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1.
Biochem Biophys Res Commun ; 732: 150399, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39033551

RESUMO

The imbalance of vascular endothelial cell homeostasis is the key mechanism for the progression of many vascular diseases. RNA modification, particularly N6-Methyladenosine (m6A), plays important function in numerous biological processes. Nevertheless, the regulatory function of m6A RNA methylation in endothelial dysfunction remains insufficiently characterized. In this study, we established that the m6A methyltransferase METTL3 is critical for regulating endothelial function. Functionally, depletion of METTL3 results in decreased endothelial cells proliferation, survival and inflammatory response. Conversely, overexpression of METTL3 elicited the opposite effects. Mechanistically, MeRIP-seq identified that METTL3 catalyzed m6A modification of TRAF1 mRNA and enhanced TRAF1 translation, thereby up-regulation of TRAF1 protein. Over-expression of TRAF1 successfully rescued the inhibition of proliferation and adhesion of endothelial cells due to METTL3 knockdown. Additionally, m6A methylation-mediated TRAF1 expression can be reversed by the demethylase ALKBH5. Knockdown of ALKBH5 upregulated the level of m6A and protein level of TRAF1, and also increased endothelial cells adhesion and inflammatory response. Collectively, our findings suggest that METTL3 regulates vascular endothelium homeostasis through TRAF1 m6A modification, suggesting that targeting the METTL3-m6A-TRAF1 axis may hold therapeutic potential for patients with vascular diseases.


Assuntos
Adenosina , Proliferação de Células , Células Endoteliais da Veia Umbilical Humana , Inflamação , Metiltransferases , Fator 1 Associado a Receptor de TNF , Metiltransferases/metabolismo , Metiltransferases/genética , Humanos , Metilação , Inflamação/metabolismo , Inflamação/genética , Inflamação/patologia , Fator 1 Associado a Receptor de TNF/metabolismo , Fator 1 Associado a Receptor de TNF/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Metilação de RNA
2.
Small ; : e2404310, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39252649

RESUMO

Azobenzene (azo)-based photothermal energy storage systems have garnered great interest for their potential in solar energy conversion and storage but suffer from limitations including rely on solvents and specific wavelengths for charging process, short storage lifetime, low heat release temperature during discharging, strong rigidity and poor wearability. To address these issues, an azo-based fabric composed of tetra-ortho-fluorinated photo-liquefiable azobenzene monomer and polyacrylonitrile fabric template is fabricated using electrospinning. This fabric excels in efficient photo-charging (green light) and discharging (blue light) under visible light range, solvent-free operation, long-term energy storage (706 days), and good capacity of releasing high-temperature heat (80-95 °C) at room temperature and cold environments. In addition, the fabric maintains high flexibility without evident loss of energy-storage performance upon 1500 bending cycles, 18-h washing or 6-h soaking. The generated heat from charged fabric is facilitated by the Z-to-E isomerization energy, phase transition latent heat, and the photothermal effect of 420 nm light irradiation. Meanwhile, the temperature of heat release can be personalized for thermal management by adjusting the light intensity. It is applicable for room-temperature thermal therapy and can provide heat to the body in cold environments, that presenting a promising candidate for wearable personal thermal management.

3.
Environ Sci Technol ; 58(28): 12532-12541, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38940696

RESUMO

While partial nitrification (PN) has the potential to reduce energy for aeration, it has proven to be unstable when treating low-strength wastewater. This study introduces an innovative combined strategy incorporating a low rate of oxygen supply, pH control, and sulfide addition to selectively inhibit nitrite-oxidizing bacteria (NOB). This strategy led to a stable PN in a laboratory-scale membrane aerated biofilm reactor (MABR). Over a period of 260 days, the nitrite accumulation ratio exceeded 60% when treating synthetic sewage containing 50 mg NH4+-N/L. Through in situ activity testing and high-throughput sequencing, the combined strategy led to low levels of nitrite-oxidation activity (<5.5 mg N/m2 h), Nitrospira species (relative abundance <1%), and transcription of nitrite-oxidation genes (undetectable). The addition of sulfide led to simultaneous PN and autotrophic denitrification in the single-stage MABR, resulting in over 60% total inorganic nitrogen removal. Sulfur-based autotrophic denitrification consumed nitrite and inhibited NOB conversion of nitrite to nitrate. The combined strategy has potential to be applied in large-scale sewage treatment and deserves further exploration.


