Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 481
Filtrar
1.
Plant Cell ; 34(11): 4366-4387, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-35972379

RESUMO

Ethylene plays essential roles in adaptive growth of rice (Oryza sativa). Understanding of the crosstalk between ethylene and auxin (Aux) is limited in rice. Here, from an analysis of the root-specific ethylene-insensitive rice mutant mao hu zi 10 (mhz10), we identified the tryptophan aminotransferase (TAR) MHZ10/OsTAR2, which catalyzes the key step in indole-3-pyruvic acid-dependent Aux biosynthesis. Genetically, OsTAR2 acts downstream of ethylene signaling in root ethylene responses. ETHYLENE INSENSITIVE3 like1 (OsEIL1) directly activated OsTAR2 expression. Surprisingly, ethylene induction of OsTAR2 expression still required the Aux pathway. We also show that Os indole-3-acetic acid (IAA)1/9 and OsIAA21/31 physically interact with OsEIL1 and show promotive and repressive effects on OsEIL1-activated OsTAR2 promoter activity, respectively. These effects likely depend on their EAR motif-mediated histone acetylation/deacetylation modification. The special promoting activity of OsIAA1/9 on OsEIL1 may require both the EAR motifs and the flanking sequences for recruitment of histone acetyltransferase. The repressors OsIAA21/31 exhibit earlier degradation upon ethylene treatment than the activators OsIAA1/9 in a TIR1/AFB-dependent manner, allowing OsEIL1 activation by activators OsIAA1/9 for OsTAR2 expression and signal amplification. This study reveals a positive feedback regulation of ethylene signaling by Aux biosynthesis and highlights the crosstalk between ethylene and Aux pathways at a previously underappreciated level for root growth regulation in rice.


Assuntos
Etilenos , Ácidos Indolacéticos , Oryza , Raízes de Plantas , Triptofano Transaminase , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Triptofano Transaminase/genética , Triptofano Transaminase/metabolismo
2.
New Phytol ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509454

RESUMO

Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear. Here, through analysis of a suppressor for the OsEIN2 over-expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre-mRNA for efficient splicing and stabilization, allowing for subsequent DNG701-mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre-mRNA, leading to transgene silencing. SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000-grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele. Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.

3.
BMC Ophthalmol ; 24(1): 157, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594720

RESUMO

BACKGROUND: Aniridia is a rare eye disorder with a high incidence of glaucoma, and surgical intervention is often needed to control the intraocular pressure (IOP). Here, we reported a case of illuminated microcatheter-assisted circumferential trabeculotomy (MAT) performed on an aniridic glaucoma patient following a previous failed angle surgery. The surgical procedures for aniridic glaucoma were also reviewed. CASE PRESENTATION: A 21-year-old man, diagnosed with aniridic glaucoma, came to our hospital consulting for the poor control of left eye's IOP despite receiving goniotomy surgery 3 years ago. The IOP was 26 mmHg with maximum topical antiglaucoma eyedrops. The central cornea was opaque and the majority of iris was absent. The gonioscopy and ultrasound biomicroscopy (UBM) demonstrated that 360° anterior chamber angle was closed. The whole exome sequencing of peripheral blood confirmed a 13.39 Mb copy number loss at chromosome 11p15.1p13, containing PAX6 and WT1 gene. The 360° MAT surgery was performed on his left eye. At 1-year follow-up, the IOP was 19mmHg with 2 kinds of topical antiglaucoma medications, and the postoperative UBM demonstrated the successful incision of the anterior chamber angle. CONCLUSIONS: The case presented here exhibited a case of aniridic glaucoma treated by MAT surgery. The MAT surgery may be an effective option for IOP control in aniridic glaucoma patients following a previous failed angle surgery.


Assuntos
Aniridia , Glaucoma , Trabeculectomia , Humanos , Masculino , Adulto Jovem , Seguimentos , Glaucoma/diagnóstico , Glaucoma/cirurgia , Gonioscopia , Pressão Intraocular , Fator de Transcrição PAX6 , Estudos Retrospectivos , Trabeculectomia/métodos , Resultado do Tratamento
4.
Nucleic Acids Res ; 50(4): 1829-1848, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35166828

RESUMO

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand-G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.


