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1.
Nature ; 619(7970): 533-538, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37407823

RESUMO

Weather forecasting is important for science and society. At present, the most accurate forecast system is the numerical weather prediction (NWP) method, which represents atmospheric states as discretized grids and numerically solves partial differential equations that describe the transition between those states1. However, this procedure is computationally expensive. Recently, artificial-intelligence-based methods2 have shown potential in accelerating weather forecasting by orders of magnitude, but the forecast accuracy is still significantly lower than that of NWP methods. Here we introduce an artificial-intelligence-based method for accurate, medium-range global weather forecasting. We show that three-dimensional deep networks equipped with Earth-specific priors are effective at dealing with complex patterns in weather data, and that a hierarchical temporal aggregation strategy reduces accumulation errors in medium-range forecasting. Trained on 39 years of global data, our program, Pangu-Weather, obtains stronger deterministic forecast results on reanalysis data in all tested variables when compared with the world's best NWP system, the operational integrated forecasting system of the European Centre for Medium-Range Weather Forecasts (ECMWF)3. Our method also works well with extreme weather forecasts and ensemble forecasts. When initialized with reanalysis data, the accuracy of tracking tropical cyclones is also higher than that of ECMWF-HRES.

3.
J Am Chem Soc ; 145(2): 1118-1128, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36546850

RESUMO

A normal phosphorylation state is essential for the function of proteins. Biased regulation frequently results in morbidity, especially for the hyperphosphorylation of oncoproteins. The hyperphosphorylation of ASK1 at Thr838 leads to a persistently high activity state, which accelerates the course of gastric cancer. Under normal conditions, PP5 specifically dephosphorylates p-ASK1T838 in cells, thereby weakening ASK1 to a low-basal activity state. However, in tumor types, PP5 shows low activity with a self-inhibition mechanism, making p-ASK1T838 remain at a high level. Thus, we aim to design phosphatase recruitment chimeras (PHORCs) through a proximity-mediated effect for specifically accelerating the dephosphorylation of p-ASK1T838. Herein, we describe DDO3711 as the first PP5-recruiting PHORC, which is formed by connecting a small molecular ASK1 inhibitor to a PP5 activator through a chemical linker, to effectively decrease the level of p-ASK1T838 in vitro and in vivo. DDO3711 shows preferable antiproliferative activity (IC50 = 0.5 µM) against MKN45 cells through a direct binding and proximity-mediated mechanism, while the ASK1 inhibitor and the PP5 activator, used alone or in combination, exhibit no effect on MKN45 cells. Using DDO3711, PHORCs are identified as effective tools to accelerate the dephosphorylation of POIs and provide important evidence to achieve precise phosphorylation regulation, which will promote confidence in the further regulation of abnormally phosphorylated oncoproteins.


Assuntos
MAP Quinase Quinase Quinase 5 , Fosfoproteínas Fosfatases , Apoptose , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatases/química , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Transdução de Sinais , Antineoplásicos/química , MAP Quinase Quinase Quinase 5/química
4.
Appl Opt ; 62(6): 1575-1581, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821319

RESUMO

Employing functional and structured thin films on fiber optic sensors has tremendously improved capabilities in humidity sensing applications. In this paper, we demonstrate fabrication of a fiber optic evanescent wave humidity sensor based on S i O 2/porous polymethyl methacrylate (PMMA) thin films. With the exposure to moisture, S i O 2/porous PMMA thin films absorb water molecules. The refractive index and absorption coefficient of thin films change with ambient humidity, resulting in modulation of the light intensity transmitted in fiber. A good linearity is determined between the logarithm of output light intensity and relative humidity (RH). An optimal average sensitivity of 188.3 lux/%RH is achieved with an increase of 11.7 fold in the RH range of 5% to 95%. The response and recovery times are 8 s and 23 s, respectively. Furthermore, the sensor exhibits low hysteresis, and excellent stability and repeatability.

