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1.
J Med Chem ; 67(5): 4083-4099, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38348878

RESUMO

Inhibition of the PD-1/PD-L1 interaction through small-molecule inhibitors is a promising therapeutic approach in cancer immunotherapy. Herein, we utilized BMS-202 as the lead compound to develop a series of novel PD-1/PD-L1 small-molecule inhibitors with a naphthyridin scaffold. Among these compounds, X14 displayed the most potent inhibitory activity for the PD-1/PD-L1 interaction (IC50 = 15.73 nM). Furthermore, X14 exhibited good binding affinity to both human PD-L1 (KD = 14.62 nM) and mouse PD-L1 (KD = 392 nM). In particular, X14 showed favorable pharmacokinetic properties (oral bioavailability, F = 58.0%). In the 4T1 (mouse breast cancer cells) syngeneic mouse model, intragastric administration of X14 at 10 mg/kg displayed significant antitumor efficacy (TGI = 66%). Mechanistic investigations revealed that X14 effectively enhanced T-cell infiltration within the tumor microenvironment. Our study demonstrates that compound X14 exhibits potential as a candidate compound for the development of orally effective small-molecule inhibitors targeting PD-1/PD-L1.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Camundongos , Animais , Antígeno B7-H1 , Receptor de Morte Celular Programada 1/metabolismo , Imunoterapia , Neoplasias/terapia
2.
Life Sci ; 336: 122294, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38007147

RESUMO

Doublecortin-like kinase 1 (DCLK1), a significant constituent of the protein kinase superfamily and the doublecortin family, has been recognized as a prooncogenic factor that exhibits a strong association with the malignant progression and clinical prognosis of various cancers. DCLK1 serves as a stem cell marker that governs tumorigenesis, tumor cell reprogramming, and epithelial-mesenchymal transition. Multiple studies have indicated the capable of DCLK1 in regulating the DNA damage response and facilitating DNA damage repair. Additionally, DCLK1 is involved in the regulation of the immune microenvironment and the promotion of tumor immune evasion. Recently, DCLK1 has emerged as a promising therapeutic target for a multitude of cancers. Several small-molecule inhibitors of DCLK1 have been identified. Nevertheless, the biological roles of DCLK1 are mainly ambiguous, particularly with the disparities between its α- and ß-form transcripts in the malignant progression of cancers, which impedes the development of more precisely targeted drugs. This article focuses on tumor stem cells, tumor epithelial-mesenchymal transition, the DNA damage response, and the tumor microenvironment to provide a comprehensive overview of the association between DCLK1 and tumor malignant progression, address unsolved questions and current challenges, and project future directions for targeting DCLK1 for the diagnosis and treatment of cancers.


Assuntos
Quinases Semelhantes a Duplacortina , Neoplasias , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/genética , Quinases Semelhantes a Duplacortina/antagonistas & inibidores , Quinases Semelhantes a Duplacortina/genética , Quinases Semelhantes a Duplacortina/imunologia , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/imunologia , Células-Tronco Neoplásicas , Reparo do DNA/genética , Reparo do DNA/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Evasão Tumoral/genética , Inibidores de Proteínas Quinases/uso terapêutico , Humanos , Isoformas de Proteínas
3.
Microbiol Spectr ; 11(3): e0179223, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37222634

RESUMO

Amino acids play a crucial role in the growth and development of insects. Aphids cannot ingest enough amino acids in plant phloem to meet their requirements, and therefore, they are mainly dependent on the obligate symbiont Buchnera aphidicola to synthesize essential amino acids. Besides Buchnera, aphids may harbor another facultative symbiont, Arsenophonus, which alters the requirement of the cotton-melon aphid Aphis gossypii for amino acid. However, it is unclear how Arsenophonus regulates the requirement. Here, we found that Arsenophonus ameliorated growth performance of A. gossypii on an amino acid-deficient diet. A deficiency in lysine (Lys) or methionine (Met) led to changes in the abundance of Arsenophonus. Arsenophonus suppressed the abundance of Buchnera when aphids were fed a normal amino acid diet, but this suppression was eliminated or reversed when aphids were on a Lys- or Met-deficient diet. The relative abundance of Arsenophonus was positively correlated with that of Buchnera, but neither of them was correlated with the body weight of aphids. The relative expression levels of Lys and Met synthase genes of Buchnera were affected by the interaction between Arsenophonus infections and Buchnera abundance, especially in aphids reared on a Lys- or Met-deficient diet. Arsenophonus coexisted with Buchnera in bacteriocytes, which strengthens the interaction. IMPORTANCE The obligate symbiont Buchnera can synthesize amino acids for aphids. In this study, we found that a facultative symbiont, Arsenophonus, can help improve aphids' growth performance under amino acid deficiency stress by changing the relative abundance of Buchnera and the expression levels of amino acid synthase genes. This study highlights the interaction between Arsenophonus and Buchnera to ameliorate aphid growth under amino acid stress.