Assuntos
Antineoplásicos/química , Neoplasias da Mama , Quadruplex G , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Desenho de Fármacos , Feminino , Genes myc , Humanos , Ligantes , Células MCF-7 , Camundongos , Regiões Promotoras Genéticas , Telômero
5.
J Integr Neurosci ; 23(2): 38, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38419449

RESUMO

Perioperative neurocognitive disorders (PND) are a cognitive impairment that occurs after anesthesia, especially in elderly patients and significantly affects their quality of life. The hippocampus, as a critical region for cognitive function and an important location in PND research, has recently attracted increasing attention. However, in the hippocampus the impact of anesthesia and its underlying mechanisms remain unclear. This review focuses on investigation of the effects of anesthesia on the hippocampal dopamine (DA) system and explores its potential association with PND. Through comprehensive review of existing studies, it was found that anesthesia affects the hippocampus through various pathways involved in metabolism, synaptic plasticity and oxygenation. Anesthesia may also influence the DA neurotransmitter system in the brain which plays a role in emotions, rewards, learning and memory functions. Specifically, anesthesia may participate in the pathogenesis of PND by affecting the DA system within the hippocampus. Future studies should explore the molecular mechanisms of these effects through techniques such as neuroimaging to study real-time effects to improve animal models to better simulate clinical observations. For clinical application, it is recommended that physicians exercise caution when selecting and managing anesthetic drugs by adopting comprehensive cognitive assessment methods to reduce post-anesthesia cognitive risk. Overall, this review provides a better understanding of the relationship between the hippocampal DA system and perioperative neurocognitive function and provides valuable guidance for prevention and treatment strategies for PND.


Assuntos
Disfunção Cognitiva , Dopamina , Animais , Humanos , Idoso , Dopamina/metabolismo , Dopamina/farmacologia , Qualidade de Vida , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/patologia , Hipocampo/metabolismo
6.
New Phytol ; 240(6): 2436-2454, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37840365

RESUMO

Seed size and weight are important factors that influence soybean yield. Combining the weighted gene co-expression network analysis (WGCNA) of 45 soybean accessions and gene dynamic changes in seeds at seven developmental stages, we identified candidate genes that may control the seed size/weight. Among these, a PLATZ-type regulator overlapping with 10 seed weight QTLs was further investigated. This zinc-finger transcriptional regulator, named as GmPLATZ, is required for the promotion of seed size and weight in soybean. The GmPLATZ may exert its functions through direct binding to the promoters and activation of the expression of cyclin genes and GmGA20OX for cell proliferation. Overexpression of the GmGA20OX enhanced seed size/weight in soybean. We further found that the GmPLATZ binds to a 32-bp sequence containing a core palindromic element AATGCGCATT. Spacing of the flanking sequences beyond the core element facilitated GmPLATZ binding. An elite haplotype Hap3 was also identified to have higher promoter activity and correlated with higher gene expression and higher seed weight. Orthologues of the GmPLATZ from rice and Arabidopsis play similar roles in seeds. Our study reveals a novel module of GmPLATZ-GmGA20OX/cyclins in regulating seed size and weight and provides valuable targets for breeding of crops with desirable agronomic traits.


Assuntos
Glycine max , Transcriptoma , Glycine max/genética , Transcriptoma/genética , Melhoramento Vegetal , Locos de Características Quantitativas , Sementes/genética
7.
J Med Virol ; 95(1): e28226, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36251738

RESUMO

Host-targeting antivirals (HTAs) have received increasing attention for their potential as broad-spectrum antivirals that pose relatively low risk of developing drug resistance. The repurposing of pharmaceutical drugs for use as antivirals is emerging as a cost- and time- efficient approach to developing HTAs for the treatment of a variety of viral infections. In this study, we used a virus titer method to screen 30 small molecules for antiviral activity against Herpes simplex virus-1 (HSV-1). We found that the small molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of B-RAF V600E, reduced viral loads of HSV-1 by 4 orders of magnitude in Vero cells and reduced virus proliferation in vivo. RAF265 mediated cytoskeleton rearrangement and targeted the host cell's translation machinery, which suggests that the antiviral activity of RAF265 may be attributed to a dual inhibition strategy. This study offers a starting point for further advances toward clinical development of antivirals against HSV-1.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Animais , Chlorocebus aethiops , Humanos , Células Vero , Replicação Viral , Antivirais/farmacologia , Antivirais/uso terapêutico , Citoesqueleto
8.
Plant Cell Environ ; 46(4): 1060-1074, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36397123

