Bioinformatics resources facilitate understanding and harnessing clinical research of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented threat to public health. The pandemic has been sweeping the globe, impacting more than 200 countries, with more outbreaks still lurking on the horizon. At the time of the writing, no approved drugs or vaccines are available to treat COVID-19 patients, prompting an urgent need to decipher mechanisms underlying the pathogenesis and develop curative treatments. To fight COVID-19, researchers around the world have provided specific tools and molecular information for SARS-CoV-2. These pieces of information can be integrated to aid computational investigations and facilitate clinical research. This paper reviews current knowledge, the current status of drug development and various resources for key steps toward effective treatment of COVID-19, including the phylogenetic characteristics, genomic conservation and interaction data. The final goal of this paper is to provide information that may be utilized in bioinformatics approaches and aid target prioritization and drug repurposing. Several SARS-CoV-2-related tools/databases were reviewed, and a web-portal named OverCOVID (http://bis.zju.edu.cn/overcovid/) is constructed to provide a detailed interpretation of SARS-CoV-2 basics and share a collection of resources that may contribute to therapeutic advances. These information could improve researchers' understanding of SARS-CoV-2 and help to accelerate the development of new antiviral treatments.

Advances in spray-dried probiotic microcapsules for targeted delivery: a review.

Probiotics have gained significant attention owing to their roles in regulating human health. Recently, spray drying has been considered as a promising technique to produce probiotic powders due to its advantages of high efficiency, cost-saving, and good powder properties. However, the severe environmental conditions from drying and digestion can significantly reduce cell viability, resulting in poor bioaccessibility and bioavailability of live cells. Therefore, there is a need to develop effective targeted delivery systems using spray drying to protect bacteria and to maintain their physiological functions in the targeted sites. This review highlights recent studies about spray-dried targeted delivery vehicles for probiotics, focusing on key strategies to protect bacteria when encountering external stresses, the formation mechanism of particles, the targeted release and colonization mechanisms of live cells in particles with different structures. Advances in the targeted delivery of live probiotics via spray-dried vehicles are still in their early stages. To increase the possibilities for industrialization and commercialization, functional improvement of microcapsules in terms of protection, targeted release, and colonization of bacteria, as well as the effect of spray drying on bacterial physiological functions in the host, need to be further investigated.

Marixanthotalea marina gen. nov., sp. nov., a bacterium in the family Flavobacteriaceae isolated from seawater.

A Gram-stain-negative, yellow-pigmented, non-motile, rod-shaped, catalase-positive, strictly aerobic marine bacterium, designated XHP0103T, was isolated from seawater collected from the southern Yellow Sea, PR China (34° 45' 53″ N 119° 25' 30″ E). Strain XHP0103T grew optimally at 28 °C, pH 7.5 and in 1.0-3.0 % (w/v) sea salt. MK-6 was the major respiratory quinone. The major cellular fatty acids (>10%) were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The polar lipid profile contained phosphatidylethanolamine, an unidentified aminolipid, an unidentified glycolipid and an unidentified lipid. Results of 16S rRNA gene sequence analysis indicated that strain XHP0103T displayed highest sequence similarity to Aestuariibaculum marinum IP7T (94.1 %). However, the phylogenetic trees based on 16S rRNA gene sequences suggested that strain XHP0103T clustered with Tamlana crocina HST1-43T (93.4 % sequence similarity) and Aestuariivivens insulae AH-MY3T (93.5 %). Genome sequencing revealed that strain XHP0103T comprised 3 134 388 bp with 2770 protein-coding genes, and the DNA G+C content was 35.5 %. The average nucleotide identity and digital DNA-DNA hybridization values between strain XHP0103T and T. crocina HST1-43T were 73.6 and 17.3 %, respectively. Based on phylogenetic, phenotypic, genomic and chemotaxonomic evidence, strain XHP0103T represents a novel genus in the family Flavobacteriaceae, for which the name Marixanthotalea marina gen. nov., sp. nov. is proposed. The type strain is XHP0103T (=MCCC 1K06060T=JCM 34682T).

Time-course RNA-seq analysis reveals stage-specific and melatonin-triggered gene expression patterns during the hair follicle growth cycle in Capra hircus.

BACKGROUND: Cashmere goat is famous for its high-quality fibers. The growth of cashmere in secondary hair follicles exhibits a seasonal pattern arising from circannual changes in the natural photoperiod. Although several studies have compared and analyzed the differences in gene expression between different hair follicle growth stages, the selection of samples in these studies relies on research experience or morphological evidence. Distinguishing hair follicle growth cycle according to gene expression patterns may help to explore the regulation mechanisms related to cashmere growth and the effect of melatonin from a molecular level more accurately. RESULTS: In this study, we applied RNA-sequencing to the hair follicles of three normal and three melatonin-treated Inner Mongolian cashmere goats sampled every month during a whole hair follicle growth cycle. A total of 3559 and 988 genes were subjected as seasonal changing genes (SCGs) in the control and treated groups, respectively. The SCGs in the normal group were divided into three clusters, and their specific expression patterns help to group the hair follicle growth cycle into anagen, catagen and telogen stages. Some canonical pathways such as Wnt, TGF-beta and Hippo signaling pathways were detected as promoting the hair follicle growth, while Cell adhesion molecules (CAMs), Cytokine-cytokine receptor interaction, Jak-STAT, Fc epsilon RI, NOD-like receptor, Rap1, PI3K-Akt, cAMP, NF-kappa B and many immune-related pathways were detected in the catagen and telogen stages. The PI3K-Akt signaling, ECM-receptor interaction and Focal adhesion were found in the transition stage between telogen to anagen, which may serve as candidate biomarkers for telogen-anagen regeneration. A total of 16 signaling pathways, 145 pathway mRNAs, and 93 lncRNAs were enrolled to construct the pathway-mRNA-lncRNA network, which indicated the function of lncRNAs through interacting with their co-expressed mRNAs. Pairwise comparisons between the control and melatonin-treated groups also indicated 941 monthly differentially expressed genes (monthly DEGs). These monthly DEGs were mainly distributed from April and September, which revealed a potential signal pathway map regulating the anagen stage triggered by melatonin. Enrichment analysis showed that Wnt, Hedgehog, ECM, Chemokines and NF-kappa B signaling pathways may be involved in the regulation of non-quiescence and secondary shedding under the influence of melatonin. CONCLUSIONS: Our study decoded the key regulators of the whole hair follicle growth cycle, laying the foundation for the control of hair follicle growth and improvement of cashmere yield.

An Outbreak of Coxsackievirus A6 Infection in Adults of a Collective Unit, China, 2019.

Outbreaks/epidemics caused by coxsackievirus A6 (CVA6) have been reported continuously since 2008. However, outbreaks of ocular conjunctival hemorrhage caused by CVA6 in adults in a collective unit have not been reported. Methods. The epidemiological investigations were carried out according to the monitoring program, and the clinical data were collected from the treated hospitals. The nasopharyngeal swab specimens were collected to extract the total nucleic acid (DNA/RNA). The pathogen was determined using nucleic acid detection kits for 22 respiratory pathogens. The VP1 gene of this pathogen was amplified and sequenced. Sequence alignment and analysis were performed using BioEdit 7.0. The gene phylogenetic tree was constructed with MEGA4.0. Results. The factory emerged patients in succession from February 14 and reached the peak on the 18th. A total of 19 workers had symptoms in this factory up to March 31, 2019, giving an attack rate of 8.26%. The main symptoms were rash, ocular conjunctival hemorrhage, fever, and sore throat. The laboratory results showed that coxsackievirus A6 was the main pathogen causing this outbreak. The risk of taking a bath in the bathroom was 7.37 times higher than that of not taking a bath (95% confidence interval (CI): 1.67-32.79). Conclusion. This manuscript further enriched the infection-related information of CVA6, which was helpful to better identify and deal with the epidemic in the future.

On-off Bodipy chemosensor for recognition of iron(III) ion based on the inner filter effect and its applications in cellular and bacterial imaging.

One strong fluorescent Bodipy-containing derivative was synthesized and characterized using 1 H NMR, electrospray ionization mass spectrometry and elemental analysis. Its electrochemical and photophysical properties were investigated. In addition, the Bodipy derivative could be used as an on-off fluorescent probe for the detection of Fe3+ ions based on the inner filter effect because the absorption band of the Fe3+ ion overlaps the excitation band of Bodipy very well upon irradiation with UV light. Furthermore, the Bodipy-based sensor has obvious advantages including simplicity, rapid response, high selectivity, sensitivity and a detection limit of 1.2 µmol/L, and has been demonstrated in real water samples including tap water, mineral water and water from Lake Tai. Moreover, the fluorescent probe could also be used as a probe for the determination of Fe3+ in cellular and bacterial imaging. Copyright © 2016 John Wiley & Sons, Ltd.

The synthesis and effects of a novel TRPC6 inhibitor, BP3112, on hepatocellular carcinoma.

Aims: Transient receptor potential canonical-6 (TRPC6) is a therapeutic target for hepatocellular carcinoma. The authors aimed to synthesize and determine whether indole-2-carboxamide derivatives have anti-hepatocellular carcinoma activities targeting TRPC6. Materials & methods: Molecular docking was carried out to design these derivatives. The top five compounds were synthesized for activity validation using microscale thermophoresis. Cell cytotoxicity, flow cytometry, western blotting and cell transfection were used to investigate the anti-hepatocellular carcinoma activities and mechanisms in vitro. Xenografts of nude mice were used for in vivo evaluation. Results: The indole-2-carboxamide derivative, BP3112, promoted apoptosis and G1-phase arrest in HCCs via inhibiting TRPC6, and dose-dependently inhibit tumor growth in vivo. Conclusion: BP3112 as a specific inhibitor of TRPC6 is a potential therapeutic agent for hepatocellular carcinoma.

Corrigendum: An integrative serum pharmacology-based approach to study the anti-tumor activity of B. Paniculatum aqueous bulb extract on the human hepatocellular carcinoma cell line BEL-7404.

[This corrects the article DOI: 10.3389/fphar.2020.01261.].

TRPC channels blockade abolishes endotoxemic cardiac dysfunction by hampering intracellular inflammation and Ca2+ leakage.

Intracellular Ca2+ dysregulation is a key marker in septic cardiac dysfunction; however, regulation of the classic Ca2+ regulatory modules cannot successfully abolish this symptom. Here we show that the knockout of transient receptor potential canonical (TRPC) channel isoforms TRPC1 and TRPC6 can ameliorate LPS-challenged heart failure and prolong survival in mice. The LPS-triggered Ca2+ release from the endoplasmic reticulum both in cardiomyocytes and macrophages is significantly inhibited by Trpc1 or Trpc6 knockout. Meanwhile, TRPC's molecular partner - calmodulin - is uncoupled during Trpc1 or Trpc6 deficiency and binds to TLR4's Pococurante site and atypical isoleucine-glutamine-like motif to block the inflammation cascade. Blocking the C-terminal CaM/IP3R binding domain in TRPC with chemical inhibitor could obstruct the Ca2+ leak and TLR4-mediated inflammation burst, demonstrating a cardioprotective effect in endotoxemia and polymicrobial sepsis. Our findings provide insight into the pathogenesis of endotoxemic cardiac dysfunction and suggest a novel approach for its treatment.

Biosugarcane-based carbon support for high-performance iron-based Fischer-Tropsch synthesis.