Assuntos
Afídeos , Buchnera , Gammaproteobacteria , Animais , Buchnera/genética , Afídeos/fisiologia , Aminoácidos , Simbiose , Metionina , Lisina
4.
Crit Rev Biotechnol ; 43(4): 503-520, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35430940

RESUMO

Chemical resources and techniques have long been used in the history of bulk polyester production and still dominate today's chemical industry. The sustainable development of the polyester industry demands more renewable resources and environmentally benign polyester products. Accordingly, the rapid development of biotechnology has enabled the production of an extensive range of aliphatic and aromatic polyesters from renewable bio-feedstocks. This review addresses the production of representative commercial polyesters (polyhydroxyalkanoates, polylactic acid, poly ε-caprolactone, polybutylene succinate, polyethylene terephthalate, polybutylene terephthalate, polypropylene terephthalate, polyethylene furandicarboxylate, polypropylene furandicarboxylate, and polybutylene furandicarboxylate) or their monomers (lactic acid, succinic acid, 1,4-butanediol, ethylene glycol, terephthalic acid, 1,3-propanediol, and 2,5-furandicarboxylic acid) from renewable bioresources. In addition, this review summarizes advanced biotechniques in the treatment of polyester wastes, representing the near-term trends and future opportunities for waste-to-value recycling and the remediation of polyester wastes under sustainable models. For future prospects, it is essential to further expand: non-food bioresources, optimize bioprocesses and biotechniques in the preparation of bioderived or biodegradable polyesters with promising: material performance, biodegradability, and low production cost.


Assuntos
Poli-Hidroxialcanoatos , Polipropilenos , Poliésteres , Biotecnologia/métodos , Ácido Láctico
5.
Sci Total Environ ; 822: 153538, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35104521

RESUMO

In this study, hydrogen-autotrophic microorganisms and zero-valent iron (Fe0) were filled into columns to investigate hydrogenotrophic denitrification effect on cadmium (Cd(II)) removal and column life-span with sand, microorganisms, Fe0 and bio-Fe0 columns as controls. In terms of the experiment results, the nitrate-mediated bio-Fe0 column showed a slow Cd(II) migration rate of 0.04 cm/PV, while the values in the bio-Fe0 and Fe0 columns were 0.06 cm/PV and 0.14 cm/PV respectively, indicating much higher Cd(II) removal efficiency and longer service life of the nitrate-mediated bio-Fe0 column. The XRD and SEM-EDX results implied that this improvement was attributed to hydrogenotrophic denitrification that caused more serious iron corrosion and larger amount of secondary mineral generation (e.g., green rust, lepidocrocite and goethite). These active minerals provided more reaction sites for Cd(II) adsorption and further immobilization. In addition, the decrease of Cd(II) migration front and the increase of removal capacity along the bio-Fe0 column mediated by nitrate presented an uneven distribution in reactive zone. The latter half part was identified to be a more active region for Cd(II) immobilization. The above results indicate that the introduction of nitrate and microorganisms will improve the performance of iron-based permeable reactive barriers for the remediation of Cd(II)-containing groundwater.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Anaerobiose , Cádmio , Ferro , Nitratos/análise , Poluentes Químicos da Água/análise
6.
J Hazard Mater ; 423(Pt A): 127116, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34523487