RESUMO

Rice is an important food crop in the world and the study of its growth and plasticity has a profound influence on sustainable development. Ethylene modulates multiple agronomic traits of rice as well as abiotic and biotic stresses during its lifecycle. It has diverse roles, depending on the organs, developmental stages and environmental conditions. Compared to Arabidopsis (Arabidopsis thaliana), rice ethylene signalling pathway has its own unique features due to its special semiaquatic living environment and distinct plant structure. Ethylene signalling and responses are part of an intricate network in crosstalk with internal and external factors. This review will summarize the current progress in the mechanisms of ethylene-regulated coleoptile growth in rice, with a special focus on ethylene signaling and interaction with other hormones. Insights into these molecular mechanisms may shed light on ethylene biology and should be beneficial for the genetic improvement of rice and other crops.


Assuntos
Arabidopsis , Oryza , Reguladores de Crescimento de Plantas/metabolismo , Plântula/metabolismo , Oryza/genética , Cotilédone/metabolismo , Etilenos/metabolismo , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas
9.
Plant Cell ; 32(5): 1626-1643, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32184349

RESUMO

Ethylene plays important roles in plant growth and development, but the regulation of ethylene signaling is largely unclear, especially in crops such as rice (Oryza sativa). Here, by analysis of the ethylene-insensitive mutant mao huzi 11 (mhz11), we identified the GDSL lipase MHZ11, which modulates ethylene signaling in rice roots. MHZ11 localized to the endoplasmic reticulum membrane and has acyl-hydrolyzing activity. This activity affects the homeostasis of sterols in rice roots and is required for root ethylene response. MHZ11 overexpression caused constitutive ethylene response in roots. Genetically, MHZ11 acts with the ethylene receptor ETHYLENE RESPONSE SENSOR2 (OsERS2) upstream of CONSTITUTIVE TRIPLE RESPONSE2 (OsCTR2) and ETHYLENE INSENSITIVE2 (OsEIN2). The mhz11 mutant maintains more OsCTR2 in the phosphorylated form whereas MHZ11 overexpression promotes ethylene-mediated inhibition of OsCTR2 phosphorylation. MHZ11 colocalized with the ethylene receptor OsERS2, and its effect on OsCTR2 phosphorylation requires ethylene perception and initiation of ethylene signaling. The mhz11 mutant overaccumulated sterols and blocking sterol biosynthesis partially rescued the mhz11 ethylene response, likely by reducing receptor-OsCTR2 interaction and OsCTR2 phosphorylation. We propose that MHZ11 reduces sterol levels to impair receptor-OsCTR2 interactions and OsCTR2 phosphorylation for triggering ethylene signaling. Our study reveals a mechanism by which MHZ11 participates in ethylene signaling for regulation of root growth in rice.


Assuntos
Etilenos/metabolismo , Lipase/metabolismo , Oryza/metabolismo , Raízes de Plantas/metabolismo , Transdução de Sinais , Retículo Endoplasmático/metabolismo , Genes de Plantas , Hidrólise , Metabolismo dos Lipídeos , Mutação/genética , Oryza/genética , Fenótipo , Fosforilação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Plantas Geneticamente Modificadas
10.
Chemistry ; 29(6): e202203110, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36305483

RESUMO

Azulene, a simple polar polycyclic aromatic hydrocarbon with connected electron donor and acceptor (DA), ignites the hope of designing second-order nonlinear optical (NLO) molecular materials from pure nonpolar carbon nanomaterials. In this work, a butterfly-shaped nanographene (π-DA-π) was designed by incorporating azulene between two coronenes. One more electron in a N atom or one electron fewer in a B atom with respect to a C atom can polarize charge distribution in carbon nanomaterials, and further doping of B and N in the designed butterfly-shaped nanographene changes the system from π-DA-π to D-π-A, leading to strong NLO responses. For example, the largest static first hyperpolarizability even reaches 173.89×10-30  esu per heavy atom. The synergetic role of B, N and azulene in the nanographene is scrutinized, and such a doping strategy is found to provide an effective means for the design of carbon-based functional materials. The strong second-order NLO responses of these butterfly-shaped carbon-based nanographenes under external fields, for example, sum frequency generation and difference frequency generation, could inspire future experimental exploration.

