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1.
Neuron ; 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32616470

RESUMO

Presynaptic CaV2 channels are essential for Ca2+-triggered exocytosis. In addition, there are two competing models for their roles in synapse structure. First, Ca2+ channels or Ca2+ entry may control synapse assembly. Second, active zone proteins may scaffold CaV2s to presynaptic release sites, and synapse structure is CaV2 independent. Here, we ablated all three CaV2s using conditional knockout in cultured hippocampal neurons or at the calyx of Held, which abolished evoked exocytosis. Compellingly, synapse and active zone structure, vesicle docking, and transsynaptic nano-organization were unimpaired. Similarly, long-term blockade of action potentials and Ca2+ entry did not disrupt active zone assembly. Although CaV2 knockout impaired the localization of ß subunits, α2δ-1 localized normally. Rescue with CaV2 restored exocytosis, and CaV2 active zone targeting depended on the intracellular C-terminus. We conclude that synapse assembly is independent of CaV2s or Ca2+ entry through them. Instead, active zone proteins recruit and anchor CaV2s via CaV2 C-termini.

2.
J Biochem Mol Toxicol ; : e22589, 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32720422

RESUMO

BACKGROUND: The function of miR-20a-5p in pulmonary artery smooth muscle cells (PASMCs) and the underlying mechanism remains largely unknown. METHODS: C57BL/6J mice and PASMCs were used for constructing pulmonary artery hypertension (PAH) animal and cell models, respectively. Reverse transcription polymerase chain reaction (RT-PCR) was employed to detect miR-20a-5p and ATP-binding cassette subfamily A member 1 (ABCA1) messenger RNA expression. CCK-8, Transwell, and TUNEL experiments were used to determine PASMCs proliferation, migration, and apoptosis. The relationship between miR-20a-5p and ABCA1 was detected by luciferase reporter experiment, Western blot analysis, and qRT-PCR. RESULTS: miR-20a-5p was remarkably elevated in PASMCs of PAH mice and human PASMCs treated by hypoxia, while ABCA1 was remarkably decreased. After transfection of miR-20a-5p mimics, PASMCs proliferation and migration were promoted and PASMCs apoptosis was suppressed. ABCA1 was confirmed to be a target of miR-20a-5p and restoration of ABCA1 reversed the function of miR-20a-5p. CONCLUSION: miR-20a-5p enhances the proliferation and migration of PASMCs to promote the development of PAH via targeting ABCA1.

3.
Database (Oxford) ; 20202020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32539087

RESUMO

Exposure to toxic substances in the environment is one of the most important causes of cancer. However, the time-consuming process for the identification and characterization of carcinogens is not applicable to a huge amount of testing chemicals. The data gaps make the carcinogenic risk uncontrollable. An efficient and effective way of prioritizing chemicals of carcinogenic concern with interpretable mechanism information is highly desirable. This study presents a curation work for genes and pathways associated with 11 hallmarks of cancer (HOCs) reported by the Halifax Project. To demonstrate the usefulness of the curated HOC data, the interacting HOC genes and affected HOC pathways of chemicals of the three carcinogen lists from IARC, NTP and EPA were analyzed using the in silico toxicogenomics ChemDIS system. Results showed that a higher number of affected HOCs were observed for known carcinogens than the other chemicals. The curated HOC data is expected to be useful for prioritizing chemicals of carcinogenic concern. Database URL: The HOC database is available at https://github.com/hocdb-KMU-TMU/hocdb and the website of Database journal as Supplementary Data.