RESUMO

Trace metal(loid)s (TMs) in soils can seriously threaten the ecological environment and human health. With the limitation of resources and costs, determining priority control factor is critical for managing soil TM pollution. To explore the pollution characteristics, source apportionment, and human health risk of TMs, a total of 209 surface soil samples were collected from Anqing City, China. Results showed that all the average values of TM concentration, except for Cr, were higher than their corresponding background value. Using a Positive matrix factorization model coupled with Correlation analysis, four sources (including agricultural sources, atmospheric deposition sources, industrial sources, and natural sources) were identified as the determinants for the accumulation of soil TMs, with the contribution rates of 12.4%, 8.1%, 64.1%, and 15.4%, respectively. The assessment of probabilistic health risks revealed that Non- carcinogenic risks of all populations were acceptable (HI < 1), while Carcinogenic risks were all at a high level (TCR > 10E-04). Agricultural pollution and As were identified as priority control factors, according to the analysis results of the relationship among TMs, pollution sources and health risks. Our findings provide scientific support for decision-makers to formulate target control policies and reduce management costs of soil pollution.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
7.
J Environ Sci (China) ; 111: 61-74, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34949374

RESUMO

Nowadays, more people tend to spend their recreational time in large national parks, and trace metal(loid)s in soils have attracted long-term attention due to their possible harm to human health. To investigate the pollution levels, potential sources and health risks of trace metal(loid)s in road soils, a total of eight trace metal(loid)s (including As, Cd, Cr, Cu, Ni, Pb, Zn and Hg) from 47 soil samples along roads were studied in the Huangshan National Park in Southeast China. The results showed that the concentrations of As, Cd, Pb, Zn and Hg appeared different degrees of pollution compared with their corresponding background values. According to the pollution indices, Hg and Cd were recognized as significant pollutants presenting moderate to high ecological risk. Combining principal component analysis and positive matrix factorization model, the results showed that traffic, industrial, agricultural and natural sources were the potential origins of trace metal(loid)s in this area, with contribution rates of 39.93%, 25.92%, 10.53% and 23.62%, respectively. Non-carcinogenic risks were all negligible, while the carcinogenic risk of As was higher than the limit (1 × 10-6). Moreover, children were more susceptible to trace metal(loid)s by ingestion which appeared to be a more important exposure pathway than dermal contact and inhalation. The contribution rates of different sources to non-carcinogenic risks and carcinogenic risks were similar among children and adults, while traffic and industrial sources have a significant impact on health risks. This study will give more insights to control the environmental risks of trace metal(loid)s in national parks.


Assuntos
Metaloides , Metais Pesados , Poluentes do Solo , Adulto , Criança , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Parques Recreativos , Medição de Risco , Solo , Poluentes do Solo/análise
8.
Appl Microbiol Biotechnol ; 105(11): 4343-4356, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34021813

RESUMO

Diversified members of hop bitter acids (α- and ß-acids) have been found in hop (Humulus lupulus). Mixtures of hop bitter acids have been traditionally applied in brewing and food industries as bitterness flavors or food additives. Recent studies have discovered novel applications of hop bitter acids and their derivatives in medicinal and pharmaceutical fields. The increasing demands of purified hop bitter acid promoted biosynthesis efforts for the heterologous biosynthesis of objective hop bitter acids by engineered microbial factories. In this study, the updated information of hop bitter acids and their representative application in brewing, food, and medicine fields are reviewed. We also speculate future trends on the development of robust microbial cell factories and biotechnologies for the biosynthesis of hop bitter acids. KEY POINTS: • Structures and applications of hop bitter acids are summarized in this study. • Biosynthesis of hop bitter acids remains challenging. • We discuss potential strategies in the microbial production of hop bitter acids.


Assuntos
Humulus , Ácidos
9.
J Hazard Mater ; 415: 125629, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-33740718

RESUMO

Urban Parks are important places for residents to engage in outdoor activities, and whether heavy metal(loid)s (HMs) in park soils are harmful to human health has aroused people's concern. A total of 204 topsoil samples containing nine HMs were collected from 78 urban parks of Shanghai in China, and used to assess the health risks caused by HMs in soils. The results revealed that the Hg, Cd and Pb were the main enriched pollutants and posed higher ecological risks than the other HMs. Four HM sources (including natural sources, agricultural activities, industrial production and traffic emissions) were identified by combining the Positive matrix factorization model and Correlation analysis, with the contribution rate of 48.24%, 7.03%, 13.04% and 31.69%, respectively. The assessment of Probabilistic health risks indicated that the Non-carcinogenic risks for all populations were negligible. However, the Total carcinogenic risk cannot be negligible and children were more susceptible than adults. The assessment results of source-oriented health risks showed that industrial production and traffic emissions were estimated to be the most important anthropogenic sources of health risks for all populations. Our results provide scientific support needed for the prevention and control of HM pollution in urban parks.


