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1.
Neoplasma ; 71(3): 279-288, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38958715

RESUMO

Osteosarcoma (OS) is a common primary bone tumor in children and adolescents. Circular RNA (circRNA)-IARS acts as an oncogene in multiple human tumors. However, the circ-IARS function in OS is unclear. This research aimed to elucidate the roles and mechanisms of circ-IARS in OS. In this study, circ-IARS expressions were raised in OS tissues and cells. circ-IARS expressions were closely related to clinical stage and distant metastasis. Furthermore, overall survival rates were reduced in OS patients with high circ-IARS levels. Also, silencing circ-IARS weakened OS cell proliferation and invasion, yet enhanced cell ferroptosis. Mechanistically, circ-IARS targeted miR-188-5p to regulate RAB14 expressions in OS cells. Moreover, circ-IARS knockdown repressed OS cell proliferation, invasion, and induced ferroptosis, yet these impacts were abolished by co-transfection with anti-miR-188-5p or pcDNA-RAB14. Meanwhile, interference with circ-IARS reduced OS cell proliferation, and decreased RAB14 (a member of the RAS oncogene family), GPX4, and xCT (crucial ferroptosis regulators) expressions in vivo. In conclusion, circ-IARS facilitated OS progression via miR-188-5p/RAB14.


Assuntos
Neoplasias Ósseas , Proliferação de Células , Ferroptose , MicroRNAs , Osteossarcoma , RNA Circular , Proteínas rab de Ligação ao GTP , Humanos , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/metabolismo , MicroRNAs/genética , RNA Circular/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo , Ferroptose/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Masculino , Linhagem Celular Tumoral , Feminino , Progressão da Doença , Camundongos , Animais , Regulação Neoplásica da Expressão Gênica
2.
Plant Physiol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976569

RESUMO

Temperature is one of the key environmental factors influencing crop fertility and yield. Understanding how plants sense and respond to temperature changes is, therefore, crucial for improving agricultural production. In this study, we characterized a temperature-sensitive male-sterile mutant in rice (Oryza sativa), glutamyl-tRNA synthetase 1-2 (ers1-2), that shows reduced fertility at high temperatures and restored fertility at low temperatures. Mutation of ERS1 resulted in severely delayed pollen development and meiotic progression at high temperatures, eventually leading to male sterility. Moreover, meiosis-specific events, including synapsis and crossover formation, were also delayed in ers1-2 compared with the wild type. However, these defects were all mitigated by growing ers1-2 at low temperatures. Transcriptome analysis and measurement of ascorbate, glutathione, and hydrogen peroxide (H2O2) contents revealed that the delayed meiotic progression and male sterility in ers1-2 were strongly associated with changes in reactive oxygen species (ROS) homeostasis. At high temperatures, ers1-2 exhibited decreased accumulation of ROS scavengers and overaccumulation of ROS. In contrast, at low temperatures, the antioxidant system of ROS was more active, and ROS contents were lower. These data suggest that ROS homeostasis in ers1-2 is disrupted at high temperatures but restored at low temperatures. We speculate that ERS1 dysfunction leads to changes in ROS homeostasis under different conditions, resulting in delayed or rescued meiotic progression and thermosensitive male fertility. ers1-2 may hold great potential as a thermosensitive material for crop heterosis breeding.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 693-701, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38926955

RESUMO

OBJECTIVE: To analyze the factors affecting overall survival (OS) of adult patients with core-binding factor acute myeloid leukemia (CBF-AML) and establish a prediction model. METHODS: A total of 216 newly diagnosed patients with CBF-AML in the First Affiliated Hospital of Zhengzhou University from May 2015 to July 2021 were retrospectively analyzed. The 216 CBF-AML patients were divided into the training and the validation cohort at 7∶3 ratio. The Cox regression model was used to analyze the clinical factors affecting OS. Stepwise regression was used to establish the optimal model and the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the model performance. RESULTS: Age(≥55 years old), peripheral blood blast(≥80%), fusion gene (AML1-ETO), KIT mutations were identified as independent adverse factors for OS. The area under the ROC curve at 3-year was 0.772 and 0.722 in the training cohort and validation cohort, respectively. The predicted value of the calibration curve is in good agreement with the measured value. DCA shows that this model performs better than a single factor. CONCLUSION: This prediction model is simple and feasible, and can effectively predict the OS of CBF-AML, and provide a basis for treatment decision.