4.
Zhongguo Zhen Jiu ; 40(6): 605-9, 2020 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-32538010

RESUMO

OBJECTIVE: To observe the clinical effect of acupuncture at lower-he acupoints and front-mu acupoints combined with Tongxieyaofang (TXYF) for diarrhea-type irritable bowel syndrome (IBS-D) of liver depression and spleen deficiency, and to explore its possible mechanism. METHODS: A total of 123 IBS-D patients with syndrome of liver depression and spleen deficiency were randomly divided into an acupuncture+TXYF group, a TXYF group and a medication group, 41 cases in each group. The patients in TXYF group were treated with oral administration of TXYF, three times a day. The patients in acupuncture+TXYF group were treated with oral administration of TXYF and routine acupuncture at Shangjuxu (ST 37), Tianshu (ST 25), Taichong (LR 3), Sanyinjiao (SP 6) and Zusanli (ST 36), once a day. The patients in medication group were treated with oral administration of pinaverium bromide, 50 mg, three times a day. All the treatment was given for four weeks. The total score of TCM syndrome scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS) scores as well as the expression of calcitonin gene-related peptide (CGRP), vasoactive peptide (VIP) and MAPK signal pathway indicators of ERK1 mRNA and ERK2 mRNA were compared before and after treatment; the clinical effect was also compared. RESULTS: After treatment, the total score of TCM syndrome scale and SAS and SDS scores in each group were significantly reduced (P<0.05), and the scores in the acupuncture+TXYF group were lower than those in TXYF group and medication group (P<0.05). The total effective rate was 87.8% (36/41) in the acupuncture+TXYF group, which was higher than 78.0% (32/41) in the TXYF group and 68.3% (28/41) in the medication group (P<0.05). After treatment, the levels of CGRP and VIP in each group were decreased (P<0.05), and the levels in the acupuncture+TXYF group were lower than those in the TXYF group and the medication group (P<0.05). After treatment, the levels of ERK1 mRNA and ERK2 mRNA in each group were decreased (P<0.05), and the levels in acupuncture+TXYF group were lower than those in medication group (P<0.05). CONCLUSION: The acupuncture at lower-he acupoints and front-mu acupoints combined with TXYF could effectively alleviate the clinical symptoms, improve anxiety and depression in IBS-D patients with syndrome of liver depression and spleen deficiency, and its mechanism may be related to regulating the expression of ERK1 mRNA and ERK2 mRNA in MAPK signaling pathway, and reducing the serum levels of CGRP and VIP.

5.
Cell Rep ; 31(10): 107712, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32521280

RESUMO

Neurons face unique transport challenges. They need to deliver cargo over long axonal distances and to many presynaptic nerve terminals. Rab GTPases are master regulators of vesicular traffic, but essential presynaptic Rabs have not been identified. Here, we find that Rab6, a Golgi-derived GTPase for constitutive secretion, associates with mobile axonal cargo and localizes to nerve terminals. ELKS1 is a stationary presynaptic protein with Golgin homology that binds to Rab6. Knockout and rescue experiments for ELKS1 and Rab6 establish that ELKS1 captures Rab6 cargo. The ELKS1-Rab6-capturing mechanism can be transferred to mitochondria by mistargeting ELKS1 or Rab6 to them. We conclude that nerve terminals have repurposed mechanisms from constitutive exocytosis for their highly regulated secretion. By employing Golgin-like mechanisms with anchored ELKS extending its coiled-coils to capture Rab6 cargo, they have spatially separated cargo capture from fusion. ELKS complexes connect to active zones and may mediate vesicle progression toward release sites.

6.
Oncol Rep ; 43(5): 1479-1490, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32323804

RESUMO

Glioblastoma (GBM) is the most prevalent and lethal primary intrinsic brain cancer. The disease is essentially incurable, with glioblastomas characterized by resistance to both chemotherapy and radiotherapy, as well as by rapid tumor progression, all of which are mainly ascribed to glioma stem­like cells (GSLCs). In the present study, an improved model that is more similar to clinical GBM was constructed. Twenty clinical glioma samples were collected to obtain primary low­grade tumor cells. The cells were either maintained in serum­free medium as primary glioma­based cells (PGBCs) or cultured in the same medium with CHIR99021 as GSLCs. Then, the molecular and ultrastructural differences between the two cell groups were determined. Furthermore, the proliferation and migration of the GSLCs were examined and the potential mechanisms were investigated. Finally, temozolomide resistance in vitro and in the mouse model was assessed to study the properties of the induced GSLCs. The primary low­grade tumor cells extracted from surgical samples were enriched with GSLC properties, with high expression levels of CD133 and Nestin in 100 nM CHIR99021. The GSLCs exhibited high proliferation and migration. Furthermore, the expression of the PI3K/AKT signaling pathway and that of related genes and proteins were significantly enhanced by CHIR99021. The animal study also revealed high levels of STAT3, mTOR, NF­κB, and VEGF in the GSLC­transplanted mice. CHIR99021 could stably enhance GSLC properties in patient­derived glioma samples. It may provide a useful model for further study, helping to understand the pathogenesis of therapeutic resistance and to screen drug candidates.

7.
Theranostics ; 10(7): 3293-3307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194869

RESUMO

Rationale: Choroidal neovascularization (CNV) is a major cause of severe vision loss and occurs in many ocular diseases, especially neovascular age-related macular degeneration (nAMD). Circular RNAs (circRNAs) are emerging as a new class of endogenous noncoding RNAs, which have been implicated in the regulation of endothelial cell dysfunction in diabetes mellitus and cancer. In this study, we aimed to determine the role of circRNA-ZBTB44 (cZBTB44) in the pathogenesis of CNV. Methods: Quantitative polymerase chain reaction was conducted to detect cZBTB44 expression pattern during CNV development. Isolectin B4 staining, hematoxylin and eosin (HE) staining, and choroidal sprouting assay ex vivo were conducted to evaluate the role of cZBTB44 in the development of CNV. Endothelial cell proliferation, migration and tube formation assays were conducted to determine the role of cZBTB44 in angiogenic effect in vitro. Bioinformatics analysis, RNA immunoprecipitation assay, luciferase assay, and in vitro studies were conducted to investigate the mechanism of cZBTB44-mediated CNV development. Results: cZBTB44 expression was significantly up-regulated in a laser-induced CNV mouse model in vivo and in endothelial cells upon hypoxia stress in vitro. cZBTB44 silencing retarded CNV development, while overexpression of cZBTB44 showed the opposite effects. The role of cZBTB44 in CNV development was confirmed in choroidal sprouting assay ex vivo. cZBTB44 silencing reduced endothelial cell viability, proliferation, migration and tube formation in vitro. cZBTB44 acted as miR-578 sponge to sequester and inhibit miR-578 activity, which led to increased expression of vascular endothelial growth factor A (VEGFA) and vascular cell adhesion molecule-1 (VCAM1). Overexpression of miR-578 mimicked cZBTB44 silencing-mediated anti-angiogenic effects in vivo and in vitro. Furthermore, dysregulated cZBTB44 expression was detected in the clinical samples of nAMD patients. Conclusions: This study provided novel insights into the molecular pathogenesis of CNV. The cZBTB44-miR-578-VEGFA/VCAM1 axis might be a potential source of novel therapeutic targets for neovascularization-related diseases.

8.
EMBO J ; 39(10): e103111, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187724

RESUMO

The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion. We further demonstrate that CHK2-mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2-/- mice display aggravated infarct phenotypes and reduced Beclin 1 p-Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2-induced autophagy in cell survival. Taken together, these results indicate that the ROS-ATM-CHK2-Beclin 1-autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress-induced tissue damage.

9.
Plant Cell Rep ; 39(4): 543-552, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32025802

RESUMO

KEY MESSAGE: BIG regulates the shoot stem cell population. The shoot apical meristem (SAM) contains a population of self-renewing cells, and provides daughter cells for initiation and development of aerial parts of plants. However, the underlying mechanisms of SAM size regulation remain largely unclear. Here, we identified a mutant that displayed a large SAM, designated big-shoot meristem (big-m), in Arabidopsis thaliana. The phenotype of big-m is caused by a new T-DNA insertion allele of BIG, causing a loss of function. The big-m mutant had more stem cells in the SAM than in the wild type. Expression of WUSCHEL (WUS) and SHOOTMERISTEMLESS (STM) was promoted in big-m compared with the wild type, showing that BIG functions upstream of WUS and STM. Therefore, BIG is an important regulator of the stem cell population in the SAM. Furthermore, genetic analysis indicated that BIG acts synergistically with PIN-FORMED1 (PIN1) in controlling SAM size. Our results suggest that BIG plays an important role in controlling Arabidopsis thaliana SAM growth via PIN1-mediated auxin homeostasis.

10.
Arch Toxicol ; 94(2): 485-494, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897520

RESUMO

The evaluation of developmental and reproductive toxicity of food contact materials (FCMs) is an important task for food safety. Since traditional experiments are both time-consuming and labor-intensive, only a small number of FCMs have sufficient toxicological data for evaluating their effects on human health. While computational methods such as structural alerts and quantitative structure-activity relationships can serve as first-line tools for the identification of chemicals of high toxicity concern, models with binary outputs and unsatisfied accuracy and coverage prevent the use of computational methods for prioritizing chemicals of high concern. This study proposed a genetic algorithm-based method to develop a weight-of-evidence (WoE) model leveraging complementary methods of structural alerts, quantitative structure-activity relationships and in silico toxicogenomics models for chemical prioritization. The WoE model was applied to evaluate 623 food contact chemicals and identify 26 chemicals of high toxicity concern, where 13 chemicals have been reported to be developmental or reproductive toxic and further experiments are suggested for the remaining 13 chemicals without toxicity data related to developmental and reproductive effects. The proposed WoE model is potentially useful for prioritizing chemicals of high toxicity concern and the methodology may be applied to toxicities other than developmental and reproductive toxicity.

11.
Sci Total Environ ; 715: 135298, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31859061

RESUMO

Arsenic (As) hyperaccumulator Pteris vittata is efficient in As uptake, translocation and accumulation, but the impacts of soil As concentrations on As accumulation and distribution in P. vittata are still unclear. The impacts of soil As (7.3, 63 and 228 mg kg-1) on plant growth and As accumulation in P. vittata after 6 months of growth were evaluated. Arsenic concentrations in the roots, midribs and pinna margin of P. vittata fronds of different maturity were determined by inductively coupled plasma mass spectrometry (ICP-MS) and scanning electron microscopy coupled with an energy dispersive spectrometer (SEM-EDS). While moderate As level at As63 didn't impact P. vittata growth, higher As at As228 decreased plant biomass by 38%. Under As stress, more As was accumulated in the senescing fronds (47%) and mature fronds (11%) than the young fronds. In senescing fronds, As concentrations in pinna margin were 2.3 times that of the midribs, consistent with As-induced necrotic symptom. Arsenic distribution based on SEM-EDS analysis revealed good correlation between Si and As in the pinnae (r = 0.49). Our data showed that As accumulation in pinna margin caused necrosis and Si may have a potential role in As detoxification in P. vittata.


Assuntos
Pteris , Arsênico , Biodegradação Ambiental , Raízes de Plantas , Solo , Poluentes do Solo
12.
Huan Jing Ke Xue ; 40(11): 4783-4790, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854543

RESUMO

Forty-one metal elements, including rare earth elements and the lead isotope ratio in rain water in Xiamen were measured by inductively coupled plasma mass spectrometry. Sources of metal elements were identified by combined enrichment factor, isotope analysis, and positive matrix factorization analysis. The results showed that the concentration sequence of total metal elements in rainwater in Xiamen was winter-suburban (213.964 µg·L-1) > winter-urban (176.357 µg·L-1) > summer-suburban (75.401 µg·L-1). There were seasonal and regional differences in the content of rare earth elements, and their standardized distribution patterns were inconsistent with each potential source, indicating that their sources were relatively complex. Enrichment factor analysis showed that Ni, Cu, Zn, and Cd were significantly affected by human sources, whereas Be, Ti, V, Mn, Cr, Co, Ga, Rb, Y, Cs, rare earth elements, Th, and U were mainly affected by natural sources. The result of Pb-isotopic-analysis showed that Pb in rainwater was significantly affected by coal sources with a contribution rate of 63.67%, and soil parent material, garbage incineration, motor vehicle exhaust, and cement dust with a contribution rate of 36.33%. The result of positive matrix factorization combined with the enrichment factor and isotope method showed that the metal elements in rainwater were affected by coal burning, natural sources, industry, and traffic.

13.
Sci Total Environ ; 690: 1178-1189, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31470481

RESUMO

Microbial arsenic transformation is important in As biogeochemical cycles in the environment. In this study, a new As-resistant bacterial strain Leclercia adecarboxylata As3-1 was isolated and its associated mechanisms in As resistance and detoxification were evaluated based on genome sequencing and gene annotations. After subjecting strain As3-1 to medium containing arsenate (AsV), AsV reduction occurred and an AsV-enhanced bacterial growth was observed. Strain As3-1 lacked arsenite (AsIII) oxidation ability and displayed lower AsIII resistance than AsV, probably due to its higher AsIII accumulation. Polymerase chain reaction and phylogenetic analysis showed that strain As3-1 harbored a typical AsV reductase gene (arsC) on the plasmids. Genome sequencing and gene annotations identified four operons phoUpstBACS, arsHRBC, arsCRDABC and ttrRSBCA, with 8 additional genes outside the operons that might have involved in As resistance and detoxification in strain As3-1. These included 5 arsC genes explaining why strain As3-1 tolerated high AsV concentrations. Besides ArsC, TtrB, TtrC and TtrA proteins could also be involved in AsV reduction and consequent energy acquisition for bacterial growth. Our data provided a new example of diverse As-regulating systems and AsV-enhanced growth without ArrA in bacteria. The information helps to understand the role of As in selecting microbial systems that can transform and utilize As.


Assuntos
Arsênico/metabolismo , Enterobacteriaceae/fisiologia , Poluentes Ambientais/metabolismo , Adaptação Fisiológica , Proteínas de Bactérias/genética , Enterobacteriaceae/genética , Genômica
14.
Mar Drugs ; 17(8)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394862

RESUMO

Acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC) from the skin of river puffer (ASC-RP and PSC-RP) and tiger puffer (ASC-TP and PSC-TP) were extracted and physicochemically examined. Denaturation temperature (Td) for all the collagens was found to be 25.5-29.5 °C, which was lower than that of calf skin collagen (35.9 °C). Electrophoretic patterns indicated all four samples were type I collagen with molecular form of (α1)2α2. FTIR spectra confirmed the extracted collagens had a triple-helical structure, and that the degree of hydrogen bonding in ASC was higher than PSC. All the extracted collagens could aggregate into fibrils with D-periodicity. The fibril formation rate of ASC-RP and PSC-RP was slightly higher than ASC-TP and PSC-TP. Turbidity analysis revealed an increase in fibril formation rate when adding a low concentration of NaCl (less than 300 mM). The fibril formation ability was suppressed with further increasing of NaCl concentration, as illustrated by a reduction in the turbidity and formation degree. SEM analysis confirmed the well-formed interwoven structure of collagen fibrils after 24 h of incubation. Summarizing the experimental results suggested that the extracted collagens from the skin of river puffer and tiger puffer could be considered a viable substitute to mammalian-derived collagens for further use in biomaterial applications.


Assuntos
Colágeno Tipo I/química , Colágenos Associados a Fibrilas/química , Proteínas de Peixes/química , Pele/química , Takifugu/metabolismo , Tetraodontiformes/metabolismo , Ácidos/química , Aminoácidos/química , Animais , Ligação de Hidrogênio , Pepsina A/química , Rios , Solubilidade , Temperatura
15.
Sci Rep ; 9(1): 11526, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395921

RESUMO

In this work, we designed ZnO/TiO2 nanolaminates by atomic layer deposition (ALD) as anode material for lithium ion batteries. ZnO/TiO2 nanolaminates were fabricated on copper foil by depositing unit of 26 cycles ZnO/26 cycles TiO2 repeatedly using ALD. ZnO/TiO2 nanolaminates are much more stable than pristine ZnO films during electrochemical cycling process. Therefore, ZnO/TiO2 nanolaminates exhibit excellent lithium storage performance with an improved cycling performance and superior rate capability compared to pristine ZnO films. Moreover, coulombic efficiency (CE) of ZnO/TiO2 nanolaminates is above 99%, which is much higher than the value of pristine ZnO films. Excellent ultralong-life performance is gained for ZnO/TiO2 nanolaminates, retaining a reversible capacity of ~667 mAh g-1 within cut-off voltage of 0.05-2.5 V after 1200 cycles of charge-discharge at 500 mA g-1. Constructing nanolaminates structures via ALD might open up new opportunities for improving the performance of anode materials with large volume expansion in lithium ion batteries.

16.
J Org Chem ; 84(19): 12259-12267, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31315398

RESUMO

A general one-step synthesis of symmetrical or unsymmetrical 1,4-di(organo)fullerenes from organo(hydro)fullerenes (RC60H) is realized by direct oxidative arylation. The new combination of catalytic trifluoromethanesulfonic acid (TfOH) and stoichiometric o-chloranil is the first to be used to directly generate an R-C60+ intermediate from common RC60H. Unexpectedly, the in situ generated R-C60+ intermediate is shown to be quite stable in whole 13C NMR spectroscopy characterization in the absence of cation quenching reagents. Because the direct oxidation of common RC60H to form the corresponding R-C60+ has never been realized, the present combination of TfOH and o-chloranil solves the challenges associated with the formation of stable RC60+ cations from common RC60H without any coordination of an R group.

17.
Sci Rep ; 9(1): 10389, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316117

RESUMO

Dendrobium is known for its pharmacological actions including anti-cancer effect, anti-fatigue effect, gastric ulcer protective effect, and so on. At present, only studies on endophytic fungi of Dendrobium affecting the metabolites of host plants have been reported, very little research has been done on endophytic bacteria. In this study, we have demonstrated the great diversity of endophytic bacteria in 6 Dendrobium samples from different origins and cultivars. According to the results of the culture-independent method, the endophytic bacterial community in Dendrobium stems showed obvious different in the 6 samples and was influenced by origin and cultivar. Some bacteria including Ralstonia, Comamonas and Lelliottia were first detected in Dendrobium in this study. Based on the culture-dependent method, a total of 165 cultivable endophytic bacteria isolates were isolated from the sterilized Dendrobium stems, and were classified into 43 species according to the 16S rRNA gene sequence analysis. Moreover, 14 of the 43 strains showed antimicrobial activity against phytopathogen using the Kirby-Bauer method. Strain NA-HTong-7 (Bacillus megaterium, 99.12%) showed the highest antimicrobial activity. This study was the first comprehensive study on endophytic bacteria of Dendrobium from different origins and cultivars, which provides new insights into the endophytic bacteria from Dendrobium.

