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1.
DNA Cell Biol ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32352838

RESUMO

The roof plate-specific spondin (RSPO) family of proteins has critical roles in the tumorigenesis and progression of several carcinomas; however, little is known about their functions in bladder cancer (BLCA). This study aimed to investigate RSPO in terms of their expression levels, prognostic value, and potential mechanisms of action in BLCA. mRNA expression profiles and clinical information of BLCA patients were collected from The Cancer Genome Atlas database. Genetic alteration and DNA methylation data were obtained from cBioPortal and MethHC databases, respectively, and SurvExpress was used to determine the prognostic risk score of each RSPO. R software was used to analyze the expression levels and prognostic roles of RSPOs in BLCA. The effects of RSPO2 overexpression in BLCA cells were detected using MTT, colony formation, and Transwell invasion assays. Gene set enrichment analysis (GSEA) was used to analyze the functions of RSPOs and associated signaling pathways in BLCA. All members of the RSPO family were differentially expressed in BLCA cells compared with normal control cells. Aberrant RSPO expression levels were associated with higher histological stages and worse prognosis. The frequency of genetic alterations in RSPO genes was very high, which was related to a less favorable prognosis. Moreover, the effects of mutations in the RSPO2 gene were reversed using a Wnt/ß-catenin inhibitor, IWP-2. In addition, GSEA demonstrated that RSPOs were associated with focal adhesion and immune cell infiltration, which was then confirmed by tumor immune cell infiltration analysis. RSPOs are potential biomarkers for predicting the prognosis of patients with BLCA and may serve as novel therapeutic targets. Moreover, overexpressed RSPO2 promoted BLCA cell growth and invasion through the Wnt/ß-catenin pathway. In addition, RSPOs may regulate the progression of BLCA through modulating cell adhesion, focal adhesion, and CD4+ T cell and macrophage infiltration.

2.
FEMS Yeast Res ; 20(3)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32391887

RESUMO

Cryptococcus neoformans is an important invasive fungal pathogen that causes life-threatening meningoencephalitis in humans. Its biological and pathogenic regulatory mechanisms remain largely unknown, particularly due to the presence of those core transcription factors (TFs). Here, we conducted a detailed characterization of the TF Liv4 in the biology and virulence of C. neoformans. Deletion of TF Liv4 protein resulted in growth defect under both normal and stress conditions (such as high temperature and cell wall/membrane damaging agents), drastic morphological damage and also attenuated virulence in C. neoformans. These phenotypic changes might be contributed to transcriptional abnormality in the liv4Δ mutant, in which several cryptococcal genes involved in energy metabolism and cell wall integrity were downregulated. Furthermore, ChIP-seq and ChIP-qPCR assays suggested TF Liv4 might exert its regulatory function in transcription by its activation of RBP1 in C. neoformans. Taken together, our work highlights the importance of TF Liv4 in the growth and virulence of C. neoformans, and it facilitates a better understanding of cryptococcal pathogenesis mechanisms.

3.
Phys Chem Chem Phys ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400803

RESUMO

Determining the precise structures of small gold clusters is an essential step towards understanding their chemical and physical properties. Due to the relativistic nature of gold, its clusters remain planar (2D) up to appreciable sizes. Ion mobility experiments have suggested that positively charged gold clusters adopt three-dimensional (3D) structures from n = 8 onward. Computations predict, depending on the level of theory, 2D or 3D structures as putative energy-minimum for n = 8. In this work, far-infrared multiple photon dissociation spectroscopy, using Ar as tagging element, is combined with density-functional theory calculations to determine the structures of Aun+ (n ≤ 9) clusters formed by laser ablation. While the Au frameworks in Au6Arm+ and Au7Arm+ complexes are confirmed to be planar and that in Au9Arm+ three-dimensional, we demonstrate the coexistence of 3D and planar Au8Arm+ (m = 1-3) isomers. Thus, it is revealed that at finite temperatures, the formal 2D to 3D transition takes place at n = 8 but is not sharp.