Assuntos
Reatores Biológicos , Desnitrificação , Nitrificação , Sulfetos , Sulfetos/química , Processos Autotróficos , Nitritos/metabolismo , Esgotos , Biofilmes , Águas Residuárias/química
4.
Environ Sci Technol ; 57(29): 10733-10744, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37429742

RESUMO

Highly efficient sulfate reduction coupled to autotrophic denitrification plus nitrification is demonstrated by integrating an anaerobic membrane bioreactor (AnMBR) with a membrane aerated biofilm reactor (MABR). Concurrent chemical oxygen demand (COD) removal and sulfate reduction were accomplished in the AnMBR, while simultaneous nitrification and autotrophic denitrification were carried out in the MABR. Separate operation of the MABR achieved >90% total nitrogen (TN) removal when the N/S ratio was controlled at 0.4 gN/gS. The integrated AnMBR-MABR system efficiently resisted influent variability, realizing >95% COD removal in the AnMBR and >75% TN removal in the MABR when the influent COD/N ratio was above 4 gCOD/gN. Membrane fouling did not happen during ∼170 days of operation. Due to sulfide oxidation, a large amount of elemental sulfur (S0) accumulated in the MABR biofilm, where it served as an electron donor for denitrification. Microbial community analysis indicated that Nitrospira and Thiobacillus played key roles in nitrification and sulfide-driven denitrification, respectively, and that they occurred in different layers of the biofilm. This novel process offers advantages of a small land-area footprint, modular operation, and high efficiency electron-donor and oxygen utilizations, particularly for wastewater with a low COD/N ratio.


Assuntos
Nitrificação , Águas Residuárias , Desnitrificação , Nitrogênio , Biofilmes , Reatores Biológicos , Sulfatos
5.
Angew Chem Int Ed Engl ; 61(47): e202211635, 2022 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129393

RESUMO

Rh-catalyzed dynamic kinetic intramolecular [4+2] cycloaddition reaction of 1,3-disubstituted allene-1,3-dienes afforded cis-fused [4.3.0]bicyclic products with an excellent chemo-, diastereo-, and enantio-selectivity. Many synthetically useful functional groups are tolerated. The synthetic utility has been demonstrated. Based on the careful experimental studies, a mechanism involving the rapid racemization of the allene moiety in the starting materials has been proposed.


Assuntos
Ródio , Reação de Cicloadição , Estereoisomerismo , Catálise , Estrutura Molecular
6.
Genome ; : 1-16, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648728

RESUMO

Soybean can provide rich protein and fat and has great economic value worldwide. Cadmium (Cd) is a toxic heavy metal to organisms. It can accumulate in plants and be transmitted to the human body via the food chain. Cd is a serious threat to soybean development, particularly root growth. Some soybean cultivars present tolerant symptoms under Cd stress; however, the potential mechanisms are not fully understood. Here, we optimized RNA-seq to identify the differentially expressed genes (DEGs) in Cd-sensitive (KUAI) and Cd-tolerant (KAIYU) soybean roots and compared the DEGs between KAIYU and KUAI. A total of 1506 and 1870 DEGs were identified in the roots of KUAI and KAIYU, respectively. Through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and gene function analyses, we found that genes related to antioxidants and sequestration were responsible for Cd tolerance in KAIYU. In addition, overexpression of Glyma11g02661, which encodes a heavy metal-transporting ATPase, significantly improved Cd tolerance in transgenic hairy roots. These results provide a preliminary understanding of the tolerance mechanisms in response to Cd stress in soybean root development and are of great importance in developing Cd-resistant soybean cultivars by using the identified DEGs through genetic modification.

7.
J Environ Manage ; 255: 109860, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759200

RESUMO

Papermaking is a capital-intensive industry that requires a high consumption of plant fibers, energy, and water. Previous sustainability assessments of papermaking industry primarily focused on separate evaluations for multiple criteria without the integration for criteria and could not compare the overall priority of the production alternatives. The life cycle sustainability for the most representative boxboard production is analyzed as a case study in this work. Life cycle water consumption, energy consumption, greenhouse gas emissions, and internal costs are selected as the assessment criteria. The two multi-criteria decision-making methods are applied to integrate the above criteria to obtain the sustainability sequence under different production pathways. When the papermaking enterprises are regarded as decision-makers, the alternative using waste paper as raw material to manufacture boxboard is the most sustainable, following by mixed fiber. The sustainability sequence of the alternatives using wood and straw as raw materials is controversial due to the different calculation models. Changing the proportion of raw materials and the criteria weights might adjust sustainability sequence of the alternatives.