Assuntos
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Masculino , Mutação , Curva ROC , Fatores de Ligação ao Core/genética , Nomogramas , Adulto , Proteína 1 Parceira de Translocação de RUNX1/genética , Proteínas Proto-Oncogênicas c-kit/genética , Modelos de Riscos Proporcionais , Proteínas de Fusão Oncogênica/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética
4.
Elife ; 132024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864853

RESUMO

Cohesin is a multi-subunit protein that plays a pivotal role in holding sister chromatids together during cell division. Sister chromatid cohesion 3 (SCC3), constituents of cohesin complex, is highly conserved from yeast to mammals. Since the deletion of individual cohesin subunit always causes lethality, it is difficult to dissect its biological function in both mitosis and meiosis. Here, we obtained scc3 weak mutants using CRISPR-Cas9 system to explore its function during rice mitosis and meiosis. The scc3 weak mutants displayed obvious vegetative defects and complete sterility, underscoring the essential roles of SCC3 in both mitosis and meiosis. SCC3 is localized on chromatin from interphase to prometaphase in mitosis. However, in meiosis, SCC3 acts as an axial element during early prophase I and subsequently situates onto centromeric regions following the disassembly of the synaptonemal complex. The loading of SCC3 onto meiotic chromosomes depends on REC8. scc3 shows severe defects in homologous pairing and synapsis. Consequently, SCC3 functions as an axial element that is essential for maintaining homologous chromosome pairing and synapsis during meiosis.


Assuntos
Proteínas de Ciclo Celular , Proteínas Cromossômicas não Histona , Pareamento Cromossômico , Meiose , Oryza , Meiose/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Oryza/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Coesinas , Mitose , Complexo Sinaptonêmico/metabolismo , Complexo Sinaptonêmico/genética , Sistemas CRISPR-Cas
5.
J Phys Chem Lett ; 15(23): 6216-6221, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38838259

RESUMO

Heterogeneous metal-nitrogen-carbon (M-N-C) single-atom catalysts (SACs) have garnered considerable attention in the two-electron CO2 reduction reaction (2e-CO2RR). Interestingly, almost M-N-C SACs mainly produce CO, while Sb is one of the few SACs reported so far that can produce HCOOH. Nevertheless, the underlying factors for different selectivities on Sb-N-C SAC remain controversial, and the lack of in-depth understanding of limiting factors hampers further regulations. Here, by using constant-potential first-principles calculations, we revealed that the high HCOOH selectivity of Sb-N-C SAC is mainly attributed to their weak charge accumulation ability. Remarkably, considering the highly tunable geometric structure of M-N-C SACs, we provide that Sb-N-C SAC with the SbN3S1 center is a promising candidate for CO production. Our work provides the mechanism insight into 2e-CO2RR selectivity and further paves the way toward electrocatalyst regulation and design.

6.
Front Microbiol ; 15: 1374910, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765678

RESUMO

Drug combinations and repurposing have recently provided promising alternatives to cope with the increasingly severe issue of antibiotic resistance and depletion of natural drug molecular repertoires that undermine traditional antibacterial strategies. Closantel, an effective adjuvant, reverses antibiotic resistance in gram-negative bacteria. Herein, the combined antibacterial enantioselectivity of closantel is presented through separate enantiomer studies. Despite yielding unexpected differences, two closantel enantiomers (R, S) increased colistin activity against gram-negative bacteria both in vitro and in vivo. The fractional inhibitory concentration indices of R-closantel and S-closantel combined with colistin against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli ranged from 0.0087 to 0.5004 and from 0.0117 to 0.5312, respectively. This difference was further demonstrated using growth inhibition assays and time-killing curves. Mechanistically, a higher intracellular concentration of R-CLO is more effective in enhancing the antimicrobial activity of combination. A mouse cutaneous infection model confirmed the synergistic stereoselectivity of closantel. This discovery provides novel insights for developing precision medication and containment of increasing antibiotic resistance.

7.
J Inorg Biochem ; 257: 112615, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38772187

RESUMO

A series of bis-naphthyl ferrocene derivatives were synthesized and characterized. Based on the results obtained from UV-visible absorption titration and ethidium bromide (EB) displacement experiments, it was observed that the synthesized compounds exhibited a strong binding ability to dsDNA. In comparison to the viscosity curve of EB, the tested compounds demonstrated a bisintercalation binding mode when interacting with CT-DNA. Differential pulse voltammetry (DPV) was employed to assess the binding specificity of these indicators towards ssDNA and dsDNA. All tested indicators displayed more pronounced signal differences before and after hybridization between probe nucleic acids and target nucleic acids compared to Methylene Blue (MB). Among the evaluated compounds, compound 3j containing an ether chain showed superior performance as an indicator, making it suitable for constructing DNA-based biosensors. Under optimized conditions including probe ssDNA concentration and indicator concentration, this biosensor exhibited good sensitivity, reproducibility, stability, and selectivity. The limit of detection was calculated as 4.53 × 10-11 mol/L. Furthermore, when utilizing 3j as the indicator in serum samples, the biosensor achieved satisfactory recovery rates for detecting the BRCA1 gene.


Assuntos
Técnicas Biossensoriais , DNA , Compostos Ferrosos , Metalocenos , Compostos Ferrosos/química , Técnicas Biossensoriais/métodos , Metalocenos/química , DNA/química , Técnicas Eletroquímicas/métodos , Humanos , DNA de Cadeia Simples/química
8.
Angew Chem Int Ed Engl ; : e202407339, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714494

RESUMO

Two-electron oxidative addition is one of the most important elementary reactions for d-block transition metals but it is uncommon for f-block elements. Here, we report the first examples of intermolecular oxidative addition of E-H (E=C, N) bonds to uranium(II) centers. The transient U(II) species was formed in-situ by reducing a heterometallic cluster featuring U(IV)-Pd(0) bonds with potassium-graphite (KC8). Oxidative addition of C-H or N-H bonds to the U(II) centers was observed when this transient U(II) species was treated with benzene, carbazole or 1-adamantylamine, respectively. The U(II) centers could also react with tetracene, biphenylene or N2O, leading to the formation of arene reduced U(IV) products and uranyl(VI) species via two- or four-electron processes. This study demonstrates that the intermolecular two-electron oxidative addition reactions are viable for actinide elements.

9.
J Am Chem Soc ; 146(22): 14954-14958, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38804682

RESUMO

Copper (Cu) single-atom catalysts (SACs) exhibit great potential for generating multicarbon (C2+) products, but the intrinsic activity of single-atom Cu (Cu1) under realistic conditions remains controversial. Herein, we perform extensive calculations with explicit solvation to investigate the underlying mechanism of Cu SACs, disclosing the absence of C2+ activity in Cu1 sites regardless of the different substrates. The original Cu1 sites (first taking Cu1 stably anchored on carbon nitride as an example) cannot facilitate *CO hydrogenation and CO-CO coupling due to the lack of active sites nearby, and they are unstable under operation, causing leaching and aggregation to form small Cu clusters. The derived Cu clusters composed of at least three Cu atoms can efficiently promote CO-CO coupling, as revealed by kinetic analyses. We extend the modeling to other typical Cu SACs and reveal that all of the Cu1 sites are inactive, while the C2+ performance of the derived Cu-cluster catalysts is substrate-dependent. This study offers mechanistic insights into Cu SACs and provides practical guidance for their rational optimization.

10.
Cardiovasc Diabetol ; 23(1): 164, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724987

RESUMO

Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.


Assuntos
Cardiomiopatias Diabéticas , Dinaminas , Células Endoteliais , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Células Cultivadas , Circulação Coronária , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/enzimologia , Cardiomiopatias Diabéticas/etiologia , Modelos Animais de Doenças , Dinaminas/metabolismo , Dinaminas/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Endoteliais/enzimologia , Células Endoteliais/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Mitocôndrias Cardíacas/enzimologia , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética
11.
J Ethnopharmacol ; 332: 118375, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38789094

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The quality control methods of different specifications of Corydalis Rhizoma in Zhejiang China (ZJ CR) are the same, so the quality of each specification couldnot be guaranteed. To clarify the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications could provide reference for the quality control of ZJ CR. AIM OF THE STUDY: The purpose of this study was to establish a quality control method for ZJ CR with different specifications and to screen out the pharmacodynamic material basis of ZJ CR with different specifications. MATERIALS AND METHODS: Firstly, according to the existing grading standards, the medicinal materials were divided into specifications, and the character indexes of ZJ CR with different specifications were established. The quality indexes were established by HPLC, network pharmacology and literature retrieval. The correlation between the trait indexes and quality indexes of ZJ CR with different specifications was analyzed, and the best quality control method was established. Further combined with the pharmacodynamic indexes of ZJ CR with different specifications, the pharmacodynamic material basis of ZJ CR with different specifications was screened out by spectrum-effect analysis. The correlation between trait indexes and pharmacodynamic indexes was analyzed to verify the rationality of grade standard. RESULTS: The three specifications of ZJ CR were CR (Diameter ≥1.1 cm), CR (Diameter <1.1 cm), and CR (No size distinction). Diameter, width, thickness, grain weight, volume and 50 g grain number could be used as the trait indexes of ZJ CR. Protopine (CR1), palmatine hydrochloride (CR2), berberine hydrochloride (CR3), dehydrocorydaline (CR4), tetrahydropalmatine (CR5), tetrahydroberberine (CR6), corydaline (CR7), stylopine (CR8) and isoimperatorin (CR9) were identified. Total components, core components (CR5, CR6, CR7 and CR8), alcohol-soluble extracts (ASE) could be used as quality indexes. The best quality control methods of the three specifications respectively were: the larger the diameter and grain weight, the smaller the number of 50 g grains; The larger the diameter, the smaller the volume, thickness, width and number of 50 g particles; The larger the grain weight and volume, the smaller the number of 50 g grains. The main analgesic components of the three specifications respectively were: CR1, CR2 and core components; CR2, CR4; CR8, CR9. The larger the diameter and the less the number of 50 g grains, the better the analgesic effect of ZJ CR, and the grade standard was reasonable. CONCLUSIONS: This study showed that the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications were different, which may be caused by the differences in traits and the contribution of main active ingredients. This study constructed an evaluation model combining external traits, internal quality and overall efficacy, and provided theoretical support for the rationality of ZJ CR grade standard.


Assuntos
Corydalis , Medicamentos de Ervas Chinesas , Controle de Qualidade , Rizoma , Corydalis/química , Rizoma/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Medicamentos de Ervas Chinesas/farmacologia , China , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/análise , Animais , Cromatografia Líquida de Alta Pressão
12.
Talanta ; 276: 126274, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38788379

RESUMO

A novel electrochemical biosensor was developed for the detection of epinephrine (EP) by immobilizing double-strand DNA (dsDNA) bound with copper ions on a gold electrode (Cu2+/dsDNA/MCH/AuE). The electrochemical behavior of EP at Cu2+/dsDNA/MCH/AuE was examined, and the results demonstrated a significant enhancement in the electrocatalytic oxidation peak current of EP due to the formation of a stable G-Cu(II)-G sandwich structure between Cu2+ and guanine at the modified electrode. The modification process of the electrode was characterized by scanning electron microscopy, infrared spectroscopy, electrochemical impedance spectroscopy, and differential pulse voltammetry. A study on the effect of pH in phosphate buffer solution on the electrochemical oxidation of EP indicated that the catalytic oxidation process was pH-dependent. A plot of catalytic current versus EP concentration exhibited a dual-linear relationship within two ranges: 1.0-12.5 µM and 12.5-1000.0 µM, with correlation coefficients of 0.995 and 0.997, respectively. The limit of detection was determined to be 47 nM (S/N = 3). According to the calculated Hill coefficient (0.99), it can be concluded that the electrocatalytic process followed the Michaelis-Menten kinetic mechanism. The maximum catalytic current Im was 25 µA, while the apparent Michaelis-Menten constant Km was 1.425 mM. These findings indicated excellent electrocatalytic activity of the modified electrode towards oxidation of EP. The developed biosensor successfully detected EP in spiked mouse serum as well as epinephrine hydrochloride injection with high selectivity, sensitivity, stability, and accuracy.


Assuntos
Técnicas Biossensoriais , Cobre , DNA , Técnicas Eletroquímicas , Eletrodos , Epinefrina , Ouro , Epinefrina/análise , Epinefrina/sangue , Cobre/química , Técnicas Biossensoriais/métodos , DNA/química , Técnicas Eletroquímicas/métodos , Ouro/química , Limite de Detecção , Animais , Oxirredução , Concentração de Íons de Hidrogênio
13.
Phys Chem Chem Phys ; 26(21): 15120-15124, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38752288

RESUMO

Covalent organic frameworks (COFs) exhibit great potential for electrocatalysis. Here, using DFT calculations and constant-potential modelling, we report the feasibility of a series of COFs toward NO reduction via regulating their central metal atoms and linking ligands. A COF with single-atom Mn is identified to possess superior activity while maintaining high NH3 selectivity.

14.
Ecotoxicol Environ Saf ; 278: 116354, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691882

RESUMO

After the resumption of work and production following the COVID-19 pandemic, many cities entered a "transition phase", characterized by the gradual recovery of emission levels from various sources. Although the overall PM2.5 emission trends have recovered, the specific changes in different sources of PM2.5 remain unclear. Here, we investigated the changes in source contributions and the evolution pattern of pollution episodes (PE) in Wuhan during the "transition period" and compared them with the same period during the COVID-19 lockdown. We found that vehicle emissions, industrial processes, and road dust exhibited significant recoveries during the transition period, increasing by 5.4%, 4.8%, and 3.9%, respectively, during the PE. As primary emissions increased, secondary formation slightly declined, but it still played a predominant role (accounting for 39.1∼ 43.0% of secondary nitrate). The reduction in industrial activities was partially offset by residential burning. The evolution characteristics of PE exhibited significant differences between the two periods, with PM2.5 concentration persisting at a high level during the transition period. The differences in the evolution patterns of the two periods were also reflected in their change rates at each stage, which mostly depend on the pre-PE concentration level. The transition period shows a significantly higher value (8.4 µg m-3 h-1) compared with the lockdown period, almost double the amount. In addition to local emissions, regional transport should be a key consideration in pollution mitigation strategies, especially in areas adjacent to Wuhan. Our study quantifies the variations in sources between the two periods, providing valuable insights for optimizing environmental planning to achieve established goals.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Cidades , Monitoramento Ambiental , Material Particulado , China/epidemiologia , COVID-19/epidemiologia , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Material Particulado/análise , Humanos , Emissões de Veículos/análise , SARS-CoV-2 , Indústrias , Pandemias
15.
Biomed Chromatogr ; 38(7): e5870, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38664069

RESUMO

Spleen deficiency can lead to various abnormal physiological functions of the spleen. Atractylodis Macrocephalae Rhizoma (AMR) is a traditional Chinese medicine used to invigorate the spleen and tonify qi. The study aimed to identify the primary active components influencing the efficacy of AMR in strengthening the spleen and replenishing qi through spectrum-effect relationship and chemometrics. Network pharmacology was used to investigate the mechanism by which AMR strengthens the spleen and replenishes qi, with molecular docking utilized for validation purposes. The findings indicated that bran-fried AMR exhibited superior efficacy, with atractylenolides and atractylone identified as the primary active constituents. Atractylenolide II emerged as the most influential component impacting the effectiveness of AMR, while the key target was androgen receptor. Furthermore, crucial pathways implicated included the mitogen-activated protein cascade (MAPK) cascade, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, and RNA polymerase II sequence-specific DNA-binding transcription factor binding. In summary, our study has identified the primary active components associated with the efficacy of AMR and has provided an initial exploration of its mechanism of action. This offers a theoretical foundation for future investigations into the material basis and molecular mechanisms underlying the pharmacodynamics of AMR.


Assuntos
Atractylodes , Medicamentos de Ervas Chinesas , Lactonas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Sesquiterpenos , Baço , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Animais , Atractylodes/química , Lactonas/química , Lactonas/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Baço/efeitos dos fármacos , Baço/metabolismo , Rizoma/química , Masculino
16.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 196-201, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678606

RESUMO

The superiority of drug-coated balloon (DCB) in treating small vessels, branching lesions, and high-risk bleeding lesions in coronary heart disease patients has been confirmed. However, its safety and efficacy in large vessels are still unclear. We aimed to investigate whether the efficacy of DCB in large vessels is not inferior to that of drug-eluting stent (DES). From November 2019 to April 2022, a total of 88 patients in our hospital who underwent coronary angiography for the first time and decided to receive DCB or DES treatment were selected. Indicators including late lumen loss (LLL), major adverse cardiovascular event (MACE) rate, major bleeding and all-cause mortality were evaluated at 9 months and 1-year post percutaneous coronary intervention (PCI) therapy. The primary endpoint of 9-month LLL was -0.07 in the DCB group and 0.19 mm in the DES group (p value<0.001). 1-year cumulative MACE rates were similar in the DCB and DES groups (3.03% vs. 7.23%, P=0.519), TLR rates were similar (3.03% vs. 7.23%, P=0.519), Major bleeding was similar (3.03% vs. 5.45%, P=0.580), and 1 case of Cardiac death in DES group. For LLL, the DCB-only strategy was non-inferior to DES in treating de novo large lesions in the coronary arteries. Furthermore, the efficacy of DCB was comparable to DES at 1 year of follow-up for secondary clinical endpoints.