11.
Theor Appl Genet ; 136(8): 169, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37418156

RESUMO

KEY MESSAGE: By integrating QTL mapping, transcriptomics and metabolomics, 138 hub genes were identified in rapeseed root response to aluminum stress and mainly involved in metabolism of lipids, carbohydrates and secondary metabolites. Aluminum (Al) toxicity has become one of the important abiotic stress factors in areas with acid soil, which hinders the absorption of water and nutrients by roots, and consequently retards the growth of crops. A deeper understanding of the stress-response mechanism of Brassica napus may allow us to identify the tolerance gene(s) and use this information in breeding-resistant crop varieties. In this study, a population of 138 recombinant inbred lines (RILs) was subjected to aluminum stress, and QTL (quantitative trait locus) mapping was used to preliminarily locate quantitative trait loci related to aluminum stress. Root tissues from seedlings of an aluminum-resistant (R) line and an aluminum-sensitive (S) line from the RIL population were harvested for transcriptome sequencing and metabolome determination. By combining the data on quantitative trait genes (QTGs), differentially expressed genes (DEGs), and differentially accumulated metabolites (DAMs), key candidate genes related to aluminum tolerance in rapeseed were determined. The results showed that there were 3186 QTGs in the RIL population, 14,232 DEGs and 457 DAMs in the comparison between R and S lines. Lastly, 138 hub genes were selected to have a strong positive or negative correlation with 30 important metabolites (|R|≥ 0.95). These genes were mainly involved in the metabolism of lipids, carbohydrates and secondary metabolites in response to Al toxicity stress. In summary, this study provides an effective method for screening key genes by combining QTLs, transcriptome sequencing and metabolomic analysis, but also lists key genes for exploring the molecular mechanism of Al tolerance in rapeseed seedling roots.


Assuntos
Brassica napus , Brassica rapa , Plântula/genética , Brassica napus/genética , Transcriptoma , Alumínio/toxicidade , Melhoramento Vegetal , Metabolômica , Brassica rapa/genética , Lipídeos
12.
J Cardiovasc Pharmacol ; 82(2): 148-156, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37295072

RESUMO

PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Ticagrelor/efeitos adversos , Aspirina , Inibidores da Agregação Plaquetária , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , População do Leste Asiático , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Ácido Salicílico/uso terapêutico , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento
13.
Phys Chem Chem Phys ; 25(45): 31481-31492, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37962477

RESUMO

Push-pull π-conjugated molecules are one of the paradigms of second order nonlinear optical (NLO) materials and have been extensively explored. However, high-performance second order NLO materials with an optimum electron donor (D), π-bridge (π) and acceptor (A) under this paradigm are still the most sought-after. In the present work, D-π-A molecules with optimal D, π and A combination for strong second order NLO properties are proposed based on molecular orbital theories. The optimal D-π-A push-pull molecule achieves an unprecedentedly strong NLO response under the D-π-A paradigm, i.e., the static first hyperpolarizability reaches -453.92 × 10-30 esu per heavy atom using azulene as part of the π-bridge and acceptor to synergistically reinforce the strength of the acceptor. The protocols of D-π-A NLO molecule design through frontier molecular orbital matching of D, π and A with optimal combination of electron donating and accepting strengths shed light on future molecular NLO materials exploration. The simulated two-dimensional second order spectra provide useful information (e.g., sum frequency generation) on the applications of those D-π-A push-pull molecules in nonlinear optics.

