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1.
Proc Natl Acad Sci U S A ; 119(34): e2202821119, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-35969743

RESUMEN

Sonic hedgehog (Shh) signaling plays a critical role in regulating cerebellum development by maintaining the physiological proliferation of granule neuron precursors (GNPs), and its dysregulation leads to the oncogenesis of medulloblastoma. O-GlcNAcylation (O-GlcNAc) of proteins is an emerging regulator of brain function that maintains normal development and neuronal circuitry. Here, we demonstrate that O-GlcNAc transferase (OGT) in GNPs mediate the cerebellum development, and the progression of the Shh subgroup of medulloblastoma. Specifically, OGT regulates the neurogenesis of GNPs by activating the Shh signaling pathway via O-GlcNAcylation at S355 of GLI family zinc finger 2 (Gli2), which in turn promotes its deacetylation and transcriptional activity via dissociation from p300, a histone acetyltransferases. Inhibition of OGT via genetic ablation or chemical inhibition improves survival in a medulloblastoma mouse model. These data uncover a critical role for O-GlcNAc signaling in cerebellar development, and pinpoint a potential therapeutic target for Shh-associated medulloblastoma.


Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Animales , Carcinogénesis/genética , Carcinogénesis/metabolismo , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/metabolismo , Cerebelo/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Meduloblastoma/genética , Meduloblastoma/metabolismo , Ratones , Neurogénesis/fisiología
2.
Anal Chem ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953489

RESUMEN

26% of the world's population lacks access to clean drinking water; clean water and sanitation are major global challenges highlighted by the UN Sustainable Development Goals, indicating water security in public water systems is at stake today. Water monitoring using precise instruments by skilled operators is one of the most promising solutions. Despite decades of research, the professionalism-convenience trade-off when monitoring ubiquitous metal ions remains the major challenge for public water safety. Thus, to overcome these disadvantages, an easy-to-use and highly sensitive visual method is desirable. Herein, an innovative strategy for one-to-nine metal detection is proposed, in which a novel thiourea spectroscopic probe with high 9-metal affinity is synthesized, acting as "one", and is detected based on the 9 metal-thiourea complexes within portable spectrometers in the public water field; this is accomplished by nonspecialized personnel as is also required. During the processing of multimetal analysis, issues arise due to signal overlap and reproducibility problems, leading to constrained sensitivity. In this innovative endeavor, machine learning (ML) algorithms were employed to extract key features from the composite spectral signature, addressing multipeak overlap, and completing the detection within 30-300 s, thus achieving a detection limit of 0.01 mg/L and meeting established conventional water quality standards. This method provides a convenient approach for public drinking water safety testing.

3.
Small ; 20(21): e2307390, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38100300

RESUMEN

Tumor immunotherapy has become a research hotspot in cancer treatment, with macrophages playing a crucial role in tumor development. However, the tumor microenvironment restricts macrophage functionality, limiting their therapeutic potential. Therefore, modulating macrophage function and polarization is essential for enhancing tumor immunotherapy outcomes. Here, a supramolecular peptide amphiphile drug-delivery system (SPADS) is utilized to reprogram macrophages and reshape the tumor immune microenvironment (TIM) for immune-based therapies. The approach involved designing highly specific SPADS that selectively targets surface receptors of M2-type macrophages (M2-Mφ). These targeted peptides induced M2-Mφ repolarization into M1-type macrophages by dual inhibition of endoplasmic reticulum and oxidative stresses, resulting in improved macrophagic antitumor activity and immunoregulatory function. Additionally, TIM reshaping disrupted the immune evasion mechanisms employed by tumor cells, leading to increased infiltration, and activation of immune cells. Furthermore, the synergistic effect of macrophage reshaping and anti-PD-1 antibody (aPD-1) therapy significantly improved the immune system's ability to recognize and eliminate tumor cells, thereby enhancing tumor immunotherapy efficacy. SPADS utilization also induced lung metastasis suppression. Overall, this study demonstrates the potential of SPADS to drive macrophage reprogramming and reshape TIM, providing new insights, and directions for developing more effective immunotherapeutic approaches in cancer treatment.