5.
J Sci Food Agric ; 103(5): 2602-2617, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36571565

RESUMO

BACKGROUND: Nitrogen (N) is the key nutrient required for high cotton production; however, its excessive use can increase the cost of production and environmental problems. Reducing the application of N while sustaining the yield is an important issue to be solved. Therefore, this study was designed to investigate the genotypic variations in subtending leaf physiology and its contribution to seed cotton yield of contrasting N-efficient cotton genotypes under various N levels in pot and field conditions. RESULTS: The results showed that the application of N increased the enzymatic activities related to carbon (C) and N metabolisms. Under the same N level, the C/N metabolisms of the N-efficient genotypes were significantly higher than N-inefficient genotypes, indicating a strong N assimilation and photoassimilation ability in N-efficient genotypes, especially under low N level. Moreover, the antioxidant enzymatic activities were significantly higher, whereas malondialdehyde content was lower in N-efficient cotton genotypes than in N-inefficient ones. Therefore, N-efficient cotton genotypes showed strong resistance, higher C/N metabolisms, and provided sufficient dry matter for boll development. As a result, the yield, N use efficiency, and value cost ratio of the N-efficient cotton genotypes were higher than in the N-inefficient genotypes. CONCLUSION: It was confirmed that the higher C/N metabolisms in the cotton subtending leaves of N-efficient cotton genotypes could support higher seed cotton yield under relatively low N application. © 2022 Society of Chemical Industry.


Assuntos
Carbono , Nitrogênio , Nitrogênio/metabolismo , Carbono/metabolismo , Folhas de Planta/metabolismo , Genótipo , Gossypium/metabolismo
6.
Appl Opt ; 61(7): 1834-1840, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35297866

RESUMO

A fiber optic humidity sensor based on polyvinyl alcohol (PVA)/Tween 20 film has been fabricated by modulating the intensity of light transmitted in optical fiber. PVA/Tween 20 film was used as the cladding and humidity-sensitive material of optical fiber. The logarithmic of output light intensity exhibited a linear increase with the increase of humidity (22%-82%RH). With the addition of Tween 20 in the formation of film, average sensitivity increased by 13-fold. Fast equilibrium on adsorption and desorption of water molecules were also achieved on the film. The response and recovery times were determined to be 11 s and 9 s, respectively. Moreover, the sensor possesses good repeatability. The sensing mechanism was probably based on the swelling of PVA after adsorbing water molecules, which affected scattering of evanescent waves in the cladding. The output light intensity varied with the decay of evanescent waves.

7.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430741

RESUMO

The NPF (NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY) transports various substrates, including nitrogen (N), which is essential for plant growth and development. Although many NPF homologs have been identified in various plants, limited studies on these proteins have been reported in cotton. This study identified 75, 71, and 150 NPF genes in Gossypium arboreum, G. raimondii, and G. hirsutum, respectively, via genome-wide analyses. The phylogenetic tree indicated that cotton NPF genes are subdivided into eight subgroups, closely clustered with Arabidopsis orthologues. The chromosomal location, gene structure, motif compositions, and cis-elements have been displayed. Moreover, the collinearity analysis showed that whole-genome duplication event has played an important role in the expansion and diversification of the NPF gene family in cotton. According to the transcriptome and qRT-PCR analyses, several GhNPFs were induced by the nitrogen deficiency treatment. Additional functional experiments revealed that virus-induced silencing (VIGS) of the GhNPF6.14 gene affects the growth and N absorption and accumulation in cotton. Thus, this study lays the foundation for further functional characterization of NPF genes in cotton.


Assuntos
Estudo de Associação Genômica Ampla , Gossypium , Gossypium/metabolismo , Filogenia , Genoma de Planta , Família Multigênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nitrogênio/metabolismo
8.
Int J Mol Sci ; 21(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098345

RESUMO

Nitrogen (N) is the most important limiting factor for cotton production worldwide. Genotype-dependent ability to cope with N shortage has been only partially explored in cotton, and in this context, the comparison of molecular responses of cotton genotypes with different nitrogen use efficiency (NUE) is of particular interest to dissect the key molecular mechanisms underlying NUE. In this study, we employed Illumina RNA-Sequencing to determine the genotypic difference in transcriptome profile using two cotton genotypes differing in NUE (CCRI-69, N-efficient, and XLZ-30, N-inefficient) under N starvation and resupply treatments. The results showed that a large genetic variation existed in differentially expressed genes (DEGs) related to amino acid, carbon, and nitrogen metabolism between CCRI-69 and XLZ-30. Further analysis of metabolic changes in cotton genotypes under N resupply showed that nitrogen metabolism and aromatic amino acid metabolism pathways were mainly enriched in CCRI-69 by regulating carbon metabolism pathways such as starch and sucrose metabolism, glycolysis/gluconeogenesis, and pentose phosphate pathway. Additionally, we performed an expression network analysis of genes related to amino acid, carbon, and nitrogen metabolism. In total, 75 and 33 genes were identified as hub genes in shoots and roots of cotton genotypes, respectively. In summary, the identified hub genes may provide new insights into coordinating carbon and nitrogen metabolism and improving NUE in cotton.


