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1.
Plant Cell Environ ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828861

RESUMO

Cadmium (Cd) is a toxic metal that poses serious threats to human health. Rice is a major source of dietary Cd but how rice plants transport Cd to the grain is not fully understood. Here, we characterize the function of the ZIP (ZRT, IRT-like protein) family protein, OsZIP2, in the root-to-shoot translocation of Cd and intervascular transfer of Cd in nodes. OsZIP2 is localized at the plasma membrane and exhibited Cd2+ transport activity when heterologously expressed in yeast. OsZIP2 is strongly expressed in xylem parenchyma cells in roots and in enlarged vascular bundles in nodes. Knockout of OsZIP2 significantly enhanced root-to-shoot translocation of Cd and alleviated the inhibition of root elongation by excess Cd stress; whereas overexpression of OsZIP2 decreased Cd translocation to shoots and resulted in Cd sensitivity. Knockout of OsZIP2 increased Cd allocation to the flag leaf but decreased Cd allocation to the panicle and grain. We further reveal that the variation of OsZIP2 expression level contributes to grain Cd concentration among rice germplasms. Our results demonstrate that OsZIP2 functions in root-to-shoot translocation of Cd in roots and intervascular transfer of Cd in nodes, which can be used for breeding low Cd rice varieties.

2.
J Exp Bot ; 73(6): 1766-1774, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34864981

RESUMO

Molybdenum (Mo) is an essential element for almost all living organisms. After being taken up into the cells as molybdate, it is incorporated into the molybdenum cofactor, which functions as the active site of several molybdenum-requiring enzymes and thus plays crucial roles in multiple biological processes. The uptake and transport of molybdate is mainly mediated by two types of molybdate transporters. The homeostasis of Mo in plant cells is tightly controlled, and such homeostasis likely plays vital roles in plant adaptation to local environments. Recent evidence suggests that Mo is more than an essential element required for plant growth and development; it is also involved in local adaptation to coastal salinity. In this review, we summarize recent research progress on molybdate uptake and transport, molybdenum homeostasis network in plants, and discuss the potential roles of the molybdate transporter in plant adaptation to their local environment.


Assuntos
Proteínas de Membrana Transportadoras , Molibdênio , Transporte Biológico , Proteínas de Membrana Transportadoras/metabolismo , Molibdênio/metabolismo
3.
Environ Sci Technol ; 56(11): 7163-7173, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35483018

RESUMO

The interaction between water vapor and atmospheric aerosol leads to enhancement in aerosol water content, which facilitates haze development, but its concentrations, sources, and impacts remain largely unknown in polluted urban environments. Here, we show that the Indian capital, Delhi, which tops the list of polluted capital cities, also experiences the highest aerosol water yet reported worldwide. This high aerosol water promotes secondary formation of aerosols and worsens air pollution. We report that severe pollution events are commonly associated with high aerosol water which enhances light scattering and reduces visibility by 70%. Strong light scattering also suppresses the boundary layer height on winter mornings in Delhi, inhibiting dispersal of pollutants and further exacerbating morning pollution peaks. We provide evidence that ammonium chloride is the largest contributor to aerosol water in Delhi, making up 40% on average, and we highlight that regulation of chlorine-containing precursors should be considered in mitigation strategies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Cloreto de Amônio , China , Monitoramento Ambiental , Índia , Material Particulado/análise , Estações do Ano
4.
Environ Res ; 211: 113107, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35305979

RESUMO

The oxidation of polycyclic aromatic hydrocarbons (PAHs) determines their lifetime, toxicity and consequent environmental and climate impacts. The residential solid fuel burning composes of a substantial fraction of PAH emissions; however, their oxidation rate is yet to be explicitly understood, which is complicated by the contrasting emission factors under different combustion conditions and their subsequent evolution in the atmosphere. Here we used a plume evolution chamber using ambient oxidants to simulate the evolution of residential solid fuel burning emissions under real-world solar radiation, and then to investigate the oxidation process of the emitted PAHs. Contrasting oxidation rate of PAHs was found to be influenced by particles with or without presence of substantial amount of black carbon (BC). In the flaming burning phase, which contained 46% of BC mass fraction and 8% of organic aerosol (OA) internally mixed with BC, the larger PAHs (with 4-7 rings) was rapidly oxidized 12% for every hour of evolution under solar radiation; however, the larger PAHs from smoldering phase tended to maintain unmodified during the evolution, when 95% of OA was externally mixed with only minor fraction of BC (<5%). This may be ascribed to the complex morphology of BC, allowing more exposure for the internally-mixed OA to the oxidants; in contrast with those externally-mixed OA which was prone to be coated by condensed secondary substances. This raises an important consideration about the particle mixing state in influencing the oxidation of PAHs, particularly the coating on PAHs which may extend their lifetime and environmental impacts.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Aerossóis/análise , Poluentes Atmosféricos/análise , Biomassa , Monitoramento Ambiental , Oxidantes , Hidrocarbonetos Policíclicos Aromáticos/análise , Fuligem
5.
Faraday Discuss ; 226: 239-254, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33241817