Asunto(s)
Neoplasias de la Mama , Inmunoterapia , Nanosferas , Péptidos , Microambiente Tumoral , Macrófagos Asociados a Tumores , Microambiente Tumoral/efectos de los fármacos , Inmunoterapia/métodos , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Animales , Nanosferas/química , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Péptidos/química , Péptidos/farmacología , Femenino , Ratones , Línea Celular Tumoral , Humanos , Ratones Endogámicos BALB C
4.
J Transl Med ; 22(1): 626, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965561

RESUMEN

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.


Asunto(s)
Biomarcadores , COVID-19 , Complejo de la Endopetidasa Proteasomal , Humanos , COVID-19/mortalidad , COVID-19/sangre , Masculino , Femenino , Complejo de la Endopetidasa Proteasomal/metabolismo , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , SARS-CoV-2 , Pronóstico , Adulto , Esteroides/biosíntesis , Esteroides/sangre , Enfermedad Aguda , Estudios de Casos y Controles , Aprendizaje Automático
5.
Phys Chem Chem Phys ; 26(6): 5377-5386, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38269624

RESUMEN

Due to the crucial regulatory mechanism of cyclin-dependent kinase 9 (CDK9) in mRNA transcription, the development of kinase inhibitors targeting CDK9 holds promise as a potential treatment strategy for cancer. A structure-based virtual screening approach has been employed for the discovery of potential novel CDK9 inhibitors. First, compounds with kinase inhibitor characteristics were identified from the ZINC15 database via virtual high-throughput screening. Next, the predicted binding modes were optimized by molecular dynamics simulations, followed by precise estimation of binding affinities using absolute binding free energy calculations based on the free energy perturbation scheme. The binding mode of molecule 006 underwent an inward-to-outward flipping, and the new binding mode exhibited binding affinity comparable to the small molecule T6Q in the crystal structure (PDB ID: 4BCF), highlighting the essential role of molecular dynamics simulation in capturing a plausible binding pose bridging docking and absolute binding free energy calculations. Finally, structural modifications based on these findings further enhanced the binding affinity with CDK9. The results revealed that enhancing the molecule's rigidity through ring formation, while maintaining the major interactions, reduced the entropy loss during the binding process and, thus, enhanced binding affinities.


Asunto(s)
Quinasa 9 Dependiente de la Ciclina , Ensayos Analíticos de Alto Rendimiento , Unión Proteica , Entropía , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular
6.
Ecotoxicol Environ Saf ; 270: 115833, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38181602

RESUMEN

Elaborating on the fate tendency of thifluzamide (thiazole-amide fungicide) in buckwheat based on nationwide application is vital for grain security and human health based on nationwide application. A rapid and sensitive analytical method was developed to trace thifluzamide in buckwheat matrices using an ultrahigh-performance liquid chromatography-tandem triple quadrupole mass spectrometer (UHPLC-MS/MS), with a retention time of 2.90 min and limit of quantitation (LOQ) of 0.001 mg/kg. Thifluzamide could be stably stored for 84 d in buckwheat matrices under -20 °C under dark condition. The occurrence, dissipation and terminal magnitudes of thifluzamide were reflected by the primary deposition of 0.02-0.55 mg/kg, half-lives of 12-14 d, and highest residues of 0.41 mg/kg. The long-term risks (ADI%) of thifluzamide were 37.268 %-131.658 % in registered crops, and the risks for the rural population were significantly higher than those of the urban population. The unacceptable dietary risks of thifluzamide should be continuously emphasized for children aged 2-7 with an ADI% values of 100.750 %-131.658 %. A probabilistic model was further introduced to evaluate the risk discrepancy of thifluzamide in buckwheat, showing the risks in Tartary buckwheat (Fagopyrum tararicum Gaerth) were 1.5-75.4 times than that in sweet buckwheat (Fagopyrum esculentum Moench). Despite the low risks for dietary buckwheat, the high-potential health hazards of thifluzamide should be pay more attention given the increasing applications and cumulative effects.


