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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117428, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31376727

RESUMO

Room temperature phosphorescence (RTP) materials have become a hot topic in fields of organic light-emitting dioes, biological sensing and imaging. The present work reports firstly that 1,3,5-trifluoro-2,4,6-triiodobenzene (TITFB) can act as a simple pure organic NIR phosphor due to its novel function in promoting n-π∗ transition. Also, TITFB crystal has longer phosphorescence lifetime than other ordinary multiiodoluminophors and TITFB powder. Based on the TITFB crystal structure, σ-hole and π-hole capture mechanism of n-electron is proposed, i.e., the excited state energy is decreased and n-electrons are stabilized to cause slower radiative decay rate due to the restriction of σ-hole and π-hole bond. Both computational and experimental studies support the mechanism. The new electron-capture mode is more conducive to understanding pure organic ultralong lifetime RTP.

2.
Biomed Pharmacother ; 121: 109632, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707347

RESUMO

The Chinese herbal prescription Xiaoji decoction (XJD) has been used as an adjuvant treatment of cancer for decades. However, the molecular mechanisms underlying XJD enhancement of the efficiency of chemotherapy were undetermined. In this study, we observed that combination of XJD and cisplatin (DDP) showed a greater inhibition on growth and induced a high magnitude of apoptosis in non-small cell lung cancer (NSCLC) cells. We also found that XJD decreased lncRNA PVT1 and increased miR181a-5p expressions. There was a reciprocal interaction between PVT1 and miR181a-5p. XJD decreased SP1 protein, which were overcame by overexpressed PVT1 and inhibitors of miR181a-5p. Overexpressed SP1 reversed the inhibitory effect of XJD on cell growth. Importantly, XJD and DDP exhibited synergy on regulation of PVT1, miR181a-5p, and SP1 expressions. The similar results were observed in one in vivo model. In conclusions, XJD inhibits NSCLC cell growth via reciprocal interaction of PVT1 and miR181a-5p followed by reducing SP1 expression. XJD and DDP exhibit synergy. This study provides a novel mechanism by which XJD enhances the anti-cancer effect of DDP in NSCLC cells.

3.
Front Biosci (Landmark Ed) ; 25: 798-816, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585918

RESUMO

Previous studies have shown that amentoflavone (AF) elicits anti-inflammatory and neuroprotective effects. To further investigate the effects of AF on the microglia cell line BV-2, proteomic analysis was performed to screen potential key regulators. The top 5 canonical pathways associated with AF treatment were EIF2 signaling, regulation of eIF4 and p70s6k signaling, mTOR signaling, protein ubiquitination pathway and phagosome maturation. The top up-regulated genes were DOCK2, SEC23A, ME1, UGGT1 and STOM, while the most down-regulated molecules were IGF2R, ATP5O, DDX47, WBP11 and IKBIP. AF significantly decreased BV-2 cell proliferation. It induced cell cycle arrest at G2/M, increased CDK2, p27Kip1 and p53/p-p53, and decreased CDK1/CDC2 and cyclin B1. Cell apoptosis was induced, with increased levels of BAX, c-caspase-3 and c-caspase-9, and decreased levels of BCL-XL. Increased level of autophagosome induced by AF was observed, and increased Beclin-1 and decreased phosphorylation of PI3K and Erk1 were found as well. In conclusion, AF induces cell cycle arrest at G2/M, promotes apoptosis and autophagy in BV-2 cells, which may account for the anti-inflammatory effect of AF in epilepsy.

4.
Int J Cancer ; 146(2): 542-552, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31584197

RESUMO

Our previous researches have identified immunoevasive subtype muscle-invasive bladder cancer (MIBC) characterized with immune cells infiltration patterns. Our study explored the clinical significance, immunoregulatory role and therapeutic value of intratumoral IL22-producing cells in MIBC. Two hundred and fifty-nine formalin-fixed paraffin-embedded MIBC samples and 83 freshly resected MIBC tissues and 391 TCGA MIBC samples were retrospectively evaluated. Immunohistochemistry and flow cytometry were applied to identify immune cell infiltration and functional status. In vitro intervention studies were to test the therapeutic and predictive potential of IL22+ cells. Our data revealed patients with high IL22+ cells infiltration suffered poor overall survival and recurrence-free survival in both training and validation cohorts. Only pT2 patients of combined cohort with low IL22+ cells infiltration gained survival benefits from adjuvant chemotherapy (ACT) significantly. Besides, immune contexture featured with increased pro-tumor cells and immunosuppressive cytokines was identified in patients with high IL22+ cells density. The expression pattern of exhausted and effector markers in CD8+ T cells from high IL22+ cells subgroup indicated their dysfunctional status. Importantly, nivolumab showed tumor-killing efficacy in tumors with high IL22+ cells infiltration, and immunosuppressive contexture with CD8+ T cells exhaustion was abrogated in tumors treated with anti-IL22 antibody. In summary, IL22+ cells infiltration determined immunosuppressive contexture with CD8+ T cell dysfunction. Tumor-infiltrating IL22+ cells could be used as an independent marker to predict prognosis and ACT responses. IL22+ cells infiltration possessed the potential to be a favorable predictor for nivolumab application and IL22 blockade could be a novel therapeutic strategy in MIBC.

5.
Toxicology ; : 152338, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31785310

RESUMO

An impaired gut-liver axis is a potential factor that contributes to alcoholic liver disease. Specifically, ethanol decreases intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is negatively altered following acute ethanol exposure. This study aimed to determine whether kaempferol could protect against alcoholic liver injury (AALI) in mice by regulating tight junction (TJ) proteins and butyrate receptors and transporters in intestines. Male Institute of Cancer Research (ICR) mice were randomly divided into five treatment groups: control, ethanol administered (5 g/kg), and the low-, medium- and high-dosage kaempferol (25, 50, 100 mg/kg) treatments. Intestinal expression was evaluated for the TJ proteins ZO-1 and occludin and the butyrate receptor GPR109A and butyrate transporter SLC58A proteins, in addition to plasma ALT and AST levels and pathomorphological changes in liver and intestinal tissues. The expression of the TJ proteins ZO-1 and occludin, butyrate receptors, and butyrate transporters in the ileum and proximal colon decreased in AALI mice, while plasma ALT and AST levels markedly increased. Kaempferol supplementation reversed these effects. These results suggest that kaempferol could serve as a prophylactic treatment against AALI in mice by increasing the expression of butyrate receptors, transporters, and TJ proteins in the intestinal mucosa.

6.
Virol Sin ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792738

RESUMO

Viruses evolve rapidly and continuously threaten animal health and economy, posing a great demand for rapid and efficient genome editing technologies to study virulence mechanism and develop effective vaccine. We present a highly efficient viral genome manipulation method using CRISPR-guided cytidine deaminase. We cloned pseudorabies virus genome into bacterial artificial chromosome, and used CRISPR-guided cytidine deaminase to directly convert cytidine (C) to uridine (U) to induce premature stop mutagenesis in viral genes. The editing efficiencies were 100%. Comprehensive bioinformatic analysis revealed that a large number of editable sites exist in pseudorabies virus (PRV) genomes. Notably, in our study viral genome exists as a plasmid in E. coli, suggesting that this method is virus species-independent. This application of base-editing provided an alternative approach to generate mutant virus and might accelerate study on virulence and vaccine development.

7.
Inorg Chem ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793774

RESUMO

A novel tungsten nitride, MoC-type WN, was synthesized at 6 GPa and 1200 °C via nitridation of tungsten by ammonium chloride as a nitrogen source. This compound is isostructural with γ'-MoC, which has a hexagonal structure with a space group of P63/mmc (No. 194). Micrometer-sized single crystals of MoC-type WN were grown in molten ammonium chloride flux. In addition, NaCl-type WN and WC-type WN were synthesized via nitridation by ammonium chloride at 6 GPa and 1000 °C. Ammonium chloride is appropriate as a nitrogen source for nitride synthesis under high pressure. The new WN phase crystallizes in the hexagonal structure with unit cell parameters of a = 2.89248(2) Å and c = 10.17069(7) Å. The chemical formula of MoC-type WN refined by the Rietveld analysis from powder X-ray diffraction data was WN0.60(1). The zero-pressure bulk modulus, K0, of MoC-type WN was determined to be 338(3) GPa, which can be expected to be a hard material.

8.
Bioconjug Chem ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31751118

RESUMO

The narrow absorption and emission bands, long fluorescence lifetime, and excellent stability of rare earth nanoparticles (referred to as RE NPs) make them very attractive for multimodal imaging and therapy of cancer. Their narrow absorption requires the careful selection of laser wavelength to achieve the best performance, particularly for RE NPs simultaneously having photothermal and photoluminescent properties (e.g., Nd-based nanoparticles), which has not been investigated. Herein, we prepared a series of different-sized NaNdF4 nanoparticles (referred to as NNF NPs) (i.e., 4.7, 5.9, 12.8, and 15.6 nm) from ultrasmall nanoclusters and investigated their in vitro and in vivo size-dependent photothermal conversion and photoluminescence under irradiation by a 793 nm laser and an 808 nm laser, respectively. We find that all nanoparticles exhibited the better photothermal conversion performance under the irradiation of the 808 nm laser than under the 793 nm laser, of which 12.8 nm NNF NPs showed the best performance, and the temperature of their solution can be quickly increased from 30 °C to around 60 °C within 10 min under the irradiation of the 808 nm laser with a power intensity of 0.75 W/cm2. When we used the 793 nm laser to excite these NNF NPs, we found that all nanoparticles exhibited the stronger photoluminescence in the second near-infrared window (NIR-II) than under the excitation by the 808 nm laser, of which 15.6 nm NNF NPs possessed the strongest NIR-II luminescence. We then modified 12.8 nm NNF NPs with phospholipid carboxyl PEG and functionalized with RGD for actively targeted imaging of cancer. The NaNdF4@PEG@RGD nanoparticles (referred to as NNF-P-R NPs) have good biocompatibility, stability, and excellent targeting capability. The in vivo result show that 12.8 nm NNF NPs exhibited better photothermal conversion performance under the irradiation of the 808 nm laser, and stronger NIR-II fluorescence under irradiation of the 793 nm laser, which are consistent with the in vitro result. This work demonstrates the significance of selection of the proper laser wavelength for maximally taking advantage of RE nanoparticles for the diagnosis and treatment of cancer.

9.
Transl Oncol ; 13(1): 32-41, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31760267

RESUMO

BACKGROUND: Escaping cell death pathways is an important event during carcinogenesis. We previously identified anti-TNFα-induced apoptosis (ATIA, also known as vasorin) as an antiapoptotic factor that suppresses reactive oxygen species (ROS) production. However, the role of vasorin in lung carcinogenesis has not been investigated. METHODS: Vasorin expression was examined in human lung cancer tissues with immunohistochemistry and database analysis. Genetic and pharmacological approaches were used to manipulate protein expression and autophagy activity in human bronchial epithelial cells (HBECs). ROS generation was measured with fluorescent indicator, apoptosis with release of lactate dehydrogenase, and cell transformation was assessed with colony formation in soft agar. RESULTS: Vasorin expression was increased in human lung cancer tissues and cell lines, which was inversely associated with lung cancer patient survival. Cigarette smoke extract (CSE) and benzo[a]pyrene diol epoxide (BPDE)-induced vasorin expression in HBECs. Vasorin knockdown in HBECs significantly suppressed CSE-induced transformation in association with enhanced ROS accumulation and autophagy. Scavenging ROS attenuated autophagy and cytotoxicity in vasorin knockdown cells, suggesting that vasorin potentiates transformation by impeding ROS-mediated CSE cytotoxicity and improving survival of the premalignant cells. Suppression of autophagy effectively inhibited CSE-induced apoptosis, suggesting that autophagy was pro-apoptotic in CSE-treated cells. Importantly, blocking autophagy strongly potentiated CSE-induced transformation. CONCLUSION: These results suggest that vasorin is a potential lung cancer-promoting factor that facilitates cigarette smoke-induced bronchial epithelial cell transformation by suppressing autophagy-mediated apoptosis, which could be exploited for lung cancer prevention.

10.
BMC Musculoskelet Disord ; 20(1): 570, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775707

RESUMO

BACKGROUND: The surgical procedures for mid-thoracic spinal tuberculosis mainly include anterior transthoracic debridement and fusion and posterior transpedicular debridement and fusion. Until now, the surgical choice is still controversial. This study aims to compare the clinical efficacy of anterior transthoracic debridement and fusion with posterior transpedicular debridement and fusion in the treatment of mid-thoracic (T5-9) spinal tuberculosis in adult patients. METHODS: Eighty-seven cases with mid-thoracic spinal tuberculosis were treated with anterior transthoracic debridement and fusion (Group A, n = 39) and posterior transpedicular debridement and fusion (Group B, n = 48) from January 2007 to June 2014. Parameters including the operation time, blood loss, time of ESR and CRP decreasing to the normal level, time of abscess disappearance, time of bone graft fusion, rate of surgical complications, Visual Analog Scale (VAS) score, kyphosis angle and SF-36 scale were compared between two groups to evaluate their therapeutic effects. RESULTS: All patients were followed up for 5-10 years with the mean of 6.2 ± 1.1 years. No significant differences were observed regarding the gender composition ratio, age, course of disease, number of lesion segments, and preoperative indexes of ESR, CRP, VAS score, kyphosis angle and SF-36 scale between the two groups. Besides, no significant differences were observed regarding VAS score, kyphosis angle and SF-36 scale between the two groups in the 5th postoperative year (P > 0.05). However, the operation time (158.2 ± 10.7 min vs. 183.7 ± 14.1 min), blood loss (517.9 ± 76.5 ml vs.714.6 ± 57.4 ml), time of ESR (2.3 ± 1.1 months vs.3.1 ± 1.4 months) and CRP (1.1 ± 0.3 months vs.1.2 ± 0.6 months) decreasing to the normal level, time of abscess disappearance (2.7 ± 1.6 months vs.4.9 ± 1.9 months), and time of bone graft fusion (6.6 ± 0.8 months vs.8.0 ± 9.6 months) in Group A were less than those in Group B (P < 0.05). CONCLUSIONS: Both anterior transthoracic debridement and fusion and posterior transpedicular debridement and fusion have a low risk of surgical complications and provide good quality of life for the patients with mid-thoracic (T5-9) spinal tuberculosis followed up in the mid-term. Moreover, the anterior procedure leads to early resolution of the disease and faster fusion.

11.
Nanoscale ; 11(47): 22734-22742, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31763653

RESUMO

Hydrogen production by water electrolysis is a common strategy for the development of renewable energy. However, meeting the industrial requirement for high efficiency and low cost is difficult to achieve with the existing methods. Herein, a novel and simple synthesis route for a dendritic self-supported electrode consisting of oxygen vacancy-rich NiO embedded within ultrathin 2D/3D nanostructures (NiO-Vo@2D/3D NS@DSE) for overall water splitting is developed for the first time. Based on the simple compound synthesis by jet electrodeposition and in situ acid etching, 2D nanosheets adhering uniformly to 3D nanospheres are successfully obtained on the dendritic self-supported skeleton surface. The experiments and density functional calculations illustrate that this electrode integrates the advantages including numerous active sites, intrinsic catalytic activity, good electrical conductivity, and outstanding reaction kinetic performance. Moreover, NiO-Vo@2D/3D NS@DSE shows excellent oxygen evolution reaction and hydrogen evolution reaction activities in 1 M KOH with overpotentials of 230 and 51 mV at 10 mA cm-2, respectively. Additionally, the electrode, as an alkali-electrolyzer, displays a potential of 1.51 V at 10 mA cm-2 with favorable stability that is superior to that of IrO2@nickel foam (NF)//Pt/C@NF (1.62 V). Surprisingly, the cost of NiO-Vo@2D/3D NS@DSE is ≈1/120 of the price of noble electrocatalysts with the same mass. This research opens up a new pathway for the design of bifunctional electrocatalysts.

12.
Biomed Res Int ; 2019: 6508094, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737672

RESUMO

In cartilage tissue engineering, the target cells' functional performance depends on the biomaterials. However, it is difficult to develop an appropriate scaffold to differentiate mouse adipose-derived stem cells (mADSCs) into chondrocyte despite an increasing number of studies on biological scaffold materials. The purpose of this study was to create a novel scaffold for mADSC culture and chondrogenic differentiation with a new series of microgels based on polyethyleneimine (PEI), polyethylene glycol (PEG), and poly (L-lactic acid) (PLLA) and able to resist swelling with changes in temperature, pH, and polymer concentration. The biocompatibility and ability of the nonswelling microgels were then examined and served as scaffolds for cell culture and for cartilage differentiation. The results show that the new microgels are a novel biomaterial that both retains its nonswelling properties under various conditions and facilitates important scaffold functions such as cell adhesion, proliferation, and cartilage induction.

13.
J Am Chem Soc ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31701745

RESUMO

Dinitrogen conversion to ammonia via electrochemical reduction with over 10% Faradaic efficiency is demonstrated in this work. Co-doped MoS2-x polycrystalline nanosheets with S vacancies as the catalysts are loaded onto carbon cloth by hydrothermal growth from Mo, Co, and S precursors. A sulfur vacancy on the MoS2-x basal plane mimicking the natural Mo-nitrogenase active site is modified by Co doping and exhibits superior dinitrogen-to-ammonia conversion activity. Density-functional simulation reveals that the free energy barrier, which can be compensated by applied overpotential, is reduced from 1.62 to 0.59 eV after Co doping. Meanwhile, dinitrogen tends to be chemically adsorbed to defective MoS2-x, which effectively activates the dinitrogen molecule for the dissociation of the N≡N triple bond. This process is further accelerated by Co doping, resulting from the modulation of Mo-N bonding configuration.

14.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1865(2): 158547, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678514

RESUMO

Atherosclerosis (AS) is characterized by lipids metabolism disorder and inflammatory response. Accumulating evidence has demonstrated that Wingless type 5a (Wnt5a) is implicated in cardiovascular diseases through non-canonical Wnt cascades. However, its precise role during the pathogenesis of AS is still unclear. Therefore, the present study aims to investigate the role and the underlying mechanism of Wnt5a/receptor tyrosine kinase-like orphan receptor 2 (Ror2) pathways in the promotion of AS process through affecting lipid accumulation and inflammation. In atherosclerotic clinical samples, Wnt5a levels were measured by using enzyme-linked immunosorbent assay (ELISA) assay. In vivo experiments were conducted by using apolipoprotein E knockout (apoE-/-) mice model. Vascular smooth muscle cells (VSMCs) were applied for in vitro studies. Wnt5a was highly expressed in both of atherosclerotic clinical samples and apoE-/- mice. The knockdown of Wnt5a significantly inhibited cholesterol accumulation and inflammatory response. Additionally, the lipopolysaccharide (LPS)-induced inflammation aggravated the cholesterol accumulation and decreased adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression in VSMCs. Depletion of intracellular cholesterol by ß-cyclodextrin (ß-CD) led to the upregulation of ABCA1 and the inhibition of inflammation. Conversely, the overexpression of Wnt5a inhibited ABCA1 expression, facilitated cholesterol accumulation, impared cholesterol efflux, promoted NF-κB nuclear translocation and the inflammatory cytokines secretion. Moreover, the knockdown of Ror2 increased ABCA1 expression and reduced Wnt5a-induced cholesterol accumulation and inflammatory responses. Furthermore, the knockdown of ABCA1 enhanced cholesterol accumulation and inflammatory response. Therefore, Wnt5a/Ror2 pathway was critical in regulating cholesterol homeostasis and inflammatory response, which might be a promising therapeutic target for AS therapy.

15.
Diabetes Res Clin Pract ; 158: 107912, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682880

RESUMO

AIMS: To compare the abilities of Intergrowth-21st standards, Institute of Medicine (IOM) recommendations and a Chinese reference on gestational weight gain (GWG) to identify women at risk of gestational diabetes (GDM) and GDM-related adverse outcomes. METHODS: A retrospective cohort study was conducted on 13,366 women delivering live singleton infants between 2013 and 2017 in Tongzhou district of Beijing, China. Poisson regression with robust error estimates was used to estimate risk ratios (RRs) of GDM in different GWG groups according to three standards. RESULTS: There were 39.97%, 46.31% and 30.03% of women gaining weight above Intergrowth-21st standards, IOM recommendations and the Chinese reference respectively. Women with GWG above Intergrowth-21st standards and the Chinese reference had 27% (aRR, 1.27 95% CI, 1.18-1.37) and 30% (aRR, 1.30; 95% CI, 1.21-1.40) increased risks of GDM respectively, as compared to 22% (aRR, 1.22; 95% CI, 1.13-1.32) for IOM recommendations. GWG above either of these three standards was associated with macrosomia and cesarean delivery (P < 0.05). CONCLUSION: Compared with IOM recommendations, GWG above Intergrowth-21st standards or the Chinese reference was associated with higher risks of GDM and GDM-related adverse outcomes. Furthermore, these two prospective standards could additionally assess the severity of abnormal GWG and are feasible for dynamic monitoring.

16.
Cancer Immunol Immunother ; 68(12): 2067-2080, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31720813

RESUMO

PURPOSE: Tumor-associated macrophages (TAMs) exist as heterogeneous subsets and have dichotomous roles in cancer-immune evasion. This study aims to assess the clinical effects of Galectin-9+ tumor-associated macrophages (Gal-9+TAMs) in muscle-invasive bladder cancer (MIBC). EXPERIMENTAL DESIGN: We identified Gal-9+TAMs by immunohistochemistry (IHC) analysis of a tumor microarray (TMA) (n = 141) from the Zhongshan Hospital and by flow cytometric analysis of tumor specimens (n = 20) from the Shanghai Cancer Center. The survival benefit of platinum-based chemotherapy in this subpopulation was evaluated. The effect of the tumor-immune microenvironment with different percentages of Gal-9+TAMs was explored. RESULTS: The frequency of Gal-9+TAMs increased with tumor stage and grade. Gal-9+TAMs predicted poor overall survival (OS) and recurrence-free survival (RFS) and were better than Gal-9-TAMs and TAMs to discriminate prognostic groups. In univariate and multivariate Cox regression analyses, patients with high percentages of Gal-9+TAMs showed the prominent survival benefit after receiving adjuvant chemotherapy (ACT). High Gal-9+TAM infiltration correlated with increasing numbers of regulatory T cells (Tregs) and mast cells and decreasing numbers of CD8+T and dendritic cells (DCs). Dense infiltration of Gal-9+TAMs was related to reduced cytotoxic molecules, enhanced immune checkpoints or immunosuppressive cytokines expressed by immune cells, as well as active proliferation of tumor cells. Additionally, the subpopulation accumulated was strongly associated with PD-1+TIM-3+CD8+T cells. CONCLUSIONS: Gal-9+TAMs predicted OS and RFS and response to ACT in MIBC patients. High Gal-9+TAMs were associated with a pro-tumor immune contexture concomitant with T cell exhaustion.


Assuntos
Galectinas/metabolismo , Macrófagos/imunologia , Músculos/patologia , Linfócitos T Reguladores/imunologia , Neoplasias da Bexiga Urinária/terapia , Adulto , Biomarcadores Farmacológicos , Movimento Celular , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Evasão Tumoral , Microambiente Tumoral , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/mortalidade
17.
BMC Genomics ; 20(1): 796, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666016

RESUMO

BACKGROUND: Clade 5 Clostridioides difficile diverges significantly from the other clades and is therefore, attracting increasing attention due its great heterogeneity. In this study, we used third-generation sequencing techniques to sequence the complete whole genomes of three ST11 C. difficile isolates, RT078 and another two new ribotypes (RTs), obtained from three independent hospitalized elderly patients undergoing antibiotics treatment. Mobile genetic elements (MGEs), antibiotic-resistance, drug resistance genes, and virulent-related genes were analyzed and compared within these three isolates. RESULTS: Isolates 10,010 and 12,038 carried a distinct deletion in tcdA compared with isolate 21,062. Furthermore, all three isolates had identical deletions and point-mutations in tcdC, which was once thought to be a unique characteristic of RT078. Isolate 21,062 (RT078) had a unique plasmid, different numbers of transposons and genetic organization, and harboring special CRISPR spacers. All three isolates retained high-level sensitivity to 11 drugs and isolate 21,062 (RT078) carried distinct drug-resistance genes and loss of numerous flagellum-related genes. CONCLUSIONS: We concluded that capillary electrophoresis based PCR-ribotyping is important for confirming RT078. Furthermore, RT078 isolates displayed specific MGEs, indicating an independent evolutionary process. In the further study, we could testify these findings with more RT078 isolates of divergent origins.

18.
Phys Chem Chem Phys ; 21(45): 25425-25430, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31710319

RESUMO

The interaction between Candida antarctica lipase B (CALB) and graphene oxide (GO) in an anhydrous gas was studied using molecular dynamics (MD) simulations augmented with a simulated annealing procedure to accelerate relaxation toward equilibrium. Three kinds of GO sheets with different oxygen contents were constructed to elucidate their effectiveness for stabilizing the active CALB conformation. It was shown that electrostatic forces are pivotal for the formation of CALB/GO complexes, and that a GO sheet with a higher oxygen content leads to stronger association with the protein. The simulation results suggest replacement of protein-binding water molecules by the GO surface, which was confirmed by thermogravimetric analysis. The CALB/GO assembly stabilizes the active enzyme conformation at elevated temperatures and, moreover, increases the protein flexibility near its active sites. The molecular details of GO interaction with CALB and the consequential effects on CALB stability and functionality are important for the development of unprecedented applications of gaseous enzymatic catalysis.

19.
BMJ Open ; 9(11): e027902, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678935

RESUMO

INTRODUCTION: Obesity is a public health concern that is becoming increasingly more serious worldwide. Effective and sustainable childhood obesity prevention strategies may help to reduce the prevalence of obesity and may have an impact on lifelong health. However, few such strategies have been rigorously evaluated for Chinese children in different regions of China. METHODS AND ANALYSIS: The Diet, ExerCIse and CarDiovascular hEalth-Children is a cluster-randomised controlled trial that aims to assess the effectiveness and sustainability of a school-based, multi-faceted intervention to prevent obesity among Grade 4 primary school students (8-10 years old) in China. Twenty-four schools (approximately 1200 students) from above average, average and below average developed regions in China will be randomised to an intervention (12 schools) or usual practice (12 schools) group. The intervention will last for one school year (9 months) and consists of activities towards students, parents and school environment. A smartphone application will be used to assist in providing information on, monitoring and providing feedback on the behaviours and body weight of the students. Data will be collected at baseline, 4 months, 9 months and 21 months. The primary outcome will be the difference between groups in the change in students' body mass index at 9 months after the baseline investigation. The secondary outcomes will include the differences between groups in the changes in anthropometric measures, diet, physical activity levels and other measures at the follow-up visits. A variety of process evaluation methods will be used to evaluate the implementation process of the complex intervention. ETHICS AND DISSEMINATION: This study was approved by the Peking University Institution Review Board (IRB00001052-18021). The results will be disseminated through publication in peer-reviewed journals, presentations at conferences and in lay summaries provided to school staff and participants. TRIAL REGISTRATION NUMBER: NCT03665857.

20.
Burns ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31676250

RESUMO

Sepsis is the leading cause of death in burn patients. Monocytes/macrophages rapidly exhibit impaired production of proinflammatory cytokines and an elevated generation of anti-inflammatory cytokines in septic patients with immunosuppression. However, the expression patterns of Tim4 and Nod-like receptor protein 3 (NALP3) inflammasome and their roles during immunosuppression in septic shock patients are not well understood. Tim4 and NALP3 inflammasome expression in monocytes were downregulated in immunosuppressive patients with sepsis compared with healthy volunteers. Meanwhile, NALP3 inflammasome expression was upregulated by Tim4 overexpression in murine bone marrow-derived macrophages (BMDMs) and J774A.1 macrophages. Tim4 overexpression improved the ability of BMDMs and J774A.1 macrophages to produce proinflammatory cytokines and increased the expression of cleaved-caspase-1 (p10) after LPS/ATP stimulation. In addition, overexpression of Tim4 enhanced phagocytosis of apoptotic polymorphonuclear neutrophils (PMNs) by BMDMs and J774A.1 macrophages, while depletion of NALP3 in Tim4 overexpressing BMDMs and J774A.1 macrophages decreased phagocytosis of apoptotic PMNs. In summary, the expression of Tim4 and NALP3 inflammasome in monocytes/macrophages was downregulated in septic shock patients, and diminished expression of Tim4 and NALP3 inflammasome in monocytes/macrophages might play a critical role in sepsis-elicited immunosuppression.

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