Assuntos
Metais Pesados , Poluentes do Solo , Adulto , Criança , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Método de Monte Carlo , Medição de Risco , Solo , Poluentes do Solo/análise
10.
Sci Total Environ ; 765: 144431, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33387923

RESUMO

Perfluorooctanoic acid (PFOA) and its substitute GenX are toxic chemicals that are widespread in the aquatic environment. However, there is little information about their toxicity mechanisms to aquatic organisms. In this study, Chlorella pyrenoidosa (C. pyrenoidosa) was treated with two concentrations (100 ng L-1 and 100 µg L-1) of PFOA or GenX for 12 days. The results showed that these two concentrations of PFOA and GenX began to inhibit the growth of algae after 6 days of treatment, and the Chlorophyll content and photosynthetic activity of C. pyrenoidosa were also negatively affected by these two chemicals. The transcriptomic results indicated that most of the genes related to the photosynthetic metabolism of C. pyrenoidosa were down-regulated (in 100 ng L-1 treatment groups) on the 12th day. Besides, GenX and PFOA showed similar effects on algae photosynthesis including physical damage and metabolic disorders. According to this study, GenX might not be an ideal substitute for PFOA, and more attention should be paid on the management of emerging perfluoroalkyl substances.


Assuntos
Chlorella , Fluorocarbonos , Poluentes Químicos da Água , Caprilatos , Fluorocarbonos/toxicidade , Fotossíntese , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
11.
J Environ Qual ; 49(3): 654-662, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-33016401

RESUMO

Continuous-flow iron and bio-iron columns were used to evaluate the effects of seepage velocity and concentration on Cr(VI) removal from groundwater. Solid-phase analysis showed that microorganisms accelerated iron corrosion by excreting extracellular polymeric substances and generated highly reactive minerals containing Fe(II), which gave the bio-iron column a longer life span and enhanced capacity for Cr(VI) removal via enhanced adsorption and reduction by reactive minerals. The bio-iron column showed much higher Cr(VI) removal capacity than the iron column with increasing Cr(VI) loading, which was obtained by increasing the seepage velocity or influent Cr(VI) concentration from 95 to 1138 m yr-1 and from 5 to 40 mg L-1 , respectively. When the Cr(VI) loading varied in a range of 0 to 10 mg L-1 h-1 , the bio-iron column had a 60% longer longevity and one- to sixfold higher Cr(VI) elimination capacity than the iron column. This result indicated that, under fluctuating hydraulic conditions [e.g., seepage velocity and Cr(VI) concentration], the presence of microorganisms can significantly boost Cr(VI) removal using Fe0 -based permeable reactive barriers.


Assuntos
Água Subterrânea , Poluentes Químicos da Água/análise , Adsorção , Cromo , Ferro
12.
Artigo em Inglês | MEDLINE | ID: mdl-32635623

RESUMO

Understanding the environmental risks of soil heavy metals (HMs) and identifying their main sources are the essential prerequisites for the prevention and management of soil pollution. Based on a detailed survey of soil HMs (Cu, Cr, Ni, Zn, Pb, Cd, As and Hg) from different land use types (including agricultural land, construction land, wetland, and forest land) in an estuary alluvial island, the environmental risk and source apportionment of soil HMs were investigated. Altogether, 117 soil samples were taken in the study area to appraise the soil HMs environmental risk by using the geo-accumulation index (Igeo), potential ecological risk index (RI), and human health risk assessment (HRA) and to identify its main sources by using positive matrix factorization (PMF) model. The average concentrations of soil HMs (except As) surpassed their reference background values in China. There were no significant differenced in the mean concentrations of HMs in different land use types, except that the Hg concentration in the construction land was significantly higher than that in others. The results of Igeo showed that Cd pollution was unpolluted to moderately polluted, and that the others were unpolluted. The potential ecological risk level for Cd and Hg was "moderated potential risk", while for Cu, Cr, Ni, Zn, Pb and As was "low potential risk". Higher contamination was distributed at the west-central area. The results of the HRA indicated that the non-carcinogenic risk and the carcinogenic risk that human beings suffered from HMs in different land uses were insignificant. To more accurately identify the sources of soil HMs, the PMF model coupled with the GIS-spatial analysis was applied. The results showed that agricultural activities, natural source, industrial discharge and river transportation, and atmosphere deposition were the main determining factors for the accumulation of soil HMs in the study area, with the contribution rate of 24.25%, 23.79%, 23.84%, and 28.12%, respectively. The study provides an underlying insight needed to control of the soil HM pollutions for an estuary alluvial island.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Estuários , Humanos , Ilhas , Metais Pesados/análise , Metais Pesados/toxicidade , Medição de Risco , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
13.
J Vet Diagn Invest ; 32(5): 695-699, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32667260