Asunto(s)
Anilidas , Fagopyrum , Niño , Humanos , Fagopyrum/química , Espectrometría de Masas en Tándem , Cromatografía Liquida , Tiazoles
7.
Anal Chem ; 95(14): 6156-6162, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-36992572

RESUMEN

The rapid emergence of deep learning, e.g., deep convolutional neural networks (DCNNs) as one-click image analysis with super-resolution, has already revolutionized colorimetric determination. But it is severely limited by its data-hungry nature, which is overcome by combining the generative adversarial network (GAN), i.e., few-shot learning (FSL). Using the same amount of real sample data, i.e., 414 and 447 samples as training and test sets, respectively, the accuracy could be increased from 51.26 to 85.00% because 13,500 antagonistic samples are created and used by GAN as the training set. Meanwhile, the generated image quality with GAN is better than that with the commonly used convolution self-encoder method. The simple and rapid on-site determination of Cr(VI) with 1,5-diphenylcarbazide (DPC)-based test paper is a favorite for environment monitoring but is limited by unstable DPC, poor sensitivity, and narrow linear range. The chromogenic agent of DPC is protected by the blending of polyacrylonitrile (PAN) and then loaded onto thin chromatographic silica gel (SG) as a Cr(VI) colorimetric sensor (DPC/PAN/SG); its stability could be prolonged from 18 h to more than 30 days, and its repeatable reproducibility is realized via facile electrospinning. By replacing the traditional Ed method with DCNN, the detection limit is greatly improved from 1.571 mg/L to 50.00 µg/L, and the detection range is prolonged from 1.571-8.000 to 0.0500-20.00 mg/L. The complete test time is shortened to 3 min. Even without time-consuming and easily stained enrichment processing, its detection limit of Cr(VI) in the drinking water can meet on-site detection requirements by USEPA, WHO, and China.

8.
J Org Chem ; 88(17): 12668-12676, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37603684

RESUMEN

The influence of steric effects on the rates of hydrogen atom transfer (HAT) reactions between oxyradicals and alkanes is explored computationally. Quantum chemical density functional theory computations of transition states show that activation barriers and reaction enthalpies are both influenced by bulky substituents on the radical but very little by substituents on the alkane. The activation barriers remain roughly correlated with reaction enthalpies via the Evans-Polanyi relationship even when steric repulsion effects become important, although dispersion effects sometimes stabilize transition states. By making comparisons to previously developed Evans-Polanyi and modified Roberts-Steel relationships, we find that HAT reactions between bulky molecules remain well-described by these relationships.

9.
Korean J Physiol Pharmacol ; 27(6): 521-531, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37884284

RESUMEN

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (Emax) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

10.
J Am Chem Soc ; 144(15): 6802-6812, 2022 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-35378978

RESUMEN

Density functional theory calculations (ωB97X-D) are reported for the reactions of methoxy, tert-butoxy, trichloroethoxy, and trifluoroethoxy radicals with a series of 26 C-H bonds in different environments characteristic of a variety of hydrocarbons and substituted derivatives. The variations in activation barriers are analyzed with modified Evans-Polanyi treatments to account for polarity and unsaturation effects. The treatments by Roberts and Steel and by Mayer have inspired the development of a simple treatment involving the thermodynamics of reactions, the difference between the reactant radical and product radical electronegativities, and the absence or presence of α-unsaturation. The three-parameter equation (ΔH⧧ = 0.52ΔHrxn(1 - d) - 0.35ΔχAB2 + 10.0, where d = 0.44 when there is α-unsaturation to the reacting C-H bond), correlates well with quantum mechanically computed barriers and shows the quantitative importance of the thermodynamics of reactions (dictated by the reactant and the product bond dissociation energies) and polar effects.