Assuntos
Angioplastia Coronária com Balão , Angiografia Coronária , Doença da Artéria Coronariana , Vasos Coronários , Stents Farmacológicos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Stents Farmacológicos/efeitos adversos , Angioplastia Coronária com Balão/métodos , Angioplastia Coronária com Balão/efeitos adversos , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico por imagem , Idoso , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento , Hemorragia/etiologia
17.
Cancer Med ; 13(7): e7129, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618967

RESUMO

BACKGROUND: The RNA-binding motif single-stranded interacting protein 3 (RBMS3) is a constituent of the RNA-binding motif (RBM) protein family, which assumes a pivotal role in governing cellular biogenesis processes such as the cell cycle and apoptosis. Despite an abundance of studies elucidating RBMS3's divergent roles in the genesis and advancement of various tumors, its involvement in colon cancer remains enigmatic. METHODS: The present investigation employed data analysis from TCGA and GTEx to unveil that RBMS3 expression demonstrated a diminished presence in colon cancer tissues when juxtaposed with normal colon tissues. The effect of RBMS3 and LIM zinc finger domain 1 (LIMS1) on colon cancer was substantiated via animal models and cellular experiments. The connection between RBMS3 and LIM zinc finger domain 1 (LIMS1) was verified by molecular biology methods. RESULTS: The study conclusively ascertained that augmenting RBMS3 expression quells the proliferation, migration, and invasion of colon cancer cells. Furthermore, the inquiry unveiled a plausible mechanism through which RBMS3 impacts the expression of LIMS1 by modulating its mRNA stability. The investigation ascertained that RBMS3 inhibits the progression of colon cancer by regulating LIMS1. The inhibitory function of LIMS1 and RBMS3 is closely intertwined in colon cancer, with knocking down LIMS1 being able to rescue the inhibitory effect of RBMS3 overexpression on the functionality of colon cancer cell CONCLUSIONS: The discernments delineate RBMS3 as a novel suppressor of cancer via LIMS1, thereby bestowing fresh therapeutic possibilities and illuminating the intricacies of colon cancer.


Assuntos
Neoplasias do Colo , Animais , Apoptose , Ciclo Celular/genética , Neoplasias do Colo/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Humanos
18.
J Org Chem ; 89(8): 5871-5877, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38595315

RESUMO

A palladium-catalyzed iodine-assisted carbonylation reaction of indoles with readily available ClCF2CO2Na and alcohols has been developed. This protocol provides a practical and efficient approach to highly regioselective indole-3-carboxylates via a preiodination strategy of indoles. Different from classic carbonylation using toxic and difficult-to-handle carbon monoxide, this operationally simple and scalable reaction employed difluorocarbene as the carbonyl surrogate.

19.
Plant Commun ; 5(6): 100857, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38433446

RESUMO

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.


Assuntos
Meiose , Mitose , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Meiose/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Citocininas/metabolismo
20.
Plant J ; 118(6): 1872-1888, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38481350

RESUMO

As a plant-specific transcription factor, lateral organ boundaries domain (LBD) protein was reported to regulate plant growth and stress response, but the functional research of subfamily II genes is limited. SlMYC2, a master regulator of Jasmonic acid response, has been found to exhibit high expression levels in fruit and has been implicated in the regulation of fruit ripening and resistance to Botrytis. However, its role in fruit expansion remains unknown. In this study, we present evidence that a subfamily II member of LBD, namely SlLBD40, collaborates with SlMYC2 in the regulation of fruit expansion. Overexpression of SlLBD40 significantly promoted fruit growth by promoting mesocarp cell expansion, while knockout of SlLBD40 showed the opposite result. Similarly, SlMYC2 knockout resulted in a significant decrease in cell expansion within the fruit. Genetic analysis indicated that SlLBD40-mediated cell expansion depends on the expression of SlMYC2. SlLBD40 bound to the promoter of SlEXPA5, an expansin gene, but did not activate its expression directly. While, the co-expression of SlMYC2 and SlLBD40 significantly stimulated the activation of SlEXPA5, leading to an increase in fruit size. SlLBD40 interacted with SlMYC2 and enhanced the stability and abundance of SlMYC2. Furthermore, SlMYC2 directly targeted and activated the expression of SlLBD40, which is essential for SlLBD40-mediated fruit expansion. In summary, our research elucidates the role of the interaction between SlLBD40 and SlMYC2 in promoting cell expansion in tomato fruits, thus providing novel insights into the molecular genetics underlying fruit growth.


Assuntos
Frutas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Solanum lycopersicum , Fatores de Transcrição , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética
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