RESUMO

Atypical porcine pestivirus (APPV) had been detected in many countries. However, to date, a commercial detection kit is not available because of a lack of specific monoclonal antibodies (mAbs) to APPV. We generated 7 mAbs targeting the NS3 protein of APPV. Isotyping results indicated that all of these mAbs are IgG1 with a kappa light chain. We analyzed the epitopes recognized by mAbs 2B6, 6G11, 8D1, 8D3, and 8F12, which recognized the same linear epitope (GRIKSAYSDE); the 6H3 and 7E10 mAbs recognized 2 different conformational epitopes. Applications of these antibodies were verified by ELISA, western blot, indirect immunofluorescence assay, and flow cytometry. The antibodies were functionally workable for these immunoassays except for 8F12, which could not be used in flow cytometry.


Assuntos
Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/isolamento & purificação , Infecções por Pestivirus/veterinária , Pestivirus/imunologia , Doenças dos Suínos/imunologia , Proteínas não Estruturais Virais/isolamento & purificação , Animais , Infecções por Pestivirus/imunologia , Infecções por Pestivirus/virologia , RNA Helicases/isolamento & purificação , Serina Endopeptidases/isolamento & purificação , Sus scrofa , Suínos , Doenças dos Suínos/virologia
14.
Sci Total Environ ; 744: 140715, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32698046

RESUMO

In this study, nitrate mediated biotic zero-valent iron (Fe0) corrosion was employed to enhance cadmium (Cd) removal from groundwater. In comparison with a 17.5% Cd(II) removal treated with abiotic Fe0, a 3.9 times higher Cd(II) removal of 86.2% was recorded in the nitrate-mediated biotic Fe0 system. Solids phase characterization confirmed that biogenic minerals such as green rust and iron sulfide could be formed in the nitrate-amended biotic Fe0 system, offering large amount of adsorption sites for Cd(II) removal. The decrease of nitrate concentration and the competition with cathodic hydrogen for biological nitrate reduction by extra organic substance such as sodium acetate both showed significant inhibition on Cd(II) removal, further proving that hydrogenotrophic denitrification was the main mechanism for enhanced Cd(II) removal. Besides, a relatively high Cd(II) removal efficiency was observed over a pH range of 5-8, and it increased with declining pH values. These results demonstrated that the bio-amended iron corrosion technology coupled Fe0-assisted H2 production with hydrogenotrophic denitrification exhibited excellent Cd(II) removal capacity, which enabled this technology a promising potential for Cd(II)-contaminated groundwater treatment and an alternative strategy for Cd(II) and nitrate co-contaminated groundwater remediation.

15.
Mini Rev Med Chem ; 20(4): 331-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31644401

RESUMO

Biopolyesters represent a large family that can be obtained by polymerization of variable bio-derived hydroxyalkanoic acids. The monomer composition, molecular weight of the biopolyesters can affect the properties and applications of the polyesters. The majority of biopolyesters can either be biosynthesized from natural biofeedstocks or semi-synthesized (biopreparation of monomers followed by the chemical polymerization of the monomers). With the fast development of synthetic biology and biosynthesis techniques, the biosynthesis of unnatural biopolyesters (like lactate containing and aromatic biopolyesters) with improved performance and function has been a tendency. The presence of novel preparation methods, novel monomer composition has also significantly affected the properties, functions and applications of the biopolyesters. Due to the properties of biodegradability and biocompatibility, biopolyesters have great potential in biomedical applications (as implanting or covering biomaterials, drug carriers). Moreover, biopolyesters can be fused with other functional ingredients to achieve novel applications or improved functions. This study summarizes and compares the updated preparation methods of representative biopolyesters, also introduces the current status and future trends of their applications in biomedical fields.