Asunto(s)
Hidrocarburos , Hidrógeno , Radicales Libres/química , Hidrocarburos/química , Hidrógeno/química , Termodinámica
11.
Anal Chem ; 94(42): 14801-14809, 2022 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-36239120

RESUMEN

Via the photodegradation of dissolved iron (dFe) complexes in the euphotic zone, released free Fe(III) is the most important source of bioavailable iron for eukaryotic phytoplankton. There is an urgent need to establish bioavailability-based dissolved iron speciation (BDIS) methods. Herein, an intelligent system with dFe pretreatment and a colorimetric sensor is developed for real-time monitoring of newly generated Fe(III) ions. According to the photodegradation kinetics of dFe, including kinetic constant and photogenerated time of free Fe(III) ions, 3 sources, 6 kinds, and 12 species of dFe are determined by our photocatalytic-assisted colorimetric sensor and deep learning model within 20.0 min. The algal dFe-uptake for 4 days can be predicted by BDIS with correlation coefficient 0.85, which could be explained by the hard and soft acids and bases theory (HSAB) and density functional theory (DFT). These results successfully demonstrate the proof-of-concept for photodegradation kinetics-based speciation and bioavailability assessments of dissolved metals.


Asunto(s)
Aprendizaje Profundo , Hierro , Hierro/metabolismo , Disponibilidad Biológica , Fotólisis , Colorimetría
12.
Ecotoxicol Environ Saf ; 243: 114017, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36027715

RESUMEN

Urea, nickel (Ni) and dissolved organic matter (DOM) from land varied with different sources have a great impact on the offshore ecosystem. The heterogeneity of Ni bioavailability and toxicity of Prorocentrum donghaiense influenced by DOM fractions incubated in urea was investigated in this study. On the occasion, chlorophyll (Chl a) concentration, growth rate, and photosynthesis parameters were monitored to track changes occurring in the test organism. Chl a concentration and photosynthesis parameters in the treatment of hydrophilic DOM (HPI) with Ni-free was significantly higher than that in the control treatment, and similar data were shown in the treatment of hydrophobic DOM(HPO)with the low Ni environment (0.17µmol L-1). However, the opposite phenomena were observed in the treatments of HPO with the higher Ni environment (over 170µmol L-1). Moreover, the EC50 of Ni for P.donghaiense incubated in HPO was relatively lower than that in HPI and control treatment, which implied that HPO elevated the toxicity of Ni. Therefore, the varied DOM compositions because of different origins, as a chelating agent and potential nutrient source in coastal waters, shows the significantly different bioavailability and toxicity of Ni with the increasing inputs of urea, which in turn influences the dynamics of phytoplankton.


Asunto(s)
Dinoflagelados , Níquel , Disponibilidad Biológica , Materia Orgánica Disuelta , Ecosistema , Níquel/toxicidad , Urea
13.
J Org Chem ; 86(15): 9925-9937, 2021 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-34115516

RESUMEN

A kinetic, product, and computational study on the reactions of the cumyloxyl radical with monosubstituted cyclopentanes and cyclohexanes has been carried out. HAT rates, site-selectivities for C-H bond oxidation, and DFT computations provide quantitative information and theoretical models to explain the observed patterns. Cyclopentanes functionalize predominantly at C-1, and tertiary C-H bond activation barriers decrease on going from methyl- and tert-butylcyclopentane to phenylcyclopentane, in line with the computed C-H BDEs. With cyclohexanes, the relative importance of HAT from C-1 decreases on going from methyl- and phenylcyclohexane to ethyl-, isopropyl-, and tert-butylcyclohexane. Deactivation is also observed at C-2 with site-selectivity that progressively shifts to C-3 and C-4 with increasing substituent steric bulk. The site-selectivities observed in the corresponding oxidations promoted by ethyl(trifluoromethyl)dioxirane support this mechanistic picture. Comparison of these results with those obtained previously for C-H bond azidation and functionalizations promoted by the PINO radical of phenyl and tert-butylcyclohexane, together with new calculations, provides a mechanistic framework for understanding C-H bond functionalization of cycloalkanes. The nature of the HAT reagent, C-H bond strengths, and torsional effects are important determinants of site-selectivity, with the latter effects that play a major role in the reactions of oxygen-centered HAT reagents with monosubstituted cyclohexanes.