RESUMO

The hygroscopicity and ability of aerosol particles to act as cloud condensation nuclei (CCN) is important in determining their lifetime and role in aerosol-cloud interactions, thereby influencing cloud formation and climate. Previous studies have used the aerosol hygroscopic properties measured at the ground to evaluate the influence on cloud formation in the atmosphere, which may introduce uncertainty associated with aerosol hygroscopicity variability with altitude. In this study, the CCN behaviour and hygroscopic properties of daily filter collections of PM2.5 from three different heights (8, 120, 260 m) on a tower in Beijing were determined in the laboratory using water, water/methanol and methanol as the atomization solvents. Whilst there was substantial temporal variability in particle concentration and composition, there was little obvious difference in aerosol CCN and hygroscopic behaviour at different heights, although the planetary boundary layer height (PBLH) reduced to below the tower height during the nighttime, suggesting that use of surface hygroscopicity measurements is sufficient for the estimation of aerosol particle activation in clouds. Additionally, the critical coating thickness (in terms of mass ratio of coating/refractory BC, MRc) defining the BC transition between being hydrophobic to hydrophilic, was determined by combining hygroscopic tandem differential mobility analyser (H-TDMA), centrifugal particle mass analyzer (CPMA) and single particle soot photometer (SP2) measurements. The MRc of 250 nm BC-containing particles increased from a background value of between 0.8 and 1.6 to around 4.6 at the onset of the growth event of nanoparticles, decreasing monotonically back to the background level as the event progressed. This indicates that large particles do not act as an effective pre-existing condensation sink of the hygroscopic vapours during the nanoparticle growth events, leading to the 250 nm BC particles requiring more coating materials to transition between being hydrophobic and hydrophilic. These findings show that large particles may be less important in suppressing the new particle formation and subsequent growth in the atmosphere.

6.
Environ Sci Technol ; 55(9): 5677-5688, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33874721

RESUMO

Emissions of light-absorbing black carbon (BC) and organic aerosol (OA) from biomass burning are presented as complex mixtures, which introduce challenges in modeling their absorbing properties. In this study, we chose typical residential wood burning emission and used a novel designed chamber to investigate the early stage evolution of plumes from different burning phases under real ambient conditions. The detailed mixing state between BC and OA was evaluated, on the basis of which optical modeling was performed to achieve a closure of aerosol-absorbing properties. Intensive secondary OA (SOA) formation was observed under solar radiation. OA from flaming conditions showed a higher absorptivity than from smoldering conditions, as OA is mostly internally and externally mixed with BC, respectively. For flaming (smoldering), the imaginary refractive index of OA (kOA) was initially at 0.03 ± 0.01 (0.001) and 0.15 ± 0.02 (0.05 ± 0.02) at λ = 781 and 405 nm, respectively, with a half-decay time of 2-3 h in light but a <40% decrease under dark within 5 h. The production of less-absorbing SOA in the first 1-2 h and possible subsequent photobleaching of chromophores contributed to the decrease of kOA. The enhanced abundance but decreased absorptivity of coatings on BC resulted in a relatively maintainable absorptivity of BC-containing particles during evolution.