14.
Bioorg Chem ; 130: 106275, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36410113

RESUMO

Thirty-three (N-aryl-N-arylsulfonyl)aminoacetohydroxamic acids were synthesized in an effort to develop novel urease inhibitors. Among these compounds, 2-(N-(3-nitrophenyl)-N-(4-tert-butylphenylsulfonyl))aminoacetohydroxamic acid (e2) exhibited excellent inhibitory activity against Helicobacter pylori urease with no perceptible cytotoxicity to mammalian cells. Compound e2 showed over 690-fold higher potency than the clinical used urease inhibitor acetohydroxamic acid, reversibly inhibiting urease with a mixed mechanism. Molecular modeling revealed that (N-aryl-N-arylsulfonyl)aminoacetohydroxamic acids may possibly bind Ni ions and two hydrophobic regions with a 'Y'-like shape.


Assuntos
Helicobacter pylori , Urease , Animais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Modelos Moleculares , Antibacterianos/farmacologia , Mamíferos/metabolismo
15.
Acta Pharmacol Sin ; 44(2): 446-453, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35896694

RESUMO

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.


Assuntos
Medicamentos Biossimilares , Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Medicamentos Biossimilares/efeitos adversos , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea , Denosumab/uso terapêutico , Denosumab/farmacologia , Método Duplo-Cego , População do Leste Asiático , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Pós-Menopausa
16.
J Integr Plant Biol ; 65(7): 1636-1650, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36866859

RESUMO

Abiotic stress is one of the most important factors reducing soybean yield. It is essential to identify regulatory factors contributing to stress responses. A previous study found that the tandem CCCH zinc-finger protein GmZF351 is an oil level regulator. In this study, we discovered that the GmZF351 gene is induced by stress and that the overexpression of GmZF351 confers stress tolerance to transgenic soybean. GmZF351 directly regulates the expression of GmCIPK9 and GmSnRK, leading to stomata closing, by binding to their promoter regions, which carry two CT(G/C)(T/A)AA elements. Stress induction of GmZF351 is mediated through reduction in the H3K27me3 level at the GmZF351 locus. Two JMJ30-demethylase-like genes, GmJMJ30-1 and GmJMJ30-2, are involved in this demethylation process. Overexpression of GmJMJ30-1/2 in transgenic hairy roots enhances GmZF351 expression mediated by histone demethylation and confers stress tolerance to soybean. Yield-related agronomic traits were evaluated in stable GmZF351-transgenic plants under mild drought stress conditions. Our study reveals a new mode of GmJMJ30-GmZF351 action in stress tolerance, in addition to that of GmZF351 in oil accumulation. Manipulation of the components in this pathway is expected to improve soybean traits and adaptation under unfavorable environments.


Assuntos
Secas , Glycine max , Glycine max/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cloreto de Sódio/farmacologia , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico , Zinco/metabolismo , Regulação da Expressão Gênica de Plantas
17.
J Integr Plant Biol ; 65(8): 1983-2000, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37066995

RESUMO

Seed weight is usually associated with seed size and is one of the important agronomic traits that determine yield. Understanding of seed weight control is limited, especially in soybean plants. Here we show that Glycine max JASMONATE-ZIM DOMAIN 3 (GmJAZ3), a gene identified through gene co-expression network analysis, regulates seed-related traits in soybean. Overexpression of GmJAZ3 promotes seed size/weight and other organ sizes in stable transgenic soybean plants likely by increasing cell proliferation. GmJAZ3 interacted with both G. max RESPONSE REGULATOR 18a (GmRR18a) and GmMYC2a to inhibit their transcriptional activation of cytokinin oxidase gene G. max CYTOKININ OXIDASE 3-4 (GmCKX3-4), which usually affects seed traits. Meanwhile, the GmRR18a binds to the promoter of GmMYC2a and activates GmMYC2a gene expression. In GmJAZ3-overexpressing soybean seeds, the protein contents were increased while the fatty acid contents were reduced compared to those in the control seeds, indicating that the GmJAZ3 affects seed size/weight and compositions. Natural variation in JAZ3 promoter region was further analyzed and Hap3 promoter correlates with higher promoter activity, higher gene expression and higher seed weight. The Hap3 promoter may be selected and fixed during soybean domestication. JAZ3 orthologs from other plants/crops may also control seed size and weight. Taken together, our study reveals a novel molecular module GmJAZ3-GmRR18a/GmMYC2a-GmCKXs for seed size and weight control, providing promising targets during soybean molecular breeding for better seed traits.