Exploiting new carbon supports with adjustable metal-support interaction and low price is of prime importance to realize the maximum active iron efficiency and industrial-scale application of Fe-based catalysts for Fischer-Tropsch synthesis (FTS). Herein, a simple, tunable, and scalable biochar support derived from the sugarcane bagasse was successfully prepared and was first used for FTS. The metal-support interaction was precisely controlled by functional groups of biosugarcane-based carbon material and different iron species sizes. All catalysts synthesized displayed high activities, and the iron-time-yield of Fe4/C bio even reached 1,198.9 µmol gFe -1 s-1. This performance was due to the unique structure and characteristics of the biosugarcane-based carbon support, which possessed abundant C-O, C=O (η1(O) and η2(C, O)) functional groups, thus endowing the moderate metal-support interaction, high dispersion of active iron species, more active ε-Fe2C phase, and, most importantly, a high proportion of FexC/Fesurf, facilitating the maximum iron efficiency and intrinsic activity of the catalyst.

A hydrophobic FeMn@Si catalyst increases olefins from syngas by suppressing C1 by-products.

Although considerable efforts have been made in the selective conversion of syngas [carbon monoxide (CO) and hydrogen] to olefins through Fischer-Tropsch synthesis (FTS), ~50% of the converted CO is transformed into the undesired one-carbon molecule (C1) by-products [carbon dioxide (CO2) and methane (CH4)]. In this study, a core-shell FeMn@Si catalyst with excellent hydrophobicity was designed to hinder the formation of CO2 and CH4 The hydrophobic shell protected the iron carbide core from oxidation by water generated during FTS and shortened the retention of water on the catalyst surface, restraining the side reactions related to water. Furthermore, the electron transfer from manganese to iron atoms boosted olefin production and inhibited CH4 formation. The multifunctional catalyst could suppress the total selectivity of CO2 and CH4 to less than 22.5% with an olefin yield of up to 36.6% at a CO conversion of 56.1%.

Seed dressing with mefenpyr-diethyl as a safener for mesosulfuron-methyl application in wheat: The evaluation and mechanisms.

Mesosulfuron-methyl is always applied by foliar spraying in combination with the safener mefenpyr-diethyl to avoid phytotoxicity on wheat (Triticum aestivum L.) cultivars. However, it was observed that the tolerance of Tausch's goatgrass (Aegilops tauschii Coss.) to mesosulfuron-methyl significantly increased in the presence of mefenpyr-diethyl by performing bioassay. This confirmed phenomenon may lead to overuse of mesosulfuron-methyl and weed resistance evolution in field conditions. Therefore, we tested the effect of wheat seed dressing with mefenpyr-diethyl as a possible alternative and disclosed the underlying mechanisms by herbicide dissipation study, enzymatic analysis and transcriptome profiling. The results suggest that increase of ALS activity, enhancement of metabolic processes, and other stress responses are crucial for the regulation of herbicide detoxification induced by mefenpyr-diethyl. Additionally, transcription factors such as AP2/ERF-ERF, bHLH, NAC, and MYB, and protein kinase such as RLK-Pelle_DLSV might play vital regulatory roles. The current study has important implications for mesosulfuron-methyl application in wheat field to control Tausch's goatgrass and provides a comprehensive understanding of the protective effect of mefenpyr-diethyl.

TRPC1 promotes the genesis and progression of colorectal cancer via activating CaM-mediated PI3K/AKT signaling axis.

Transient receptor potential canonical (TRPC) channels are the most prominent nonselective cation channels involved in various diseases. However, the function, clinical significance, and molecular mechanism of TRPCs in colorectal cancer (CRC) progression remain unclear. In this study, we identified that TRPC1 was the major variant gene of the TRPC family in CRC patients. TRPC1 was upregulated in CRC tissues compared with adjacent normal tissues and high expression of TRPC1 was associated with more aggressive tumor progression and poor overall survival. TRPC1 knockdown inhibited cell proliferation, cell-cycle progression, invasion, and migration in vitro, as well as tumor growth in vivo; whereas TRPC1 overexpression promoted colorectal tumor growth and metastasis in vitro and in vivo. In addition, colorectal tumorigenesis was significantly attenuated in Trpc1-/- mice. Mechanistically, TRPC1 could enhance the interaction between calmodulin (CaM) and the PI3K p85 subunit by directly binding to CaM, which further activated the PI3K/AKT and its downstream signaling molecules implicated in cell cycle progression and epithelial-mesenchymal transition. Silencing of CaM attenuated the oncogenic effects of TRPC1. Taken together, these results provide evidence that TRPC1 plays a pivotal oncogenic role in colorectal tumorigenesis and tumor progression by activating CaM-mediated PI3K/AKT signaling axis. Targeting TRPC1 represents a novel and specific approach for CRC treatment.

An Integrative Serum Pharmacology-Based Approach to Study the Anti-Tumor Activity of B. paniculatum Aqueous Bulb Extract on the Human Hepatocellular Carcinoma Cell Line BEL-7404.

The herb Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), also known as Tu-Bei-Mu (TBM) in Chinese, has shown curative effects to treat several types of cancer as an adjunctive therapy. Thereby we intend to find its effect on the human hepatocellular carcinoma (HCC) and to understand the pharmacological mechanism behind it. In this study, an integrative serum pharmacology-based approach linking serum pharmacology and bioinformatics prediction was employed. Firstly, we used the serum taken introgastrically from the rats dministered by TBM aqueous bulb extract to culture the HCC cell line BEL-7404 and detect its anti-tumor effects. Secondly, the TBM putative targets were predicted using the ETCM database and known therapeutic targets of NPC were collected from the OMIM database. Then, a TBM-HCC putative targets network was constructed using the DAVID and STRING databases. Thirdly, key gene targets were obtained based on topological analysis and pathway enrichment analysis. The expression of 4 representative key targets were validated by Western blotting. As a result, 36 TBM targets and 26 known therapeutic targets of HCC were identified. These key targets were found to be frequently involved in 13 KEGG pathways and 4 biological processes. The expression of four representative key targets: TP53, CASP3, BCL2 and BAX further supports the suppression of TBM on HCC. In general, our study shows the curative effects of TBM against HCC. By using this integrative approach, we may find novel potential therapeutic targets to suppress HCC using TBM as an adjunctive therapy. And it could also help us understand the mechanism of HCC treatments in response to TBM.

An Na-modified Fe@C core-shell catalyst for the enhanced production of gasoline-range hydrocarbons via Fischer-Tropsch synthesis.

Although numerous studies have been conducted in the field of converting syngas to value-added fuels, selectively converting syngas to gasoline-range hydrocarbons (C5-12 hydrocarbons) remains a big challenge. Alkali metal (namely, K, Na and Li)-modified Fe@C core-shell catalysts were synthesized by a one-step hydrothermal method for Fischer-Tropsch synthesis. An optimized selectivity of 56% for the C5-12 hydrocarbons with a higher CO conversion of about 95% was obtained for the FeNa2.0@C catalyst compared to that for other alkali metal-modified Fe@C catalysts. According to the characterization results, the incorporation of alkali metals into Fe@C enhanced the conversion of FeCO3 to Fe3O4, which promoted the formation of the FTS active phase iron carbides. In particular, the strongest interaction of Fe-alkali metal and the highest amount of surface carbon layers were observed after adding an Na promoter into Fe@C in contrast to that observed for K and Li promoters, which strengthened the synergistic effect of Fe-Na metals and the spatial confinement of the core-shell structure, further improving the C5-12 hydrocarbon selectivity.

Ni nanocatalysts supported on mesoporous Al2O3-CeO2 for CO2 methanation at low temperature.

The selectivity and activity of a nickel catalyst for the hydrogenation of carbon dioxide to form methane at low temperatures could be enhanced by mesoporous Al2O3-CeO2 synthesized through a one-pot sol-gel method. The performances of the as-prepared Ni/Al2O3-CeO2 catalysts exceeded those of their single Al2O3 counterpart giving a conversion of 78% carbon dioxide with 100% selectivity for methane during 100 h testing, without any deactivation, at the low temperature of 320 °C. The influence of CeO2 doping on the structure of the catalysts, the interactions between the mesoporous support and nickel species, and the reduction behaviors of Ni2+ ions were investigated in detail. In this work, the addition of CeO2 to the composites increased the oxygen vacancies and active metallic nickel sites, and also decreased the size of the nickel particles, thus improving the low temperature catalytic activity and selectivity significantly.