Asunto(s)
Ciclohexanos , Ciclopentanos , Enlace de Hidrógeno , Cinética , Estructura Molecular
14.
Int J Mol Sci ; 22(24)2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34948028

RESUMEN

As an important gas signaling molecule, hydrogen sulfide (H2S) plays a crucial role in regulating cold tolerance. H2S cooperates with phytohormones such as abscisic acid, ethylene, and salicylic acid to regulate the plant stress response. However, the synergistic regulation of H2S and auxin in the plant response to cold stress has not been reported. This study showed that sodium hydrosulfide (NaHS, an H2S donor) treatment enhanced the cold stress tolerance of cucumber seedlings and increased the level of auxin. CsARF5, a cucumber auxin response factor (ARF) gene, was isolated, and its role in regulating H2S-mediated cold stress tolerance was described. Transgenic cucumber leaves overexpressing CsARF5 were obtained. Physiological analysis indicated that overexpression of CsARF5 enhanced the cold stress tolerance of cucumber and the regulation of the cold stress response by CsARF5 depends on H2S. In addition, molecular assays showed that CsARF5 modulated cold stress response by directly activating the expression of the dehydration-responsive element-binding (DREB)/C-repeat binding factor (CBF) gene CsDREB3, which was identified as a positive regulator of cold stress. Taken together, the above results suggest that CsARF5 plays an important role in H2S-mediated cold stress in cucumber. These results shed light on the molecular mechanism by which H2S regulates cold stress response by mediating auxin signaling; this will provide insights for further studies on the molecular mechanism by which H2S regulates cold stress. The aim of this study was to explore the molecular mechanism of H2S regulating cold tolerance of cucumber seedlings and provide a theoretical basis for the further study of cucumber cultivation and environmental adaptability technology in winter.


Asunto(s)
Cucumis sativus/crecimiento & desarrollo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Sulfuros/farmacología , Respuesta al Choque por Frío/efectos de los fármacos , Cucumis sativus/efectos de los fármacos , Cucumis sativus/genética , Cucumis sativus/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Sulfuro de Hidrógeno/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/metabolismo
15.
Biochem Biophys Res Commun ; 532(4): 541-547, 2020 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-32896380

RESUMEN

The proper development of the cerebral cortex is essential for brain formation and functioning. O-GlcNAcylation, an important posttranslational modification, regulates the pathways critical for neuronal health and the survival of the cerebral cortex in neurodegenerative diseases. However, the role of O-GlcNAcylation in regulating cerebral cortical development at the embryonic and early postnatal (0-21 days) stages is still largely unknown. Here we report that the selective deletion of O-GlcNAc transferase (OGT) in neural stem cells (NSCs) in mice led to a series of severe brain developmental deficits, including dramatic shrinkage of cortical and hippocampal histoarchitecture, widespread neuronal apoptosis, decrease in cell proliferation, induction of endoplasmic reticulum (ER) stress, and inhibition of neuronal dendritic and axonal differentiation. The pathology of corticogenesis deficits caused by OGT deletion may largely rely on complicated biological processes, such as proliferation, apoptosis and differentiation. Our results suggest that dysfunctional O-GlcNAcylation in NSCs may be an important contributor to neurodevelopmental diseases.


Asunto(s)
Corteza Cerebral/crecimiento & desarrollo , N-Acetilglucosaminiltransferasas/fisiología , Células-Madre Neurales/enzimología , Animales , Apoptosis , Axones/ultraestructura , Corteza Cerebral/anatomía & histología , Corteza Cerebral/embriología , Corteza Cerebral/enzimología , Dendritas/ultraestructura , Homólogo 4 de la Proteína Discs Large/metabolismo , Estrés del Retículo Endoplásmico , Masculino , Ratones Noqueados , Morfogénesis , Células Madre Multipotentes/enzimología , N-Acetilglucosaminiltransferasas/genética , Neuronas/citología , Neuronas/metabolismo
16.
Planta ; 251(3): 69, 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-32076872

