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1.
Environ Sci Technol ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577131

RESUMO

The formation of ammonia (NH3) as a by-product during the operation of a three-way catalyst (TWC) in a simulated exhaust stream was investigated using a commercially available Pd/Rh TWC under steady-state and lean/rich cycling conditions. Ion Molecular Reaction Mass Spectrometry (IMR-MS) was applied to determine NO, NO2 and NH3 concentrations at a time resolution of 0.6s. Catalyst ageing was shown to result in a significant increase in the amount of NH3 formed which has received limited attention in the literature to date. The selectivity towards NH3 formation has been shown to increase with the decrease in oxygen storage capacity (OSC) of a TWC induced by thermal ageing. NH3 has been shown to mainly form within the exhaust temperature range of 250-550ºC. Typical lambda and rich operational condition duration periods found in vehicle test procedures were also employed to investigate their effects on NH3 formation. The results suggest that a decrease in lambda and/or an increase in the duration of rich operating conditions will lead to an increase in the selectivity towards NH3 formation. Improving the OSC of TWCs and effectively controlling lambda near to 1.0 with limited duration in rich operating conditions are therefore significant factors in the reduction of NH3 emissions.

2.
Int J Cancer ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577838

RESUMO

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease-free survival (DFS). Furthermore, loss-of-function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial-mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC. This article is protected by copyright. All rights reserved.

3.
J BUON ; 24(3): 907-912, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424641

RESUMO

PURPOSE: The main objective of the current study was to examine the anticancer effects of Curzerenone - a naturally occurring sesquiterpene against gemcitabine-resistant lung carcinoma cells. The effects of Curzerenone on mitochondrial-mediated apoptosis, ROS, and ERK/MAPK and NF-kB signalling pathways were also investigated in the present study. METHODS: Cell proliferation was evaluated by MTT assay. Apoptosis was detected by acridine orange (AO)/ethidium bromide (EB) and DAPI staining as well as flow cytometry using annexin V apoptosis assay. The effects on reactive oxygen species (ROS) as well as mitochondrial membrane potential (MMP) were examined by flow cytometry. Protein expression was examined by western blotting. RESULTS: It was found that Curzerenone induced potent antiproliferative effects against the gemcitabine-resistant lung cancer cells and exhibited an IC50 of 24 µM. The anticancer effects of curzerenone were due to the induction of apoptosis which was also associated with alteration of apoptosis-related proteins (Bax,Bcl-2). Curzerenone also caused ROS-mediated alterations in the MMP. Curzerenone induced cell death in gemcitabine-resistant lung cancer cells by activating p38 MAPK/ERK signalling pathway while NF-kB pathway was inhibited in a dose-dependent manner. CONCLUSIONS: In conclusion, the current results strongly indicate that Curzerenone may prove a potential anticancer drug candidate against drug-resistant lung cancer.

4.
Angew Chem Int Ed Engl ; 58(41): 14764-14769, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31452325

RESUMO

Developing bifunctional catalysts for both hydrogen and oxygen evolution reactions is a promising approach to the practical implementation of electrocatalytic water splitting. However, most of the reported bifunctional catalysts are only applicable to alkaline electrolyzer, although a few are effective in acidic or neutral media that appeals more to industrial applications. Here, a lithium-intercalated iridium diselenide (Li-IrSe2 ) is developed that outperformed other reported catalysts toward overall water splitting in both acidic and neutral environments. Li intercalation activated the inert pristine IrSe2 via bringing high porosities and abundant Se vacancies for efficient hydrogen and oxygen evolution reactions. When Li-IrSe2 was assembled into two-electrode electrolyzers for overall water splitting, the cell voltages at 10 mA cm-2 were 1.44 and 1.50 V under pH 0 and 7, respectively, being record-low values in both conditions.

6.
J Zhejiang Univ Sci B ; 20(7): 563-575, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168970

RESUMO

To explore the volatile profiles and the contents of ten bioactive components (polyphenols and caffeine) of sun-dried Pu-erh tea leaves from ancient tea plants on Bulang Mountain, 17 samples of three tea varieties were analyzed by headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and high-performance liquid chromatography (HPLC). A total of 75 volatile components were tentatively identified. Laomaner (LME), Laobanzhang (LBZ), and other teas on Bulang Mountain (BL) contained 70, 53, and 71 volatile compounds, respectively. Among the volatile compounds, alcohols (30.2%-45.8%), hydrocarbons (13.7%-17.5%), and ketones (12.4%-23.4%) were qualitatively the most dominant volatile compounds in the different tea varieties. The average content of polyphenol was highest in LME (102.1 mg/g), followed by BL (98.7 mg/g) and LBZ (88.0 mg/g), while caffeine showed the opposite trend, 27.3 mg/g in LME, 33.5 mg/g in BL, and 38.1 mg/g in LBZ. Principal component analysis applied to both the volatile compounds and ten bioactive components showed a poor separation of samples according to varieties, while partial least squares-discriminant analysis (PLS-DA) showed satisfactory discrimination. Thirty-four volatile components and five bioactive compounds were selected as major discriminators (variable importance in projection (VIP) >1) among the tea varieties. These results suggest that chromatographic data combined with multivariate analysis could provide a useful technique to characterize and distinguish the sun-dried Pu-erh tea leaves from ancient tea varieties on Bulang Mountain.

7.
Biomed Pharmacother ; 117: 109117, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226635

RESUMO

BACKGROUND: Ischemic stroke is significantly affected by the dysfunction of the miRNA network. Recent research has described that disordered expression of miR-130a is associated with ischemic stroke. Here, we aimed to investigate the possible mechanism of the miR-130a-mediated neuroprotection that follows ischemia-reperfusion (I/R) injury. METHOD: This study was comprised of two models: oxygen-glucose deprivation/Reperfusion (OGDR) and middle cerebral artery occlusion (MCAO). RT-PCR and immunoblotting were used to examine gene expression levels, and MTT assay and flow cytometric analysis were used to examine cell states. We also used 2, 3, 5-triphenyltetrazolium chloride (TTC) staining to assess the cerebral infarct volume. Then, we employed bioinformatics analysis and luciferase reporter assay to identify and validate the target molecule of miR-130a, PTEN. RESULTS: Our findings indicated that miR-130a expression was lower in PC12 cells after OGDR (oxygen-glucose deprivation/reperfusion) and in rats after MCAO (middle cerebral artery occlusion). Moreover, ectopic-expression of miR-130a can significantly improve cell survival rate and reduce cell apoptosis and ROS production in PC12 cells after OGDR. In addition, re-expression of miR-130a yielded an obvious reduction in MCAO-induced infarct volume and neurological deficits in rats. Bioinformatics analysis revealed that PTEN was a miR-130a target and could overturn the effect of miR-130a on cerebral ischemia, both in vivo and in vitro. Therefore, we set out to further investigate the PTEN-affected PI3K/AKT pathway and found that upregulation of miR-130a activated the PI3K/AKT pathway. CONCLUSIONS: Our data demonstrated that miR-130a prevented cerebral I/R damage by mediating the PTEN/PI3K/AKT axis. These preliminarily findings furthered our understanding of this mechanism and identified new potential therapeutic targets for ischemic stroke.

8.
Int Urol Nephrol ; 51(8): 1451-1457, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31119517

RESUMO

PURPOSE: Peritoneal dialysis (PD) catheter implantation is necessary for patients with end-stage renal disease (ESRD) to maintain continuous ambulatory PD (CAPD). In this study, we aimed to introduce a half-percutaneous technique based on a modified trocar device for the placement of a PD catheter and to evaluate the safety and efficacy of this technique and its associated short-term postoperative outcomes. METHODS: Eighty-four ESRD patients who underwent PD catheter implantation with the half-percutaneous technique were recruited retrospectively between September 2016 and October 2017 from the Guangdong Provincial Hospital of Chinese Medicine. All catheter implantation procedures were performed by the same three nephrologists. The surgical protocol was described in detail, and the general intraoperative parameters and short-term complications were evaluated. RESULTS: All ESRD patients underwent successful PD catheterization with our novel technique. Neither conversion from this method to traditional open surgery nor major intraoperative complications were observed. The mean operative time was 20.8 ± 4.5 min, and the incision length was 2.28 ± 0.53 cm. The operative cost was CN ¥ 1762.45 (US $261), and the length of hospital stay was 7.5 ± 0.58 days. One patient (1.19%) showed leakage, and one patient (1.19%) experienced bleeding 2 weeks after the surgery. Catheter dysfunction due to catheter tip migration occurred in nine patients (10.7%) 2 weeks after the procedure, and the placement of the catheter was corrected with conservative treatment. No visceral injuries or PD-related infections were observed up to 4 weeks after the catheters were implanted. CONCLUSIONS: This half-percutaneous technique for PD catheter implantation appears to be a safe, effective and feasible procedure. This technique has the advantages of reduced surgical trauma, a shorter operative time and faster postsurgical recovery. In particular, this novel technique is easy for nephrologists to perform and therefore may help to promote and popularize PD treatment.

9.
Angew Chem Int Ed Engl ; 58(23): 7757-7761, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-30963650

RESUMO

Traditional therapeutic and diagnostic tools exhibit serious side effects, poor selectivity, and sensitivity. Herein, a multifunctional CuPc@HG@BN theranostic platform composed of hexagonal boron nitride nanosheets (h-BNNS), conjugated DNA oligonucleotide, and copper(II) phthalocyanine (CuPc) was developed in which the CuPc molecule played double key roles in photodynamic therapy (PDT) as well as in situ monitoring and imaging of miR-21 by surface-enhanced Raman spectroscopy (SERS). Owing to the designed circle amplification of miRNA and high SERS effects of CuPc on h-BNNS, miR-21 responsive concentration was achieved as low as 0.7 fm in live cells. Both in vitro and in vivo data demonstrated that the integrated nanoplatform showed remarkable enhancement in PDT efficiency with minimized damage to the normal tissues. The developed probe was also successfully utilized for early monitoring and guiding the early therapy, realizing tumor elimination.

10.
Int J Mol Med ; 43(4): 1635-1642, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816515

RESUMO

The present study describes the preparation of a dodecapeptide YHWYGYTPQNVI (GE11)­conjugated liposome bound with polyethylene glycol to enhance the therapeutic effect of resveratrol (RSV) in head and neck cancer cells. The results indicated that (RSV)­loaded GE11­conjugated liposomes (RSV­GL) exhibited a high entrapment efficiency of >95%, with an active drug loading level of 19.5% w/w. Release kinetics revealed that RSV was released in a slow and sustained manner from the RSV­GL and RSV­loaded liposome (RSV­L) nanoparticulate systems. The epidermal growth factor receptor (EGFR)­overexpressing squamous cell carcinoma HN cells specifically internalized GE11 surface­conjugated liposome in a manner that was markedly increased compared with that of the non­targeted carrier. Consistently, RSV­GL exhibited a significantly increased cytotoxic effect compared with that of the non­targeted nanoparticles. Notably, RSV­GL induced significantly increased proportions of early (~60%) and late (~10%) apoptotic cells in head and neck cancer cell populations. To the best of our knowledge, the application and development of EGFR­targeted peptide­conjugated liposome system for RSV delivery has not been studied previously in the treatment of head and neck cancer. In addition, RSV­GL exhibited the greatest antitumor efficacy compared with any other group. RSV­GL exhibited a 2­fold decrease in tumor volume compared with the free RSV and a 3­fold decrease in volume compared with the control. Overall, the nanomedicine strategy described in the present study may potentially advance the chemotherapy­based treatment of head and neck cancer, with promising applications in other EGFR­overexpressing tumors.


Assuntos
Peptídeos/farmacologia , Resveratrol/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Sequência de Aminoácidos , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Feminino , Humanos , Lipossomos , Camundongos Nus , Tamanho da Partícula , Peptídeos/química
11.
Langmuir ; 35(14): 4995-5003, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30892902

RESUMO

The fabrication of peptide assemblies to mimic the functions of natural proteins represents an intriguing aim in the fields of soft materials. Herein, we present a kind of novel peptide-based adhesive coacervate for the exploration of the environment-responsive underwater adhesion. Adhesive coacervates are designed and synthesized by self-assembled condensation of a tripeptide and polyoxometalates in aqueous solution. Rheological measurements demonstrate that the adhesive coacervates exhibit shear thinning behavior, which allows them to be conveniently delivered for interfacial spreading through a narrow gauge syringe without high pressure. The complex coacervates are susceptible to pH and metal ions, resulting in the occurrence of a phase transition from the fluid phase to the gel state. Scanning electron microscopy demonstrates that the microscale structures of the gel-like phases are composed of interconnected three-dimensional porous networks. The rheological study reveals that the gel-like assemblies exhibited mechanical stiffness and self-healing properties. Interestingly, the gel-like samples show the capacity to adhere to various wet solid substrates under the waterline. The adhesion strength of the peptide-based gel is quantified by lap shear mechanical analysis. The fluid coacervate is further exploited in the preparation of "on-site" injectable underwater adhesives triggered by environmental factors. This finding is exciting and serves to expand our capability for the fabrication of peptide-based underwater adhesives in a controllable way.

12.
Anal Chem ; 91(7): 4608-4617, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30821439

RESUMO

Due to the outstanding synergistic effects and low-toxicity, combination therapy exhibits more considerable potential in antitumor activity than monotherapy. Herein, a core-shell magnetic gold nanostar (Fe3O4@GNS, MGNS)-based system for codelivery of a mitochondrial targeting amphipathic tail-anchoring peptide (ATAP) and a membrane-associated cytokine (tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) was constructed. The magnetic core can facilitate delivery of the drug vehicle by external magnetic field, which results in accurate accumulation and enhances tumor cellular uptake for preliminary targeting. TRAIL and ATAP could sequentially target and be released toward the plasma membrane and mitochondria, initiating the extrinsic and intrinsic apoptosis pathways, respectively. The gold shell of MGNS can cause local tumor hyperthermia due to broad-band plasmon resonances in the near-infrared region, which can act as a complement with the peptide drug to further enhance apoptosis. Both in vitro and in vivo experiments revealed that rationally integrating extrinsic apoptosis, intrinsic apoptosis and hyperthermia for triplexed synergistic therapy, enabled the smart drug vehicle with pinpoint peptide drug delivery capabilities, and minimized side effects, enhancing the antitumor efficiency.

13.
Electrophoresis ; 40(11): 1580-1590, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30892714

RESUMO

Microfluidics has made a very impressive progress in the past decades due to its unique and instinctive advantages. Droplet-based microfluidic systems show excellent compatibility with many chemical and biological reagents and are capable of performing variety of operations that can implement microreactor, complex multiple core-shell structure, and many applications in biomedical research such as drug encapsulation, targeted drug delivery systems, and multifunctionalization on carriers. Droplet-based systems have been directly used to synthesize particles and encapsulate many biological entities for biomedicine applications due to their powerful encapsulation capability and facile versatility. In this paper, we review its origin, deviation, and evolution to draw a clear future, especially for droplet-based biomedical applications. This paper will focus on droplet generation, variations and complication as starter, and logistically lead to the numerous typical applications in biomedical research. Finally, we will summarize both its challenge and future prospects relevant to its droplet-based biomedical applications.

14.
Microbiome ; 7(1): 42, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890181

RESUMO

BACKGROUND: Viruses are important components of microbial communities modulating community structure and function; however, only a couple of tools are currently available for phage identification and analysis from metagenomic sequencing data. Here we employed the random forest algorithm to develop VirMiner, a web-based phage contig prediction tool especially sensitive for high-abundances phage contigs, trained and validated by paired metagenomic and phagenomic sequencing data from the human gut flora. RESULTS: VirMiner achieved 41.06% ± 17.51% sensitivity and 81.91% ± 4.04% specificity in the prediction of phage contigs. In particular, for the high-abundance phage contigs, VirMiner outperformed other tools (VirFinder and VirSorter) with much higher sensitivity (65.23% ± 16.94%) than VirFinder (34.63% ± 17.96%) and VirSorter (18.75% ± 15.23%) at almost the same specificity. Moreover, VirMiner provides the most comprehensive phage analysis pipeline which is comprised of metagenomic raw reads processing, functional annotation, phage contig identification, and phage-host relationship prediction (CRISPR-spacer recognition) and supports two-group comparison when the input (metagenomic sequence data) includes different conditions (e.g., case and control). Application of VirMiner to an independent cohort of human gut metagenomes obtained from individuals treated with antibiotics revealed that 122 KEGG orthology and 118 Pfam groups had significantly differential abundance in the pre-treatment samples compared to samples at the end of antibiotic administration, including clustered regularly interspaced short palindromic repeats (CRISPR), multidrug resistance, and protein transport. The VirMiner webserver is available at http://sbb.hku.hk/VirMiner/ . CONCLUSIONS: We developed a comprehensive tool for phage prediction and analysis for metagenomic samples. Compared to VirSorter and VirFinder-the most widely used tools-VirMiner is able to capture more high-abundance phage contigs which could play key roles in infecting bacteria and modulating microbial community dynamics. TRIAL REGISTRATION: The European Union Clinical Trials Register, EudraCT Number: 2013-003378-28 . Registered on 9 April 2014.


Assuntos
Antibacterianos/administração & dosagem , Bactérias/classificação , Bacteriófagos/genética , Mineração de Dados/métodos , Metagenômica/métodos , Algoritmos , Bactérias/isolamento & purificação , Bactérias/virologia , Sistemas CRISPR-Cas , Fezes/microbiologia , Microbioma Gastrointestinal , Voluntários Saudáveis , Humanos , Distribuição Aleatória
15.
Reprod Sci ; : 1933719119831775, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808247

RESUMO

OBJECTIVE:: The transfer of long noncoding RNAs (lncRNAs) via exosomes to modulate recipient cells represents an important mechanism for disease progression. Antisense hypoxia-inducible factor (aHIF) is a well-known angiogenesis-related lncRNA. Here, we aimed to investigate the clinical implications of aHIF and exosomal aHIF in endometriosis and the involvement of exosome-shuttled aHIF in endometriosis angiogenesis. STUDY DESIGN:: The distribution and expression of aHIF in ectopic, eutopic, and normal endometria was evaluated. Serum exosomal aHIF levels in patients with endometriosis were tested. The correlation between serum exosomal aHIF and aHIF expression in ectopic endometria was analyzed. Endometriotic cyst stromal cells (ECSCs)-derived exosomes were characterized. The internalization of exosomes by human umbilical vein endothelial cells (HUVECs) was observed. A series of in vitro assays were conducted to investigate the roles and mechanisms of exosomal aHIF in endometriosis angiogenesis. RESULTS:: Clinically, aHIF was highly expressed in ectopic endometria and serum exosomes in patients with endometriosis. Serum exosomal aHIF was significantly correlated to aHIF expression in matched ectopic endometria. In vitro, PKH67-labeled exosomes derived from aHIF high expression ECSCs were effectively internalized by recipient HUVECs. Notably, exosome-shuttled aHIF was transferred from ECSCs to HUVECs, which in turn elicited proangiogenic behavior in HUVECs by activating vascular endothelial growth factor (VEGF)-A, VEGF-D, and basic fibroblast growth factor, thereby facilitating endometriosis angiogenesis. CONCLUSION:: Our study illustrates a potential cell-cell communication between ECSCs and HUVECs in an ectopic environment, provides a novel mechanistic model explaining how ECSCs induce angiogenesis from the perspective of the "exosomal transfer of aHIF," and highlights the clinical value of circulating exosomal aHIF in endometriosis.

16.
FASEB J ; 33(3): 4404-4417, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30576233

RESUMO

Alzheimer's disease (AD) is a leading cause of dementia. However, the mechanisms responsible for development of AD, especially for the sporadic variant, are still not clear. In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting ß-site amyloid precursor protein cleaving enzyme (BACE)-1, a key enzyme responsible for Aß formation, plays an important role in the development of neuropathology in AD. In the present study, we identified that miR-338-5p, a new miRNA that also targets BACE1, contributes to AD neuropathology. We observed that expression of miR-338-5p was significantly down-regulated in the hippocampus of patients with AD and 5XFAD transgenic (TG) mice, an animal model of AD. Overexpression of miR-338-5p in the hippocampus of TG mice reduced BACE1 expression, Aß formation, and neuroinflammation. Overexpression of miR-338-5p functionally prevented impairments in long-term synaptic plasticity, learning ability, and memory retention in TG mice. In addition, we provide evidence that down-regulated expression of miR-338-5p in AD is regulated through the NF-κB signaling pathway. Our results suggest that down-regulated expression of miR-338-5p plays an important role in the development of AD.-Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., Sun, B.-G., Luo, B.-Y., Chen, C., Peng, G.-P. Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.

17.
Adv Mater ; 31(6): e1805104, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30549113

RESUMO

The development of highly efficient oxygen-evolving catalysts compatible with powerful proton-exchange-membrane-based electrolyzers in acid environments is of prime importance for sustainable hydrogen production. In this field, understanding the role of electronic structure of catalysts on catalytic activity is essential but still lacking. Herein, a family of pyrochlore oxides R2 Ir2 O7 (R = rare earth ions) is reported as acidic oxygen-evolving catalysts with superior-specific activities. More importantly, it is found that the intrinsic activity of this material significantly increases with the R ionic radius. Electronic structure studies reveal that the increased R ionic radius weakens electron correlations in these iridate oxides. This weakening induces an insulator-metal transition and an enhancement of IrO bond covalency, both of which promote oxygen evolution kinetics. This work demonstrates the importance of engineering the electron correlations to rationalize the catalytic activity toward water oxidation in strongly correlated transition-metal oxides.

18.
Anal Chem ; 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30499654

RESUMO

Cardiorenal syndrome (CRS) has posed tremendous challenges in patient management, and the detection of serum biomarkers may provide opportunities for early diagnosis and effective treatment. Herein, we introduce a novel surface-enhanced Raman scattering (SERS)-based sandwich immunoassay platform to simultaneously detect cardiac troponin I (cTnI), N-terminal prohormone of brain natriuretic peptide (NT-ProBNP) and neutrophil gelatinase-associated lipocalin (NGAL) for the early diagnosis of CRS by using Raman reporter molecules-labeled Ag-Au nanostars (Ag-Au NSs) as nanotags and three-dimensional ordered macroporous (3DOM) Au-Ag-Au plasmonic array as substrate. The Ag-Au NSs prepared by galvanic replacement feature bimetallic composition and multi-branched structure so that exhibit high SERS stability and enhancement. Meanwhile, 3DOM Au-Ag-Au plasmonic array was fabricated through Au-assisted electrodeposition and was further covered by a protective Au layer; it is characterized by large specific surface area and high homogeneity, serving as a "hot field". When the nanotags and substrate were combined, "hot spots" were generated from the plasmon near-field coupling, which greatly increased the SERS enhancement. The limits of detection (LODs) were 0.76, 0.53 and 0.41 fg mL-1 for cTnI, NT-ProBNP and NGAL, respectively, and the Raman images indicated the ap-proximate concentration ranges of the detected proteins for visual analysis. Taking advantage of the ultrasensitivity and multiplexing capability of this approach, we further analyzed clinical blood samples with high integrality, efficiency and accuracy. Therefore, the presented SERS immunoassay platform holds promise as an ideal test method for point-of-care detection and a powerful tool for investigations into the complex CRS-related biological process.

19.
Int J Biol Sci ; 14(14): 1960-1973, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30585260

RESUMO

Exosomes mediate cell-cell crosstalk in cancer progression by transferring their molecular cargos, including long noncoding RNAs (lncRNAs). Metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) is a well-known lncRNA associated with cancer angiogenesis and metastasis. However, the presence of MALAT1 in exosomes and the roles and clinical values of exosomal MALAT1 in epithelial ovarian cancer (EOC) remain unknown. The present study focused on the crosstalk between EOC cells and endothelial cells mediated by exosomal MALAT1 and aimed to explore the roles of exosomes and exosomal MALAT1 in EOC angiogenesis and to reveal the clinical relevance and prognostic predictive value of serum exosomal MALAT1 in EOC. We observed that MALAT1 was increased in both metastatic EOC cells and their secreted exosomes. Exosomal MALAT1 derived from EOC cells was transferred to recipient human umbilical vein endothelial cells (HUVECs) via exosomes. In vitro and in vivo experiments demonstrated that MALAT1 knockdown impaired the exosome-mediated proangiogenic activity of HUVECs through certain key angiogenesis-related genes. Clinically, elevated serum exosomal MALAT1 was highly correlated with an advanced and metastatic phenotype of EOC and was an independent predictive factor for EOC overall survival (OS). Moreover, a prognostic nomogram model we constructed showed a good prediction of the probability of 3-year OS of EOC patients according to the c-index (0.751, 95% confidence interval [CI]=0.691-0.811) and calibration curve. Collectively, our data provide a novel mechanism by which EOC cells transfer MALAT1 via exosomes to recipient HUVECs and influence HUVECs by stimulating angiogenesis-related gene expression, eventually promoting angiogenesis. Additionally, circulating exosomal MALAT1 can serve as a promising serum-based, noninvasive predictive biomarker for EOC prognosis.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Exossomos/metabolismo , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/metabolismo , Adenocarcinoma de Pulmão/genética , Animais , Western Blotting , Exossomos/genética , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Eletrônica de Transmissão , Análise Multivariada , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real
20.
Proc Natl Acad Sci U S A ; 115(52): E12313-E12322, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30541887

RESUMO

Dendritic cells (DCs) play pivotal roles in maintaining intestinal homeostasis, but how the DCs regulate diverse immune networks on homeostasis breakdown remains largely unknown. Here, we report that, in response to epithelial barrier disruption, colonic DCs regulate the differentiation of type 1 regulatory T (Tr1) cells through p38α-dependent IL-27 production to initiate an effective immune response. Deletion of p38α in DCs, but not in T cells, led to increased Tr1 and protected mice from dextran sodium sulfate-induced acute colitis and chronic colitis-associated colorectal cancer. We show that higher levels of IL-27 in p38α-deficient colonic cDC1s, but not cDC2s, were responsible for the increase of Tr1 cells. Moreover, p38α-dependent IL-27 enhanced IL-22 secretion from intestinal group 3 innate lymphoid cells and protected epithelial barrier function. In p38α-deficient DCs, the TAK1-MKK4/7-JNK-c-Jun axis was hyperactivated, leading to high IL-27 levels, and inhibition of the JNK-c-Jun axis suppressed IL-27 expression. ChIP assay revealed direct binding of c-Jun to the promoter of Il27p28, which was further enhanced in p38α-deficient DCs. In summary, here we identify a key role for p38α signaling in DCs in regulating intestinal inflammatory response and tumorigenesis, and our finding may provide targets for the treatment of inflammatory intestinal diseases.


Assuntos
Colite/enzimologia , Colo/imunologia , Neoplasias Colorretais/enzimologia , Células Dendríticas/enzimologia , Proteína Quinase 14 Ativada por Mitógeno/imunologia , Animais , Carcinogênese , Colite/genética , Colite/imunologia , Colite/patologia , Colo/enzimologia , Colo/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Células Dendríticas/imunologia , Feminino , Humanos , Interleucina-27/genética , Interleucina-27/imunologia , Intestinos/imunologia , Intestinos/patologia , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 14 Ativada por Mitógeno/genética , Linfócitos T Reguladores/imunologia
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