In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. ...For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
Neutrophils play essential anti-microbial and inflammatory roles in host defense, however, their activities require tight regulation as dysfunction often leads to detrimental inflammatory and ...autoimmune diseases. Here we show that the adhesion molecule GPR97 allosterically activates CD177-associated membrane proteinase 3 (mPR3), and in conjugation with several protein interaction partners leads to neutrophil activation in humans. Crystallographic and deletion analysis of the GPR97 extracellular region identified two independent mPR3-binding domains. Mechanistically, the efficient binding and activation of mPR3 by GPR97 requires the macromolecular CD177/GPR97/PAR2/CD16b complex and induces the activation of PAR2, a G protein-coupled receptor known for its function in inflammation. Triggering PAR2 by the upstream complex leads to strong inflammatory activation, prompting anti-microbial activities and endothelial dysfunction. The role of the complex in pathologic inflammation is underscored by the finding that both GPR97 and mPR3 are upregulated on the surface of disease-associated neutrophils. In summary, we identify a PAR2 activation mechanism that directs neutrophil activation, and thus inflammation. The PR3/CD177/GPR97/PAR2/CD16b protein complex, therefore, represents a potential therapeutic target for neutrophil-mediated inflammatory diseases.
Metformin may offer benefits to certain cancer populations experiencing metabolic abnormalities. To extend the anticancer studies of metformin, a tumor model was established through the implantation ...of murine Lewis Lung Carcinoma (LLC) cells to Normal Diet (ND)-fed and High-Fat Diet (HFD)-fed C57BL/6 mice. The HFD-fed mice displayed metabolic and pro-inflammatory alterations together with accompanying aggressive tumor growth. Metformin mitigated tumor growth in HFD-fed mice, paralleled by reductions in circulating glucose, insulin, soluble P-selectin, TGF-β1 and High Mobility Group Box-1 (HMGB1), as well as tumor expression of cell proliferation, aerobic glycolysis, glutaminolysis, platelets and neutrophils molecules. The suppressive effects of metformin on cell proliferation, migration and oncogenic signaling molecules were confirmed in cell study. Moreover, tumor-bearing HFD-fed mice had higher contents of circulating and tumor immunopositivity of Neutrophil Extracellular Traps (NETs)-associated molecules, with a suppressive effect from metformin. Data taken from neutrophil studies confirmed the inhibitory effect that metformin has on NET formation induced by HMGB1. Furthermore, HMGB1 was identified as a promoting molecule to boost the transition process towards NETs. The current study shows that metabolic, pro-inflammatory and NET alterations appear to play roles in the obesity-driven aggressiveness of cancer, while also representing candidate targets for anticancer potential of metformin.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion ...(QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification. Methods The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding “herb-compound-target” network of QFHXD. The protein–protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments. Results A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1β, STAT3, MMP-9, and TGF-β1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-β1/Smad2/3. Conclusions QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-β1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use of seawater electrolysis for hydrogen production faces several serious challenges, including the rapid deactivation of electrocatalysts through chloride anion (Cl − ) induced corrosion. We ...have demonstrated that Ru nanoparticles possessing an abundance of surface hydroxyl groups along with borate species (Ru–BO x –OH) exhibit high activity and stability as electrocatalysts for seawater splitting. The optimal electrocatalyst (Ru–BO x –OH-300) uncovered in this study displays an extremely high catalytic performance for both the hydrogen (HER) and oxygen (OER) evolution reactions in alkaline seawater (HER, 22 mV and OER, 235 mV at 10 mA cm −2 ), as well as a low cell voltage (1.47 V) and ultra-long-term stability (1000 hours at 10, 50 and 100 mA cm −2 ) for overall seawater splitting. Furthermore, the Ru–BO x –OH-300-based anion-exchange membrane seawater electrolyzer requires only 1.73 or 1.95 V to reach a current density of 500 or 1000 mA cm −2 , respectively, and exhibits excellent stability for 400 hours without obvious decay. The results of the experiments and theoretical calculations reveal that the high water affinity of Ru–BO x –OH-300 caused by the presence of hydroxyl and borate species on the metallic Ru surface is responsible for the superb electrocatalytic performance and that the borate species are the source of Cl − corrosion resistance. These findings provide new perspectives for the design of high-performance electrocatalysts for seawater splitting.
Elevation of intracellular cAMP levels has been implicated in glioma cell proliferation inhibition, differentiation, and apoptosis. Inhibition of phosphodiesterase is a way to elevate intracellular ...cAMP levels. The present study aimed to investigate the anti-glioma potential of dipyridamole, an inhibitor of phosphodiesterase. Upon treatment with dipyridamole, human U87 glioma cells decreased cell viability, clonogenic colonization, migration, and invasion, along with Noxa upregulation, Endoplasmic Reticulum (ER) stress, impaired autophagic flux, Yes-associated Protein 1 (YAP1) phosphorylation, and YAP1 reduction. Pharmacological and genetic studies revealed the ability of dipyridamole to initiate Noxa-guided apoptosis through ER stress. Additionally, the current study further identified the biochemical role of YAP1 in communicating with ER stress and autophagy under situations of dipyridamole treatment. YAP1 promoted autophagy and protected glioma cells from dipyridamole-induced apoptotic cell death. Dipyridamole impaired autophagic flux and rendered glioma cells more vulnerable to apoptotic cell death through ER stress-inhibitable YAP1/autophagy axis. The overall cellular changes caused by dipyridamole appeared to ensure a successful completion of apoptosis. Dipyridamole also duplicated the biochemical changes and apoptosis in glioma T98G cells. Since dipyridamole has additional biochemical and pharmacological properties, further research centered on the anti-glioma mechanisms of dipyridamole is still needed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•H-type finned tube heat exchangers are optimized using Taguchi method.•Parametric influence is investigated by intuitive analysis and analysis of variance.•Effective design parameters for overall ...thermal–hydraulic performance are fin pitch, fin height and fin thickness.•The optimal parametric combination is validated to have better overall thermal–hydraulic performance.