RESUMEN

MAIN CONCLUSION: This report proves a cross talk between H2S and IAA in cold stress response, which has presented strong evidence that IAA acts as a downstream signal mediating the H2S-induced stress tolerance in cucumber seedlings. We evaluated changes in endogenous hydrogen sulfide (H2S) and indole-3-acetic acid (IAA) emission systems, and the interactive effect of exogenous H2S and IAA on chilling tolerance in cucumber seedlings. The results showed that chilling stress increased the activity and relative mRNA expression of L-/D-cysteine desulfhydrase (L-/D-CD), which in turn induced the accumulation of endogenous H2S. Similarly, the endogenous IAA system was triggered by chilling stress. We found that 1.0 mM sodium hydrosulfide (NaHS, an H2S donor) significantly enhanced the activity of flavin monooxygenase (FMO) and relative expression of FMO-like proteins (YUCCA2), which in turn elevated endogenous IAA levels in cucumber seedlings. However, IAA had little effects on activities of L-/D-CD and endogenous H2S levels. H2S-induced IAA production accompanied by increase in chilling tolerance, as shown by the decrease in stress-induced electrolyte leakage (EL) and reactive oxygen species (ROS) accumulation, and increase in gene expressions and enzyme activities of photosynthesis. 1-naphthylphthalamic acid (NPA, an IAA polar transport inhibitor) declined H2S-induced chilling tolerance and defense genes' expression. However, scavenging of H2S had a little effect on IAA-induced chilling tolerance. These results suggest that IAA acting as a downstream signaling molecule is involved in the H2S-induced chilling tolerance in cucumber seedlings.


Asunto(s)
Aclimatación/efectos de los fármacos , Cucumis sativus/fisiología , Sulfuro de Hidrógeno/farmacología , Ácidos Indolacéticos/farmacología , Transducción de Señal/efectos de los fármacos , Aclimatación/genética , Aclimatación/fisiología , Ácido Ascórbico/análisis , Frío , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Glutatión/análisis , Especies Reactivas de Oxígeno/metabolismo , Plantones/genética , Plantones/fisiología , Estrés Fisiológico/efectos de los fármacos , Sulfuros , Transcriptoma
17.
Zhongguo Zhong Yao Za Zhi ; 45(23): 5770-5776, 2020 Dec.
Artículo en Zh | MEDLINE | ID: mdl-33496118

RESUMEN

Trace metals deficiency or excess are associated with the etiology and pathogenesis of rheumatoid arthritis(RA). Aconiti Radix Cocta(A) and Paeoniae Radix Alba(B) are commonly used together for the treatment of RA. In this study, we aim to determine anti-arthritic-related metal bioavailability in the compatibility of herb A and B for avoiding metal deficiency or excess, and optimize the combination ratio of herb A and B, accordingly. Anti-arthritic-related metal bioaccessibility were evaluated by in vitro simulator of all gastrointestinal tract(including mouth, stomach, small and large intestines), and the roles of gastrointestinal digestive enzymes and intestinal microflora were investigated. Anti-arthritic-related metal bioavailability was assessed by the affinity adsorption with liposomes. The results indicated that compatibility proportion of corresponding herbal plants, gastrointestinal digestion and microbial metabolic, which could affect metal digestion and absorption. The optimal compatibility proportion of 1 A∶1 B is recommended, according to the dose of anti-arthritic-related metal bioavailability, which is often chosen for clinical practice of RA therapy. Thus, anti-arthritic-related metal bioavailability might be the key active substances for RA treatment.


Asunto(s)
Aconitum , Medicamentos Herbarios Chinos , Paeonia , Disponibilidad Biológica
18.
Mikrochim Acta ; 186(5): 324, 2019 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-31049714