Assuntos
Ingestão de Líquidos , Gases de Efeito Estufa , Tomada de Decisões , Efeito Estufa , Madeira
8.
Chemistry ; 25(40): 9529-9533, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31033044

RESUMO

An efficient chirality transfer in the [RhCl(CO)2 ]2 -catalyzed [2+2+1] cyclization of optically active axially chiral 1,3-disubstituted allenynes with CO to access optically active bicyclopentenone compounds has been developed. The distal C=C bond of allenes reacted with the alknye unit and CO to afford [4.3.0]-bicyclic products with high ee values under mild reaction conditions with an excellent selectivity.

9.
Appl Microbiol Biotechnol ; 103(21-22): 9119-9129, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31501939

RESUMO

While previous work has demonstrated that antimonate (Sb(V)) can be bio-reduced with methane as the sole electron donor, the microorganisms responsible for Sb(V) reduction remain largely uncharacterized. Inspired by the recently reported Sb(V) reductase belonging to the dimethyl sulfoxide reductase (DMSOR) family, this study was undertaken to use metagenomics and metatranscriptomics to unravel whether any DMSOR family genes in the bioreactor had the potential for Sb(V) reduction. A search through metagenomic-assembled genomes recovered from the microbial community found that some DMSOR family genes, designated sbrA (Sb(V) reductase gene), were highly transcribed in four phylogenetically disparate assemblies. The putative catalytic subunits were found to be representatives of two distinct phylogenetic clades of reductases that were most closely related to periplasmic nitrate reductases and respiratory arsenate reductases, respectively. Putative operons containing sbrA possessed many other components, including genes encoding c-type cytochromes, response regulators, and ferredoxins, which together implement Sb(V) reduction. This predicted ability was confirmed by incubating the enrichment culture with 13C-labeled CH4 and Sb(V) in serum bottles, where Sb(V) was reduced coincident with the production of 13C-labeled CO2. Overall, these results increase our understanding of how Sb(V) can be bio-reduced in environments.


Assuntos
Antimônio/metabolismo , Bactérias/enzimologia , Proteínas de Bactérias/genética , Oxirredutases/genética , Filogenia , Bactérias/classificação , Bactérias/genética , Proteínas de Bactérias/metabolismo , Família Multigênica , Óperon , Oxirredutases/metabolismo
10.
Angew Chem Int Ed Engl ; 53(1): 277-81, 2014 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-24375740

RESUMO

Tetrahydroisoquinoline alkaloids with a C1 stereogenic center are a common unit in many natural and non-natural compounds of biological importance. Herein we describe a novel Cu(I) -catalyzed highly chemo- and enantioselective synthesis of chiral tetrahydroisoquinoline-alkaloid derivatives from readily available unsubstituted tetrahydroisoquinolines, aldehydes, and terminal alkynes in the presence of the ligand (R,R)-N-pinap. This synthetic operation installs two substituents in the 1- and 2-positions.


Assuntos
Aldeídos/química , Alcinos/síntese química , Cobre/química , Isoquinolinas/síntese química , Catálise , Isoquinolinas/química , Estrutura Molecular , Estereoisomerismo
11.
Anal Chim Acta ; 1311: 342714, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38816153

RESUMO

BACKGROUND: Antibiotics residues can accelerate the growth of drug-resistant bacteria and harm the ecological environment. Under the effect of enrichment and biomagnification, the emergence of drug-resistant pathogenic bacteria may eventually lead to humans being ineffective to drugs in the face of bacterial or fungal disease infections in the future. It is urgent to develop an efficient separation medium and analytical method for simultaneous extraction and determination of antibiotics in the water environment. RESULTS: This work doped 2,6-Di-O-methyl-ß-cyclodextrin, randomly methyl-ß-cyclodextrin, 2-hydroxypropyl-ß-cyclodextrin with thymol:fatty acid respectively to construct non-covalent interaction-dominated pH-responsive ternary supramolecular deep eutectic solvents (SUPRADESs), which can undergo a hydrophilic/hydrophobic transition with aqueous phase to achieve an efficient microextraction. Semi-empirical method illustrated that SUPRADESs have a wide range of hydrogen bond receptor sites. We developed a SUPRADES-based analytical method combined with liquid chromatography-triple quadrupole mass spectrometry for the extraction and determination of trace quinolones and sulfonamides in wastewater. The overall limits of detection of the method were 0.0021-0.0334 ng mL-1 and the limits of quantification were 0.0073-0.1114 ng mL-1. The linearity maintained good in the spiked level of 0.01-100 ng mL-1 (R2 > 0.99). The overall enrichment factors of the method were 157-201 with lower standard deviations (≤8.7). SIGNIFICANCE: The method gave an extraction recovery of 70.1-115.3 % for 28 antibiotics in livestock farming wastewater samples from Zhejiang, China, at trace levels (minimum 0.5 ng mL-1). The results demonstrated that inducing the phase transition between SUPRADES and aqueous phase by adjusting pH for extraction is a novel and efficient pretreatment strategy. To our knowledge, this is the first application of cyclodextrin-based ternary SUPRADESs with pH-responsive reversible hydrophobicity-hydrophilicity transition behavior in wastewater analysis.


Assuntos
Ciclodextrinas , Solventes Eutéticos Profundos , Quinolonas , Sulfonamidas , Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/química , Águas Residuárias/análise , Concentração de Íons de Hidrogênio , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Sulfonamidas/química , Sulfonamidas/análise , Sulfonamidas/isolamento & purificação , Quinolonas/química , Quinolonas/isolamento & purificação , Quinolonas/análise , Ciclodextrinas/química , Solventes Eutéticos Profundos/química
12.
J Med Chem ; 67(8): 6397-6409, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38602846

RESUMO

Aberrantly expressed lysine methyltransferases G9a and GLP, which catalyze mono- and dimethylation of histone H3 lysine 9 (H3K9), have been implicated in numerous cancers. Recent studies have uncovered both catalytic and noncatalytic oncogenic functions of G9a/GLP. As such, G9a/GLP catalytic inhibitors have displayed limited anticancer activity. Here, we report the discovery of the first-in-class G9a/GLP proteolysis targeting chimera (PROTAC) degrader 10 (MS8709), as a potential anticancer therapeutic. 10 induces G9a/GLP degradation in a concentration-, time-, and ubiquitin-proteasome system (UPS)-dependent manner. Futhermore, 10 does not alter the mRNA expression of G9a/GLP and is selective for G9a/GLP over other methyltransferases. Moreover, 10 displays superior cell growth inhibition to the parent G9a/GLP inhibitor UNC0642 in prostate, leukemia, and lung cancer cells and has suitable mouse pharmacokinetic properties for in vivo efficacy studies. Overall, 10 is a valuable chemical biology tool to further investigate the functions of G9a/GLP and a potential therapeutic for treating G9a/GLP-dependent cancers.


Assuntos
Antineoplásicos , Histona-Lisina N-Metiltransferase , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Camundongos , Linhagem Celular Tumoral , Proteólise/efeitos dos fármacos , Antígenos de Histocompatibilidade/metabolismo , Descoberta de Drogas , Proliferação de Células/efeitos dos fármacos , Masculino , Relação Estrutura-Atividade
13.
bioRxiv ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38464025

RESUMO

Aberrantly expressed lysine methyltransferases G9a and GLP, which catalyze mono- and di-methylation of histone H3 lysine 9 (H3K9), have been implicated in numerous cancers. Recent studies have uncovered both catalytic and non-catalytic oncogenic functions of G9a/GLP. As such, G9a/GLP catalytic inhibitors have displayed limited anticancer activity. Here, we report the discovery of the first-in-class G9a/GLP proteolysis targeting chimera (PROTAC) degrader, 10 (MS8709), as a potential anticancer therapeutic. 10 induces G9a/GLP degradation in a concentration-, time, and ubiquitin-proteasome system (UPS)-dependent manner, does not alter the mRNA expression of G9a/GLP and is selective for G9a/GLP over other methyltransferases. Moreover, 10 displays superior cell growth inhibition to the parent G9a/GLP inhibitor UNC0642 in prostate, leukemia, and lung cancer cells and has suitable mouse pharmacokinetic properties for in vivo efficacy studies. Overall, 10 is a valuable chemical biology tool to further investigate the functions of G9a/GLP and a potential therapeutic for treating G9a/GLP-dependent cancers.

14.
bioRxiv ; 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-37873443

RESUMO

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. A crucial viral protein, the non-structural protein 14 (nsp14), catalyzes the methylation of viral RNA and plays a critical role in viral genome replication and transcription. Due to the low mutation rate in the nsp region among various SARS-CoV-2 variants, nsp14 has emerged as a promising therapeutic target. However, discovering potential inhibitors remains a challenge. In this work, we introduce a computational pipeline for the rapid and efficient identification of potential nsp14 inhibitors by leveraging virtual screening and the NCI open compound collection, which contains 250,000 freely available molecules for researchers worldwide. The introduced pipeline provides a cost-effective and efficient approach for early-stage drug discovery by allowing researchers to evaluate promising molecules without incurring synthesis expenses. Our pipeline successfully identified seven promising candidates after experimentally validating only 40 compounds. Notably, we discovered NSC620333, a compound that exhibits a strong binding affinity to nsp14 with a dissociation constant of 427 ± 84 nM. In addition, we gained new insights into the structure and function of this protein through molecular dynamics simulations. We identified new conformational states of the protein and determined that residues Phe367, Tyr368, and Gln354 within the binding pocket serve as stabilizing residues for novel ligand interactions. We also found that metal coordination complexes are crucial for the overall function of the binding pocket. Lastly, we present the solved crystal structure of the nsp14-MTase complexed with SS148 (PDB:8BWU), a potent inhibitor of methyltransferase activity at the nanomolar level (IC50 value of 70 ± 6 nM). Our computational pipeline accurately predicted the binding pose of SS148, demonstrating its effectiveness and potential in accelerating drug discovery efforts against SARS-CoV-2 and other emerging viruses.

15.
Ecotoxicology ; 22(6): 1033-42, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23771790

RESUMO

The effect of citric acid (CA) and ethylene diamine tetraacetic acid (EDTA) on the growth, anatomical structure, physiological responses and lead (Pb) accumulation of Iris lactea var. chinensis seedling growing in Pb mine tailings for 30 days were studied. Results showed that the dry weights (DW) of roots decreased significantly under both levels of CA. The DWs of leaves and roots treated with 2 mmol/kg EDTA decreased significantly and were 23 and 54 %, respectively, lower than those of the control. The tolerant indexes of I. lactea var. chinensis under all treatments of organic acids were lower than control. The root tip anatomical structure was little affected under the treatments of 2 mmol/kg CA and 2 mmol/kg EDTA compared with control. However, the formation of photosynthesizing cells was inhibited by the treatment of 2 mmol/kg EDTA. The concentrations of chlorophyll a, chlorophyll b and total carotenoids in the leaves treated with 2 mmol/kg EDTA significantly decreased. Higher CA level and lower EDTA level could trigger the synthesis of ascorbic acid and higher level of EDTA could trigger the synthesis of glutathione. CA and EDTA could promote Pb accumulation of I. lactea var. chinensis and Pb concentration in the leaves and roots at 2 mmol/kg EDTA treatment increased significantly and reached to 160.44 and 936.08 µg/g DW, respectively, and 1.8 and 1.6 times higher than those of the control. The results indicated that I. lactea var. chinensis could be used to remediate Pb tailing and the role of EDTA in promoting Pb accumulation was better than CA did.


Assuntos
Ácido Cítrico/farmacologia , Ácido Edético/farmacologia , Gênero Iris/efeitos dos fármacos , Chumbo/toxicidade , Metais Pesados/toxicidade , Plântula/efeitos dos fármacos , Clorofila/análogos & derivados , Clorofila/análise , Clorofila A , Gênero Iris/crescimento & desenvolvimento , Mineração , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Poluentes do Solo/toxicidade
16.
Food Chem ; 411: 135486, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36682163

RESUMO

The existing QuEChERS-combined analytical pretreatment methods are limited by large reagent consumption, high environmental burden, and mediocre effects. To provide an efficient and green pretreatment method, this study developed pH-responsive switchable deep eutectic solvents (SDESs) to extract triazole fungicides (TFs) from fruit peel wastes, which could enhance the preconcentration effect of target compounds in food waste samples with complex matrices. The mechanisms of pH-induced phase transition and hydrophobicity-hydrophilicity conversion of pH-responsive SDESs were investigated by pH phase diagrams and chemical characterization techniques, respectively. We validated the established method by high-performance liquid chromatography-diode array detector (HPLC-DAD), and lower LOD (0.089-0.351 ng mL-1), LOQ (0.297-1.172 ng mL-1), RSD (≤8.8 %) and satisfactory recoveries (90.6 %-110.9 %) and preconcentration factors (389-512) were obtained in rotting grape peel, watermelon peel, and orange peel samples. Our findings highlight the potential of pH-responsive SDESs in the extraction and analysis of various natural food products.


Assuntos
Fungicidas Industriais , Microextração em Fase Líquida , Eliminação de Resíduos , Solventes Eutéticos Profundos , Triazóis , Alimentos , Solventes/química , Concentração de Íons de Hidrogênio , Microextração em Fase Líquida/métodos
17.
Ecotoxicology ; 21(3): 759-67, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22161020

RESUMO

The physiological responses and Cu accumulation of Paulownia fortunei (Seem) Hemsl. were studied under 15.7-157 µmol L(-1) Cu treatments in liquid culture for 14 days; the impacts of Cu concentration in the seedlings were evaluated under Cu mine tailing culture with acetic acid and EDTA treatment for 60 days. Results showed that the concentrations of Chl-a, Chl-b and Carotenoids significantly increased (p < 0.05) at 15.7-78.7 µmol L(-1)Cu treatment and significantly decreased at 157 µmol L(-1) treatment after 14 days of Cu exposure. The activities of superoxide dismutase (SOD) and catalase (CAT) significantly increased as Cu levels were enhanced and the activities of both SOD and CAT under 157 µmol L(-1) Cu stress were 2.9 and 1.9 times higher than that of control, respectively. The concentrations of proline and soluble sugars in the leaves of P. fortunei significantly increased as the Cu concentrations were elevated. Cu concentrations in roots, stems and leaves of P. fortunei increased significantly as Cu levels increased and reached 1911, 101 and 93 µg g(-1) dry weights (DW) at 157 µmol L(-1) Cu treatment, respectively. The seedlings of P. fortunei cultivated in Cu tailing experienced unsuccessful growth and loss of leaves in all treatments due to poor nutrition of the Cu tailing. The dry weight of P. fortunei increased under all the treatments of acetic acid after 60 days exposure. However, dry weight significantly decreased under both levels of EDTA. The Cu concentrations increased significantly in roots and decreased in leaves when each was treated with both concentrations of acetic acid. The Cu concentrations in the roots, stems and leaves increased significantly, and the concentrations of Cu in the stems and leaves under the treatment of 2 µmol L(-1) EDTA reached 189.5 and 763.1 µg g(-1) DW, respectively. The result indicated that SOD, CAT, proline and soluble sugars played an important role in coping with the oxidative stress of copper. Acetic acid could promote growth and EDTA at the experimental levels, which could also enhance Cu absorption and translocation into the stems and leaves of P. fortune. Furthermore, acetic acid and EDTA could be rationally utilized in Cu-contaminated soil.


Assuntos
Cobre/toxicidade , Poluentes Ambientais/toxicidade , Mineração , Scrophulariaceae/efeitos dos fármacos , Ácido Acético/farmacologia , Biodegradação Ambiental , Quelantes/farmacologia , Cobre/metabolismo , Ácido Edético/farmacologia , Poluentes Ambientais/metabolismo , Resíduos Industriais , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Estruturas Vegetais/efeitos dos fármacos , Estruturas Vegetais/crescimento & desenvolvimento , Estruturas Vegetais/metabolismo , Eliminação de Resíduos , Scrophulariaceae/crescimento & desenvolvimento , Scrophulariaceae/metabolismo
18.
Protein Sci ; 31(9): e4395, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36040262

RESUMO

SARS-CoV-2 nsp10-nsp16 complex is a 2'-O-methyltransferase (MTase) involved in viral RNA capping, enabling the virus to evade the immune system in humans. It has been considered a valuable target in the discovery of antiviral therapeutics, as the RNA cap formation is crucial for viral propagation. Through cross-screening of the inhibitors that we previously reported for SARS-CoV-2 nsp14 MTase activity against nsp10-nsp16 complex, we identified two compounds (SS148 and WZ16) that also inhibited nsp16 MTase activity. To further enable the chemical optimization of these two compounds towards more potent and selective dual nsp14/nsp16 MTase inhibitors, we determined the crystal structure of nsp10-nsp16 in complex with each of SS148 and WZ16. As expected, the structures revealed the binding of both compounds to S-adenosyl-L-methionine (SAM) binding pocket of nsp16. However, our structural data along with the biochemical mechanism of action determination revealed an RNA-dependent SAM-competitive pattern of inhibition for WZ16, clearly suggesting that binding of the RNA first may help the binding of some SAM competitive inhibitors. Both compounds also showed some degree of selectivity against human protein MTases, an indication of great potential for chemical optimization towards more potent and selective inhibitors of coronavirus MTases.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Humanos , Metiltransferases/química , RNA Viral/metabolismo , Proteínas não Estruturais Virais/química
19.
Front Plant Sci ; 12: 727966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759937