Assuntos
Poluentes Atmosféricos , Madeira , Aerossóis/análise , Poluentes Atmosféricos/análise , Atmosfera , Biomassa , Carbono , Fumaça , Fuligem/análise , Madeira/química
7.
Nano Lett ; 20(10): 6974-6980, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32845157

RESUMO

Radiative cooling, a passive cooling technique, has shown great potentials in recent years to lower the power consumption of air conditioning. With the ever-increasing cooling power being reported, the theoretical cooling limit of such a technique is still unclear. In this work, we proposed a theoretical limit imposing an upper bound for the attainable cooling power. To approach this limit, we exploited the localized surface plasmon resonance (LSPR) of self-doped In2O3 nanoparticles, which enhance the emissivity in both primary and secondary atmospheric windows. The measured cooling power of poly(methyl methacrylate) (PMMA) films containing 4.5% In2O3 nanoparticles is very close to the limit with the closest value only about 0.4 W/m2 below the limit. Hopefully, this work may help the researchers better evaluating the performance of their device in the future and pave the way for achieving even higher radiative cooling powers during the daytime operations with the help of LSPR.

8.
Twin Res Hum Genet ; 21(5): 361-368, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30064533

RESUMO

Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5'UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.


Assuntos
Cromossomos Humanos X/genética , Genoma Humano/genética , Gemelaridade Monozigótica/genética , Sequenciamento Completo do Genoma , Variações do Número de Cópias de DNA/genética , Família , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos
9.
J Theor Biol ; 427: 10-16, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28551365

RESUMO

There is much uncertainty about the risks of seed germination after repeated or protracted environmental low-dose ionizing radiation exposure. The purpose of this study is to explore the influence mechanism of low-dose ionizing radiation on wheat seed germination using a model linking physiological characteristics and developmental-dynamics simulation. A low-dose ionizing radiation environment simulator was built to investigate wheat (Triticum aestivum L.) seeds germination process and then a kinetic model expressing the relationship between wheat seed germination dynamics and low-dose ionizing radiation intensity variations was developed by experimental data, plant physiology, relevant hypotheses and system dynamics, and sufficiently validated and accredited by computer simulation. Germination percentages were showing no differences in response to different dose rates. However, root and shoot lengths were reduced significantly. Plasma governing equations were set up and the finite element analysis demonstrated H2O, CO2, O2 as well as the seed physiological responses to the low-dose ionizing radiation. The kinetic model was highly valid, and simultaneously the related influence mechanism of low-dose ionizing radiation on wheat seed germination proposed in the modeling process was also adequately verified. Collectively these data demonstrate that low-dose ionizing radiation has an important effect on absorbing water, consuming O2 and releasing CO2, which means the risk for embryo and endosperm development was higher.


Assuntos
Germinação/efeitos da radiação , Sementes/fisiologia , Triticum/crescimento & desenvolvimento , Relação Dose-Resposta à Radiação , Triticum/efeitos da radiação , Incerteza
11.
Org Biomol Chem ; 13(27): 7487-99, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26068795

RESUMO

Human carbonyl reductase 1 (CBR1), a member of the short-chain dehydrogenase/reductase superfamily, reduces anthracycline anticancer drugs to their less potent anticancer C-13 hydroxy metabolites, which are linked with pathogenesis of cardiotoxicity, a side effect of the drugs. CBR1 inhibitors are thought to be promising agents for adjuvant therapy with a twofold beneficial effect in prolonging the anticancer efficacy of the anthracyclines while decreasing cardiotoxicity. In order to search for new potential inhibitors of CBR1, we synthesized a series of des-methoxyphenyl derivatives of (Z)-2-(4-methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide (1) that was developed previously as a potent inhibitor of aldo-keto reductase (AKR) 1B10 and AKR1B1. Among the newly synthesized inhibitors, 8-hydroxy-2-imino-2H-chromene-3-carboxylic acid (2-chlorophenyl)amide (13h) was the most potent competitive inhibitor of CBR1, showing a Ki value of 15 nM. 13h also showed high selectivity to CBR1 over its isozyme CBR3 and other enzymes with CBR activity (AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C4, DXCR and DHRS4). Furthermore, 13h inhibited the cellular metabolism by CBR1 at its concentration of 4 µM. The structure-activity relationship of the derivatives, site-directed mutagenesis of putative binding residues (Met141 and Trp229) and molecular docking of 13h in CBR1 revealed that the interactions of 13h with the substrate-binding residues (Ser139, Met141, Tyr193 and Trp229) are important for the tight binding.