Assuntos
Materiais Biocompatíveis/síntese química , Pesquisa Biomédica , Poliésteres/síntese química , Materiais Biocompatíveis/química , Poliésteres/química , Polimerização
16.
Plant Sci ; 285: 34-43, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203892

RESUMO

Seed germination is a critical stage during the initiation of the plant lifecycle and is strongly affected by endogenous phytohormones and environmental stress. High temperature (HT) upregulates endogenous abscisic acid (ABA) to suppress seed germination, and ABA-INSENSITIVE 5 (ABI5) is the key positive regulator in the ABA signal-mediated modulation of seed germination. In plants, hydrogen sulfide (H2S) is a small gas messenger that participates in multiple physiological processes, but its role in seed germination thermotolerance has not been thoroughly elucidated to date. In this study, we found that H2S enhanced the seed germination rate under HT. Moreover, HT accelerates the efflux of the E3 ligase CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1) from the nucleus to the cytoplasm, which results in increased nuclear accumulation of ELONG HYPCOTYL 5 (HY5) to activate the expression of ABI5 and thereby suppress seed germination. However, the H2S signal reversed the HT effect, as characterized by increased COP1 in the nucleus, which resulted in increased degradation of HY5 and reduced expression of ABI5 and thereby enhanced the seed germination thermotolerance. Thus, our findings reveal a novel role for the H2S signal in the modulation of seed germination thermotolerance through the nucleocytoplasmic partitioning of COP1 and the downstream HY5 and ABI5 pathways.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Germinação/fisiologia , Sulfeto de Hidrogênio/metabolismo , Proteínas Nucleares/metabolismo , Sementes/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/fisiologia , Arabidopsis/fisiologia , Proteínas de Arabidopsis/fisiologia , Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Núcleo Celular/enzimologia , Núcleo Celular/metabolismo , Giberelinas/metabolismo , Giberelinas/fisiologia , Temperatura Alta , Proteínas Nucleares/fisiologia , Reguladores de Crescimento de Plantas/fisiologia , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Sementes/fisiologia , Transdução de Sinais/fisiologia , Termotolerância , Ubiquitina-Proteína Ligases/fisiologia
17.
Plant Sci ; 284: 91-98, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084884

RESUMO

Seeds germination or dormancy is strictly controlled by endogenous phytohormone signal and environment cues. High temperature (HT) suppresses seeds germination or triggers seeds dormancy but underlying mechanism by which HT mediates seeds germination thermoinhibition needs more investigating. SOM is reported as the critical factor negatively controls light-irradiation seeds germination by altering Abscisic acid (ABA) and gibberellin acid (GA) biosynthesis. Here we found that HT accelerates SOM expressing through ABA signal transduction component ABI3, both of abi3 and som mutants seeds show high germination rate under HT in contrast to wild type seeds. Using ABI3 as the bait, we identified the epigenetic factor Powerdress (PWR) as the ABI3 interaction protein. Genetic and physiological analysis showed that PWR negatively control the expressing of SOM, and overexpressing PWR enhanced, while pwr mutant reduced, seeds germination thermotolerance. Without HT stress, PWR accelerated the histone H3 deacetylation level and H2A.Z deposition at SOM locus, and thus suppressed ABI3-dependent SOM transcription for seeds germination, HT stress block PWR transcriptional level, thus attenuated the inhibition effect of PWR on SOM expressing, resulting into seeds germination thermoinhibition. Thus our finding propose a new function of PWR in controlling seeds germination under HT through histone acetylation modification and H2A.Z deposition.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Transporte/metabolismo , Germinação , Sementes/crescimento & desenvolvimento , Fatores de Transcrição/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Proteínas de Transporte/fisiologia , Germinação/fisiologia , Resposta ao Choque Térmico , Código das Histonas , Plantas Geneticamente Modificadas , Sementes/metabolismo , Fatores de Transcrição/fisiologia , Técnicas do Sistema de Duplo-Híbrido
18.
Appl Microbiol Biotechnol ; 103(9): 3705-3714, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30877355

