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1.
J Agric Food Chem ; 72(26): 14557-14569, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38957088

RESUMO

This study aimed to investigate the mechanisms by which dark septate endophytes (DSE) regulate salt tolerance and the accumulation of bioactive constituents in licorice. First, the salt stress tolerance and resynthesis with the plant effect of isolated DSE from wild licorice were tested. Second, the performance of licorice inoculated with DSE, which had the best salt-tolerant and growth-promoting effects, was examined under salt stress. All isolated DSE showed salt tolerance and promoted plant growth, withCurvularia lunata D43 being the most effective. Under salt stress, C. lunata D43 could promote growth, increase antioxidant enzyme activities, enhance glycyrrhizic acid accumulation, improve key enzyme activities in the glycyrrhizic acid synthesis pathway, and induce the expression of the key enzyme gene and salt tolerance gene of licorice. The structural equation model demonstrated that DSE alleviate the negative effects of salt stress through direct and indirect pathways. Variations in key enzyme activities, gene expression, and bioactive constituent concentration can be attributed to the effects of DSE. These results contribute to revealing the value of DSE for cultivating medicinal plants in saline soils.


Assuntos
Endófitos , Glycyrrhiza , Ácido Glicirrízico , Estresse Salino , Ácido Glicirrízico/metabolismo , Glycyrrhiza/química , Glycyrrhiza/metabolismo , Glycyrrhiza/microbiologia , Endófitos/metabolismo , Endófitos/genética , Tolerância ao Sal , Ascomicetos/metabolismo , Ascomicetos/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas
2.
Angew Chem Int Ed Engl ; : e202408914, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38957932

RESUMO

Dual-atom catalysts (DACs) have been proposed to break the limitation of single-atom catalysts (SACs) in the synergistic activation of multiple molecules and intermediates, offering an additional degree of freedom for catalytic regulation. However, it remains a challenge to synthesize DACs with high uniformity, atomic accuracy, and satisfactory loadings. Herein, we report a facile cascade synthetic strategy for DAC via precise electrostatic interaction control and neighboring vacancy construction. We synthesized well-defined, uniformly dispersed dual Fe sites which were connected by two nitrogen bonds (denoted as Fe-N2-Fe). The as-synthesized DAC exhibited superior catalytic performances towards oxygen reduction reaction, including good half-wave potential (0.91 V), high kinetic current density (21.66 mA cm-2), and perfect durability. Theoretical calculation revealed that the DAC structure effectively tunes the oxygen adsorption configuration and decreases the cleavage barrier, thereby improving the catalytic kinetics. The DAC-based zinc-air batteries exhibited impressive power densities of 169.8 and 52.18 mW cm-2 at 25 oC and -40 oC, which is 1.7 and 2.0 times higher than those based on Pt/C+Ir/C, respectively. We also demonstrated the universality of our strategy in synthesizing other M-N2-M DACs (M= Co, Cu, Ru, Pd, Pt, and Au), facilitating the construction of a DAC library for different catalytic applications.

3.
Int J Biol Macromol ; 276(Pt 1): 133736, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992543

RESUMO

Pea peptides can lead to degradation through oxidation, deamidation, hydrolysis, or cyclization during production, processing, and storage, which in turn limit their broader application. To stabilize pea peptides, this study employed spray drying technology to create a pea peptide micro-encapsule using maltodextrin, gum tragacanth, and pea peptides. Four key factors, including polysaccharide ratio, glycopeptide ratio, solid-liquid ratio, and inlet temperature, were optimized to enhance the antioxidant properties of the pea peptide micro-encapsule. The results indicated that the utilization of maltodextrin and gum tragacanth significantly improves the storage stability and antioxidant activity of pea peptides. Moreover, optimal storage stability for pea peptides was achieved with a polysaccharide ratio of 9:1, a glycopeptide ratio of 10:1, a solid-liquid ratio of 4:40, and an inlet temperature of 180 °C. After 60 days of storage, the encapsulated pea peptides maintained 70.22 %, 25.19 %, and 40.32 % for scavenging abilities to hydroxyl radical, superoxide anion, and ABTS radical, respectively. In contrast, the unencapsulated pea peptides showed a decline to 47.02 %, 0 %, and 24.46 % in the same antioxidant activities after storage. These findings underscore the potential of spray drying technology to enhance the functional properties of pea peptides for various applications.

4.
Respir Res ; 25(1): 270, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987833

RESUMO

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. METHODS: In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. RESULTS: Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFßR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFßR1 induced similar effects to H19 deficiency. CONCLUSIONS: In summary, our findings demonstrate that the H19/let-7 g/TGFßR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.


Assuntos
Transição Epitelial-Mesenquimal , Hipertensão Pulmonar , Hipóxia , MicroRNAs , RNA Longo não Codificante , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Crescimento Transformador beta , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Ratos , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Hipóxia/metabolismo , Hipóxia/genética , Transdução de Sinais/fisiologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Masculino , Transição Epitelial-Mesenquimal/fisiologia , Transição Epitelial-Mesenquimal/genética , Fator de Crescimento Transformador beta/metabolismo , Feminino , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Modelos Animais de Doenças , RNA Endógeno Competitivo
5.
ACS Omega ; 9(25): 27192-27203, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947808

RESUMO

Camellia polyodonta flowers contain limited information available regarding the composition of their bioactive compounds and activity. The objective of this study was to identify phenolic compounds and investigate the effect of different solvents (ethanol and methanol) on the phenolic content and antioxidant activity in C. polyodonta flowers. The analysis using UPLC-Q-TOF-MS/MS revealed the presence of 105 phytochemicals and the most common compounds were flavonols, procyanidins, and ellagitannins. Interestingly, flavonol triglycosides were identified for the first time in these flowers. The study demonstrated that the concentration of the solvent had a significant impact on the total phenolic compound (TPC), total flavonoid compound (TFC), and total proanthocyanidin content (TPAC). The TPC, TFC, and TPAC showed a remarkable increase with the increasing concentration of the solvent, reaching their maximum levels (138.23 mg GAE/g DW, 421.62 mg RE/g DW, 60.77 mg PB2E/g DW) at 70% ethanol. However, the total anthocyanin content reached its maximum at low concentrations (0.49 mg CGE/g DW). Similar trends were observed in the antioxidant activity, as measured by the DPPH· assay (DPPH radical scavenging activity), ABTS·+ assay (ABTS radical cation scavenging activity), and FRAP assay (Ferric reducing antioxidant power). The maximum antioxidant activity was observed at 100% solvents and 70% methanol. Among the 14 individual phenolic compounds, 70% methanol yielded the highest content for 8 (cyanidin-3-O-glucoside, procyanidin B2, procyanidin B4, epicatechin, rutin, kaempferol-3-O-rutinoside, astragaline and quercitrin) out of the 14 compounds. Additionally, it was found that epicatechin was the most abundant phenolic compound, accounting for approximately 20339.37 µg/g DW. Based on these findings, it can be concluded that 70% methanol is the most effective solvent for extracting polyphenols from C. polyodonta flowers. These results provided chemical information and potential antioxidant value for further research in C. polyodonta flowers.

6.
Opt Lett ; 49(13): 3765-3768, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950262

RESUMO

AlGaInP-based red light emitting diodes (LEDs) are considered as promising light sources in future full-color displays. At present, vertical chip configuration is still the mainstream device structure of AlGaInP-based red LEDs. However, current crowding around p-electrode severely hinders an efficient improvement. Here, we propose a Schottky-contact current blocking layer (SCBL) to enhance current spreading and to improve light extraction efficiency of AlGaInP-based red vertical miniaturized LEDs (mini-LEDs). By utilizing the Schottky contact between ITO and p-GaP, the SCBL can hinder current crowding around the p-electrode. The current is forced to inject into an active region through a p-GaP+ ohmic contact layer, avoiding light absorption by p-electrode. Through the transfer length method, the Schottky contact characteristics between the ITO and p-GaP as well as the ohmic contact characteristics between ITO and p-GaP+ are demonstrated. Benefiting from superior current spreading and improved light extraction, a mini-LED with SCBL realizes an enhancement of 31.8% in external quantum efficiency (EQE) at 20 mA in comparison with a mini-LED without SCBL.

7.
RSC Med Chem ; 15(7): 2357-2371, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39026657

RESUMO

To investigate atropisomers of non-steroidal glucocorticoid receptor modulator GSK866, a virtual library of substituted benzoic acid analogues was enumerated. Compounds from this library were subjected to a torsion angle scan using Spartan'20 to calculate the torsion rotation energy barrier which identified compounds predicted to be stable as atropisomers. After synthesis of the library, analysis showed that compounds 13 and 14 existed as stable atropisomers 13a, 13b, 14a and 14b, in agreement with the earlier calculations. Screening in a glucocorticoid receptor cellular assay showed that one compound from each atropisomer pair was significantly more potent than the other. Docking in a public structure of the glucocorticoid receptor (PBD code 3E7C) enabled the stereochemistry of the two most potent compounds 13a and 14b to be assigned as (R a) and (S a), respectively.

8.
Chemistry ; : e202401830, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037552

RESUMO

The catalytic direct hydroarylation of alkynamides is a highly efficient approach for accessing functionalized trisubstituted arylalkenes with amide groups. Herein, we report a rhodium-catalyzed pyridylation of alkynamides with pyridylboronic acids, yielding diverse primary, secondary, and tertiary enamides in good to excellent yields (up to 94%). This reaction demonstrates broad tolerance towards various alkyl and aryl functional groups, providing convenient access to a diverse array of alkenylpyridine derivatives. To demonstrate potential applications in late-stage hydropyridylation, we synthesized α,ß-unsaturated ketones, aldehydes, and esters with high yields from the pyridylation product of Weinreb amides. This indirect expansion of the substrate scope enhances the practicality of this strategy. Additionally, the α,ß-unsaturated ketone obtained can be further reduced to yield a chiral alcohol with a 99% ee, further demonstrating the versatility and potential utility of this approach.

9.
Antioxidants (Basel) ; 13(6)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38929101

RESUMO

Camellia polyodonta flowers are rich sources of phenolics and less attention has been paid to their potential biological activity. This study aims to explore the crude extracts and resulting purified fractions (CPFP-I, II, III, and IV) through compositional analysis and antioxidant and hypolipidemic activities in vitro and in vivo. Among four fractions, CPFP-II contained the highest total phenolic content and flavonoid content, while CPFP-III exhibited the greatest total proanthocyanidin content. Among the 14 phenolic compounds, CPFP-II displayed the highest content of procyanidin B2, B4, and C1, whereas CPFP-III contained the highest amount of 1,2,3,6-tetragalloylglucose. The DPPH, ABTS, and FRAP assessments demonstrated a consistent trend: CPFP-II > CPFP-III > CPFP-I > CPFP-IV. In vivo experiments showed that that all four fractions significantly reduced lipid levels in hyperlipidemic C. elegans (p < 0.05), with CPFP-II exhibiting the most potent effect. Furthermore, CPFP-II effectively bound to bile acids and inhibited the enzymatic activity of pancreatic lipase in vitro. Consequently, CPFP-II should be prioritized as a promising fraction for further exploration and should provide substantial support for the feasibility of the C. polyodonta flower as a natural alternative.

10.
Plants (Basel) ; 13(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38931082

RESUMO

Cadmium (Cd) is a naturally occurring toxic heavy metal that adversely affects plant germination, growth, and development. While the effects of Cd have been described on many crop species including rice, maize, wheat and barley, few studies are available on cadmium's effect on Tartary buckwheat which is a traditional grain in China. We examined nine genotypes and found that 30 µM of Cd reduced the root length in seedlings by between 4 and 44% and decreased the total biomass by 7 to 31%, compared with Cd-free controls. We identified a significant genotypic variation in sensitivity to Cd stress. Cd treatment decreased the total root length and the emergence and growth of lateral roots, and these changes were significantly greater in the Cd-sensitive genotypes than in tolerant genotypes. Cd resulted in greater wilting and discoloration in sensitive genotypes than in tolerant genotypes and caused more damage to the structure of root and leaf cells. Cd accumulated in the roots and shoots, but the concentrations in the sensitive genotypes were significantly greater than in the more tolerant genotypes. Cd treatment affected nutrient uptake, and the changes in the sensitive genotypes were greater than those in the tolerant genotypes, which could maintain their concentrations closer to the control levels. The induction of SOD, POD, and CAT activities in the roots and shoots was significantly greater in the tolerant genotypes than in the sensitive genotypes. We demonstrated that Cd stress reduced root and shoot growth, decreased plant biomass, disrupted nutrient uptake, altered cell structure, and managed Cd-induced oxidative stress differently in the sensitive and tolerant genotypes of Tartary buckwheat.

11.
J Cardiothorac Surg ; 19(1): 386, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926779

RESUMO

BACKGROUND: Computed tomography (CT)-guided biopsy (CTB) procedures are commonly used to aid in the diagnosis of pulmonary nodules (PNs). When CTB findings indicate a non-malignant lesion, it is critical to correctly determine false-negative results. Therefore, the current study was designed to construct a predictive model for predicting false-negative cases among patients receiving CTB for PNs who receive non-malignant results. MATERIALS AND METHODS: From January 2016 to December 2020, consecutive patients from two centers who received CTB-based non-malignant pathology results while undergoing evaluation for PNs were examined retrospectively. A training cohort was used to discover characteristics that predicted false negative results, allowing the development of a predictive model. The remaining patients were used to establish a testing cohort that served to validate predictive model accuracy. RESULTS: The training cohort included 102 patients with PNs who showed non-malignant pathology results based on CTB. Each patient underwent CTB for a single nodule. Among these patients, 85 and 17 patients, respectively, showed true negative and false negative PNs. Through univariate and multivariate analyses, higher standardized maximum uptake values (SUVmax, P = 0.001) and CTB-based findings of suspected malignant cells (P = 0.043) were identified as being predictive of false negative results. Following that, these two predictors were combined to produce a predictive model. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.945. Furthermore, it demonstrated sensitivity and specificity values of 88.2% and 87.1% respectively. The testing cohort included 62 patients, each of whom had a single PN. When the developed model was used to evaluate this testing cohort, this yielded an AUC value of 0.851. CONCLUSIONS: In patients with PNs, the predictive model developed herein demonstrated good diagnostic effectiveness for identifying false-negative CTB-based non-malignant pathology data.


Assuntos
Biópsia Guiada por Imagem , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Biópsia Guiada por Imagem/métodos , Tomografia Computadorizada por Raios X/métodos , Nódulos Pulmonares Múltiplos/patologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico , Reações Falso-Negativas , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico , Valor Preditivo dos Testes , Adulto
12.
J Cancer Res Clin Oncol ; 150(6): 316, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910204

RESUMO

BACKGROUND: Liver cancer (LC) is a prevalent malignancy and a leading cause of cancer-related mortality worldwide. Extensive research has been conducted to enhance patient outcomes and develop effective prevention strategies, ranging from molecular mechanisms to clinical interventions. Single-cell sequencing, as a novel bioanalysis technology, has significantly contributed to the understanding of the global cognition and dynamic changes in liver cancer. However, there is a lack of bibliometric analysis in this specific research area. Therefore, the objective of this study is to provide a comprehensive overview of the knowledge structure and research hotspots in the field of single-cell sequencing in liver cancer research through the use of bibliometrics. METHOD: Publications related to the application of single-cell sequencing technology to liver cancer research as of December 31, 2023, were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace, and R package "bibliometrix" were used to conduct this bibliometric analysis. RESULTS: A total of 331 publications from 34 countries, primarily led by China and the United States, were included in this study. The research focuses on the application of single cell sequencing technology to liver cancer, and the number of related publications has been increasing year by year. The main research institutions involved in this field are Fudan University, Sun Yat-Sen University, and the Chinese Academy of Sciences. Frontiers in Immunology and Nature Communications is the most popular journal in this field, while Cell is the most frequently co-cited journal. These publications are authored by 2799 individuals, with Fan Jia and Zhou Jian having the most published papers, and Llovet Jm being the most frequently co-cited author. The use of single cell sequencing to explore the immune microenvironment of liver cancer, as well as its implications in immunotherapy and chemotherapy, remains the central focus of this field. The emerging research hotspots are characterized by keywords such as 'Gene-Expression', 'Prognosis', 'Tumor Heterogeneity', 'Immunoregulation', and 'Tumor Immune Microenvironment'. CONCLUSION: This is the first bibliometric study that comprehensively summarizes the research trends and developments on the application of single cell sequencing in liver cancer. The study identifies recent research frontiers and hot directions, providing a valuable reference for researchers exploring the landscape of liver cancer, understanding the composition of the immune microenvironment, and utilizing single-cell sequencing technology to guide and enhance the prognosis of liver cancer patients.


Assuntos
Bibliometria , Neoplasias Hepáticas , Análise de Célula Única , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Análise de Célula Única/métodos
13.
Virology ; 597: 110155, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38943783

RESUMO

The increasing prevalence of drug-resistant Escherichia coli (E. coli) resulting from the excessive utilization of antibiotics necessitates the immediate exploration of alternative approaches to counteract pathogenic E. coli. Phages, with their unique antibacterial mechanisms, are considered promising candidates for treating bacterial infections. Herein, we isolated a lytic Escherichia phage Tequatrovirus YZ2 (phage YZ2), which belongs to the genus Tequatrovirus. The genome of phage YZ2 consists of 168,356 base pairs with a G + C content of 35.34% and 269 putative open reading frames (ORFs). Of these, 146 ORFs have been annotated as functional proteins associated with nucleotide metabolism, structure, transcription, DNA replication, translation, and lysis. In the mouse model of a skin wound infected by E. coli, phage YZ2 therapy significantly promoted the wound healing. Furthermore, histopathological analysis revealed reductions in IL-1ß and TNF-α and increased VEGF levels, indicating the potential of phages as effective antimicrobial agents against E. coli infection.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Genoma Viral , Infecção dos Ferimentos , Animais , Escherichia coli/virologia , Escherichia coli/genética , Camundongos , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/virologia , Infecção dos Ferimentos/tratamento farmacológico , Fases de Leitura Aberta , Colífagos/genética , Colífagos/fisiologia , Terapia por Fagos , Modelos Animais de Doenças , Cicatrização , Composição de Bases , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo
15.
J Am Chem Soc ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875215

RESUMO

We present an efficient one-pot photochemical skeletal editing protocol for the transformation of pyridines into diverse bicyclic pyrazolines and pyrazoles under mild conditions. The method requires no metals, photocatalysts, or additives and allows for the selective removal of specific carbon atoms from pyridines, allowing for unprecedented versatility. Our approach offers a convenient and efficient means for the late-stage modification of complex drug molecules by replacing the core pyridine skeleton. Moreover, we have successfully scaled up this procedure in stop-flow and flow-chemistry systems, showcasing its applicability to intricate transformations such as the Diels-Alder reaction, hydrogenation, [3 + 2] cycloaddition, and Heck reaction. Through control experiments and DFT calculations, we provide insights into the mechanistic underpinnings of this skeletal editing protocol.

16.
Biomed Pharmacother ; 177: 116898, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38878635

RESUMO

Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO) modification is a highly conserved post-translational modification of proteins. They are widely expressed in a variety of tissues, including the heart, liver, kidney and lung. SUMOylation of protein plays a key role in the occurrence and development of liver disease. Therefore, this study reviewed the effects of SUMO protein on non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases to provide novel strategies for targeted treatment of liver disease.

17.
Adv Sci (Weinh) ; : e2305593, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873820

RESUMO

Centromere protein A (CENP-A), a histone H3 variant specific to centromeres, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure-activity relationship (SAR) study of the cell-cycle-arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis reveals that both molecules bind to the colchicine-binding site of ß-tubulin. Treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, results in CENP-A accumulation by destabilizing Cdh1, a co-activator of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.

18.
Cell ; 187(13): 3319-3337.e18, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38810645

RESUMO

The development of perennial crops holds great promise for sustainable agriculture and food security. However, the evolution of the transition between perenniality and annuality is poorly understood. Here, using two Brassicaceae species, Crucihimalaya himalaica and Erysimum nevadense, as polycarpic perennial models, we reveal that the transition from polycarpic perennial to biennial and annual flowering behavior is a continuum determined by the dosage of three closely related MADS-box genes. Diversification of the expression patterns, functional strengths, and combinations of these genes endows species with the potential to adopt various life-history strategies. Remarkably, we find that a single gene among these three is sufficient to convert winter-annual or annual Brassicaceae plants into polycarpic perennial flowering plants. Our work delineates a genetic basis for the evolution of diverse life-history strategies in plants and lays the groundwork for the generation of diverse perennial Brassicaceae crops in the future.


Assuntos
Brassicaceae , Flores , Regulação da Expressão Gênica de Plantas , Brassicaceae/genética , Brassicaceae/fisiologia , Produtos Agrícolas/genética , Flores/genética , Flores/fisiologia , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Fenômenos Fisiológicos Vegetais , Mapeamento Cromossômico , Mutação
19.
J Agric Food Chem ; 72(22): 12832-12841, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38785419

RESUMO

Capsaicin (CAP) is a primary indicator for assessing the level of pungency. Herein, iron-based single-atom nanozymes (SAzymes) (Fe/NC) with exceptional oxidase-like activity were used to construct an immunosensor for CAP analysis. Fe/NC could imitate oxidase actions by transforming O2 to •O2- radicals in the absence of hydrogen peroxide (H2O2), which could avoid complex operations and unstable results. By regulating the Fe atom loads, an optimal Fe0.7/NC atom usage rate could improve the catalytic activity (Michaelis-Menten constant (Km) = 0.09 mM). Fe0.7/NC was integrated with goat antimouse IgG by facile mix incubation to develop a competitive enzyme-linked immunosorbent assay (ELISA). Our Fe0.7/NC immunosensing platform is anticipated to outperform the conventional ELISA in terms of stability and shelf life. The proposed immunosensor provided color responses across 0.01-1000 ng/mL CAP concentrations, with a detection limit of 0.046 ng/mL. Fe/NC may have potential as nanozymes for CAP detection in spicy foods, with promising applications in food biosensing.


Assuntos
Técnicas Biossensoriais , Capsaicina , Capsaicina/análise , Capsaicina/química , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Oxirredutases/química , Ensaio de Imunoadsorção Enzimática/métodos , Ferro/química , Ferro/análise , Limite de Detecção , Peróxido de Hidrogênio/química , Análise de Alimentos/métodos
20.
J Transl Med ; 22(1): 489, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778315

RESUMO

OBJECTIVE: Mild therapeutic hypothermia (MTH) is an important method for perioperative prevention and treatment of myocardial ischemia-reperfusion injury (MIRI). Modifying mitochondrial proteins after protein translation to regulate mitochondrial function is one of the mechanisms for improving myocardial ischemia-reperfusion injury. This study investigated the relationship between shallow hypothermia treatment improving myocardial ischemia-reperfusion injury and the O-GlcNAcylation level of COX10. METHODS: We used in vivo Langendorff model and in vitro hypoxia/reoxygenation (H/R) cell model to investigate the effects of MTH on myocardial ischemia-reperfusion injury. Histological changes, myocardial enzymes, oxidative stress, and mitochondrial structure/function were assessed. Mechanistic studies involved various molecular biology methods such as ELISA, immunoprecipitation (IP), WB, and immunofluorescence. RESULTS: Our research results indicate that MTH upregulates the O-GlcNACylation level of COX10, improves mitochondrial function, and inhibits the expression of ROS to improve myocardial ischemia-reperfusion injury. In vivo, MTH effectively alleviates ischemia-reperfusion induced cardiac dysfunction, myocardial injury, mitochondrial damage, and redox imbalance. In vitro, the OGT inhibitor ALX inhibits the OGT mediated O-GlcNA acylation signaling pathway, downregulates the O-Glc acylation level of COX10, promotes ROS release, and counteracts the protective effect of MTH. On the contrary, the OGA inhibitor ThG showed opposite effects to ALX, further confirming that MTH activated the OGT mediated O-GlcNAcylation signaling pathway to exert cardioprotective effects. CONCLUSIONS: In summary, MTH activates OGT mediated O-glycosylation modified COX10 to regulate mitochondrial function and improve myocardial ischemia-reperfusion injury, which provides important theoretical basis for the clinical application of MTH.


Assuntos
Hipotermia Induzida , Traumatismo por Reperfusão Miocárdica , Regulação para Cima , Animais , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Masculino , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Ratos Sprague-Dawley , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Mitocôndrias/metabolismo , Glicosilação , Acilação
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