Assuntos
Oxirredutases do Álcool/antagonistas & inibidores , Benzopiranos/síntese química , Benzopiranos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Iminas/síntese química , Iminas/farmacologia , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Animais , Aorta/citologia , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Inibidores Enzimáticos/química , Humanos , Simulação de Dinâmica Molecular , Mutação/genética
12.
Bioorg Med Chem ; 22(19): 5220-33, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25182963

RESUMO

Inhibitors of a human member (AKR1C3) of the aldo-keto reductase superfamily are regarded as promising therapeutics for the treatment of prostatic and breast cancers. Baccharin [3-prenyl-4-(dihydrocinnamoyloxy)cinnamic acid], a component of propolis, was shown to be both potent (Ki 56 nM) and highly isoform-selective inhibitor of AKR1C3. In this study, a series of derivatives of baccharin were synthesized by replacing the 3-prenyl moiety with aryl and alkyl ether moieties, and their inhibitory activities for the enzyme were evaluated. Among them, two benzyl ether derivatives, 6m and 6n, showed an equivalent inhibitory potency to baccharin. The molecular docking of 6m in AKR1C3 has allowed the design and synthesis of (E)-3-{3-[(3-hydroxybenzyl)oxy]-4-[(3-phenylpropanoyl)oxy]phenyl}acrylic acid (14) with improved potency (Ki 6.4 nM) and selectivity comparable to baccharin. Additionally, 14 significantly decreased the cellular metabolism of androsterone and cytotoxic 4-oxo-2-nonenal by AKR1C3 at much lower concentrations than baccharin.


Assuntos
3-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores , Tricotecenos/farmacologia , 3-Hidroxiesteroide Desidrogenases/metabolismo , Membro C3 da Família 1 de alfa-Ceto Redutase , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Hidroxiprostaglandina Desidrogenases/metabolismo , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Tricotecenos/síntese química , Tricotecenos/química , Células Tumorais Cultivadas
13.
Appl Microbiol Biotechnol ; 98(8): 3679-89, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24190495

RESUMO

The expression efficiency was improved for the recombinant single-chain variable fragment (scFv) against clenbuterol (CBL) obtained from mouse and expressed in the methylotrophic yeast Pichia pastoris GS115, by redesigning and synthesizing the DNA sequence encoding for CBL-scFv based on the codon bias of P. pastoris. The codons encoding 124 amino acids were optimized, in which a total of 156 nucleotides were changed, and the G+C ratio was simultaneously decreased from 53 to 47.2 %. Under the optimized expression conditions, the yield of the recombinant CBL-scFv (41 kDa) antibodies was 0.223 g L⁻¹ in shake culture. Compared to the non-optimized control, the expression level of the optimized recombinant CBL-scFv based on preferred codons in P. pastoris demonstrated a 2.35-fold higher yield. Furthermore, the recombinant CBL-scFv was purified by Ni-NTA column chromatography, and the purity was 95 %. The purified CBL-scFv showed good CBL recognition by a competitive indirect enzyme-linked immunoassay. The average concentration required for 50 % inhibition of binding and the limit of detection for the assay were 5.82 and 0.77 ng mL⁻¹, respectively.


Assuntos
Clembuterol/imunologia , Códon , Pichia/genética , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/metabolismo , Animais , Composição de Bases , Cromatografia de Afinidade , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Camundongos , Dados de Sequência Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Análise de Sequência de DNA , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/isolamento & purificação
14.
J Environ Sci (China) ; 26(1): 37-43, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24649689

RESUMO

The hygroscopicity and optical properties of alkylaminium sulfates (AASs) were investigated using a hygroscopicity tandem differential mobility analyzer coupled to a cavity ring-down spectrometer and a nephelometer. AAS particles do not exhibit a deliquescence phenomenon and show a monotonic increase in diameter as the relative humidity (RH) ascends. Hygroscopic growth factors (GFs) for 40, 100 and 150 nm alkylaminium sulfate particles do not show an apparent Kelvin effect when RH is less than 45%, whereas GFs of the salt aerosols increase with initial particle size when RH is higher than 45%. Calculation using the Zdanovskii-Stokes-Robinson mixing rule suggests that hygroscopic growth of triethylaminium sulfate-ammonium sulfate mixtures is non-deliquescent, occurring at very low RH, implying that the displacement of ammonia by amine will significantly enhance the hygroscopicity of (NH4)2SO4 aerosols. In addition, light extinction of AAS particles is a combined effect of both scattering and absorption under dry conditions, but is dominated by scattering under wet conditions.


Assuntos
Material Particulado/química , Ésteres do Ácido Sulfúrico/química , Aerossóis , Molhabilidade
15.
Huan Jing Ke Xue ; 45(6): 3421-3432, 2024 Jun 08.
Artigo em Zh | MEDLINE | ID: mdl-38897763

RESUMO

Addressing the issue of carbon emissions in the transportation sector, this research constructed various predictive models using multiple machine learning algorithms based on panel data from 30 provinces in China from 2005 to 2019. The study aimed to identify the optimal machine learning algorithm and key factors influencing the carbon emissions of transportation, providing potent references for policymakers and decision-makers to reduce carbon emissions and promote the sustainable development of the transportation sector. Initially, drawing from the concept of the fixed effects model, we included the heterogeneity differences among provinces as an important factor. We further employed a combined method of Pearson's correlation coefficient and Spearman's rank correlation coefficient to screen 18 factors influencing transportation carbon emissions. We then made a preliminary selection of seven common machine learning algorithms and used the screened factors as explanatory variables for model training. The three algorithms with the best performance were further optimized and trained. Subsequently, we utilized the K-fold cross-validation method; plotted learning curves to test the performance of each predictive model; and used MSE, MAE, R2, and MAPE as evaluation indicators to determine the best predictive model. SHAP values were chosen to calculate the importance of each explanatory variable in the optimal predictive model. The results indicated that the multicollinearity among the seven factors of provincial differences, total consumption of social goods, urban green space area, freight turnover, number of private cars, transportation industry output, and permanent population was weak, and all passed the significance test. They could be used as explanatory variables in the prediction model of transportation carbon emissions. The prediction results of the Random Forest and XGBoost algorithms were both outstanding, with R2 values above 0.97 and errors below 10 %, showing no signs of overfitting or underfitting. Among them, the XGBoost algorithm performed the best, whereas the KNN algorithm performed poorly. The importance ranking of the explanatory variables was as follows:provincial differences > total consumption of social goods > number of private cars > permanent population > freight turnover > urban green space area > transportation industry output. A comprehensive analysis of relevance and importance showed that provincial differences were an indispensable variable in the prediction of transportation carbon emissions. In conclusion, this study provides a new approach to the governance of carbon emissions in the transportation industry, and the results can serve as a reference for policymakers and decision-makers. In future policy design and decision-making, the distinctive factors of each province should not be overlooked. Measures targeted at specific regions need to be formulated to promote the sustainable development of the transportation industry.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38541284

RESUMO

Over the past decade, our understanding of the impact of air pollution on short- and long-term population health has advanced considerably, focusing on adverse effects on cardiovascular and respiratory systems. There is, however, increasing evidence that air pollution exposures affect cognitive function, particularly in susceptible groups. Our study seeks to assess and hazard rank the cognitive effects of prevalent indoor and outdoor pollutants through a single-centre investigation on the cognitive functioning of healthy human volunteers aged 50 and above with a familial predisposition to dementia. Participants will all undertake five sequential controlled exposures. The sources of the air pollution exposures are wood smoke, diesel exhaust, cleaning products, and cooking emissions, with clean air serving as the control. Pre- and post-exposure spirometry, nasal lavage, blood sampling, and cognitive assessments will be performed. Repeated testing pre and post exposure to controlled levels of pollutants will allow for the identification of acute changes in functioning as well as the detection of peripheral markers of neuroinflammation and neuronal toxicity. This comprehensive approach enables the identification of the most hazardous components in indoor and outdoor air pollutants and further understanding of the pathways contributing to neurodegenerative diseases. The results of this project have the potential to facilitate greater refinement in policy, emphasizing health-relevant pollutants and providing details to aid mitigation against pollutant-associated health risks.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Emissões de Veículos , Fumaça , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Material Particulado/análise , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Bioorg Med Chem ; 21(21): 6378-84, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24071447