RESUMO

Global warming will have a negative effect on agricultural production as high temperature (HT) stress can seriously threaten plant growth and reproduction. Male sterility caused by HT may be exploited by the creation of a male-sterile line, which has great potential for application in crop heterosis. Therefore, it is important to understand the molecular mechanisms of anther abortion induced by HT in wheat, which remain unclear at present. In this study, we performed phenotype improve language in the abstract and comparative transcriptome analysis of the male sterile anthers induced by HT in wheat. Compared with Normal anthers, the cytological analysis indicated that HT-induced male sterile anthers were smaller and had no starch accumulation in pollen grains, which is consistent with the results observed by scanning electron microscopy (SEM). The 9601 differentially expressed genes (DEGs) identified by transcriptome sequencing compared with the Normal anthers were noticeably involved in the following pathways: starch and sucrose metabolism, phosphatidylinositol (PI) signaling system, peroxidase activity and response to oxidative stress, and heme binding. In addition, TUNEL assays were performed and the results further confirmed the excessive accumulation of reactive oxygen species (ROS) in sterile anthers. Moreover, a total of 38 hub genes were obtained from the protein-protein interaction network analysis of these pathways, including genes, for example, heat shock protein 90 (HSP90), thioredoxin-like protein 1, peroxidase (POD), calreticulin, UDP glucose pyrophosphorylase (UGPase), sucrose synthase, phosphatidylinositol-4-phosphate 5-Kinase (PIP5K), cytochrome c, and Cystathionine beta-synthase X6-like (CBSX6-like). These findings provide insights for predicting the functions of the candidate genes, and the comprehensive analysis of our results is helpful for studying the abortive interaction mechanism induced by HT in wheat.

20.
Ecotoxicology ; 19(1): 69-76, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19629681

RESUMO

The seedling development and physiological responses of Iris pseudacorus L. to Pb and Cd and their combination were studied for 28 days liquid culture and sub-cellular localization of Pb and Cd in the root tip cells treated with 2,070 mg L(-1) Pb and 1,000 mg L(-1)Cd for 16 days sand culture was evaluated. Results showed that the dry weights (DWs) of shoots and roots of I. pseudacorus were significantly decreased at 500 mg L(-1)Pb and 25 mg L(-1)Cd + 500 mg L(-1)Pb treatments and the root DWs under all treatments were significantly decreased in comparison with that of control. The concentrations of Chla in the leaves were decreased at all treatments, while, the concentrations of Chlb and total carotenoids were not significantly decreased under 25 mg L(-1)Cd and 25 mg L(-1)Cd + 500 mg L(-1)Pb treatments. The MDA and proline concentrations and POD activities in the shoots and roots were increased under treatments of 500 mg L(-1)Pb and 25 mg L(-1)Cd + 500 mg L(-1)Pb, but POD activities in the shoots and roots and MDA concentrations in the shoots were significantly decreased at 25 mg L(-1) Cd treatment. The results of sub-cellular localization of Pb and Cd showed that numerous Pb deposits were found on the inner surface of died cell walls in the cortex treated with 2,070 mg L(-1) Pb and Cd deposits were found in the cell wall treated with 1,000 mg L(-1) Cd. Pb and Cd deposits were not found in the cytoplasm. The results indicated that POD and proline showed strong beneficial properties against Pb and Cd stress and there were some mechanisms keeping most cells with normal activities in the plant from Pb toxicity by sacrificing a few cells that accumulated a large amount Pb. Sub-cellular localizations of Pb and Cd in the root tip cells of I. pseudacorus were little difference with the localizations in other species of Iris in the previous studies.


Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Gênero Iris/efeitos dos fármacos , Gênero Iris/metabolismo , Chumbo/toxicidade , Análise de Variância , Biodegradação Ambiental , Biomassa , Cádmio/farmacocinética , Poluentes Ambientais/farmacocinética , Gênero Iris/crescimento & desenvolvimento , Chumbo/farmacocinética , Malondialdeído/metabolismo , Peroxidase/metabolismo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Prolina/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
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