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1.
Aging (Albany NY) ; 122020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32352928

RESUMO

Salidroside is the main bioactive component in Rhodiola rosea and possesses multiple biological and pharmacological properties. However, whether salidroside affects platelet function remains unclear. Our study aims to investigate salidroside's effect on platelet function. Human or mouse platelets were treated with salidroside (0-20 µM) for 1 hour at 37°C. Platelet aggregation, granule secretion, and receptors expression were measured together with detection of platelet spreading and clot retraction. In addition, salidroside (20 mg/kg) was intraperitoneally injected into mice followed by measuring tail bleeding time, arterial and venous thrombosis. Salidroside inhibited thrombin- or CRP-induced platelet aggregation and ATP release and did not affect the expression of P-selectin, glycoprotein (GP) Ibα, GPVI and αIIbß3. Salidroside-treated platelets presented decreased spreading on fibrinogen or collagen and reduced clot retraction with decreased phosphorylation of c-Src, Syk and PLCγ2. Additionally, salidroside significantly impaired hemostasis, arterial and venous thrombus formation in mice. Moreover, in thrombin-stimulated platelets, salidroside inhibited phosphorylation of AKT (T308/S473) and GSK3ß (Ser9). Further, addition of GSK3ß inhibitor reversed the inhibitory effect of salidroside on platelet aggregation and clot retraction. In conclusion, salidroside inhibits platelet function and thrombosis via AKT/GSK3ß signaling, suggesting that salidroside may be a novel therapeutic drug for treating thrombotic or cardiovascular diseases.

2.
ISME J ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32355200

RESUMO

Hydrothermal activity can generate numerous and diverse hydrocarbon compounds. However, little is known about the influence of such hydrocarbons on deep-sea hydrothermal microbial ecology. We hypothesize that certain bacteria live on these hydrocarbons. Therefore, in this study, the distribution of hydrocarbons and their associated hydrocarbon-degrading bacteria were investigated at deep-sea hydrothermal vents at the Southern Mid-Atlantic Ridge, the Southwest Indian Ridge, and the East Pacific Rise. A variety of hydrocarbon-degrading consortia were obtained from hydrothermal samples collected at the aforementioned sites after low-temperature enrichment under high hydrostatic pressures, and the bacteria responsible for the degradation of hydrocarbons were investigated by DNA-based stable-isotope probing with uniformly 13C-labeled hydrocarbons. Unusually, we identified several previously recognized sulfur-oxidizing chemoautotrophs as hydrocarbon-degrading bacteria, e.g., the SAR324 group, the SUP05 clade, and Sulfurimonas, and for the first time confirmed their ability to degrade hydrocarbons. In addition, Erythrobacter, Pusillimonas, and SAR202 clade were shown to degrade polycyclic aromatic hydrocarbons for the first time. These results together with relatively high abundance in situ of most of the above-described bacteria highlight the potential influence of hydrocarbons in configuring the vent microbial community, and have made the importance of mixotrophs in hydrothermal vent ecosystems evident.

3.
Biomed Chromatogr ; : e4878, 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386257

RESUMO

Lung cancer shows the highest incidence rate in the world. Thus, it has increasingly become an important issue to find the therapeutic drugs to treat lung cancer. Farfarae Flos (FF) has been used in the traditional Chinese medicines (TCMs) in the treatment for the pulmonary diseases such as cough, bronchitis and asthmatic disorders. In this study, the anti-proliferation effect of petroleum extracts of FF (PEFF) against Lewis lung cancer (LLC) cells and the corresponding mechanisms were studied using cell metabolomics. Fifteen differential metabolites in the cell extracts and the corresponding medium related with the anti-proliferation effect of PEFF were identified, which were probably involved with the Pyruvate metabolism and Glycine, serine and threonine metabolism. For the cellular uptake compounds of PEFF, six metabolites derived from two prototype compounds, were also tentatively identified by UHPLC-Q-Orbitrap HRMS. Network pharmacology analysis demonstrated that the anti-proliferation mechanism of PEFF was also probably related to the target genes, including Aurora-A, GSTM1, GSTP1, PGR and HO-1, and further related with the Proteoglycans and PI3K/Akt signaling pathway. Cell metabolomics and network pharmacology analysis provided a holistic method for the investigation of the anti-proliferation mechanisms of PEFF. However, further studies were still needed to validate the potential target genes, pathways and active compounds in PEFF.

5.
J Phys Chem Lett ; : 3481-3487, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32298119

RESUMO

Single-atom catalysis has recently emerged as a promising approach for catalyzing the carbon dioxide reduction reaction (CO2RR). In this study, we present a principle for designing active single-atom catalysts (SACs) for CO2RR. We systematically examine totally 24 transition metals supported by a graphitic carbon nitride (g-CN) monolayer and find that their catalytic activities are highly correlated with the adsorption free energies of two intermediate species (OH and OCH). We then identify two important intrinsic descriptors, namely, the number of electrons in the outmost d-shell and the enthalpy of vaporization of the transition metal. Test calculations on transition metals supported by a C2N monolayer indicate that both descriptors are quite universal for SACs of CO2RR. Based on these results, we show that Ni@g-CN, Cu@g-CN, and Co@C2N are promising SACs for CO2RR. This study offers an effective principle for designing highly active SACs for CO2RR on the basis of intrinsic properties of transition metals.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 484-487, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319383

RESUMO

OBJECTIVE: To investigate the prognostic influencing factors of primary central nervous system lymphoma (PCNSL) patients with diffuse large B-cell immunophenotype. METHODS: 42 PCNSL patients with diffuse large B-cell lymphoma treated in our hospital from March 2011 to October 2017 were enrolled. The effects of different treatments on overall survival of patients were analyzied. RESULTS: The analysis for 42 PCNSL patients with diffuse large B-cell immunophenotype showed that there was no affect of their clinical characteristics,such as sex, age, CSF protein content, treatment with and without temozolomide and rituximab on overall survival of the patients(P>0.05). And it was found that active treatment and the application of conventional intrathecal injection and methotrexate in the treatment could effectively prolong the overall survival time of patients. CONCLUSION: Early diagnosis of PCNSL and active standardized treatment can significantly prolong the survival time of patients, and it is further emphasized that the necessity of conventional intrathecal injection to prolong the survival of patients.

7.
Oncol Rep ; 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32319655

RESUMO

In a previous study, it was demonstrated that T­cell immune response cDNA 7 (TIRC7) levels reflect the efficacy of treatment of patients with acute graft­versus­host disease (GVHD). However, the pathogenesis of TIRC7 in acute GVHD remains poorly understood. Lymphocytes from patients with acute GVHD were selected as targeT cells, and the effects of TIRC7 on cytotoxic T lymphocyte antigen­4 (CTLA­4), T cell activation and cytokine secretion were observed by electroporation. A mouse model of acute GVHD was established; anti­TIRC7 and anti­CTLA­4 monoclonal antibodies were intraperitoneally injected into recipient mice. Then, the effects of TIRC7 and CTLA­4 on T cell activation and acute GVHD were monitored. After TIRC7 expression was downregulated, CTLA­4 levels were decreased and STAT3 phosphorylation was reduced; conversely, the activation capacity of T lymphocytes was elevated, and the secretion of interferon­Î³ and other cytokines was increased. The mice in the TIRC7 + CTLA­4 co­administration group exhibited the lowest acute GVHD scores, with the longest average survival time and shortest recovery time of hematopoietic reconstitution. In conclusion, the results indicated that TIRC7 may positively regulate the function of CTLA­4 and inhibit T cell activation, thus suppressing the development and progression of acute GVHD.

9.
Int Immunopharmacol ; 83: 106460, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32248021

RESUMO

Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1ß in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment.

10.
Sensors (Basel) ; 20(6)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168843

RESUMO

Scene recognition is an essential part in the vision-based robot navigation domain. The successful application of deep learning technology has triggered more extensive preliminary studies on scene recognition, which all use extracted features from networks that are trained for recognition tasks. In the paper, we interpret scene recognition as a region-based image retrieval problem and present a novel approach for scene recognition with an end-to-end trainable Multi-column convolutional neural network (MCNN) architecture. The proposed MCNN utilizes filters with receptive fields of different sizes to have Multi-level and Multi-layer image perception, and consists of three components: front-end, middle-end and back-end. The first seven layers VGG16 are taken as front-end for two-dimensional feature extraction, Inception-A is taken as the middle-end for deeper learning feature representation, and Large-Margin Softmax Loss (L-Softmax) is taken as the back-end for enhancing intra-class compactness and inter-class-separability. Extensive experiments have been conducted to evaluate the performance according to compare our proposed network to existing state-of-the-art methods. Experimental results on three popular datasets demonstrate the robustness and accuracy of our approach. To the best of our knowledge, the presented approach has not been applied for the scene recognition in literature.

11.
ACS Nano ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32129598

RESUMO

The growth of entirely synthetic two-dimensional (2D) materials could further expand the library of naturally occurring layered solids and provide opportunities to design materials with finely tunable properties. Among them, the synthesis of elemental 2D materials is of particular interest as they represent the chemically simplest case and serve as a model system for exploring the on-surface synthesis mechanism. Here, a pure atomically thin blue phosphorus (BlueP) monolayer is synthesized via silicon intercalation of the BlueP-Au alloy on Au(111). The intercalation process is characterized at the atomic scale by low-temperature scanning probe microscopy and further corroborated by synchrotron radiation-based X-ray photoelectron spectroscopy measurements. The evolution of the band structures from the BlueP-Au alloy into Si-intercalated BlueP are clearly revealed by angle-resolved photoemission spectroscopy and further verified by density functional theory calculations.

12.
Bioorg Med Chem Lett ; 30(9): 127070, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32143887

RESUMO

A series of novel 2-arylbenzimidazoles have been designed, synthesized and evaluated for their inhibitory activity against IDH2 R140Q mutant. The preliminary results indicated that four compounds 7b, 7c, 7m and 7r displayed the potent inhibitory activity against IDH2 R140Q mutant. Among them, compound 7c showed the highest inhibitory activity, with the IC50 value of 0.26 µM, which was more active than positive control enasidenib. The exquisite selectivity of 7c for IDH2 R140Q mutant isoform was demonstrated by the poor activity against the IDH1 R132C mutant, IDH1 R132H mutant, wild-type IDH1, IDH2 R172K mutant and the wild-type IDH2.

13.
Biochem Pharmacol ; 175: 113918, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32194056

RESUMO

BACKGROUND: Dexamethasone is widely used in the treatment of joint diseases due to its anti-inflammatory properties. However, it can cause serious adverse effects. The anterior cruciate ligament (ACL) is an important stabilizer of the knee joint. However, the effect of dexamethasone treatment on the ACL is unclear. OBJECTIVE: This study aims to explore the effects of dexamethasone on ACL tissues and cells through in vitro and in vivo experiments. RESULTS: In vitro, we found that after treatment with dexamethasone, human ACL cell apoptosis was increased, type I collagen (COL1A1) content was decreased, mineralization related genes (ENPP1 and ANKH) and calcified nodules were increased, and endoplasmic reticulum stress (ERS) was enhanced. However, ERS inhibitors could significantly inhibit the increase in calcification and the decrease in COL1A1 induced by dexamethasone. In vivo, Wistar rats received the infra-articular injection with dexamethasone (0.5 mg/kg) for 8 weeks. We found that dexamethasone treatment decreased the COL1A1 content and increased the COL2A1 content in the ACL tissues of rats and that chondroid differentiation and mineralization occurred. Meanwhile, the expression of ERS-related proteins was increased. CONCLUSION: Dexamethasone increased the calcification of ACL cells and caused ACL degeneration through ERS, suggesting that long-term treatment with dexamethasone may cause adverse effects on ACL tissue and increase the risk of long-term rupture.

14.
Brain Behav Immun ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169498

RESUMO

Since December 2019, more than 79,000 people have been diagnosed with infection of the Corona Virus Disease 2019 (COVID-19). A large number of medical staff was sent to Wuhan city and Hubei province to aid COVID-19 control. Psychological stress, especially vicarious traumatization caused by the COVID-19 pandemic, should not be ignored. To address this concern, the study employed a total of 214 general public and 526 nurses (i.e., 234 front-line nurses and 292 non-front-line nurses) to evaluate vicarious traumatization scores via a mobile app-based questionnaire. Front-line nurses are engaged in the process of providing care for patients with COVID-19. The results showed that the vicarious traumatization scores for front-line nurses including scores for physiological and psychological responses, were significantly lower than those of non-front-line nurses (P < 0.001). Interestingly, the vicarious traumatization scores of the general public were significantly higher than those of the front-line nurses (P < 0.001); however, no statistical difference was observed compared to the scores of non-front-line nurses (P > 0.05). Therefore, increased attention should be paid to the psychological problems of the medical staff, especially non-front-line nurses, and general public under the situation of the spread and control of COVID-19. Early strategies that aim to prevent and treat vicarious traumatization in medical staff and general public are extremely necessary.

15.
Biosci Rep ; 40(3)2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32175564

RESUMO

PURPOSE: To construct and analyze tumor-infiltrating immune cell and ceRNA (competitive endogenous RNA) networks in metastatic adrenal cortical carcinoma (ACC). METHODS: A ceRNA network was established to identify the ceRNAs involved in metastasis of ACC based on 92 samples from TCGA, including 18 cases of metastasis and 74 cases of non-metastatic primary tumors. And the algorithm "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)" was used to quantify the proportion of immune cells in ACC. In addition, predictive nomograms based on the types of important immune cells or ceRNAs were constructed to predict ACC prognosis. Moreover, we evaluated the relationships between metastatic ACC-specific immune cells and ceRNA networks to identify the potential immune gene characteristics. RESULTS: Ten prognostic biomarkers were identified as key members of the ceRNA network and three tumor-infiltrating immune cells were identified by CIBERSORT algorithm. Some important co-expression patterns between immune cells and ceRNAs network indicate significant correlation between Macrophages M0 and hsa-miR-130b-3p (P < 0.001), Macrophages M0 and H2AFX (P = 0.003). CONCLUSIONS: The present study inferred that the metastasis-related ceRNAs of H2AFX, hsa-miR-130b-3p and Macrophages M0 might play important roles in ACC metastasis.

16.
Med Sci Monit ; 26: e921822, 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32222722

RESUMO

BACKGROUND Acute kidney injury (AKI) is one of the most important causes of death in sepsis patients. Here, we first measured the level of DANCR (differentiation antagonizing nonprotein coding RNA) expression in AKI, and the potential mechanism was further elucidated. MATERIAL AND METHODS We used qRT-PCR to examine the level of DANCR in patient blood serum samples and in HK-2 cells. In addition, DANCR overexpression was established using lentiviral transfection in HK-2 cells. Subsequently, Cell Counting Kit-8 (CCK-8) assay and flow cytometry were applied to evaluate the role of DANCR in HK-2 cells treated with lipopolysaccharide (LPS). Enzyme linked immunosorbent assay (ELISA), western blot and recovery experiments were performed to elucidate the further mechanism. RESULTS We found that DANCR was decreased in the serum of AKI patients and HK-2 cells treated with LPS. Additionally, DANCR promoted cell viability and suppressed cell apoptosis and cytokine production in LPS-treated HK-2 cells. Bioinformatics analysis showed that DANCR served as a sponge for miR-214. Furthermore, DANCR inhibited the expression of Krüppel-like factor 6 (KLF6). CONCLUSIONS Our study suggests that AKI development could be alleviated by sponging miR-214 and regulating KLF6 expression, which provides a novel potential mechanism involved in the diagnosis and treatment of sepsis-induced AKI patients.

17.
Anal Chem ; 92(8): 5701-5707, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32212716

RESUMO

FDR control has been a huge challenge for large-scale metabolome annotation. Although recent research indicated that the target-decoy strategy could be implemented to estimate FDR, it is hard to perform FDR control due to the difficulty of getting a reliable decoy database because of the complex fragmentation mechanism of metabolites and ubiquitous isomers. To tackle this problem, we developed a decoy generation method, which generates forged spectra from the reference target database by preserving the original reference signals to simulate the presence of isomers of metabolites. Benchmarks on GNPS data sets in Passatutto showed that the decoy database generated by our method is closer to the actual FDR than other methods, especially in the low FDR range (0-0.05). Large-scale metabolite annotation on 35 data sets showed that strict FDR reduced the number of annotated metabolites but increased the spectral efficiency, indicating the necessity of quality control. We recommended that the FDR threshold should be set to 0.01 in large-scale metabolite annotation. We implemented decoy generation, database search, and FDR control into a search engine called XY-Meta. It facilitates large-scale metabolome annotation applications.

18.
Environ Sci Pollut Res Int ; 27(15): 17891-17909, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32166690

RESUMO

Impregnating CuCl2 on AC (activated coke) support to synthesize xCuCl2/AC showed superior activity with higher 90% Hg0 removal efficiency at 80-140 °C, as well as a lower oxygen demand of 2% O2 for Hg0 removal. The acceleration on Hg0 removal was observed for NO and SO2. The BET, SEM, XRD, XPS, TPD, and FT-IR characterizations revealed that the larger surface area, sufficient active oxygen species and co-existence of Cu+ and Cu2+ may account for the efficient Hg0 removal. In addition, the low demand of gaseous O2 was contributed to higher content of active oxygen and formed active Cl. After adsorbing on Cu sites, Cl sites, and surface functional groups, the Hg0(ads) removal on xCuCl2/AC was proceeded through two ways. Part of Hg0(ads) was oxidized by active O and formed Hg0, and the other part of Hg0 combined with the active Cl, which was formed by the activation of lattice Cl with the aid of active O, and formed HgCl2. Besides, the Hg2+ detected in outlet gas through mercury speciation conversion and desorption peak of HgCl2 and Hg0 further proved it. As displayed in stability test and simulated industrial application test, CuCl2/AC has a promising industrial application prospect.