RESUMO

Inhibitors of a human member (AKR1B10) of the aldo-keto reductase superfamily are regarded as promising therapeutics for the treatment of cancer. Recently, we have discovered (Z)-2-(4-methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide (1) as the potent competitive inhibitor using the virtual screening approach, and proposed its 4-methoxy group on the 2-phenylimino moiety as an essential structural prerequisite for the inhibition. In this study, 18 derivatives of 1 were synthesized and their inhibitory potency against AKR1B10 evaluated. Among them, 7-hydroxy-2-(4-methoxyphenylimino)-2H-chromene-3-carboxylic acid benzylamide (5n) was the most potent inhibitor showing a Ki value of 1.3nM. The structure-activity relationship of the derivatives indicated that the 7-hydroxyl group on the chromene ring, but not the 4-methoxy group, was absolutely required for inhibitory activity, The molecular docking of 5n in AKR1B10 and site-directed mutagenesis of the enzyme residues suggested that the hydrogen-bond interactions between the 7-hydroxyl group of 5n and the catalytic residues (Tyr49 and His111) of the enzyme, together with a π-stacking interaction of the benzylamide moiety of 5n with Trp220, are important for the potent inhibition.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Benzamidas/síntese química , Benzopiranos/química , Inibidores Enzimáticos/síntese química , Aldeído Redutase/genética , Aldeído Redutase/metabolismo , Aldo-Ceto Redutases , Benzamidas/química , Benzamidas/metabolismo , Benzopiranos/síntese química , Benzopiranos/metabolismo , Sítios de Ligação , Domínio Catalítico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Humanos , Ligação de Hidrogênio , Cinética , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Ligação Proteica , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Relação Estrutura-Atividade
18.
Biotechnol J ; 18(11): e2300135, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37464951

RESUMO

Extraction of DNA is a key step in molecular biology experiments and important for counting tiny microbial individuals. Direct boiling and mechanical cell lysis like glass beads are two independent physical extraction methods, thus crossing the barriers of thresholds of magnitude in popular reagent kits or traditional spread plate method when non-equilibrium phenomenon is ongoing. The two approaches above were combined to generate a new one. In three typical microbial species, direct boiling with glass beads significantly increased the purity of DNA solution compared with some other methods (p < 0.05). The qPCR results of them were closer to direct microscopy counting than some other methods. Therefore, it provides a new choice in extracting bacterial DNA for specific circumstances.


Assuntos
Bactérias , DNA , Humanos , DNA Bacteriano/genética , Bactérias/genética
19.
Waste Manag ; 166: 58-69, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37150044

RESUMO

Solid waste disposal is significantly important to maintaining normal operation of both natural and artificial ecosystems. In this study, a kinetic model of solid waste treatment unit (SWTU) was upfront developed based on microbial ecology, system dynamics, cybernetics and digital simulation, which accurately described the relationships and interactions between solid waste decomposition (SWD) processes and biotic/abiotic factors. Then a specific SWTU prototype was designed and built from this kinetic model. A 370-day experiment demonstrated that SWTU maintained normal operation with robust stability and desired dynamic behaviors, and effectively disposed the solid waste. Therefore, this kinetic model was highly valid due to its high structural and behavioral similarity with the prototype. This research could lay a strong theoretical foundation for further closed-loop control as well as optimization of SWTU, and provide scientific guidance to environmental management as well as sustainable development.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Resíduos Sólidos/análise , Simulação por Computador , Conservação dos Recursos Naturais , Modelos Teóricos , Ecossistema
20.
Ying Yong Sheng Tai Xue Bao ; 34(6): 1474-1482, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37694408

RESUMO

The rapid urbanization adversely affects landscape pattern of mountainous cities. It is of great practical significance to explore the spatial and temporal evolution of ecological networks in mountainous areas to achieve regional ecological security. Taking Qianshan City in Anhui Province as an example, based on the land use data in 2012 and 2020, we simulated the land use situation in 2036 with PLUS model, and constructed the ecological networks in 2020 and 2036, respectively. We further analyzed its spatial and temporal evolution characteristics and explored the optimization path of ecological network. The results showed that the scale of various land use types in Qianshan City would change little from 2020 to 2036. The construction land would be centered on the built-up area, expanding in a point and block shape to the surrounding area. The ecological space would be continuously squeezed and encroached. The overall complexity and connectivity of ecological networks in Qianshan City would increase. The number and area of ecological source sites would increase, expanding spatially to the southwest and northeast. The overall density and number of ecological corridors would increase, with a lack of ecological corridor connections in the east-west direction, which need urgent improvement. The stability of ecological networks could be improved through three major measures, including protection and restoration of source sites, optimization and cultivation of corridors, and zoning control.


Assuntos
Planejamento de Cidades , Urbanização , Cidades , Simulação por Computador
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