4.
BMC Infect Dis ; 20(1): 330, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32384874

RESUMO

BACKGROUND: Dynamically changed levels of serum cytokines might predict the development of active TB from latent tuberculosis infection (LTBI) and monitor preventive treatment effectiveness. The aim of the study was to identify potential serum cytokines associated with LTBI treatment which might predict active disease development in a Chinese population. METHODS: Based on a randomized controlled trial aiming to explore short-course regimens for LTBI treatment, the dynamic changes of serum cytokines determined by bead-based multiplex assays were investigated for the participants who developed active TB during follow-up and age and gender matched controls stayed healthy. RESULTS: Totally, 21 patients diagnosed with active tuberculosis (TB) during the 2-year follow-up (12 from treated groups and 9 from untreated controls) and 42 age and gender matched healthy controls (24 from treated groups and 18 from untreated controls) were included in the study. Before treatment, serum IL-1ra was statistically higher among those who developed active disease during follow-up as compared with those stayed healthy. As for treated participants, the levels of IL-1ra were significantly lower after treatment in comparison with those before treatment both in active TB group (p = 0.002) and non-TB group (p = 0.009). For untreated participants, the levels of IL-1ra were not statistically different between different time points both in active TB group (p = 0.078) and non-TB group (p = 0.265). CONCLUSION: Our results suggested that declined serum level of IL-1ra was associated with LTBI treatment. Further studies are needed to verify whether it could be used to evaluate LTBI treatment and to predict active disease development.

5.
Med Phys ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32428969

RESUMO

PURPOSE: Pulmonary nodules are a potential manifestation of lung cancer. In computer-aided diagnosis (CAD) of lung cancer, it is of great significance to extract the complete boundary of the pulmonary nodules in the CT (computed tomography) scans accurately. It can provide doctors with important information such as tumor size and density, which assist doctors in subsequent diagnosis and treatment. In addition to this, in the molecular subtype and radiomics of lung cancer, segmentation of lung nodules also plays a pivotal role. Existing methods are difficult to use only one model to simultaneously treat the boundaries of multiple types of lung nodules in CT images. METHOD: In order to solve the problem, this paper proposed a 3D-UNET network model optimized by 3D-CRF (three-dimensional conditional random field) to segment pulmonary nodules. On the basis of 3D-UNET, the 3D-CRF is used to optimize the sample output of the training set, so as to update the network weights in training process, reduce the model training time and reduce the loss rate of the model. We selected 936 sets of pulmonary nodules data onto the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) 1 database to train and test the model. What's more, we used clinical data from partner hospitals for additional validation. RESULTS AND CONCLUSIONS: The results show that our method is accurate and effective. Particularly, it shows more significant for the optimization of the segmentation of adhesive pulmonary nodules (the juxta-pleural and juxta-vascular nodules) and ground glass pulmonary nodules (GGNs).

6.
Int J Nanomedicine ; 15: 2971-2986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431496

RESUMO

Background: Due to their extraordinary physical and chemical properties, MoS2 nanosheets (MSNs) are becoming more widely used in nanomedicine. However, their influence on immune systems remains unclear. Materials and Methods: Two few-layered MSNs at sizes of 100-250 nm (S-MSNs) and 400-500 nm (L-MSNs) were used in this study. Bone marrow-derived dendritic cells (DCs) were exposed to both MSNs at different doses (0, 8, 16, 32, 64, 128 µg/mL) for 48 h and subjected to analyses of surface marker expression, cytokine secretion, lymphoid homing and in vivo T cell priming. Results: Different-sized MSNs of all doses did not affect the viability of DCs. The expression of CD40, CD80, CD86 and CCR7 was significantly higher on both S-MSN- and L-MSN-treated DCs at a dose of 128 µg/mL. As the dose of MSN increased, the secretion of IL-12p70 remained unchanged, the secretion of IL-1ß decreased, and the production of TNF-α increased. A significant increase in IL-6 was observed in the 128 µg/mL L-MSN-treated DCs. In particular, MSN treatment dramatically improved the ex vivo movement and in vivo homing ability of both the local resident and blood circulating DCs. Furthermore, the cytoskeleton rearrangement regulated by ROS elevation was responsible for the enhanced homing ability of the MSNs. More robust CD4+ and CD8+ T cell proliferation and activation (characterized by high expression of CD107a, CD69 and ICOS) was observed in mice vaccinated with MSN-treated DCs. Importantly, exposure to MSNs did not interrupt LPS-induced DC activation, homing and T cell priming. Conclusion: Few-layered MSNs ranging from 100 to 500 nm in size could play an immunostimulatory role in enhancing DC maturation, migration and T cell elicitation, making them a good candidate for vaccine adjuvants. Investigation of this study will not only expand the applications of MSNs and other new transition metal dichalcogenides (TMDCs) but also shed light on the in vivo immune-risk evaluation of MSN-based nanomaterials.

7.
Asian J Psychiatr ; 52: 102144, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32417746

RESUMO

BACKGROUND: The reliability and validity of the Griffiths Development Scales-Chinese (GDS-C) for autistic children in China are unknown. Thus, it is urgent to verify the instrument's reliability and validity in this population. The aim of the study was to explore whether the GDS-C is reliable and valid for assessing neurodevelopment in autistic children. METHOD: This study included 296 autistic children and 141 typically developing children from 3 to 8 years of age in China. The reliability of the scale was estimated based on its internal consistency, test-retest reliability and interrater reliability. The validity of the scale was calculated based on the construct validity, discriminate validity and criterion validity. Receiver operating characteristic curves were used to calculate the general quotients (GQs) corresponding to the diagnostic classification within the Childhood Autism Rating Scale (CARS) scores. RESULTS: This study shows sufficient reliability (Cronbach's alpha = 0.957; test-retest reliability = 0.945 for the whole scale and 0.830-0.919 for the subscales; interrater reliability = 0.925 for the whole scale and 0.796-0.919 for the subscales). The results also provide good support for the validity of the GDS-C. In the discriminant analysis, 85.5% of the children in the autistic sample were correctly classified. The cutoff value for distinguishing autistic children from normal children within the CARS scale corresponds to a GQ of 84.83, and that for distinguishing severely autistic children from mild or moderately autistic children corresponds to a GQ of 66.60. CONCLUSION: Our findings suggest that the GDS-C may be a valid and reliable tool for assessing the neurodevelopment of autistic children.

8.
Elife ; 92020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374261

RESUMO

The histone modification writer Prdm9 has been shown to deposit H3K4me3 and H3K36me3 at future double-strand break (DSB) sites during the very early stages of meiosis, but the reader of these marks remains unclear. Here, we demonstrate that Zcwpw1 is an H3K4me3 reader that is required for DSB repair and synapsis in mouse testes. We generated H3K4me3 reader-dead Zcwpw1 mutant mice and found that their spermatocytes were arrested at the pachytene-like stage, which phenocopies the Zcwpw1 knock-out mice. Based on various ChIP-seq and immunofluorescence analyses using several mutants, we found that Zcwpw1's occupancy on chromatin is strongly promoted by the histone-modification activity of PRDM9. Zcwpw1 localizes to DMC1-labelled hotspots in a largely Prdm9-dependent manner, where it facilitates completion of synapsis by mediating the DSB repair process. In sum, our study demonstrates the function of ZCWPW1 that acts as part of the selection system for epigenetics-based recombination hotspots in mammals.

9.
Cell Death Dis ; 11(5): 367, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409702

RESUMO

Sunitinib has been used as the main therapy to treat the metastatic clear cell renal cell carcinoma (ccRCC) as it could function via suppressing the tumor growth and angiogenesis. Yet most ccRCC tumors may still regrow due to the development of sunitinib-resistance, and detailed mechanisms remain to be further investigated. The angiopoietin family includes angiopoietin-1 and angiopoietin-2 (ANGPT-1 and -2). It was reported that estradiol regulates expression of ANGPT-1, but not ANGPT-2, through estrogen receptor α (ERα) in an experimental stroke model. To date, there is no finding to link the E2/ER signal on regulating ANGPT-2. Our study is the first to explore (i) how estrogen receptor ß (ERß) can up-regulate ANGPT-2 in RCC cells, and (ii) how ERß-increased ANGPT-2 can promote the HUVEC tube formation and reduce sunitinib sensitivity. Mechanistic studies revealed that ERß could function via transcriptional regulation of the cytokine ANGPT-2 in the ccRCC cells. We found the up-regulated ANGPT-2 of RCC cells could then increase the Tie-2 phosphorylation to promote the angiogenesis and increase sunitinib treatment resistance of endothelial cells. In addition to the endothelial cell tube formation and aortic ring assay, preclinical studies with a mouse RCC model also confirmed the finding. Targeting this newly identified ERß/ANGPT-2/Tie-2 signaling pathway with the FDA-approved anti-estrogen, Faslodex, may help in the development of a novel combined therapy with sunitinib to better suppress the ccRCC progression.

10.
Sci Rep ; 10(1): 8010, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409739

RESUMO

This retrospective study aimed to analyze the clinical outcomes of two regimens of intravitreal injections of conbercept [1+pro re nata (PRN) and 3 + Q3M] for the therapy of exudative age-related macular degeneration (AMD). In total, 105 eyes diagnosed with exudative AMD were enrolled. The eyes in the 1+PRN group (n = 51) received intravitreal injection of conbercept one time, followed by PRN retreatment. The eyes in the 3 + Q3M group (n = 54) received intravitreal injection of conbercept on three consecutive monthly, subsequently, once every three months for three times. After treatment, patients were followed up for 12 months. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), and choroidal neovascularization (CNV) leakage area were compared before and after treatment. Moreover, the number of injections and adverse reactions were recorded. Compared with the 1+PRN group, BCVA was significantly improved and CRT was remarkably decreased in the 3 + Q3M group at 3, 6 and 12 months after operation. The disappeared or reduced CNV leakage area (93%) of the 3 + Q3M group was higher than that of the 1 + PRN group at the last follow-up. Moreover, the mean numbers of conbercept injections of the 1 + PRN group were less than the 3 + Q3M group. During the follow-up, there were no serious adverse reactions or ocular complications. This study reveals that intravitreal injection of conbercept using 3 + Q3M regimen has certain advantages than 1 + PRN regimen in extending drug delivery interval, improving patient's vision, and reducing CRT.

11.
Gene ; 750: 144759, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32423892

RESUMO

Zinc transporters play vital roles in regulating zinc content and localization by mobilizing zinc across cellular and intracellular membranes. Pacific oyster Crassostrea gigas is one of the most zinc-rich animals, which has been regarded as an excellent food for zinc supplement. But the information about zinc transporters and their involvements in zinc accumulation in oysters is still limited. In the present study, a total of 28 zinc transporter genes, including nine Zinc transporter genes (CgZnTs) and 19 Zrt/Irt-like protein genes (CgZIPs), were identified in C. gigas genome using a genome-wide search strategy. There were five ZIP10 homologs in C. gigas, which were much more than those in mammals, fish and other mollusks. Among oyster zinc transporters, immense variations were detected in their gene structure, protein length and physicochemical properties. Phylogenetic analysis showed that most of these transporters were distinctly clustered with their homologs from Homo sapiens, Danio rerio and other mollusks, and the most closely related transporters shared similar motif compositions. The highest zinc content was detected in the oyster mantle and gill, while the lowest level was found in the adductor muscle. The mRNA of all tested CgZnTs and CgZIPs were constitutively expressed in oyster tissues, and most of them were highly expressed in the gill or hepatopancreas. The analysis of RNA-seq data from gill and hepatopancreas showed that all the transporters exhibited divergent response patterns under zinc stress, except for CgZIP4 whose expression was almost undetectable in the two tissues. The results indicated that zinc transporters played important roles in the regulation of zinc homeostasis in C. gigas, which provided a solid foundation for further functional analysis of zinc transporters in oysters and other mollusks.

12.
Gigascience ; 9(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32315029

RESUMO

BACKGROUND: Jellyfish belong to the phylum Cnidaria, which occupies an important phylogenetic location in the early-branching Metazoa lineages. The jellyfish Rhopilema esculentum is an important fishery resource in China. However, the genome resource of R. esculentum has not been reported to date. FINDINGS: In this study, we constructed a chromosome-level genome assembly of R. esculentum using Pacific Biosciences, Illumina, and Hi-C sequencing technologies. The final genome assembly was ∼275.42 Mb, with a contig N50 length of 1.13 Mb. Using Hi-C technology to identify the contacts among contigs, 260.17 Mb (94.46%) of the assembled genome were anchored onto 21 pseudochromosomes with a scaffold N50 of 12.97 Mb. We identified 17,219 protein-coding genes, with an average CDS length of 1,575 bp. The genome-wide phylogenetic analysis indicated that R. esculentum might have evolved more slowly than the other scyphozoan species used in this study. In addition, 127 toxin-like genes were identified, and 1 toxin-related "hub" was found by a genomic survey. CONCLUSIONS: We have generated a chromosome-level genome assembly of R. esculentum that could provide a valuable genomic background for studying the biology and pharmacology of jellyfish, as well as the evolutionary history of Cnidaria.