In this paper, a three-dimensional numerical model of H-type finned tube heat exchangers has been built. In order to optimize its structure and improve its performance, Taguchi method is applied to investigate the influence of seven geometric parameters including slit width, row number, fin height, spanwise tube pitch, longitudinal tube pitch, fin thickness and fin pitch. Numerical simulations are performed on eighteen cases with different combinations of seven geometric parameters and the overall thermal–hydraulic performance and its characteristics of heat transfer and flow friction are discussed in detail. The results show that fin pitch and fin height play a significant role on the heat transfer characteristics while the flow friction characteristics are mainly affected by fin height, spanwise tube pitch and fin pitch. The intuitive analysis and analysis of variance show that fin pitch, fin height and fin thickness have much stronger influence on its overall thermal–hydraulic performance than the rest four parameters. Finally, the optimal parametric combination of the H-type finned tube is obtained with an improvement of overall thermal–hydraulic performance by 11.4–16% for Re in range from 9000 to 24,000.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
48.
Past and future on nanodielectrics Zhong, Shao-Long; Dang, Zhi-Min; Zhou, Wen-Ying ...
IET Nanodielectrics,
April 2018, Volume:
1, Issue:
1
Journal Article
Peer reviewed
Open access
Flexible polymer-matrix nanodielectrics have recently been attracting more attention in the fields of frontier research internationally since the beginning of the 21st century. It would accelerate a ...technical reformation for the applications in new energies, bioscience and biomedical engineering, artificial intelligence, electronic skin, wearable electronic clothing, Internet of things, and electrical insulation. This review summarises the recent development and achievements of nanodielectrics, including space charge suppression, high energy density storage, partial discharge resistance, non-linear field grading properties, high thermal conductivity, and future applications in biomedical area. Special attention is given to two representative interface models that are the Lewis's diffusion electrical double-layer model and Tanaka's multi-core model. At last, some issues related to the technology of nanodielectrics have also been discussed.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Myocardial ischemia and reperfusion injury (MIRI) includes major drawbacks, such as excessive formation of free radicals and also overload of calcium, which lead to cell death, tissue scarring, and ...remodeling. The current study aims to explore whether KRT1 silencing may ameliorate MIRI via the Notch signaling pathway in mouse models. Myocardial tissues were used for the determination of the positive rate of KRT1 protein expression, apoptosis of myocardial cells, creatine kinase (CK) and lactate dehydrogenase (LDH) expression, expression of related biomarkers as well as myocardial infarction area. The transfected myocardial cells were treated with KRT1‐siRNA, Jagged1, and DAPT (inhibitor of Notch‐1 signaling pathway). The expression of KRT1, NICD, Hes1, Bcl‐2, and Bax protein was detected. The MTT assay was applied for cell proliferation and flow cytometry was used for cell apoptosis. Mice with MIRI had a higher positive rate of KRT1 protein expression, apoptosis of myocardial cells, CK and LDH expression, myocardial infarction area, increased expression of MDA, NO, SDH, IL‐1, IL‐6, TNF‐α, CRP, KRT1, Bax protein, CK, and LDH, and decreased expression of SOD, NICD, Hes1, and Bcl‐2. The downregulation of KRT1 led to decreased expression of KRT1 and Bax protein, increased expression of NICD, Hes1, and Bcl‐2, decreased cell apoptosis, and improved cell proliferation. The inhibition of the Notch signaling pathway leads to reduced expression of Bax, increased expression of NICD, Hes1, and Bcl 2, and also decreased cell apoptosis and increased cell proliferation. Our data conclude that KRT1 silencing is able to make MIRI better by activating the Notch signaling pathway in mice.
Our data conclude that KRT1 silencing is able to alleviate MIRI by activating the Notch signaling pathway in mice.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Detecting viable circulating tumor cells (CTCs) without disruption to their functions for in vitro culture and functional study could unravel the biology of metastasis and promote the development of ...personalized anti-tumor therapies. However, existing CTC detection approaches commonly include CTC isolation and subsequent destructive identification, which damages CTC viability and functions and generates substantial CTC loss. To address the challenge of efficiently detecting viable CTCs for functional study, we develop a nanosphere-based cell-friendly one-step strategy. Immunonanospheres with prominent magnetic/fluorescence properties and extraordinary stability in complex matrices enable simultaneous efficient magnetic capture and specific fluorescence labeling of tumor cells directly in whole blood. The collected cells with fluorescent tags can be reliably identified, free of the tedious and destructive manipulations from conventional CTC identification. Hence, as few as 5 tumor cells in ca. 1mL of whole blood can be efficiently detected via only 20min incubation, and this strategy also shows good reproducibility with the relative standard deviation (RSD) of 8.7%. Moreover, due to the time-saving and gentle processing and the minimum disruption of immunonanospheres to cells, 93.8±0.1% of detected tumor cells retain cell viability and proliferation ability with negligible changes of cell functions, capacitating functional study on cell migration, invasion and glucose uptake. Additionally, this strategy exhibits successful CTC detection in 10/10 peripheral blood samples of cancer patients. Therefore, this nanosphere-based cell-friendly one-step strategy enables viable CTC detection and further functional analyses, which will help to unravel tumor metastasis and guide treatment selection.
•CTCs and WBCs were efficiently and specifically labeled with different IFNs tags.•Simultaneous capture and identification of CTCs were realized by coupled IMNs and IFNs.•One-step strategy shortened time consumption and improved efficiency of CTC detection.•The strategy was cell-friendly to detect viable CTCs for culture and functional study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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