Assuntos
Carbono/metabolismo , Perfilação da Expressão Gênica/métodos , Genes de Plantas/genética , Gossypium/genética , Redes e Vias Metabólicas/genética , Nitrogênio/metabolismo , Metabolismo Energético/genética , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Genótipo , Gossypium/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/genética , Brotos de Planta/metabolismo
9.
Int J Mol Sci ; 21(8)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32326540

RESUMO

Chemical defoliation is an important part of cotton mechanical harvesting, which can effectively reduce the impurity content. Thidiazuron (TDZ) is the most used chemical defoliant on cotton. To better clarify the mechanism of TDZ promoting cotton leaf abscission, a greenhouse experiment was conducted on two cotton cultivars (CRI 12 and CRI 49) by using 100 mg L-1 TDZ at the eight-true-leaf stage. Results showed that TDZ significantly promoted the formation of leaf abscission zone and leaf abscission. Although the antioxidant enzyme activities were improved, the reactive oxygen species and malondialdehyde (MDA) contents of TDZ increased significantly compared with CK (water). The photosynthesis system was destroyed as net photosynthesis (Pn), transpiration rate (Tr), and stomatal conductance (Gs) decreased dramatically by TDZ. Furthermore, comparative RNA-seq analysis of the leaves showed that all of the photosynthetic related genes were downregulated and the oxidation-reduction process participated in leaf shedding caused by TDZ. Consequently, a hypothesis involving possible cross-talk between ROS metabolism and photosynthesis jointly regulating cotton leaf abscission is proposed. Our findings not only provide important insights into leaf shedding-associated changes induced by TDZ in cotton, but also highlight the possibility that the ROS and photosynthesis may play a critical role in the organ shedding process in other crops.


Assuntos
Desfolhantes Químicos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Gossypium/metabolismo , Compostos de Fenilureia/farmacologia , Fotossíntese/efeitos dos fármacos , Folhas de Planta/metabolismo , Tiadiazóis/farmacologia , Carboidratos/análise , Clorofila/análise , Fibra de Algodão , Desfolhantes Químicos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Ontologia Genética , Gossypium/efeitos dos fármacos , Gossypium/genética , Malondialdeído/análise , Microscopia Eletrônica de Varredura , Epiderme Vegetal/anatomia & histologia , Epiderme Vegetal/efeitos dos fármacos , Epiderme Vegetal/ultraestrutura , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/ultraestrutura , Estômatos de Plantas/efeitos dos fármacos , Estômatos de Plantas/fisiologia , RNA-Seq , Espécies Reativas de Oxigênio/metabolismo , Plântula/anatomia & histologia , Plântula/crescimento & desenvolvimento
10.
J Sci Food Agric ; 100(6): 2761-2773, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32020619

RESUMO

BACKGROUND: Although nitrogen (N) availability is a major determinant of cotton production, little is known about the importance of plants' preference for ammonium versus nitrate for better growth and nitrogen use efficiency (NUE). We aimed to assess the growth, physiology, and NUE of contrasting N-efficient cotton genotypes (Z-1017, N-efficient and GD-89, N-inefficient) supplied with low and high concentrations of ammonium- and nitrate-N. RESULTS: The results revealed that ammonium fed plants showed poor root growth, lower dry biomass, N content, leaf chlorophyll and gas exchange than those under nitrate irrespective of the concentration. However, the highest N uptake and utilization efficiency were obtained with nitrate fed plants, which also resulted in the highest dry biomass, N content, leaf chlorophyll and gas exchange as well as root growth. The results further confirmed that N-efficient (Z-1017) genotype performed better under both N sources, showing more flexibility to contrasting N condition by increasing growth and NUE in either source of N. Moreover, multivariate analysis showed a strong relationship of root morphological traits with N utilization efficiency, suggesting the physiological importance of roots over shoots in response to low nitrate concentration. CONCLUSION: Thus, it was confirmed that nitrate-N is superior to ammonium-N and the use of nitrate and N-efficient genotype is the best option for optimum cotton growth and NUE. Further, field evaluation is required to confirm the hypothesis that nitrate is a preferred N source for better cotton production and NUE. © 2020 Society of Chemical Industry.