13.
Respir Res ; 21(1): 83, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293449

RESUMO

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.


Assuntos
Infecções por Coronavirus , Mortalidade Hospitalar , Peptídeo Natriurético Encefálico/análise , Pandemias , Fragmentos de Peptídeos/análise , Pneumonia Viral , Adulto , Idoso , Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Valor Preditivo dos Testes , Prognóstico , Valores de Referência , Estudos Retrospectivos , Fatores de Risco
14.
J Med Virol ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32301508

RESUMO

Several systematic reviews (SRs) have been conducted on the COVID-19 outbreak, which together with the SRs on previous coronavirus outbreaks, form important sources of evidence for clinical decision and policy making. Here, we investigated the methodological quality of SRs on COVID-19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). Online searches were performed to obtain SRs on COVID-19, SARS, and MERS. The methodological quality of the included SRs was assessed using the AMSTAR-2 tool. Descriptive statistics were used to present the data. In total, of 49 SRs that were finally included in our study, 17, 16, and 16 SRs were specifically on COVID-19, MERS, and SARS, respectively. The growth rate of SRs on COVID-19 was the highest (4.54/month) presently. Of the included SRs, 6, 12, and 31 SRs were of moderate, low, and critically low quality, respectively. SRs on SARS showed the optimum quality among the SRs on the three diseases. Subgroup analyses showed that the SR topic (P < .001), the involvement of a methodologist (P < .001), and funding support (P = .046) were significantly associated with the methodological quality of the SR. According to the adherence scores, adherence to AMSTAR-2 items sequentially decreased in SRs on SARS, MERS, and COVID-19. The methodological quality of most SRs on coronavirus outbreaks is unsatisfactory, and those on COVID-19 have higher risks of poor quality, despite the rapid actions taken to conduct SRs. The quality of SRs should be improved in the future. Readers must exercise caution in accepting and using the results of these SRs.

15.
Adv Mater ; 32(19): e1908314, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32239583

RESUMO

Materials possessing structural phase transformations exhibit a rich set of physical and chemical properties that can be used for a variety of applications. In 2D materials, structural transformations have so far been induced by strain, lasers, electron injection, electron/ion beams, thermal loss of stoichiometry, and chemical treatments or by a combination of such approaches and annealing. However, stoichiometry-preserving, purely thermal, reversible phase transitions, which are fundamental in physics and can be easily induced, have not been observed. Here, the fabrication of monolayer Cu2 Se, a new 2D material is reported, demonstrating the existence of a purely thermal structural phase transition. Scanning tunneling microscopy, scanning transmission electron microscopy, and density functional theory (DFT) identify two structural phases at 78 and 300 K. DFT calculations trace the phase-transition mechanism via the existence/absence of imaginary (unstable) phonon modes at low and high temperatures. In situ, variable-temperature low-energy electron diffraction patterns demonstrate that the phase transition occurs across the whole sample at ≈147 K. Angle-resolved photoemission spectra and DFT calculations show that a degeneracy at the Γ point of the energy bands of the high-temperature phase is lifted in the low-temperature phase. This work opens up possibilities for studying such phase transitions in 2D materials.

16.
J Integr Med ; 18(3): 229-241, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32307268

RESUMO

OBJECTIVE: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS. METHODS: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS. RESULTS: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CLpro), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CLpro inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches. CONCLUSION: RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.


Assuntos
Antivirais/química , Betacoronavirus/química , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Pneumonia Viral/tratamento farmacológico , Antivirais/uso terapêutico , Betacoronavirus/enzimologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Cisteína Endopeptidases/química , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Espectrometria de Massas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Mapas de Interação de Proteínas , Proteínas não Estruturais Virais/química
17.
Mol Oncol ; 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306523

RESUMO

High-mobility group protein B1 (HMGB1) has important functions in cancer cell proliferation and metastasis. However, the mechanisms of HMGB1 function in non-small-cell lung cancer (NSCLC) remain unclear. This study aimed to investigate the underlying mechanism of HMGB1-dependent tumor cell proliferation and NSCLC metastasis. Firstly, we found high HMGB1 expression in NSCLC and showed that HMBG1 promoted proliferation, migration, and invasion of NSCLC cells. HMGB1 could bind to SNAI1 promoter and activate the expression of SNAI1. In addition, HMGB1 could transcriptionally regulate the lncRNA RSF1-IT2. RSF1-IT2 was found to function as ceRNA, sponging miR-129-5p, which targets SNAI1. Notably, HMGB1 was also identified as a target of miR-129-5p, which indicates the establishment of a positive feedback loop. Consequently, high expression of RSF1-IT2 and SNAI1 was found to closely correlate with tumor progression in both HMGB1-overexpressing xenograft nude mice and patients with NSCLC. Taken together, our findings provide new insights into molecular mechanisms of HMGB1-dependent tumor metastasis. Components of the HMGB1-RSF1-IT2-miR-129-5p-SNAI1 pathway may have a potential as prognostic and therapeutic targets in NSCLC.

18.
J Cell Mol Med ; 24(10): 5797-5810, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32281273

RESUMO

At present, the overall genetic and epigenetic effects of Krüppel-like factors (KLFs) on prostate cancer (PCa) remain unclear. Therefore, we systematically investigated the molecular differences in KLFs of transcription expression, promoter methylation and genetic alteration. Univariate and multivariate Cox proportional hazard regression was used to analyse the effect on RFS and establish the prognostic signature in the TCGA cohort, MSKCC and GSE116918 cohorts employed to validate the signature. Biological pathway enrichment and the potential response to immunotherapy and chemotherapy were inferred. The transcription levels of most KLFs are associated with the clinical outcome of PCa. Gleason score (P = .009), pathology T stage (P = .006), KLF3 (P = .034), KLF5 (P = .002) and KLF7 (P = .035) were independent prognostic factors. A prognostic signature was established in the TCGA cohort (P < .001) and validated in the MSKCC (P < .001) and GSE116918 cohorts (P = .006). Demethylation of KLF5 by 5-azacytidine led to increased protein levels, whereas knockdown of KLF5 promoted cell proliferation. Patients in KLF-F were more likely to respond to immunotherapy (P < .001) and bicalutamide (P < .001). In summary, we found that the KLFs and clinical feature-based signatures may improve prognosis prediction in PCa and further promote patient stratification and disease management.

19.
J Hazard Mater ; 395: 122698, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32334279

RESUMO

Vanadium slag contains high contents of vanadium and chromium with complex and dense structures, hence microwave heating instead of conventional methods is expected to destroy the dense structure and further to improve the extraction rate of vanadium and chromium, and exploring its dielectric properties is the prerequisite work. Microwave absorption properties and thermal behavior of vanadium slag were investigated. Results indicated that vanadium slag endowed excellent microwave absorption properties, with minimum εr' value of 34.447 (F/M). Dielectric properties of vanadium slag varied with temperature, which changing trend was matched to the three stages of microwave heating characteristics identified by heating rates. Meanwhile, the changing process of dielectric properties also corresponded to the three processes of thermogravimetric characteristics: dehydration stage (30 °C-280 °C), oxidation decomposition of olivine phase and normal spinel phase (280 °C-650 °C), and oxidation decomposition of vanadium chromium spinel (650 °C-950 °C). Moreover, the maximum dielectric constant and highest microwave heating rate of vanadium slag both appeared at the temperature regime of 500 °C-550 °C, which was also the main temperature regime for oxidation decomposition of olivine phase and normal spinel phase in vanadium slag, demonstrating the appropriate process temperature for microwave heating technology to recycle vanadium slag.

20.
Nanoscale ; 12(14): 7857-7863, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32227006

RESUMO

Simultaneously achieving low friction and fine electrical conductance of sliding electrical contacts is a crucial factor but a great challenge for designing high-performance microscale and nanoscale functional devices. Through atomistic simulations, we propose an effective design strategy to obtain both low friction and high conductivity in sliding electrical contacts. By constructing graphene(Gr)/MoS2 two-dimensional (2D) heterojunctions between sliding Cu surfaces, superlubricity can be achieved with a remarkably lowered sliding energy barrier as compared to that of the homogeneous MoS2 lubricated Cu contact. Moreover, by introducing vacancy defects into MoS2 and substituting Cu with active metal Ti, the Schottky and tunneling barriers can be substantially suppressed without losing the superlubricious properties of the tribointerface. Consequently, a high conductivity ohmic contact with low sliding friction could be realized in our proposed Ti-MoS1.5-Gr-Ti system, which provides a potential strategy for tackling the well-known dilemma for high performance sliding electrical contacts.

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