RESUMO

The variant strains of porcine epidemic diarrhea virus (PEDV) severely threaten the pig industry worldwide and cause up to 100% mortality in suckling piglets. It is critically important and urgent to develop tools for detection of PEDV infection. In this study, we developed six monoclonal antibodies (mAbs) targeting N protein of PEDV and analyzed their applications on enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), western blot assay, and flow cytometry assay. The results demonstrated that all these six mAbs were IgG1 isotype and κ chain. Among these six mAbs, 3F12 recognizes a linear epitope (VAAVKDALKSLGI) while the other five mAbs recognize different conformational epitopes formed by a specific peptide fragment or the full length of N protein. The functional analysis showed that all these six mAbs were applicable to ELISA, western blot, IFA, and flow cytometry assay. In conclusion, we developed six mAbs against PEDV-N protein to facilitate the early detection of PEDV infection using ELISA, western blot, IFA, and flow cytometry.


Assuntos
Anticorpos Monoclonais/análise , Anticorpos Antivirais/análise , Infecções por Coronavirus/veterinária , Nucleocapsídeo/análise , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Doenças dos Suínos/virologia , Animais , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Imunização , Camundongos Endogâmicos BALB C , Nucleocapsídeo/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Suínos , Doenças dos Suínos/diagnóstico
19.
Biotechnol Adv ; 36(7): 1917-1927, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30063950

RESUMO

Compared with the better-studied canonical amino acids, the distribution, metabolism and functions of natural non-canonical amino acids remain relatively obscure. Natural non-canonical amino acids have been mainly discovered in plants as secondary metabolites that perform diversified physiological functions. Due to their specific characteristics, a broader range of natural and artificial non-canonical amino acids have recently been applied in the development of functional materials and pharmaceutical products. With the rapid development of advanced methods in biotechnology, non-canonical amino acids can be incorporated into peptides, proteins and enzymes to improve the function and performance relative to their natural counterparts. Therefore, biotechnological application of non-canonical amino acids in artificial bio-macromolecules follows the central goal of synthetic biology to: create novel life forms and functions. However, many of the non-canonical amino acids are synthesized via chemo- or semi-synthetic methods, and few non-canonical amino acids can be synthesized using natural in vivo pathways. Therefore, further research is needed to clarify the metabolic pathways and key enzymes of the non-canonical amino acids. This will lead to the discovery of more candidate non-canonical amino acids, especially for those that are derived from microorganisms and are naturally bio-compatible with chassis strains for in vivo biosynthesis. In this review, we summarize representative natural and artificial non-canonical amino acids, their known information regarding associated metabolic pathways, their characteristics and their practical applications. Moreover, this review summarizes current barriers in developing in vivo pathways for the synthesis of non-canonical amino acids, as well as other considerations, future trends and potential applications of non-canonical amino acids in advanced biotechnology.


Assuntos
Aminoácidos/biossíntese , Biotecnologia , Engenharia Metabólica , Biologia Sintética , Redes e Vias Metabólicas , Peptídeos/metabolismo , Proteínas/metabolismo
20.
Materials (Basel) ; 11(8)2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30042344

RESUMO

With the rapid development of synthetic biology and metabolic engineering, a broad range of biochemicals can be biosynthesized, which include polyhydroxyalkanoates and isoprenoids. However, some of the bio-approaches in chemical synthesis have just started to be applied outside of laboratory settings, and many require considerable efforts to achieve economies of scale. One of the often-seen barriers is the low yield and productivity, which leads to higher unit cost and unit capital investment for the bioconversion process. In general, higher carbon economy (less carbon wastes during conversion process from biomass to objective bio-based chemicals) will result in higher bioconversion yield, which results in less waste being generated during the process. To achieve this goal, diversified strategies have been applied; matured strategies include pathway engineering to block competitive pathways, enzyme engineering to enhance the activities of enzymes, and process optimization to improve biomass/carbon yield. In this review, we analyze the impact of carbon sources from different types of biomass on the yield of bio-based chemicals (especially for polyhydroxyalkanoates and isoprenoids). Moreover, we summarize the traditional strategies for improving carbon economy during the bioconversion process and introduce the updated techniques in building up non-natural carbon pathways, which demonstrate higher carbon economies than their natural counterparts.

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