Assuntos
Gossypium/crescimento & desenvolvimento , Gossypium/genética , Nitrogênio/metabolismo , Compostos de Amônio/metabolismo , Genótipo , Gossypium/metabolismo , Nitratos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo
11.
Fish Shellfish Immunol ; 58: 210-219, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27591045

RESUMO

White spot syndrome virus (WSSV) infects all shrimp species and is the greatest detriment to shrimp culture. To better understand the mechanism of molecular responses to WSSV infection in "Huanghai No. 2" Fenneropenaeus chinensis, a microarray technique was used. Microarray gene expression profiling of 59,137 unigenes identified Differentially Expressed Genes (DEGs) both in live and moribund shrimp at early, peak and late phases. In live shrimp, 1307, 1479 and 1539 DEGs were obtained in the early, peak and late phase, respectively. Meanwhile, 1536, 2181 and 1591 DEGs were obtained in moribund shrimp. Twenty known annotation genes are uniquely expressed in the late phase of live shrimp, including adhesion regulating molecule 1, arginine kinase, BUD31 homolog, and QM. Compared to WSSV-susceptible shrimp, 75 known annotation genes are uniquely expressed in WSSV-resistant shrimp, including arginine kinase, BUD31 homolog, clottable protein 2, caspase 2, cathepsin C, calnexin, HMGBb, Histone 3, and selenoprotein M. The gene expression patterns of the infected shrimp were altered by WSSV infection. To further confirm the expression of differentially expressed genes, real-time RT-PCR was performed to test six randomly selected genes. The data will provide valuable information to understand the immune mechanism of shrimp's response to WSSV.


Assuntos
Proteínas de Artrópodes/genética , Análise de Sequência com Séries de Oligonucleotídeos , Penaeidae/genética , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Proteínas de Artrópodes/metabolismo , Regulação da Expressão Gênica/imunologia , Hepatopâncreas/imunologia , Penaeidae/imunologia , Penaeidae/virologia , Reação em Cadeia da Polimerase , Transcriptoma
12.
Crit Rev Oncol Hematol ; 196: 104292, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38403093

RESUMO

BACKGROUND: Numerous studies have reported the efficacy of antibody-drug conjugates (ADCs) for treating breast cancer. However, during cytotoxic drug treatment, long-term disabling fatigue is common. Moreover, studies in the relevant literature have indicated that fatigue can significantly increase the incidence of depression and sleep disorders. Therefore, this meta-analysis aims to evaluate the incidence of fatigue in breast cancer survivors treated with ADCs. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for articles and conference abstracts published before March 16, 2023. Further, two authors independently extracted data from the included studies. The primary outcome of this study was the incidence of all-grade fatigue caused by the use of ADCs in patients with breast cancer. Finally, a random-effects model was used to calculate the incidence and 95% confidence intervals (CIs) of the outcome. RESULTS: Overall, 7963 patients from 31 studies were included in this meta-analysis to assess the incidence of fatigue caused by the use of approved and marketed ADCs in patients with breast cancer. Notably, the incidence of all-grade fatigue during ADC monotherapy was 39.84% (95% CI, 35.09%-44.69%). In subgroup analyses, among ADCs, the incidence of trastuzumab deruxtecan-induced fatigue was the highest, with an all-grade fatigue incidence of 47.05% (95% CI, 42.38%-51.75%). Meanwhile, the incidence of trastuzumab emtansine (T-DM1)-induced all-grade fatigue was 35.17% (95% CI, 28.87%-41.74%), which was the lowest among ADCs. Further, the incidence of all-grade fatigue due to sacituzumab govitecan was 42.82% (95% CI, 34.54%-51.32%), which was higher than that due to T-DM1. Moreover, the incidence of fatigue was higher with T-DM1 combination therapy than with monotherapy. CONCLUSIONS: Clinicians have highlighted the high incidence of ADC-related fatigue and its negative impact on patients' physical and mental health, making fatigue an important research variable. The results of this study will further contribute to a comprehensive understanding of ADCs, which have some clinical importance and are of great benefit to patients with breast cancer.


