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1.
Plant Cell ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235115

RESUMEN

Multiple plant hormones, including strigolactone (SL), play key roles in regulating flowering time. The Arabidopsis (Arabidopsis thaliana) DWARF14 (AtD14) receptor perceives SL and recruits F-box protein MORE AXILLARY GROWTH2 (MAX2) and the SUPPRESSOR OF MAX2-LIKE (SMXL) family proteins. These interactions lead to the degradation of the SMXL repressor proteins, thereby regulating shoot branching, leaf shape, and other developmental processes. However, the molecular mechanism by which SL regulates plant flowering remains elusive. Here, we demonstrate that intact strigolactone biosynthesis and signaling pathways are essential for normal flowering in Arabidopsis. Loss-of-function mutants in both SL biosynthesis (max3) and signaling (Atd14 and max2) pathways display earlier flowering, whereas the repressor triple mutant smxl6/7/8 (s678) exhibits the opposite phenotype. Retention of AtD14 in the cytoplasm leads to its inability to repress flowering. Moreover, we show that nuclear-localized AtD14 employs dual strategies to enhance the function of the AP2 transcription factor TARGET OF EAT1 (TOE1). AtD14 directly binds to TOE1 in an SL-dependent manner and stabilizes it. In addition, AtD14-mediated degradation of SMXL7 releases TOE1 from the repressor protein, allowing it to bind to and inhibit the FLOWERING LOCUS T (FT) promoter. This results in reduced FT transcription and delayed flowering. In summary, AtD14 perception of SL enables the transcription factor TOE1 to repress flowering, providing insights into hormonal control of plant flowering.

2.
Crit Rev Eukaryot Gene Expr ; 34(3): 1-15, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38305284

RESUMEN

Breast cancer is one of the malignant tumors with a high incidence and mortality rate among women worldwide, and its prevalence is increasing year by year, posing a serious health risk to women. UTP23 (UTP23 Small Subunit Processome Component) is a nucleolar protein that is essential for ribosome production. As we all know, disruption of ribosome structure and function results in improper protein function, affecting the body's normal physiological processes and promoting cancer growth. However, little research has shown a connection between UTP23 and cancer. We analyzed the mRNA expression of UTP23 in normal tissue and breast cancer using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, and the protein expression of UTP23 using The Human Protein Atlas (HPA) database. Next, we examined the relationship between UTP23 high expression and Overall Survival (OS) using Kaplan-Meier Plotters and enriched 980 differentially expressed genes in UTP23 high and low expression samples using GO/KEGG and GSEA to identify potential biological functions of UTP23 and signaling pathways that it might influence. Finally, we also investigated the relationship between UTP23 and immune infiltration and examined the effect of UTP23 on the proliferation of human breast cancer cell lines by knocking down UTP23. We found that UTP23 levels in breast cancer patient samples were noticeably greater than those in healthy individuals and that high UTP23 levels were strongly linked with poor prognoses (P = 0.008). Functional enrichment analysis revealed that UTP23 expression was connected to the humoral immune response. Besides, UTP23 expression was found to be positively correlated with immune cell infiltration. Furthermore, UTP23 knockdown has been shown to inhibit the proliferation of human breast cancer cells MDA-MB-231 and HCC-1806. Taken together, our study demonstrated that UTP23 is a promising target in detecting and treating breast cancer and is intimately linked to immune infiltration.


Asunto(s)
Neoplasias de la Mama , Proteínas Nucleares , Femenino , Humanos , Biomarcadores , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Pronóstico , Proteínas Nucleares/genética
3.
BMC Cancer ; 24(1): 92, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38233754

RESUMEN

OBJECTIVE: The efficacy and safety of subxiphoid thoracoscopic thymectomy (SVATS) for early thymoma are unknown. The purposes of this meta-analysis were to evaluate the effectiveness and safety of SVATS for early thymoma, to compare it with unilateral intercostal approach video thoracoscopic surgery (IVATS) thymectomy, and to investigate the clinical efficacy of modified subxiphoid thoracoscopic thymectomy (MSVATS) for early anterior mediastinal thymoma. METHODS: Original articles describing subxiphoid and unilateral intercostal approaches for thoracoscopic thymectomy to treat early thymoma published up to March 2023 were searched from PubMed, Embase, and the Cochrane Library. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and analyzed for heterogeneity. Clinical data were retrospectively collected from all Masaoka stage I and II thymoma patients who underwent modified subxiphoid and unilateral intercostal approach thoracoscopic thymectomies between September 2020 and March 2023. The operative time, intraoperative bleeding, postoperative drainage, extubation time, postoperative hospital stay, postoperative visual analog pain score (VAS), and postoperative complications were compared, and the clinical advantages of the modified subxiphoid approach for early-stage anterior mediastinal thymoma were analyzed. RESULTS: A total of 1607 cases were included in the seven studies in this paper. Of these, 591 cases underwent SVATS thymectomies, and 1016 cases underwent IVATS thymectomies. SVATS thymectomy was compared with IVATS thymectomy in terms of age (SMD = - 0.09, 95% CI: -0.20 to - 0.03, I2 = 20%, p = 0.13), body mass index (BMI; SMD = - 0.10, 95% CI: -0.21 to - 0.01, I2 = 0%, p = 0.08), thymoma size (SMD = - 0.01, 95% CI: -0.01, I2 = 0%, p = 0.08), operative time (SMD = - 0.70, 95% CI: -1.43-0.03, I2 = 97%, p = 0.06), intraoperative bleeding (SMD = - 0.30. 95% CI: -0.66-0.06, I2 = 89%, p = 0.10), time to extubation (SMD = - 0.34, 95%CI: -0.73-0.05, I2 = 91%, p = 0.09), postoperative hospital stay (SMD = - 0.40, 95% CI: -0.93-0.12, I2 = 93%, p = 0.13), and postoperative complications (odds ratio [OR] = 0.94, 95% CI: 0.42-2.12, I2 = 57%, p = 0.88), which were not statistically significantly different between the SVATS and IVATS groups. However, the postoperative drainage in the SVATS group was less than that in the IVATS group (SMD = - 0.43, 95%CI: -0.84 to - 0.02, I2 = 88%, p = 0.04), and the difference was statistically significant. More importantly, the postoperative VAS was lower in the SVATS group on days 1 (SMD = - 1.73, 95%CI: -2.27 to - 1.19, I2 = 93%, p < 0.00001), 3 (SMD = - 1.88, 95%CI: -2.84 to - 0.81, I2 = 97%, p = 0.0005), and 7 (SMD = - 1.18, 95%CI: -2.28 to - 0.08, I2 = 97%, p = 0.04) than in the IVATS group, and these differences were statistically significant. A total of 117 patients undergoing thoracoscopic thymectomy for early thymoma in the Department of Thoracic Surgery of the Second Hospital of Jilin University were retrospectively collected and included in the analysis, for which a modified subxiphoid approach was used in 42 cases and a unilateral intercostal approach was used in 75 cases. The differences between the two groups (MSVATS vs. IVATS) in general clinical characteristics such as age, sex, tumor diameter, Masaoka stage, Word Health Organization (WHO) stage, and intraoperative and postoperative conditions, including operative time, postoperative drainage, extubation time, postoperative hospital stay, and postoperative complication rates, were not statistically significant (p > 0.05), while BMI, intraoperative bleeding, and VAS on postoperative days 1, 3, and 7 were all statistically significant (p < 0.05) in the MSVATS group compared with the IVATS group. CONCLUSION: The meta-analysis showed that the conventional subxiphoid approach was superior in terms of postoperative drainage and postoperative VAS pain scores compared with the unilateral intercostal approach. Moreover, the modified subxiphoid approach had significant advantages in intraoperative bleeding and postoperative VAS pain scores compared with the unilateral intercostal approach. These results indicate that MSVATS can provide more convenient operation conditions, a better pleural cavity view, and a more complete thymectomy in the treatment of early thymoma, indicating that is a safe and feasible minimally invasive surgical method.


Asunto(s)
Timoma , Neoplasias del Timo , Humanos , Timoma/patología , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/efectos adversos , Cirugía Torácica Asistida por Video/métodos , Neoplasias del Timo/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Dolor Postoperatorio/etiología
4.
Surg Endosc ; 38(1): 240-252, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37978082

RESUMEN

BACKGROUND: Few cases describing patients with a right aortic arch (RAA) or double aortic arch (DAA) and esophageal cancer (EC) have been reported. METHODS: We analyzed RAA and DAA cases treated with esophagectomy in our center's database and reported in English-language studies until April 1, 2023. Our study assessed the malformation characteristics and surgical details of EC patients with RAA and DAA. RESULTS: We extracted data of 24 EC patients with RAAs and 10 EC patients with DAAs. In both groups, the patients were more likely to be Japanese and male, to have squamous cell carcinoma and to have tumors located in the upper thoracic esophagus or middle thoracic esophagus. Left thoracotomy was commonly applied for RAA patients. For DAA patients, the proportions of left-sided and right-sided approaches were similar. Esophagectomy under video-assisted thoracoscopic surgery (VATS) in RAA or DAA patients had been performed on a routine basis in recent years. There were two anastomotic leakages in each group. Specifically, Kommerell diverticulum rupture occurred in 1 RAA patient; gastric tube dilation occurred in 1 DAA patient; and recurrent laryngeal nerve (RLN) injury occurred in 2 RAA patients. The postoperative course was uneventful for most patients in both cohorts. CONCLUSIONS: Esophageal carcinoma is rarely seen in patients with an RAA or DAA. To adequately dissect superior mediastinal LNs, an auxiliary incision (such as sternotomy), the left door open method or a preceding cervical procedure should be used appropriately. Esophagectomy, whether via thoracotomy or thoracoscopic surgery, can be performed safely for both RAA and DAA.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Anillo Vascular , Humanos , Masculino , Anillo Vascular/complicaciones , Anillo Vascular/cirugía , Anillo Vascular/patología , Aorta Torácica/cirugía , Aorta Torácica/anomalías , Aorta Torácica/patología , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Cirugía Torácica Asistida por Video , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos
5.
Thorax ; 78(2): 211-213, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36261274

RESUMEN

Rosai-Dorfman disease (RDD) is a non-malignant condition mainly manifesting as a proliferation of histiocytes in lymph nodes. Endotracheal RDD (ERDD) with an acute onset presentation is extremely rare. There are few case reports of ERDD mainly concerning its pathology, diagnostics and bronchoscopic treatment, without providing sufficient clinical information from a comprehensive perspective. As a novel and challenging technique, tracheal resection and reconstruction (TRR) with spontaneous-ventilation video-assisted thoracoscopic surgery (SV-VATS) has been reported as feasible and safe in highly selected patients, but few centres have shared their experience with this approach. This case-based discussion includes not only practical issues in the management of a life-threatening ERDD patient, but also specialists' views on the management of acute obstructive airway, and the surgeons' reflection on TRR with SV-VATS.


Asunto(s)
Obstrucción de las Vías Aéreas , Histiocitosis Sinusal , Humanos , Histiocitosis Sinusal/diagnóstico , Histiocitosis Sinusal/cirugía , Histiocitosis Sinusal/patología , Tráquea/cirugía , Tráquea/patología , Histiocitos/patología
6.
Transfusion ; 63(3): 586-600, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36752125

RESUMEN

BACKGROUND: The formation of extracellular vesicles (EVs) occurs during cold storage of RBCs. Transfusion of EVs may contribute to adverse responses in recipients receiving RBCs. However, EVs are poorly characterized with limited data on whether distinct vesicles are formed, their composition, and potential biological effects. STUDY DESIGN AND METHODS: Stored RBC-derived EVs were purified using protocols that separate larger microvesicle-like EVs (LEVs) from smaller exosome-like vesicles (SEVs). Vesicles were analyzed by electron microscopy, content of hemoglobin, heme, and proteins (by mass spectrometry), and the potential to mediate lipid peroxidation and endothelial cell permeability in vitro. RESULTS: SEVs were characterized by having an electron-dense double membrane whereas LEVs had more uniform electron density across the particles. No differences in hemoglobin nor heme levels per particle were observed, however, due to smaller volumes, SEVs had higher concentrations of oxyHb and heme. Both particles contained antioxidant proteins peroxiredoxin-2 and copper/zinc superoxide dismutase, these were present in higher molecular weight fractions in SEVs suggesting either oxidized proteins are preferentially packaged into smaller vesicles and/or that the environment associated with SEVs is more pro-oxidative. Furthermore, total glutathione (GSH + GSSG) levels were lower in SEVs. Both EVs mediated oxidation of liposomes that were prevented by hemopexin, identifying heme as the pro-oxidant effector. Addition of SEVs, but not LEVs, induced endothelial permeability in a process also prevented by hemopexin. CONCLUSION: These data show that distinct EVs are formed during cold storage of RBCs with smaller particles being more likely to mediate pro-oxidant and inflammatory effects associated with heme.


Asunto(s)
Vesículas Extracelulares , Hemopexina , Humanos , Hemopexina/análisis , Hemopexina/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Vesículas Extracelulares/metabolismo , Eritrocitos/metabolismo , Hemoglobinas/análisis , Hemo/metabolismo
7.
J Org Chem ; 88(12): 7736-7747, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-36749177

RESUMEN

The asymmetric Mannich reaction of 2-fluoroindanone with ketimine was developed under the catalysis of a kind of chiral copper complex, affording a chiral tetrahedral center containing fluorine. A series of ß-fluoroamine derivatives can be obtained in excellent yields (73-94%) with high diastereoselectivities (>99:1 dr) and enantioselectivities (89-99%). The possible transition state was supported by density functional theory calculation.


Asunto(s)
Iminas , Nitrilos , Estereoisomerismo , Catálisis
8.
Nature ; 551(7680): 360-363, 2017 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-29088704

RESUMEN

Granular materials such as sand, powders and foams are ubiquitous in daily life and in industrial and geotechnical applications. These disordered systems form stable structures when unperturbed, but in the presence of external influences such as tapping or shear they 'relax', becoming fluid in nature. It is often assumed that the relaxation dynamics of granular systems is similar to that of thermal glass-forming systems. However, so far it has not been possible to determine experimentally the dynamic properties of three-dimensional granular systems at the particle level. This lack of experimental data, combined with the fact that the motion of granular particles involves friction (whereas the motion of particles in thermal glass-forming systems does not), means that an accurate description of the relaxation dynamics of granular materials is lacking. Here we use X-ray tomography to determine the microscale relaxation dynamics of hard granular ellipsoids subject to an oscillatory shear. We find that the distribution of the displacements of the ellipsoids is well described by a Gumbel law (which is similar to a Gaussian distribution for small displacements but has a heavier tail for larger displacements), with a shape parameter that is independent of the amplitude of the shear strain and of the time. Despite this universality, the mean squared displacement of an individual ellipsoid follows a power law as a function of time, with an exponent that does depend on the strain amplitude and time. We argue that these results are related to microscale relaxation mechanisms that involve friction and memory effects (whereby the motion of an ellipsoid at a given point in time depends on its previous motion). Our observations demonstrate that, at the particle level, the dynamic behaviour of granular systems is qualitatively different from that of thermal glass-forming systems, and is instead more similar to that of complex fluids. We conclude that granular materials can relax even when the driving strain is weak.

9.
J Sep Sci ; 46(24): e2300518, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37853838

RESUMEN

Qiangxin Lishui Prescription (QLP) has been clinically applied for treating heart failure with remarkable curative effects. A multi-component pharmacokinetic research is very necessary for determining active substances in it. This study aims to profile the traits and differences in the pharmacokinetics of salvianolic acid B, astragaloside IV, calycosin-7-O-ß-D-glucoside and kaempferol in QLP between normal and chronic heart failure (CHF) rats by microdialysis combined with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Sensitive, selective, and online microdialysis combined with the UHPLC-MS/MS method was successfully established and applied to study the pharmacokinetics of QLP. The pathological condition of CHF could lead to the enhancement of systematic exposure and reduction of the metabolic rate of four bioactive components for better bioavailability and therapeutic efficacy. The pharmacokinetic results will provide data support for the clinical application of QLP.


Asunto(s)
Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Ratas , Animales , Ratas Sprague-Dawley , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Microdiálisis , Medicamentos Herbarios Chinos/análisis , Prescripciones , Administración Oral , Insuficiencia Cardíaca/tratamiento farmacológico
10.
J Sep Sci ; 46(20): e2300175, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37568244

RESUMEN

Previous clinical studies have found that the efficacy of processed Qixue Shuangbu Prescription has been significantly improved in the treatment of chronic heart failure. However, the absorbed constituents and synergistic mechanisms of processed Qixue Shuangbu Prescription to enhance the therapeutic effect of chronic heart failure remain unclear. In this study, we propose an integrated strategy combining plasma metabolomics, network pharmacology, and molecular docking to study the absorbed constituents and synergistic mechanisms of processed Qixue Shuangbu Prescription. A total of 34 prototype constituents and 24 metabolites were identified in rat plasma after administration of crude and processed Qixue Shuangbu Prescription. As a result, six potential absorbed constituents and six potential targets for the treatment of chronic heart failure were identified. In addition, the result of molecular docking indicated that the key constituents exhibited good affinity to hub targets. This study showed that the multiomics approach could effectively clarify absorbed constituents and synergistic mechanisms of traditional Chinese medicine processing from a new perspective.


Asunto(s)
Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Ratas , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Simulación del Acoplamiento Molecular , Medicina Tradicional China/métodos , Metabolómica/métodos , Biología Computacional , Insuficiencia Cardíaca/tratamiento farmacológico
11.
J Enzyme Inhib Med Chem ; 38(1): 2220558, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37357755

RESUMEN

Heat shock protein 90 (Hsp90) is considered an attractive therapeutic target for cancer treatment due to its high expression in many cancers. In this study, four potent Hsp90 inhibitors (HPs 1-4) were identified using structure-based virtual screening. Among them, HP-4 exhibited the most potent inhibitory effects (IC50 = 17.64 ± 1.45 nM) against the Hsp90 protein, which was about 7.7 times stronger than that of MPC-3100 (a positive inhibitor targeting Hsp90). In vitro cytotoxicity assay suggested that HP-4 could effectively inhibit the proliferation of a series of tumour cells, including HCT-116, HeLa, A549, A2780, DU145, HepG2 and A498. Furthermore, in vivo assay displayed that HP-4 had significant anti-tumour effects on HCT-116 cell-derived xenograft models. These data demonstrate that HP-4 could be a potential lead compound for the further investigation of anti-tumour drugs.


Asunto(s)
Descubrimiento de Drogas , Proteínas HSP90 de Choque Térmico , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos/métodos , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Ratones Endogámicos BALB C , Ratones Desnudos , Simulación del Acoplamiento Molecular , Farmacóforo , Humanos , Animales , Ratones
12.
J Enzyme Inhib Med Chem ; 38(1): 2241118, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37528657

RESUMEN

Prostate cancer (PCa) is a clinically heterogeneous disease with a progressively increasing incidence. Concurrent inhibition of coactivator-associated arginine methyltransferase 1 (CARM1) and histone deacetylase 2 (HDAC2) could potentially be a novel strategy against PCa. Herein, we identified seven compounds simultaneously targeting CARM1 and HDAC2 through structure-based virtual screening. These compounds possessed potent inhibitory activities at the nanomolar level in vitro. Among them, CH-1 was the most active inhibitor which exhibited excellent and balanced inhibitory effects against both CARM1 (IC50 = 3.71 ± 0.11 nM) and HDAC2 (IC50 = 4.07 ± 0.25 nM). MD simulations presented that CH-1 could stably bind the active pockets of CARM1 and HDAC2. Notably, CH-1 exhibited strong anti-proliferative activity against multiple prostate-related tumour cells (IC50 < 1 µM). In vivo, assessment indicated that CH-1 significantly inhibited tumour growth in a DU145 xenograft model. Collectively, CH-1 could be a promising drug candidate for PCa treatment.


Asunto(s)
Antineoplásicos , Neoplasias de la Próstata , Masculino , Humanos , Histona Desacetilasa 2/metabolismo , Antineoplásicos/farmacología , Proteína-Arginina N-Metiltransferasas/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Inhibidores de Histona Desacetilasas/farmacología
13.
J Enzyme Inhib Med Chem ; 38(1): 2212327, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37194732

RESUMEN

Both receptor-binding domain in spike protein (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human neuropilin-1 (NRP1) are important in the virus entry, and their concomitant inhibition may become a potential strategy against the SARS-CoV-2 infection. Herein, five novel dual S-RBD/NRP1-targeting peptides with nanomolar binding affinities were identified by structure-based virtual screening. Particularly, RN-4 was found to be the most promising peptide targeting S-RBD (Kd = 7.4 ± 0.5 nM) and NRP1-BD (the b1 domain of NRP1) (Kd = 16.1 ± 1.1 nM) proteins. Further evidence in the pseudovirus infection assay showed that RN-4 can significantly inhibit the SARS-CoV-2 pseudovirus entry into 293 T cells (EC50 = 0.39 ± 0.09 µM) without detectable side effects. These results suggest that RN-4, a novel dual S-RBD/NRP1-targeting agent, holds potential as an effective therapeutic to combat the SARS-CoV-2 infection.


Asunto(s)
COVID-19 , Simulación de Dinámica Molecular , Humanos , SARS-CoV-2 , Neuropilina-1 , Péptidos/farmacología , Unión Proteica
14.
Environ Toxicol ; 38(7): 1712-1722, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37040338

RESUMEN

The conjecture of breast cancer is uncertain because of its explosive growth and the complicated molecular mechanisms. Circular RNAs (circRNAs) are regulatory RNA sequences present in the genome and their regulatory mechanism involves the sponging of microRNAs (miRNAs). In this study, we explored the regulation between circular forms of dedicator of cytokinesis 1 (circDOCK1) (hsa_circ_0007142) and miR-128-3p, and its implication on the pathogenesis of breast cancer modulated by never in mitosis (NIMA) related kinase 2 (NEK2). We revealed an increase in circDOCK1 and NEK2 expression, and a decrease in miR-128-3p expression in breast cancer tissues and cell lines. Bioinformatics analysis and experimental validation indicated a positive correlation between circDOCK1 and NEK2 expression but a negative correlation was recorded between miR-128-3p and circDOCK1 or NEK2, respectively. Furthermore, inhibition of circDOCK1 expression was followed by an increase in miR-128-3p and a decrease in NEK2 levels in vitro and in vivo. The luciferase assay concluded that miR-128-3p was a direct target of circDOCK1 while NEK2 was the direct target of miR-128-3p. Furthermore, circDOCK1 inhibition hindered breast cancer development by repressing NEK2 and thus promoting the increased expression of miR-128-3p both in vitro and in vivo. We therefore conclude that circDOCK1 promotes breast cancer progression by targeting miR-128-3p-mediated downregulation of NEK2 and that the circDOCK1/hsa-miR-128-3p/NEK2 axis may be a novel therapeutic target for breast cancer treatment.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Humanos , Femenino , Neoplasias de la Mama/genética , Citocinesis/genética , Proliferación Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Mitosis/genética , Movimiento Celular/genética , Quinasas Relacionadas con NIMA/genética , Quinasas Relacionadas con NIMA/metabolismo
15.
Molecules ; 28(13)2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37446701

RESUMEN

As a valuable traditional Chinese herbal medicine, Radix Astragali has attracted much attention due to its extensive pharmacological activities. In this study, density functional theory (DFT) was used thermodynamically and kinetically in detail to predict the antioxidant activity and reaction mechanisms involved in the free radical scavenging reactions of three representative isoflavonoids (formononetin, calycosin, and calycosin-7-glucoside) extracted from Radix Astragali. Three main mechanisms, including hydrogen atom transfer (HAT), proton transfer after electron transfer (SET-PT), and sequential proton loss electron transfer (SPLET) were examined by calculating the thermodynamic parameters. It was found that HAT is the predominant mechanism in the gas phase, while SPLET is supported in the solvent environment. The isoflavonoids' order of antioxidant activity was estimated as: calycosin > calycosin-7-glucoside > formononetin. For the calycosin compound, the result revealed the feasibility of double HAT mechanisms, which involve the formation of stable benzodioxazole with significantly reduced energy in the second H+/e- reaction. In addition, the potential energy profiles and kinetic calculations show that the reaction of •OH into the 3'-OH site of calycosin has a lower energy barrier (7.2 kcal/mol) and higher rate constant (4.55 × 109 M-1 s-1) compared with other reactions in the gas phase.


Asunto(s)
Medicamentos Herbarios Chinos , Flavonas , Antioxidantes/farmacología , Protones , Modelos Teóricos , Hidrógeno , Glucósidos , Termodinámica
16.
Molecules ; 28(16)2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37630230

RESUMEN

Myclobutanil residue poses a potential threat to consumers' health. This work aims to investigate the degradation behavior, residue levels, processing factors (PFs) and dietary risk of myclobutanil in tomato. Myclobutanil was analyzed using a modified quick, easy, cheap, effective, rugged, safe (QuEChERS) method combined with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS), and average recoveries ranged from 82% to 102% with relative standard deviations RSDs ≤ 9.1%. After spraying myclobutanil miscible oil under field conditions, the initial concentration of myclobutanil was 0.055 mg/kg, and its dissipation followed the first-order kinetics equation with a half-life of 2.88 days. Myclobutanil was mainly present in the tomato skin, and its concentration was about four times that in the whole tomato. The initial concentration of myclobutanil in raw tomato was 0.100 mg/kg. After washing, peeling, homogenization, simmering and canning, the residual level of myclobutanil decreased to 0.067 mg/kg, 0.023 mg/kg, 0.013 mg/kg, 0.044 mg/kg and 0.041 mg/kg, respectively. Although the procedure of simmering led to an increase in myclobutanil concentration, the PFs were all less than 1 in the whole process, showing that the processing procedure significantly decreased the residual level of myclobutanil canned tomato paste in comparison with the raw agricultural commodity. Washing, peeling, and homogenization played critical roles in reducing pesticide residues. The residues of myclobutanil during the processing of tomato pose low dietary exposure risks to consumers in China, which were acceptable. However, the acute and chronic risk quotient for children revealed that it was necessary to monitor the dietary exposure of pesticide residues for children closely.


Asunto(s)
Residuos de Plaguicidas , Solanum lycopersicum , Niño , Humanos , Cromatografía Liquida , Exposición Dietética , Espectrometría de Masas en Tándem
17.
Molecules ; 28(12)2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37375316

RESUMEN

Spirotetramat is a potential tetronic acid pesticide for controlling various pests with piercing-sucking mouthparts. To clarify its dietary risk on cabbage, we established an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and then investigated the residual levels of spirotetramat and its four metabolites in cabbage collected from field experiments under good agricultural practices (GAPs). The average recoveries of spirotetramat and its metabolites in cabbage were 74~110%, while the relative standard deviation (RSD) was 1~6%, and the limit of quantitation (LOQ) was 0.01 mg kg-1. The terminal residue of spirotetramat was in the range of <0.05~0.33 mg kg-1, the chronic dietary risk (RQc) was 17.56%, and the acute dietary risk (RQa) was 0.025~0.049%, which means an acceptable dietary intake risk. This study provides data to guide on the use of spirotetramat and to establish the maximum residue limits (MRLs) of spirotetramat on cabbage.


Asunto(s)
Brassica , Residuos de Plaguicidas , Cromatografía Líquida de Alta Presión , Brassica/química , Espectrometría de Masas en Tándem , Medición de Riesgo , Residuos de Plaguicidas/análisis
18.
Molecules ; 28(20)2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37894602

RESUMEN

Fenpyroximate is an efficient, broad-spectrum phenoxypyrazole acaricide which is used for controlling various mites. In this study, we measured the levels of terminal fenpyroximate residues in citrus fruits, and estimated the dietary intake risks posed by fenpyroximate. To this end, a QuEChERS analytical method was used in combination with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to determine the residual levels of fenpyroximate and its Z-isomer (Z-fenpyroximate) in citrus fruits collected from 12 fields under good agricultural practices (GAPs). The average recoveries of fenpyroximate in whole fruits and citrus flesh were 104-110% and 92-109%, respectively, with corresponding RSDs of 1-4% and 1-3%. The average recoveries of Z-fenpyroximate were 104-113% and 90-91%, respectively, with RSDs of 1-2% in both cases. Each limit of quantification (LOQ) was 0.01 mg kg-1. Fifteen days after application with 56 mg kg-1, the terminal residues of fenpyroximate in whole fruits and citrus flesh were <0.010-0.18 mg kg-1 and <0.010-0.063 mg kg-1, respectively; the corresponding values for total fenpyroximate (the sum of fenpyroximate and Z-fenpyroximate) were <0.020-0.19 and <0.020-0.053 mg kg-1. The levels of terminal fenpyroximate residues in citrus fruit were less than the maximum residue limits (MRLs) specified in all the existing international standards. In addition, the risk quotients RQc and RQa were both less than 100%, indicating that the long-term and short-term dietary intake risks posed to Chinese consumers by fenpyroximate in citrus fruit are both acceptable after a 15-day harvest interval.


Asunto(s)
Citrus , Residuos de Plaguicidas , Cromatografía Líquida de Alta Presión , Citrus/química , Espectrometría de Masas en Tándem/métodos , Residuos de Plaguicidas/análisis
19.
Molecules ; 28(20)2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37894703

RESUMEN

Isoxaflutole and atrazine are representative pesticides for weed control in corn fields. Formulations containing these two pesticides have been registered in China, and their residues may threaten food safety and human health. In this study, a method for simultaneous determination of isoxaflutole, atrazine, and their metabolites in fresh corn, corn kernels, and corn straw was established based on modified QuEChERS pre-treatment and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The linearity of seven compounds was good (R2 ≥ 0.9912), and the matrix effect was 48.5-77.1%. At four spiked levels of 0.01, 0.02, 0.05, and 0.5 mg kg-1, all compounds' average recovery was 76% to 116%, with relative standard deviation (RSD) less than 18.9%. Field experiments were conducted in Liaoning, Heilongjiang, Inner Mongolia, Shanxi, Beijing, and Yunnan provinces to study the terminal residues. The terminal residues of all compounds were below the LOQ (0.01 mg kg-1) in fresh corn and corn kernels, and atrazine residues in corn straw ranged from <0.05 mg kg-1 to 0.17 mg kg-1. Finally, a dietary risk assessment was conducted based on residues from field trials, food consumption, and acceptable daily intake (ADI). For all populations, the chronic dietary risk probability (RQc) of atrazine was between 0.0185% and 0.0739%, while that of isoxaflutole was 0.0074-0.0296%, much lower than 100%. The results may provide scientific guidance for using isoxaflutole and atrazine in corn field ecosystems.


Asunto(s)
Atrazina , Residuos de Plaguicidas , Plaguicidas , Humanos , Cromatografía Líquida de Alta Presión , Residuos de Plaguicidas/análisis , Espectrometría de Masas en Tándem/métodos , Zea mays/química , Ecosistema , China , Plaguicidas/análisis , Medición de Riesgo
20.
Sensors (Basel) ; 22(14)2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35891102

RESUMEN

Nowadays low Earth orbit (LEO) Earth observation (EO) satellites commonly use constant coding modulation (CCM) or variable coding modulation (VCM) schemes for data transmission to ground stations (G/S). Compared with CCM and VCM, the adaptive coding modulation (ACM) could further improve the data throughput of the link by making full use of link resource and the time-varying characteristics of atmospheric attenuation. In order to comprehensively study the data transmission performance, one new index which could be utilized as a quantitative index for the satellite-to-ground data transmission scheme selection, the transmission efficiency factor (TEF) of LEO satellites is proposed and defined as "the product of the link availability and the average useful data rate". Then, the transmission efficiency of CCM, VCM and ACM at typical G/S with different weather characteristics at Ka-band is compared and analyzed. The results show that ACM is more suitable for the G/S with moderate and abundant rainfall. Compared with the CCM of MCS 28, for Beijing G/S and Sanya G/S, ACM not only improves the transmission efficiency with the TEF increased by 3.62% and 24.51%, respectively, but also improves the link availability with the outage period reduced by 82.47% and 75.18%, respectively.

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