RESUMEN

A surface-graphenized pencil graphite electrode (SGPGE) served as an amperometric sensor for dopamine (DA). It was prepared through a one-step in-situ electrochemical graphene delamination. The graphite particles on the outer surface of the pencil graphite electrode (PGE) were delaminated by controlling the electrochemical delaminating conditions such as the applied anodic voltage and polarization duration, as well as the kind of electrolytes. The best conditions were identified by scanning electron microscopy, Raman spectra, cyclic voltammetry and differential pulse voltammetry (DPV). As a result, the electrode was endowed with an optimum combination of graphene delamination efficiency and electrochemical activity. The electrochemical treatment activates the surface sensing sites and improves the sensing performance. The NaOH-teated anodically graphenized electrode was used to sense dopamine by DPV. The best oxidation voltage of dopamine is at around 0.17 V (vs. SCE). The electrode respondsy to dopamine in the ranges of 0.15 to 45 µM, the detection limit is 8.2 nM (S/N = 3), and the sensitivity is 20.81 µA µM-1 cm-2. In real human urine samples, the sensor exhibited detection recoveries of 97.4-98.8% and low relative standard deviations of 3.49-3.92%. Graphical abstract Schematic presentation of a surface-graphenized pencil graphite electrode (SGPGE) for detecting dopamine. It was prepared by a one-step in situ electrochemical graphene delamination.

19.
Physiol Plant ; 163(2): 247-258, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29230823

RESUMEN

In northern China, low temperature is the most common abiotic stresses for tomato plants cultivated in solar-greenhouse in winter. We recently found that the expression and enzyme activity of fructose-1,6-bisphosphate aldolases (FBAs) in tomato, which are important enzymes in the Calvin-Benson cycle (CBC), were significantly altered in tomato seedlings subjected to heat/cold stresses. In order to study the role of FBA in photosynthesis and in regulating cold stress responses of tomato seedlings (Solanum lycopersicum), we transformed a tomato inbred line (FF) with RNA interference (RNAi) vector containing SlFBA7 reverse tandem repeat sequence. We found that the decreased SlFBA7 expression led to the decreased activities of FBA, as well as the activities of other main enzymes in the CBC. We also noticed a decrease in net photosynthetic rate, ribulose-1,5-bisphosphate and soluble sugar content, stem diameter, dry weight and seed size in RNAi SlFBA7 plants compared to wild-type. However, there are no changes in starch contents in the RNAi transgenic plants. RNAi SlFBA7 plants showed a decreased germination rate, and an increased levels of superoxide anions (O2·- ) and hydrogen peroxide (H2 O2 ) under low temperature (8/5°C) and low-light intensity (100 µmol m-2  s-1 photon flux density) growth conditions. These findings demonstrated the important role of SlFBA7 in regulating growth and chilling tolerance of tomato seedlings, and suggested that the catalytic activity of FBA in the CBC is sensitive to temperature.


Asunto(s)
Aldehído-Liasas/metabolismo , Solanum lycopersicum/enzimología , Aldehído-Liasas/genética , Frío , Regulación de la Expresión Génica de las Plantas , Solanum lycopersicum/genética , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/fisiología , Fotosíntesis , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Interferencia de ARN , Plantones/enzimología , Plantones/genética , Plantones/crecimiento & desarrollo , Plantones/fisiología , Semillas/enzimología , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/fisiología , Estrés Fisiológico
20.
Mikrochim Acta ; 185(2): 134, 2018 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-29594419

RESUMEN

Bulk g-C3N4 was transformed into water-soluble graphitic carbon nitride quantum dots (g-CNQDs) via a chemical oxidation and liquid exfoliation process. The g-CNQDs possess a size distribution ranging from 1 to 5 nm (centered at 3 nm), excellent crystallinity, and are water soluble. It is found that Fe(III) ions are adsorbed on the surface of the g-CNQDs via electrostatic interaction, and that the blue fluorescence of the g-CNQDs is reduced by Fe(III) via an inner filter effect. By using the g-CNQDs as a fluorescent probe, Fe(III) can be determined at excitation/emission wavelengths of 241/368 nm in spiked natural water samples within 1 min and with good selectivity over other ions. Response is linear in the 0.2-60 µmol·L-1 Fe(III) concentration range, and the detection limit is 23 nmol·L-1. Graphical abstract Graphitic carbon nitride quantum dots (g-CNQDs) emit blue fluorescence at an excitation wavelength of 241 nm. Fe(III) ions are quickly adsorbed on the g-CNQDs via electrostatic interaction, and fluorescence is quenched due to an inner filter effect.

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