Assuntos
Glycine max , Sementes , Glycine max/metabolismo , Fenótipo , Sementes/genética , Sementes/metabolismo , Perfilação da Expressão Gênica , Ácidos Graxos/metabolismo
18.
Cancer Sci ; 113(2): 733-743, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34859546

RESUMO

Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer-caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel could be an effective strategy for inhibiting breast cancer metastasis. However, their inherent defects, in terms of short blood circulation half-life and lack of tumor targeting, not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by a nanodelivery system, and explore its mechanism. Herein, a paclitaxel-conjugated and mifepristone-loaded hydrogel (PM-nano) was prepared by self-assembly. Its characterizations were studied. The antimetastatic effect was evaluated in vitro and in vivo and its mechanism was also explored by western blot assay. The resultant PM-nano was developed with favorable water solubility and good biocompatibility. Moreover, PM-nano displayed increased cell uptake properties and stimulated drug release in the tumor micro-acidic environment. The PM-nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. The PM-nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase-like orphan receptor 1 and MMPs. Taken together, PM-nano showed superior antimetastatic effects against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for limiting metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hidrogéis/uso terapêutico , Mifepristona/uso terapêutico , Paclitaxel/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Disponibilidade Biológica , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Portadores de Fármacos/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Mifepristona/química , Mifepristona/farmacologia , Nanoestruturas/uso terapêutico , Paclitaxel/química , Paclitaxel/farmacologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Opt Express ; 30(22): 40712-40727, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36299001

RESUMO

We investigate the propagation and interaction dynamics of the optical dark bound solitons for the defocusing Lakshmanan-Porsezian-Daniel equation, which is a physically relevant generalization of the nonlinear Schrödinger equation involving the higher-order effects. Explicit N-dark soliton solutions in the compact determinant form are constructed via the binary Darboux transformation method. Bound states of the dark solitons are discussed when the incoherent solitons have the same velocity. We find an interesting phenomenon that dark soliton molecules and double-valley dark solitons (DVDSs) can be obtained by controlling the interval of the bound state dark solitons, and abundant interaction modalities between them can be formed. Moreover, dark soliton molecules always undergo elastic interactions with other solitons, while interactions for the DVDSs are usually inelastic, and special parameter conditions for elastic interaction of DVDSs through asymptotic analysis are obtained. Numerical simulations are employed to verify the stability of the bound state dark solitons. Analytical results obtained in this paper are expected to be useful for the experimental realization of bound-state dark solitons in optical fibers with higher-order effects and a further understanding of their optical transmission properties..

20.
Genome ; 65(8): 443-457, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849843

RESUMO

Aquilaria sinensis is an important non-timber tree species for producing high-value agarwood, which is widely used as a traditional medicine and incense. Agarwood is the product of Aquilaria trees in response to injury and fungal infection. The APETALA2/ethylene responsive factor (AP2/ERF) transcription factors (TFs) play important roles in plant stress responses and metabolite biosynthesis. In this study, 119 AsAP2/ERF genes were identified from the A. sinensis genome and divided into ERF, AP2, RAV, and Soloist subfamilies. Their conserved motif, gene structure, chromosomal localization, and subcellular localization were characterized. A stress/defense-related ERF-associated amphiphilic repression (EAR) motif and an EDLL motif were identified. Moreover, 11 genes that were highly expressed in the agarwood layer in response to whole-tree agarwood induction technique (Agar-Wit) treatment were chosen, and their expression levels in response to methyl jasmonate (MeJA), salicylic acid (SA), or salt treatment were further analyzed using the quantitative real time PCR (qRT-PCR). Among the 11 genes, eight belonged to subgroup B-3. All 11 genes were significantly upregulated under salt treatment, while eight genes were significantly induced by both MeJA and SA. In addition, the gene clusters containing these upregulated genes on chromosomes were observed. The results obtained from this research not only provide useful information for understanding the functions of AP2/ERF genes in A. sinensis but also identify candidate genes and gene clusters to dissect their regulatory roles in agarwood formation for future research.


Assuntos
Regulação da Expressão Gênica de Plantas , Thymelaeaceae , Etilenos , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Thymelaeaceae/genética , Thymelaeaceae/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA