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2.
Environ Res ; 182: 109120, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927247

RESUMO

Human exposure to PM2.5, represented by population-weighted mean PM2.5 concentration (cρ), declines under three conditions: (1) mean PM2.5 concentration declines, (2) PM2.5 concentration within urban areas goes through more of a decrease than within rural areas, or (3) city planning relocates people into cleaner areas. Decomposing these effects on human exposure is essential to guide future environmental policies. The lack of ground PM2.5 observations limits the assessment of human exposure to PM2.5 over China. This study proposed a novel diagnostic framework using satellite observations to decompose the variation in cρ resulting from change in the mean PM2.5 concentration, spatial difference in PM2.5 change, and demographic change. In this framework, we decomposed cρ into mean PM2.5 concentration (c0) and pollution-population-coincidence induced PM2.5 exposure (PPCE). We then used this framework to decompose the variation in cρ over China within three recent Five-Year Plans (FYPs) (2001-2015). The results showed that the decline in c0 reduced cρ in most provinces within the eleventh and twelfth FYPs. The spatial difference in PM2.5 change reduced the PPCE and cρ in most provinces within the tenth and twelfth FYPs, with the most substantial reduction rate of -3.64 µg m-3·yr-1 in Tianjin within the twelfth FYP. Rural-to-urban migration resulting from rapid urbanization, however, increased the PPCE and cρ (by as much as 0.22 µg m-3·yr-1) in all provinces except Taiwan within all three FYPs. The demographic change reduced cρ in Taiwan because of the migration of population into less polluted areas. To better reduce human exposure, it is recommended that control efforts further target populous residential areas and urbanization planning relocates people into less polluted areas. Our decomposition framework paves a new way to decompose the human exposure to other air pollutants in China and other regions.

3.
J Phys Chem Lett ; : 1228-1238, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31990196

RESUMO

Sonodynamic therapy eliminates cancer cells with reactive oxygen species (ROS) triggered by ultrasound whose energy is spatiotemporally controllable, is safe to human tissues and organs, and penetrates deeply through tissues. Its application, however, is hindered by the scarcity of sonodynamic sensitizers. We herein demonstrate piezoelectric materials as a new source of sonodynamic sensitizers, using few-layer black phosphorus (BP) nanosheet as a model. BP nanosheet exhibited ultrasound-excited cytotoxicity to cancer cells via ROS generation, thereby suppressing tumor growth and metastasis without causing off-target toxicity in tumor-bearing mouse models. The ultrasonic wave introduces mechanical strain to the BP nanosheet, leading to piezoelectric polarization which shifts the conduction band of BP more negative than O2/·O2- while its valence band more positive than H2O/·OH, thereby accelerating the ROS production. This work identifies a new mechanism for discovering sonodynamic sensitizers and suggests BP nanosheet as an excellent sensitizer for tumor sonodynamic therapy.

4.
Toxicology ; 431: 152366, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31926187

RESUMO

Kidney injury is a major adverse effect of cisplatin use. Metabolomics has been used to characterize physiological or pathological conditions through identification of metabolites and characterization of the metabolic pathway. Metabolomics profiling could allow for identification of nephrotoxic mechanisms of cisplatin and identification of biomarkers of cisplatin-induced injury. In this study, we performed metabolomics analysis to characterize key changes in metabolite levels during cisplatin-induced acute kidney injury (AKI) in rats, and screened for sensitive biomarkers for early diagnosis using HPLC-TOF/MS. Rats were intraperitoneally injected with 7.5 mg/kg or 15 mg/kg of cisplatin, or normal saline, and 12 h urine and kidney samples were collected after 72 h. Serum biochemical parameters and kidney histological evaluations showed dose-dependent AKI in response to cisplatin. Metabolomics analysis showed that 37 and 35 endogenous metabolite levels changed in rat urine and kidneys, respectively. Seven key metabolic pathways were disrupted, including the tricarboxylic acid cycle (TCA cycle), phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism, d-glutamine and d-glutamate metabolism, and nicotinate and nicotinamide metabolism. These pathways are involved in energy generation, and amino acid and lipid metabolism, and disruption of these pathways could contribute to oxidative stress injury, inflammation, and cell membrane damage. Furthermore, 11 sensitive metabolites in urine were screened as potential biomarkers of AKI. To validate these biomarkers, we quantified 4 off these biomarkers, and confirmed that levels of these metabolites were altered in urine of rats treated with CDDP.