19.
Proc Natl Acad Sci U S A ; 117(7): 3748-3758, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32015106

RESUMO

Increased expression of extracellular matrix (ECM) proteins in circulating tumor cells (CTCs) suggests potential function of cancer cell-produced ECM in initiation of cancer cell colonization. Here, we showed that collagen and heat shock protein 47 (Hsp47), a chaperone facilitating collagen secretion and deposition, were highly expressed during the epithelial-mesenchymal transition (EMT) and in CTCs. Hsp47 expression induced mesenchymal phenotypes in mammary epithelial cells (MECs), enhanced platelet recruitment, and promoted lung retention and colonization of cancer cells. Platelet depletion in vivo abolished Hsp47-induced cancer cell retention in the lung, suggesting that Hsp47 promotes cancer cell colonization by enhancing cancer cell-platelet interaction. Using rescue experiments and functional blocking antibodies, we identified type I collagen as the key mediator of Hsp47-induced cancer cell-platelet interaction. We also found that Hsp47-dependent collagen deposition and platelet recruitment facilitated cancer cell clustering and extravasation in vitro. By analyzing DNA/RNA sequencing data generated from human breast cancer tissues, we showed that gene amplification and increased expression of Hsp47 were associated with cancer metastasis. These results suggest that targeting the Hsp47/collagen axis is a promising strategy to block cancer cell-platelet interaction and cancer colonization in secondary organs.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 218-224, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027280

RESUMO

OBJECTIVE: To study the level and clinical value of Th17 cell subset in the peripheral blood of the patients with aplastic anemia (AA). METHODS: Eighty-five patients with aplastic anemia in our hospital from May 2017 to February 2018 were selected. Among them, 51 patients with poor curative effect were enrolled in group A. and the 34 patients with good curative effect were enrolled in group B, the 35 healthy persons were selected as controls. The levels of serum IL-17, IL-6, IL-4 and IFN-ß were analyzed by ELISA; the levels of peripheral blood Th17 cell subset were analyzed by flow cytometry; the expression levels of RORγt and STAT3 mRNA in lymphocytes were analyzed by RT-PCR; the expression levels of RORγt and STAT3 protein in lymphocytes were analyzed by Western blot. RESULTS: There was no significant difference in sex, age, WBC count and complications between group A and group B (P>0.05). Non-severe aplastic anemia (NSAA) in group B accounted for 23 cases, and the NSAA ratio (23/34) was significantly higher than that in group A (20/51) (P<0.05). The Hb level (86.25±7.9 g/L) and Plt count (54.7 ± 6.3×109/L) in group B were significantly higher than those in group A (P<0.05). ELISA showed that the levels of IL-17 and IL-6 in group A were significantly higher than those in control group (P<0.05); the levels of IL-17 and IL-6 in group B were significantly lower than those in group A (P<0.05); the levels of IL-4 and IFN-ß in group A were significantly lower than those in control group (P<0.05); the levels of IL-4 and IFN-ßin group B were significantly higher than those in group A (P<0.05). Flow cytometry showed that the proportion of Th17 cells in peripheral blood of group A was higher than that of group B (P<0.05). RT-PCR showed that the levels of RORγt and STAT3 mRNA in group A were significantly higher than those in control group (P<0.05), and the mRNA levels of RORγt and STAT3 in group B were significantly lower than those in group A (P<0.05). Western blot showed that the protein levels of RORγt and STAT3 in group A were significantly higher than those in control group (P<0.05), and the protein levels of RORγt and STAT3 in group B were significantly lower than those in group A (P<0.05). CONCLUSION: The Th17 cells in peripheral blood of AA patients increase, and the inflammatory reaction in the patients are enhanced. It may be related with the rise of RORγt and STAT3 gene expression, which provides a research direction for clinical treatment of AA.


Assuntos
Anemia Aplástica , Células Th17 , Citometria de Fluxo , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , RNA Mensageiro
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