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1.
Opt Express ; 32(11): 19910-19923, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859113

RESUMO

Dielectric nanostructures exhibit low-loss electrical and magnetic resonance, making them ideal for quantum information processing. In this study, the periodic double-groove silicon nanodisk (DGSND) is used to support the anapole state. Based on the distribution properties of the electromagnetic field in anapole states, the anapoles are manipulated by cutting the dielectric metamaterial. Quantum dots (QDs) are used to stimulate the anapole and control the amplification of the photoluminescence signal within the QDs. By opening symmetrical holes in the long axis of the nanodisk in the dielectric metamaterial, the current distribution of Mie resonance can be adjusted. As a result, the toroidal dipole moment is altered, leading to an enhanced electric field (E-field) and Purcell factor. When the dielectric metamaterial is deposited on the Ag substrate separated by the silicon dioxide (SiO2) layer, the structure exhibits ultra-narrow perfect absorption with even higher E-field and Purcell factor enhancement compared to silicon (Si) nanodisks.

2.
J Org Chem ; 89(15): 10538-10550, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38996186

RESUMO

C3-functionalized dihydroquinolinones represent a class of important biologically active compounds. Although methods for synthesizing C2/4-functionalized dihydroquinolinones have been extensively reported, research on the synthesis of C3-functionalized dihydroquinolinone is extremely rare. Herein, we report for the first time a method for C3-alkenylated dihydroquinolinones via iron(III)-catalyzed amine-release triple condensation of enaminones. These reactions exhibit broad substrate scope and offer operationally simple, low-cost catalyzed procedures in a single step. Subsequent intramolecular and intermolecular additions to the alkene moiety provide diverse C3-functionalized dihydroquinolinone derivatives.

3.
BMC Genomics ; 24(1): 482, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620754

RESUMO

BACKGROUND: The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease, metabolites, and microbes can provide efficient and targeted solutions towards understanding the mechanism of complex disease and development of new markers and drugs. RESULTS: We developed Gut Microbial Metabolite Association with Disease (GMMAD), a manually curated database of associations among human diseases, gut microbes, and metabolites of gut microbes. Here, this initial release (i) contains 3,836 disease-microbe associations and 879,263 microbe-metabolite associations, which were extracted from literatures and available resources and then experienced our manual curation; (ii) defines an association strength score and a confidence score. With these two scores, GMMAD predicted 220,690 disease-metabolite associations, where the metabolites all belong to the gut microbes. We think that the positive effective (with both scores higher than suggested thresholds) associations will help identify disease marker and understand the pathogenic mechanism from the sense of gut microbes. The negative effective associations would be taken as biomarkers and have the potential as drug candidates. Literature proofs supported our proposal with experimental consistence; (iii) provides a user-friendly web interface that allows users to browse, search, and download information on associations among diseases, metabolites, and microbes. The resource is freely available at http://guolab.whu.edu.cn/GMMAD . CONCLUSIONS: As the online-available unique resource for gut microbial metabolite-disease associations, GMMAD is helpful for researchers to explore mechanisms of disease- metabolite-microbe and screen the drug and marker candidates for different diseases.


Assuntos
Produtos Biológicos , Microbioma Gastrointestinal , Humanos , Bases de Dados Factuais , Levamisol
4.
Acta Pharmacol Sin ; 44(9): 1768-1776, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37142682

RESUMO

Voltage-gated sodium channel 1.7 (Nav1.7) remains one of the most promising drug targets for pain relief. In the current study, we conducted a high-throughput screening of natural products in our in-house compound library to discover novel Nav1.7 inhibitors, then characterized their pharmacological properties. We identified 25 naphthylisoquinoline alkaloids (NIQs) from Ancistrocladus tectorius to be a novel type of Nav1.7 channel inhibitors. Their stereostructures including the linkage modes of the naphthalene group at the isoquinoline core were revealed by a comprehensive analysis of HRESIMS, 1D, and 2D NMR spectra as well as ECD spectra and single-crystal X-ray diffraction analysis with Cu Kα radiation. All the NIQs showed inhibitory activities against the Nav1.7 channel stably expressed in HEK293 cells, and the naphthalene ring in the C-7 position displayed a more important role in the inhibitory activity than that in the C-5 site. Among the NIQs tested, compound 2 was the most potent with an IC50 of 0.73 ± 0.03 µM. We demonstrated that compound 2 (3 µM) caused dramatical shift of steady-state slow inactivation toward the hyperpolarizing direction (V1/2 values were changed from -39.54 ± 2.77 mV to -65.53 ± 4.39 mV, which might contribute to the inhibition of compound 2 against the Nav1.7 channel. In acutely isolated dorsal root ganglion (DRG) neurons, compound 2 (10 µM) dramatically suppressed native sodium currents and action potential firing. In the formalin-induced mouse inflammatory pain model, local intraplantar administration of compound 2 (2, 20, 200 nmol) dose-dependently attenuated the nociceptive behaviors. In summary, NIQs represent a new type of Nav1.7 channel inhibitors and may act as structural templates for the following analgesic drug development.


Assuntos
Alcaloides , Canal de Sódio Disparado por Voltagem NAV1.7 , Camundongos , Animais , Humanos , Células HEK293 , Dor/tratamento farmacológico , Neurônios , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Gânglios Espinais , Bloqueadores dos Canais de Sódio/farmacologia , Bloqueadores dos Canais de Sódio/uso terapêutico
5.
J Environ Sci (China) ; 132: 83-97, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37336612

RESUMO

Daytime HONO photolysis is an important source of atmospheric hydroxyl radicals (OH). Knowledge of HONO formation chemistry under typical haze conditions, however, is still limited. In the Multiphase chemistry experiment in Fogs and Aerosols in the North China Plain in 2018, we investigated the wintertime HONO formation and its atmospheric implications at a rural site Gucheng. Three different episodes based on atmospheric aerosol loading levels were classified: clean periods (CPs), moderately polluted periods (MPPs) and severely polluted periods (SPPs). Correlation analysis revealed that HONO formation via heterogeneous conversion of NO2 was more efficient on aerosol surfaces than on ground, highlighting the important role of aerosols in promoting HONO formation. Daytime HONO budget analysis indicated a large missing source (with an average production rate of 0.66 ± 0.26, 0.97 ± 0.47 and 1.45 ± 0.55 ppbV/hr for CPs, MPPs and SPPs, respectively), which strongly correlated with photo-enhanced reactions (NO2 heterogeneous reaction and particulate nitrate photolysis). Average OH formation derived from HONO photolysis reached up to (0.92 ± 0.71), (1.75 ± 1.26) and (1.82 ± 1.47) ppbV/hr in CPs, MPPs and SPPs respectively, much higher than that from O3 photolysis (i.e., (0.004 ± 0.004), (0.006 ± 0.007) and (0.0035 ± 0.0034) ppbV/hr). Such high OH production rates could markedly regulate the atmospheric oxidation capacity and hence promote the formation of secondary aerosols and pollutants.


Assuntos
Poluentes Ambientais , Ácido Nitroso , Ácido Nitroso/análise , Poluentes Ambientais/análise , Dióxido de Nitrogênio/análise , China , Aerossóis/análise
6.
Br J Nutr ; 127(6): 823-836, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-33988091

RESUMO

To unveil the adaptation of Litopenaeus vannamei to elevated ambient ammonia-N, crustacean hyperglycaemic hormone (CHH) was knocked down to investigate its function in glucose metabolism pathway under ammonia-N exposure. When CHH was silenced, haemolymph glucose increased significantly during 3-6 h, decreased significantly during 12-48 h and recovered to the control groups' level at 72 h. After CHH knock-down, dopamine (DA) contents reduced significantly during 3-24 h, which recovered after 48 h. Besides, the expressions of guanylyl cyclase (GC) and DA1R in the hepatopancreas decreased significantly, while DA4R increased significantly. Correspondingly, the contents of cyclic AMP (cAMP), cyclic GMP (cGMP) and diacylglycerol (DAG) and the expressions of protein kinase A (PKA), protein kinase G (PKG), AMP active protein kinase α (AMPKα) and AMPKγ were significantly down-regulated, while the levels of protein kinase C (PKC) and AMPKß were significantly up-regulated. The expressions of cyclic AMP response element-binding protein (CREB) and GLUT2 decreased significantly, while GLUT1 increased significantly. Moreover, glycogen content, glycogen synthase and glycogen phosphorylase activities in hepatopancreas and muscle were significantly increased. Furthermore, the levels of key enzymes hexokinase, pyruvate kinase and phosphofructokinase in glycolysis (GLY), rate-limiting enzymes citrate synthase in tricarboxylic acid and critical enzymes phosphoenolpyruvate carboxykinase, fructose diphosphate and glucose-6-phosphatase in gluconeogenesis (GNG) were significantly decreased in hepatopancreas. These results suggest that CHH affects DA and then they affect their receptors to transmit glucose metabolism signals into the hepatopancreas of L. vannamei under ammonia-N stress. CHH acts on the cGMP-PKG-AMPKα-CREB pathway through GC, and CHH affects DA to influence cAMP-PKA-AMPKγ-CREB and DAG-PKC-AMPKß-CREB pathways, thereby regulating GLUT, inhibiting glycogen metabolism and promoting GLY and GNG. This study contributes to further understand glucose metabolism mechanism of crustacean in response to environmental stress.


Assuntos
Hiperglicemia , Penaeidae , Amônia , Animais , Proteínas de Artrópodes , Glucose/metabolismo , Glicogênio/metabolismo , Hormônios de Invertebrado , Proteínas do Tecido Nervoso , Nitrogênio/metabolismo , Interferência de RNA
7.
Med Sci Monit ; 28: e933782, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35034947

RESUMO

BACKGROUND This study aimed to survey the overall situation of birth defects (BDs) among citizens of Hangzhou, China, and the risk factors of different BD types. MATERIAL AND METHODS We collected the data of 4349 perinatal infants with BDs in Hangzhou. The potentially associated risk factors of BDs were recorded and logistic regression analysis was used to predict the high incidence of BDs. RESULTS Among all perinatal infants with BDs, there were 4105 (94.3%) single births, 225 (5.2%) twin births, and 10 (0.2%) multiple births. In clinical outcomes, there were 2477 (57.0%) live births, 1806 (41.5%) dead fetuses, and 11 (0.3%) stillbirths. Down syndrome ranked first, accounting for 30.7% of the total births, followed by cleft lip and polydactyly. Low family income, nulliparity, high parity, high education level, and taking contraceptives in early pregnancy were found to be risk factors of Down syndrome. Low parity, low education level, and pesticide exposure were found to be risk factors of cleft lip. For polydactyly, young age of the mother and a parity above 0 were identified as risk factors. CONCLUSIONS Different risks factors can influence BD development and potentially help to predict specific BD types, such as demographic features and harmful exposure in early pregnancy.


Assuntos
Anormalidades Congênitas/epidemiologia , Adulto , China/epidemiologia , Fenda Labial/epidemiologia , Anticoncepcionais/efeitos adversos , Síndrome de Down/epidemiologia , Escolaridade , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Idade Materna , Paridade , Praguicidas/efeitos adversos , Pobreza/estatística & dados numéricos , Gravidez , Fatores de Risco
8.
Build Environ ; 219: 109224, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35645454

RESUMO

The public transport system, containing a large number of passengers in enclosed and confined spaces, provides suitable conditions for the spread of respiratory diseases. Understanding how diseases are transmitted in public transport environment is of vital importance to public health. However, this is a highly multidisciplinary matter and the related physical processes including the emissions of respiratory droplets, the droplet dynamics and transport pathways, and subsequently, the infection risk in public transport, are poorly understood. To better grasp the complex processes involved, a synthesis of current knowledge is required. Therefore, we conducted a review on the behaviors of respiratory droplets in public transport system, covering a wide scope from the emission profiles of expiratory droplets, the droplet dynamics and transport, to the transmission of COVID-19 in public transport. The literature was searched using related keywords in Web of Science and PubMed and screened for suitability. The droplet size is a key parameter in determining the deposition and evaporation, which together with the exhaled air velocity largely determines the horizontal travel distance. The potential transmission route and transmission rate in public transport as well as the factors influencing the virus-laden droplet behaviors and virus viability (such as ventilation system, wearing personal protective equipment, air temperature and relative humidity) were also discussed. The review also suggests that future studies should address the uncertainties in droplet emission profiles associated with the measurement techniques, and preferably build a database based on a unified testing protocol. Further investigations based on field measurements and modeling studies into the influence of different ventilation systems on the transmission rate in public transport are also needed, which would provide scientific basis for controlling the transmission of diseases.

9.
Faraday Discuss ; 226: 207-222, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33284304

RESUMO

Fine-particle pollution associated with winter haze threatens the health of more than 400 million people in the North China Plain. The Multiphase chemistry experiment in Fogs and Aerosols in the North China Plain (McFAN) investigated the physicochemical mechanisms leading to haze formation with a focus on the contributions of multiphase processes in aerosols and fogs. We integrated observations on multiple platforms with regional and box model simulations to identify and characterize the key oxidation processes producing sulfate, nitrate and secondary organic aerosols. An outdoor twin-chamber system was deployed to conduct kinetic experiments under real atmospheric conditions in comparison to literature kinetic data from laboratory studies. The experiments were spanning multiple years since 2017 and an intensive field campaign was performed in the winter of 2018. The location of the site minimizes fast transition between clean and polluted air masses, and regimes representative for the North China Plain were observed at the measurement location in Gucheng near Beijing. The consecutive multi-year experiments document recent trends of PM2.5 pollution and corresponding changes of aerosol physical and chemical properties, enabling in-depth investigations of established and newly proposed chemical mechanisms of haze formation. This study is mainly focusing on the data obtained from the winter campaign 2018. To investigate multiphase chemistry, the results are presented and discussed by means of three characteristic cases: low humidity, high humidity and fog. We find a strong relative humidity dependence of aerosol chemical compositions, suggesting an important role of multiphase chemistry. Compared with the low humidity period, both PM1 and PM2.5 show higher mass fraction of secondary inorganic aerosols (SIA, mainly as nitrate, sulfate and ammonium) and secondary organic aerosols (SOA) during high humidity and fog episodes. The changes in aerosol composition further influence aerosol physical properties, e.g., with higher aerosol hygroscopicity parameter κ and single scattering albedo SSA under high humidity and fog cases. The campaign-averaged aerosol pH is 5.1 ± 0.9, of which the variation is mainly driven by the aerosol water content (AWC) concentrations. Overall, the McFAN experiment provides new evidence of the key role of multiphase reactions in regulating aerosol chemical composition and physical properties in polluted regions.

10.
Proc Natl Acad Sci U S A ; 115(50): E11595-E11603, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30478047

RESUMO

Wildfires inject large amounts of black carbon (BC) particles into the atmosphere, which can reach the lowermost stratosphere (LMS) and cause strong radiative forcing. During a 14-month period of observations on board a passenger aircraft flying between Europe and North America, we found frequent and widespread biomass burning (BB) plumes, influencing 16 of 160 flight hours in the LMS. The average BC mass concentrations in these plumes (∼140 ng·m-3, standard temperature and pressure) were over 20 times higher than the background concentration (∼6 ng·m-3) with more than 100-fold enhanced peak values (up to ∼720 ng·m-3). In the LMS, nearly all BC particles were covered with a thick coating. The average mass equivalent diameter of the BC particle cores was ∼120 nm with a mean coating thickness of ∼150 nm in the BB plume and ∼90 nm with a coating of ∼125 nm in the background. In a BB plume that was encountered twice, we also found a high diameter growth rate of ∼1 nm·h-1 due to the BC particle coatings. The observed high concentrations and thick coatings of BC particles demonstrate that wildfires can induce strong local heating in the LMS and may have a significant influence on the regional radiative forcing of climate.

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