Assuntos
Neoplasias da Mama , Imunoconjugados , Feminino , Humanos , Ado-Trastuzumab Emtansina/farmacologia , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Imunoconjugados/efeitos adversos , Incidência
13.
Int Immunopharmacol ; 133: 111961, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38608442

RESUMO

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy as a first-line treatment for triple-negative breast cancer (TNBC) has been associated with many adverse reactions. Thyroid dysfunction, the most common adverse reaction of the endocrine system, has also attracted significant attention. This study aimed to analyse the effect of ICIs combined with chemotherapy on thyroid function in patients with TNBC. METHODS: As of November 4, 2023, we searched the PubMed, Web of Science, and Cochrane Library databases for clinical trials of ICIs combined with chemotherapy for the treatment of TNBC. The incidence of hypothyroidism and hyperthyroidism was calculated using a random-effects model. RESULTS: In the final analysis, 3,226 patients from 19 studies were included. The total incidence of all-grade hypothyroidism induced by the combination of ICIs and chemotherapy in treating TNBC (12% (95% confidence intervals(CI): 0.10-0.15)) was higher than that of hyperthyroidism (5% (95% CI: 0.04-0.06)). Pembrolizumab combined with chemotherapy caused the highest incidence of all grades of hypothyroidism for 13% (95% CI: 0.05-0.06). Durvalumab combined with chemotherapy caused the highest incidence of all grades of hyperthyroidism, at 7% (95% CI: 0.03-0.11). ICIs combined with chemotherapy caused a higher incidence of all grades of hypothyroidism in advanced TNBC (15% (95% CI: 0.13-0.17)) than in early stage TNBC (10% (95% CI: 0.07-0.13)). CONCLUSION: In TNBC, the incidence of hypothyroidism caused by the combination of ICIs and chemotherapy was significantly higher than that caused by hyperthyroidism. Pembrolizumab combined with chemotherapy resulted in the highest incidence of hypothyroidism. The incidence of hypothyroidism in patients with advanced TNBC was significantly higher than that in patients with early stage TNBC. In addition, ICIs combined with chemotherapy resulted in 16 out of 3,226 patients experiencing grade ≥ 3 thyroid dysfunction. Although the incidence of severe thyroid dysfunction is low, it requires attention. PROSPERO: CRD42023477933.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores de Checkpoint Imunológico , Humanos , Incidência , Inibidores de Checkpoint Imunológico/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/epidemiologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Feminino , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/epidemiologia , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/epidemiologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/imunologia
14.
J Adv Res ; 58: 31-43, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37236544

RESUMO

INTRODUCTION: Defoliation by applying defoliants before machine picking is an important agricultural practice that enhances harvesting efficiency and leads to increased raw cotton purity. However, the fundamental characteristics of leaf abscission and the underlying genetic basis in cotton are not clearly understood. OBJECTIVES: In this study, we aimed to (1) reveal the phenotypic variations in cotton leaf abscission, (2) discover the whole-genome differentiation sweeps and genetic loci related to defoliation, (3) identify and verify the functions of key candidate genes associated with defoliation, and (4) explore the relationship between haplotype frequency of loci and environmental adaptability. METHODS: Four defoliation-related traits of 383 re-sequenced Gossypium hirsutum accessions were investigated in four environments. The genome-wide association study (GWAS), linkage disequilibrium (LD) interval genotyping and functional identification were conducted. Finally, the haplotype variation related to environmental adaptability and defoliation traits was revealed. RESULTS: Our findings revealed the fundamental phenotypic variations of defoliation traits in cotton. We showed that defoliant significantly increased the defoliation rate without incurring yield and fiber quality penalties. The strong correlations between defoliation traits and growth period traits were observed. A genome-wide association study of defoliation traits identified 174 significant SNPs. Two loci (RDR7 on A02 and RDR13 on A13) that significantly associated with the relative defoliation rate were described, and key candidate genes GhLRR and GhCYCD3;1, encoding a leucine-rich repeat (LRR) family protein and D3-type cell cyclin 1 protein respectively, were functional verified by expression pattern analysis and gene silencing. We found that combining of two favorable haplotypes (HapRDR7 and HapRDR13) improved sensitivity to defoliant. The favorable haplotype frequency generally increased in high latitudes in China, enabling adaptation to the local environment. CONCLUSION: Our findings lay an important foundation for the potentially broad application of leveraging key genetic loci in breeding machine-pickable cotton.


Assuntos
Estudo de Associação Genômica Ampla , Gossypium , Gossypium/genética , Melhoramento Vegetal , Genômica , Folhas de Planta
15.
Eur J Med Chem ; 254: 115350, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37054560

RESUMO

Phosphorylation of proteins is reversibly controlled by the kinases and phosphatases in many posttranslational regulation patterns. Protein phosphatase 5 (PPP5C) is a serine/threonine protein phosphatase showing dual function by simultaneously exerting dephosphorylation and co-chaperone functions. Due to this special role, PPP5C was found to participate in many signal transductions related to various diseases. Abnormal expression of PPP5C results in cancers, obesity, and Alzheimer's disease, making it a potential drug target. However, the design of small molecules targeting PPP5C is struggling due to its special monomeric enzyme form and low basal activity by a self-inhibition mechanism. Through realizing the PPP5C's dual function as phosphatase and co-chaperone, more and more small molecules were found to regulate PPP5C with a different mechanism. This review aims to provide insights into PPP5C's dual function from structure to function, which could provide efficient design strategies for small molecules targeting PPP5C as therapeutic candidates.


Assuntos
Neoplasias , Fosfoproteínas Fosfatases , Humanos , Fosfoproteínas Fosfatases/metabolismo , Proteínas Nucleares , Fosforilação , Descoberta de Drogas , Proteína Fosfatase 2/metabolismo
16.
Antioxidants (Basel) ; 11(4)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35453304

RESUMO

The oxidative stress response pathway is one of the hotspots of current pharmaceutical research. Many proteins involved in these pathways work through protein-protein interactions (PPIs). Hence, targeting PPI to develop drugs for an oxidative stress response is a promising strategy. In recent years, small molecules targeting protein-protein interactions (PPIs), which provide efficient methods for drug discovery, are being investigated by an increasing number of studies. However, unlike the enzyme-ligand binding mode, PPIs usually exhibit large and dynamic binding interfaces, which raise additional challenges for the discovery and optimization of small molecules and for the biochemical techniques used to screen compounds and study structure-activity relationships (SARs). Currently, multiple types of PPIs have been clustered into different classes, which make it difficult to design stationary methods for small molecules. Deficient experimental methods are plaguing medicinal chemists and are becoming a major challenge in the discovery of PPI inhibitors. In this review, we present current methods that are specifically used in the discovery and identification of small molecules that target oxidative stress-related PPIs, including proximity-based, affinity-based, competition-based, structure-guided, and function-based methods. Our aim is to introduce feasible methods and their characteristics that are implemented in the discovery of small molecules for different types of PPIs. For each of these methods, we highlight successful examples of PPI inhibitors associated with oxidative stress to illustrate the strategies and provide insights for further design.

17.
Antioxidants (Basel) ; 11(8)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-36009240

RESUMO

Silicon (Si) could alleviate the adverse effect of salinity in many crops, but the effect in cotton remains unclear. In this study, we evaluated the role of Si in regulating the salt stress tolerance of cotton by analyzing the induced morpho-physiological changes. A hydroponic experiment was conducted by using contrasting salt-tolerant cotton genotypes (sensitive Z0102; tolerant Z9807) and four treatments (CK, control; CKSi, 0.4 mM Si; NaCl, 150 mM NaCl; NaClSi, 150 mM NaCl+0.4 mM Si). The results showed that Si significantly enhanced the net photosynthesis rate and improved the growth of cotton seedling under salt stress in both salt-sensitive and salt-tolerant genotypes. Exogenous Si significantly reduced the accumulation of reactive oxygen species (ROS) and decreased the malondialdehyde (MDA) content in salt-stressed cotton. In addition, the application of Si up-regulated the expression of CAT1, SODCC and POD, and significantly enhanced the antioxidant enzymatic activities, such as catalase (CAT) and peroxidase (POD), of the salt-stressed cotton seedlings. Further, Si addition protected the integrity of the chloroplast ultrastructure, including key enzymes in photosynthesis such as ferredoxin-NADP reeducates (FNR), ATP synthase (Mg2+Ca2+-ATPase) and ribulose-1, 5-bisphosphate carboxylase/oxygenase (RubisCO), and the structure and function of the photosynthetic apparatus PSII from salt stress. Moreover, Si significantly increased the effective stomatal density and stomatal aperture in the salt-stressed cotton seedlings. Taken together, Si could likely ameliorate adverse effects of salt stress on cotton by improving the ROS scavenging ability and photosynthetic capacity.

18.
Crop Sci ; 61(4): 2745-2758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413536

RESUMO

Xinjiang is currently the most dominant cotton (Gossypium hirsutum L.)-growing region in China and possesses abundant radiation resource. The cultivation techniques such as wide and narrow row-spacing and high density are widely adopted to obtain high cotton yield in the region. However, the region is facing some problems including poor light transmittance in the field and low exploitation for light resources under the current planting pattern which impedes further growth in cotton yields. Therefore, it is essential to develop some cultivation practices to increase radiation use efficiency (RUE) and cotton yields in Xinjiang. Here we conducted a field experiment to quantify the effects of row spacing pattern and plant density on RUE, intercepted photosynthetically active radiation from May to August (IRAR5-8), and lint yield during 2017 and 2018. In this study, we designed two row-spacing configurations (R1, wide and narrow configuration, 66 cm + 10 cm; R2, uniform row-spacing configuration, 76 cm) and six plant densities (4.5, 9.0, 13.5, 18.0, 22.5, and 27.0 plants m-2). The RUE, lint yield, and number of bolls were higher in R2 than R1 by 4.1-5.9, 2.5-4.8, and 9.1-14.2%, respectively. The RUE significantly increased with plant density, but lint yield stabilized at 18.0 plants m-2. Moreover, RUE had more significant positive effects on boll number and lint yield. Overall, we found that R2 combined with optimal plant densities (13.5-18.0 plants m-2) would be an effective strategy to achieve higher RUE and yields in the Xinjiang cotton system.

19.
Plants (Basel) ; 9(2)2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32075340

RESUMO

Cotton production is highly sensitive to nitrogen (N) fertilization, whose excessive use is responsible for human and environmental problems. Lowering N supply together with the selection of N-efficient genotypes, more able to uptake, utilize, and remobilize the available N, could be a challenge to maintain high cotton production sustainably. The current study aimed to explore the intraspecific variation among four cotton genotypes in response to various N supplies, in order to identify the most distinct N-efficient genotypes and their nitrogen use efficiency (NUE)-related traits in hydroponic culture. On the basis of shoot dry matter, CCRI-69 and XLZ-30 were identified as N-efficient and N-inefficient genotypes, respectively, and these results were confirmed by their contrasting N metabolism, uptake (NUpE), and utilization efficiency (NUtE). Overall, our results indicated the key role of shoot glutamine synthetase (GS) and root total soluble protein in NUtE. Conversely, tissue N concentration and N-metabolizing enzymes were considered as the key traits in conferring high NUpE. The remobilization of N from the shoot to roots by high shoot GS activity may be a strategy to enhance root total soluble protein, which improves root growth for N uptake and NUE. In future, multi-omics studies will be employed to focus on the key genes and pathways involved in N metabolism and their role in improving NUE.

20.
Plants (Basel) ; 9(2)2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32024197

RESUMO

Drought is one of the most important abiotic stresses and hampers many plant physiological processes under suboptimal nitrogen (N) concentration. Seedling tolerance to drought stress is very important for optimum growth and development, however, the enhancement of plant stress tolerance through N application in cotton is not fully understood. Therefore, this study investigates the role of high N concentration in enhancing drought stress tolerance in cotton. A hydroponic experiment supplying low (0.25 mM) and high (5 mM) N concentrations, followed by 150 g L-1 polyethylene glycol (PEG)-induced stress was conducted in a growth chamber. PEG-induced drought stress inhibited seedling growth, led to oxidative stress from excessive malondialdehyde (MDA) generation, and reduced N metabolism. High N concentrations alleviated oxidative damage and stomatal limitation by increasing antioxidant enzymatic activities, leaf relative water content, and photosynthesis in cotton seedlings under drought stress. The results revealed that the ameliorative effects of high N concentration may be ascribed to the enhancement of N metabolizing enzymes and an increase in the amounts of osmoprotectants like free amino acids and total soluble protein. The present data suggest that relatively high N concentrations may contribute to drought stress tolerance in cotton through N metabolism, antioxidant capacity, and osmotic adjustment.

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