5.
J Membr Biol ; 253(1): 43-55, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820013

RESUMO

Lysophosphatidylcholine (LPC) is a major atherogenic lipid that stimulates an increase in mitochondrial reactive oxygen species (mtROS) and the release of cytokines under inflammasome activation. However, the potential receptors of LPC in macrophages are poorly understood. Members of the transient receptor potential (TRP) channel superfamily, which is crucially involved in transducing environmental irritant stimuli into nociceptor activity, are potential receptors of LPC. In this study, we investigated whether LPC can induce the activation of transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily. The functional expression of TRPA1 was first detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and calcium imaging in human acute monocytic leukemia cell line (THP-1)-derived macrophages. The mechanism by which LPC induces the activation of macrophages through TRPA1 was verified by cytoplasmic and mitochondrial calcium imaging, mtROS detection, a JC-1 assay, enzyme-linked immunosorbent assay, the CCK-8 assay and the lactate dehydrogenase (LDH) cytotoxic assay. LPC induced the activation of THP-1-derived macrophages via calcium influx, and this activation was suppressed by potent and selective inhibitors of TRPA1. These results indicated that TRPA1 can mediate mtROS generation, mitochondrial membrane depolarization, the secretion of IL-1ß and cytotoxicity through cellular and mitochondrial Ca2+ influx in LPC-treated THP-1-derived macrophages. Therefore, the inhibition of TRPA1 may protect THP-1-derived macrophages against LPC-induced injury.

6.
Immunopharmacol Immunotoxicol ; 42(1): 28-36, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31876196

RESUMO

Background: Epidemiological studies have shown that environmental factors accelerate the progress of primary Sjögren's syndrome (pSS). Bisphenol A (BPA), a classic endocrine disrupting chemical, affects the immune system. However, the impact of BPA on pSS has not yet been reported. The present study aimed to evaluate the potential relationship between BPA, estrogen receptor (ER), and pSS.Methods: We studied the impact of BPA on monocyte-derived dendritic cells (moDCs) from pSS patients and age-matched healthy controls (HCs). Morphological effects were observed under inverted microscope. Surface markers were analyzed by flow cytometry. ER and cytokine profiles were assessed using real-time polymerase chain reaction. The ability of moDCs to stimulate CD4+ T cells activation was assessed by mixed lymphocyte reaction (MLR).Results: moDCs from both pSS patients and HCs expressed ERα as well as ERß. After BPA-exposure, expression of ERα increased significantly in pSS patients, while that of ERß remained unchanged. moDCs from BPA-exposed pSS patients showed irregular morphology and reduction in cell aggregation. BPA increased HLA-DR on moDCs of pSS patients via ERα, and promoted the secretion of IL6 and IL12. When co-cultured with BPA-treated moDCs, cytokines (IFN-γ, IL4, IL17, IL10) and transcription factors (T-bet, Gata3, RoR-γt, Foxp3) of CD4+ T cells showed imbalance of Th1/Th2/Th17/Treg polarization, with Th1 and Th17 dominating.Conclusions: BPA altered the function of moDCs through ERα, including antigen capture, secretion of inflammatory factors, and ability to stimulate T cells, as well as accelerated the progression and further deterioration of pSS.

7.
Micromachines (Basel) ; 10(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805751

RESUMO

In order to solve the problem of continuous and stable power supply for vehicle sensors, a resonant cavity piezoelectric energy harvester driven by driving wind pressure was designed. The harvester has an effective working range of wind speed. According to the energy conservation law, the cut-in (initial) wind speed of the harvester was solved. The pressure distribution law of the elastic beam in the flow field was studied by the Fluent software package, and the results were loaded into a finite element model with a method of partition loading. The relationship between the wind speed and the maximum principal stress of the piezoelectric cantilever beam was analyzed, and the critical stress method was used to study the cut-out wind speed of the energy harvester. The results show that the cut-in wind speed of the piezoelectric energy harvester is 5.29 m/s, and the cut-out wind speed is 24 m/s. Finally, an experiment on the power generation performance of the energy harvester was carried out. The experimental results show that the cut-in and cut-out wind speeds of the piezoelectric energy harvester are 5 m/s and 24 m/s, respectively, and the best matching load is 60 kΩ. The average output power, generated by the harvester when the driving wind speed is 22 m/s, is 0.145 mW, and the corresponding power density is 1.2 mW/cm3.

8.
J Pain Res ; 12: 2999-3012, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807057

RESUMO

Purpose: The purpose of this study was to explore the central analgesia mechanism of moxibustion for chronic inflammatory visceral pain (CIVP). Methods: A CIVP rat model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) plus 50% ethanol via enema. The analgesic effect of moxibustion was evaluated using the abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). The expression profile of phosphorylated proteins of the mitogen-activated protein kinase (MAPK) signaling pathway in the spinal cord was assayed by protein microarray. The differentially expressed proteins were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional clusters and corresponding signaling pathways. Results: Moxibustion exerted a significant analgesic effect for CIVP rats, mainly presenting as a decrease in the AWR score (all P<0.01) under different levels of distending pressure and an increase in MWT and TWL thresholds (all P<0.05). Compared with the normal group, 76 proteins were upregulated while 15 were downregulated, and MAPK signaling pathway was activated in the model group. Compared with the model group, there were 53 downregulated and 38 upregulated proteins in the moxibustion group, and MAPK signaling pathway was inhibited. Fold change (FC)>1.3 or <0.77 was taken as the screening standard to define the differentially expressed proteins. Fifteen differentially expressed proteins upregulated in the model group were downregulated in the moxibustion group. GO analysis showed that the differentially expressed proteins mainly controlled cellular metabolism regulation, transportation, and stress reactions. KEGG analysis revealed that these differentially expressed proteins were mostly involved in the ERK, JNK, and p38 pathways, and the ERK pathway was predominant. Conclusion: Moxibustion mitigates CIVP in rats and inhibits the phosphorylation of proteins in the spinal MAPK signaling pathway. The analgesic effect of moxibustion may be associated with the regulation of the spinal MAPK signaling pathway.

9.
Sci Total Environ ; : 135323, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31839290

RESUMO

Air pollution has shown to cause adverse health effects on mankind. Aging causes functional decline and leaves elderly people more susceptible to health threats associated with air pollution exposure. Elderly spend approximately 80% of their lifetime at home every day. To understand air pollution exposure, indoor air pollutants are the targets for consideration especially for the elderly population. However, indoor air monitoring for epidemiological studies requires a large population, is labor intensive and time consuming. As a result, a prediction model is necessary. For 3 consecutive days in summer and winter, 24-h average of mass concentrations of fine particulate matter (aerodynamic diameter <2.5 µm: PM2.5) were measured in indoors for 116 households. A PM2.5 prediction model for elderly households in Hong Kong has been developed by combining ambient PM2.5 concentrations obtained from land use regression model and questionnaire-elicited information related to the indoor PM2.5 sources. The fitted linear mixed-effects model is moderately predictive for the observed indoor PM2.5, with R2 = 0.67 (or R2 = 0.61 by cross-validation). The model shows indoor PM2.5 was positively influenced by outdoor PM2.5 levels. Meteorological factors (e.g. temperature and relative humidity) were related to the indoor PM2.5 in a relatively complex manner. Congested living areas, opening windows for extended periods for ventilation and use of liquefied petroleum gas for cooking were the factors determining the ultimate indoor air quality. This study aims to provide information about controlling household air quality and can be used for future epidemiological studies associated with indoor air pollution in large population.

10.
Onco Targets Ther ; 12: 9783-9791, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819479

RESUMO

Purpose: Chordomas are locally aggressive tumors arising from notochordal remnants. Brachyury, a protein coded by T-gene, is crucial for chordoma cell proliferation. The aim of this study was to evaluate the effects of glycogen synthase kinase 3 beta (GSK3ß) activity on brachyury expression and on the growth and survival of skull base chordoma cells. Patients and methods: In this study, 16 paraffin-embedded specimens of primary skull base chordomas were analyzed for the expression of phosphorylated GSK3ß and brachyury using immunohistochemistry. The UM-Chor1 cell line derived from a clival chordoma was treated with AR-A014418 (AR), an inhibitor of GSK3ß, and brachyury expression was analyzed by qRT-PCR and Western blotting. The possible mechanism by which brachyury regulates the Wnt/ß-catenin signaling pathway was investigated by immunocytochemistry. The effects of AR on cell proliferation as well as sensitivity to chemotherapeutic drugs were also examined. Results: The results suggested that phosphorylated GSK3ß and brachyury were upregulated in chordoma tissues. The GSK3ß inhibitor (AR) decreased brachyury expression and suppressed the growth and survival of the chordoma cells, possibly via regulation of the Wnt/ß-catenin signaling pathway. Moreover, AR increased the sensitivity of chordoma cells to chemotherapeutic drugs in vitro. Conclusion: This study provides evidence for the clinical development of the GSK3ß inhibitor (AR-A014418) as a potential chemotherapeutic adjuvant for the treatment of chordoma.

11.
Sci Rep ; 9(1): 19320, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848415

RESUMO

The drawbacks of low porosity, inferior electrolyte wettability, low thermal dimensional stability and permissive lithium dendrite growth of the conventional microporous polyolefin-based separators hinder their widely application in the high power density and safe Lithium ion batteries. Herein, highly porous polybenzimidazole-based separator is prepared by a facile non-solvent induced phase separation process (NIPS) using water, ethanol, chloroform and ethyl acetate as the coagulation bath solvent, respectively. It was found that the ethanol is suitable to fabricate uniform morphology macroporous separator with the porosity of 92%, electrolyte uptake of 594 wt.%, and strong mechanical strength of 15.9 MPa. In addition, the experimental tests (electrochemical analysis and XPS test) and density functional theory calculation suggest that the electron-rich imidazole ring of polybenzimidazle can enhance Li+ mobility electrostatic attraction interaction while the block the PF6- mobility via electrostatic repulsion interaction. Therefore, high Li+ transference number of 0.76 was obtained for the neat polybenzimidazole-based polymer electrolyte. As a proof of concept, the Li/LiFePO4 cell with the polybenzimidazole-based polymer electrolyte/1.0 M LiPF6- ethylene carbonate/dimethyl carbonate (v:v = 1:1) electrolyte exhibits excellent rate capability of >100 mAh g-1 at 6 C (1 C = 170 mA g-1) and superior cycle stability of 1000 cycles.

12.
J Geriatr Cardiol ; 16(10): 764-774, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31700516

RESUMO

Background: Qishen (QS) capsules, a Traditional Chinese Medicine, has been widely used to treat coronary heart disease in China. However, evidence of its effectiveness remains unclear. Methods: To explore whether QS has cardioprotective efficacy and/or promotes angiogenesis after myocardial infarction (MI), we performed experiments in a preclinical rat MI model. One month after left anterior descending coronary artery ligation, the rats received either QS solution (0.4 g/kg/day) or the same volume of saline by intragastric injection for four weeks. Results: Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in MI rats administered QS. Indeed, QS treatment was associated with reduced infarct scar size and heart weight index, and these beneficial effects were responsible for enhancing angiogenesis. Mechanistically, QS treatment increased phosphorylation of protein kinase B (Akt) and downregulated phosphorylation of mitogen-activated protein kinase/extracellular-regulated kinase (MEK/ERK). Conclusions: QS therapy can improve the cardiac function of rats after MI by an underlying mechanism involving increased angiogenesis, at least partially via activation of the Akt signaling pathway and inhibition of MEK/ERK phosphorylation.

14.
Genes Brain Behav ; : e12625, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730264

RESUMO

Temperature sensing is an important adaptive mechanism for warm-blooded animals such as humans. ThermoTRP ion channels are activated by distinct but overlapping physiological temperatures. Our previous research demonstrated that sorting nexin 11 (SNX11) regulates lysosomal degradation of plasma membrane TRPV3, one of ThermoTRP ion channel proteins. Here, we found that SNX11, a vesicular trafficking protein, modulates mouse behaviour in response to temperature changes. Snx11-knockout mice exhibit a stronger preference for mild temperatures along with enhanced sensitivity to harmful heat. Mechanistically, keratinocytes from Snx11-knockout mice exhibit a larger temperature-gated TRPV3 membrane current and have enhanced thermoTRPV3 expression in the plasma membrane compared to wild-type keratinocytes. Additionally, Snx11-knockout mice show higher endogenous TRPV3 protein levels in skin tissues than wild-type mice do. Therefore, our results indicate that SNX11 may regulate thermal perception via alteration of functional thermoTRPV3 on the plasma membrane of thermally sensitive cells, which is the first link between vesicular trafficking and thermal transduction.

15.
Biochem Biophys Res Commun ; 520(3): 651-656, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31629472

RESUMO

Melanocortin 4 receptor (MC4R)-deficient mice had been used for several years to study human nonalcoholic steatohepatitis (NASH). However, although liver pathologic and biochemical indicators have been examined, mice models do not always faithfully display the phenotype of the human disease. In this study, we investigated the MC4R knockout phenotype in miniature pigs. We found that pigs lacking MC4R exhibited hyperorexia, insulin resistance, hyperinsulinemia, disordered lipid metabolism and their livers accumulated significant amounts of fat. We have shown that deletion of MC4R results in hyperphagia and increased body fat, ultimately leading to hepatic steatosis without atherogenic diet.

16.
Animals (Basel) ; 9(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581597

RESUMO

Sillago sihama has high economic value and is one of the most attractive aquaculture species in China. Despite its economic importance, studies of its genome have barely been performed. In this study, we conducted a first genomic survey of S. sihama using next-generation sequencing (NGS). In total, 45.063 Gb of high-quality sequence data were obtained. For the 17-mer frequency distribution, the genome size was estimated to be 508.50 Mb. The sequence repeat ratio was calculated to be 21.25%, and the heterozygosity ratio was 0.92%. Reads were assembled into 1,009,363 contigs, with a N50 length of 1362 bp, and then into 814,219 scaffolds, with a N50 length of 2173 bp. The average Guanine and Cytosine (GC) content was 45.04%. Dinucleotide repeats (56.55%) were the dominant form of simple sequence repeats (SSR).

17.
Plants (Basel) ; 8(10)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618834

RESUMO

As the last stage of plant development, leaf senescence has a great impact on plant's life cycle. Genetic manipulation of leaf senescence has been used as an efficient approach in improving the yield and quality of crop plants. Here we describe an ethyl methane sulfonate (EMS) mutagenesis induced premature leaf senescence mutant yellow leaf 1 (yl1) in common tobacco (Nicotiana tabacum L.). The yl1 plants displayed early leaf yellowing. Physiological parameters and marker genes expression indicated that the yl1 phenotype was caused by premature leaf senescence. Genetic analyses indicated that the yl1 phenotype was controlled by a single recessive gene that was subsequently mapped to a specific interval of tobacco linkage group 11 using simple sequence repeat (SSR) markers. Exogenous plant hormone treatments of leaves showed that the yl1 mutant was more sensitive to ethylene and jasmonic acid than the wild type. No similar tobacco premature leaf senescence mutants have been reported. This study laid a foundation for finding the gene controlling the mutation phenotype and revealing the molecular regulation mechanism of tobacco leaf senescence in the next stage.

18.
Stem Cell Res ; 40: 101571, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31520889

RESUMO

Autism spectrum disorder (ASD) is a neurological disorder with complex etiologies. In this study, urine cells were collected from a 16-year-old male with ASD and reprogrammed with the human SKOM transcription factors. The patient has a heterozygous C > T mutation of FCGR1B gene that was confirmed by sequencing analysis. The pluripotency was verified by gene expression and capacity of differentiation towards the three germ layers. This kind of iPSC will be valuable for further understanding the pathogenesis of ASD and help to develop drugs for treating ASD.

19.
Opt Express ; 27(17): 24738-24746, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510358

RESUMO

We theoretically study the topological transition of dispersion types and propose a tunable planar lens based on graphene hyperbolic metamaterials (HMMs). By tuning the chemical potential (µc) of graphene, the dispersion relation of the HMM is topologically switchable between ellipse (µc<0.6 eV) and hyperbola (µc>0.6 eV) where positive and negative refractions occur respectively. Especially, for µc>0.6 eV, a Gaussian light beam is negatively refracted twice and focuses at a far-field point finally, acting well as a planar lens. Furthermore, its focal length l can be sensitively tuned by controlling µc, and Δl reaches 260 µm (from 528 to 268 µm) while µc varies with only 0.05 eV (from 0.65 to 0.7 eV). The physical reason is attributed to the different anisotropy degrees of EFCs for different µc. Such a compact, high-speed, and sensitively tunable planar lens holds great promise in photonic integration, photonic imaging, and directional coupling applications.

20.
Micromachines (Basel) ; 10(10)2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31546605

RESUMO

It is highly desirable to design optical devices with diverse optomechanical functions. Here, we investigate lateral optical force exerted on subwavelength-diameter (SD) optical fibers harnessed by input light modes with different polarizations. It is interesting to find that input light modes of circular or elliptical polarizations would bring about lateral optical force in new directions, which has not been observed in previous studies. By means of finite-difference time-domain (FDTD) simulations, detailed spatial distributions of the asymmetric transverse force density are revealed, meanwhile dependence of optical force on input light polarizations, fiber diameters, and inclination angles of fiber endfaces are all carefully discussed. It is believed that polarization-sensitive reflection, refraction, and diffraction of optical fields occur at the interface, i.e., fiber oblique endfaces, resulting in asymmetrically distributed optical fields and thereafter non-zero transverse optical force. We believe our new findings could be helpful for constructing future steerable optomechanical devices with more flexibility.

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