Toxoplasma gondii: proteomic analysis of antigenicity of soluble tachyzoite antigen.

The obligate intracellular parasite Toxoplasma gondii is an important pathogen of humans and animals. The tachyzoite of T. gondii is the main life-cycle stage that is responsible for toxoplasmosis. Study of the antigenicity of soluble tachyzoite antigen (STAg) is important for discovery of protective antigens which will aid in the detection and prevention of toxoplasmosis. At present, no complete proteome map of T. gondii STAg is established, although a large-scale whole proteomic analysis of tachyzoites is underway. In this study, 1227 protein spots of T. gondii soluble tachyzoite antigen (STAg) were fractionated by 2-dimensional electrophoresis (2-DE) at pH range 3-10. By mass spectrometry (MS) analysis, among the separated 1227 protein spots, 426 were identified by searching the Swissport and NCBI nr databases. Two hundred and thirty of these identified spots (230/426, 54%) were demonstrated to be T. gondii protein by MS. Of the 21 Toxoplasma protein spots identified by Western blot with rabbit anti-T. gondii serum, 16 had immunoregulatory functions and five had immune defense functions. Due to multiple spots for a single protein, these 16 spots represented 11 proteins: a putative protein disulfide isomerase (PDI), heat shock protein 60 (Hsp60), a pyruvate kinase (PK), a putative glutamate dehydrogenase (GDH), a coronin, a heat shock protein 70 (Hsp70), a protein kinase C receptor 1 (RACK1), a malate dehydrogenase (MDH), a major surface antigen 1 (SAG1), an uridine phosphorylase (UPase) and a peroxiredoxin (Prx). Among the identified 11 proteins, except that the antigenicity and immunogenicity of the SAG1 has been reported and antigenicity of Hsp70 has been disputed, the remaining antigenic proteins were first identified in this study. In conclusion, we obtained nine novel types of immunogenic proteins that might be potential candidates of vaccine development for toxoplasmosis, which we will confirm in later studies.

Comparative proteomic analysis of Campylobacter jejuni cultured at 37C and 42C.

Campylobacter jejuni has the potential to thrive at 37C (e.g., in the human intestinal tract) and 42C (e.g., in the poultry intestinal tract). We aimed to determine the protein expression profiles of C. jejuni cultured at 37C and 42C in vitro by two-dimensional electrophoresis (2DE). The differentially expressed spots/proteins between C. jejuni cultured at 37C and 42C were defined when their expression differed by twofold. The differently expressed spots detected from C. jejuni cultured both on agar and in broth at 37C and 42C were subjected to protein identification by MALDI-TOF/TOF. Overall, 15 and 20 differentially expressed proteins were defined for C. jejuni cultured at the two temperatures on agar and in broth, respectively. All of the identified differentially expressed proteins could be clustered as proteins involving the metabolism, regulator system, periplasmic proteins and the major antigens of C. jejuni. In conclusion, there are subsets of proteins that are optimally expressed at 37C, which may contribute to the host adaptation and/or the pathogenicity in the human intestinal tract.

Preparation of Ni based mesoporous Al2O3 catalyst with enhanced CO2 methanation performance.

A Ni based mesoporous γ-Al2O3 (MA) catalyst was prepared via partial hydrolysis without organic surfactants and employed in the carbon dioxide methanation reaction. The obtained catalysts were characterized by N2 adsorption-desorption, H2-TPR, XRD, XPS, TG, SEM and TEM-EDS techniques. CO2 methanation was performed in a fixed-bed reactor. A high surface area of MA with excellent hydrothermal stability was obtained, which promoted the dispersion of nickel species, producing a better catalytic performance. Incorporation of more NiO species into the Ni/MA catalyst increased the amount of active metallic Ni sties, further improving the catalytic activity and CH4 selectivity. Moreover, the monolithic skeleton of MA with fabric-like walls suppressed the aggregation of active metallic Ni sites and carbon deposition, enhancing the catalyst's stability, which provides a new insight for potential industrial applications.