiated glioma cells had more gap junction-like structures than GSCs. GSCs expressed very low level of connexins, Cx43 in particular, which are key components of gap junction. We observed hypermethylation in the promoter of gap junction protein α1, which encodes Cx43 in GSCs. Reconstitution of Cx43 in GSCs inhibited their capacity of self-renewal, invasiveness, and tumorigenicity via influencing E-cadherin and its coding protein, which leads to changes in the expression of Wnt/β-catenin targeting genes. Our results suggest that GSCs require the low expression of Cx43 for maintaining their malignant phenotype, and upregulation of Cx43 might be a potential strategy for treatment of malignant glioma.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/stem.1685

Connexin 43 Reverses Malignant Phenotypes of Glioma Stem Cells by Modulating E-Cadherin

The blood-brain barrier (BBB) is a critical physical and chemical barrier that maintains brain homeostasis. Researchers in academia and industry are highly motivated to develop experimental models that can accurately mimic the physiological characteristics of the BBB. Microfluidic systems, which manipulate fluids at the micrometer scale, are ideal tools for simulating the BBB microenvironment. In this review, we summarized the progress in the design and evaluation of microfluidic in vitro BBB models, including advances in chip materials, porous membranes, the use of endothelial cells, the importance of shear stress, the detection specific markers to monitor tight junction formation and integrity, measurements of TEER and permeability. We also pointed out several shortcomings of the current microfluidic models. The purpose of this paper is to let the readers understand the characteristics of different types of model design, and select appropriate design parameters according to the research needs, so as to obtain the best experimental results. We believe that the microfluidics BBB models will play an important role in neuroscience and pharmaceutical research.

https://www.mdpi.com/2072-666X/10/6/375/pdf

Yan Li

Papers

SeqKit: A Cross-Platform and Ultrafast Toolkit for FASTA/Q File Manipulation.

Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response.

Electrochemical Biosensor for DNA Methylation Detection through Hybridization Chain-Amplified Reaction Coupled with a Tetrahedral DNA Nanostructure.

Connexin 43 Reverses Malignant Phenotypes of Glioma Stem Cells by Modulating E-Cadherin

Recent Progress in Microfluidic Models of the Blood-Brain Barrier.