18.
Medicine (Baltimore) ; 98(27): e15990, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277090

RESUMO

BACKGROUND: Recent studies have demonstrated that coronary microcirculation dysfunction (CMVD) is closely correlated with adverse clinical outcomes. In this study, quantitative stress myocardial contrast echocardiography (MCE) was used to evaluate the CMVD and to investigate its association with the prognosis of patients with nonobstructive coronary artery disease (CAD). MATERIAL AND METHODS: From 2006 to 2014, 227 consecutive patients with chest pain and a diagnostic coronary angiography without significant coronary artery stenosis (<50%) who underwent adenosine triphosphate disodium (ATP) stress MCE were enrolled. Quantitative MCE measurements were analyzed using replenishment curves. RESULTS: Median follow-up time of this study was 5.3 years. Predictors of impaired coronary flow reserve (CFR) were smoking, diabetes, high apolipoprotein B, high low-density lipoprotein, serum uric acid, and low apolipoprotein A. During follow-up, 22 patients were reported to have 30 cardiac events (21 unstable angina, 3 nonfatal myocardial infarctions, 6 percutaneous coronary interventions). Using multivariate analysis, abnormal ß reserve (≤1.6), impaired CFR (≤2.0), and diabetes were independent predictors of primary endpoint events in patients with nonobstructive CAD (P < .05). Multivariate analysis showed that CFR ≤2.0 (odds ratio [OR] =  25.21, 95% confidence interval [CI]: 3.01-182.32; P = .003), ß reserve ≤1.6 (OR = 29.96, 95% CI: 3.5-241.27; P = .002), and diabetic (OR = 33.11, 95% CI: 3.65-300.02; P = .002) significantly increased the risk of the primary endpoint events. CONCLUSIONS: ATP stress quantitative MCE is a feasible and effective method to evaluate microcirculation abnormalities in human coronary arteries and it can be used for the clinical analysis, risk stratification, and treatment of early CAD.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Ecocardiografia sob Estresse/métodos , Ecocardiografia/métodos , Microcirculação/fisiologia , Trifosfato de Adenosina/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco
19.
Angew Chem Int Ed Engl ; 58(31): 10713-10717, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31155823

RESUMO

Efficient hydrogen evolution via electrocatalytic water splitting holds great promise in modern energy devices. Herein, we demonstrate that the localized surface plasmon resonance (LSPR) excitation of Au nanorods (NRs) dramatically improves the electrocatalytic hydrogen evolution activity of CoFe-metal-organic framework nanosheets (CoFe-MOFNs), leading to a more than 4-fold increase of current density at -0.236 V (vs. RHE) for Au/CoFe-MOFNs composite under light irradiation versus in dark. Mechanistic investigations reveal that the hydrogen evolution enhancement can be largely attributed to the injection of hot electrons from AuNRs to CoFe-MOFNs, raising the Fermi level of CoFe-MOFNs, facilitating the reduction of H2 O and affording decreased activation energy for HER. This study highlights the superiority of plasmonic excitation on improving electrocatalytic efficiency of MOFs and provides a novel avenue towards the design of highly efficient water-splitting systems under light irradiation.

20.
Medicine (Baltimore) ; 98(21): e15778, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124969

RESUMO

This study aimed to analyze the epidemiology of pulmonary tuberculosis (PTB) and gained insight into the future TB control plan in China.We extracted epidemiological, clinical, and geographic data from TB prevention and control institutions in 6 cities of Shandong province, China, during 2005 to 2017.Among 224,480 diagnosed PTB, rural residents accounted for 93%, smear-positive PTB 52%, and new cases 92%. The incidence rate of overall PTB declined from 40.8 to 26.25 per 100,000 during 2005 to 2017. Except smear-negative PTB (7.57-19.87 per 100,000), the incidence of smear-positive PTB and all that stratified by age, sex, and treatment history decreased. With 80% reduction, the incidence of smear-positive PTB (6.38 per 100,000) and relapse cases (1.01 per 100,000) were already very low in 2017.With persistent efforts to combat TB, the disease burden had shifted from smear-positive PTB to smear-negative PTB. While new cases need continuous attention, further reducing the incidence of smear-negative PTB and elderly patients may have a greater impact on future TB control.


Assuntos
Técnicas Bacteriológicas/estatística & dados numéricos , População Rural/estatística & dados numéricos , Tuberculose Pulmonar/epidemiologia , População Urbana/estatística & dados numéricos , Adolescente , Adulto , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium/crescimento & desenvolvimento , Estudos Retrospectivos , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
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