RESUMO
BACKGROUND: Stigma exsertion is an essential agricultural trait that can promote cross-pollination to improve hybrid seed production efficiency. However, the molecular mechanism controlling stigma exsertion remains unknown. RESULTS: In this study, the Nicotiana tabacum cv. K326 and its two homonuclear-heteroplasmic lines, MSK326 (male-sterile) and MSK326SE (male-sterile and stigma exserted), were used to investigate the mechanism of tobacco stigma exsertion. A comparison of the flowers between the three lines showed that the stigma exsertion of MSK326SE was mainly due to corolla shortening. Therefore, the corollas of the three lines were sampled and presented for RNA-seq analysis, which found 338 candidate genes that may cause corolla shortening. These genes were equally expressed in K326 and MSK326, but differentially expressed in MSK326SE. Among these 338 genes, 15 were involved in hormone synthesis or signal transduction pathways. Consistently, the content of auxin, dihydrozeatin, gibberellin, and jasmonic acid was significantly decreased in the MSK326SE corolla, whereas abscisic acid levels were significantly increased. Additionally, seven genes involved in cell division, cell cycle, or cell expansion were identified. Protein-protein interaction network analysis identified 45 nodes and 79 protein interactions, and the largest module contained 20 nodes and 52 protein interactions, mainly involved in the hormone signal transduction and pathogen defensive pathways. Furthermore, a putative hub gene coding a serine/threonine-protein kinase was identified for the network. CONCLUSIONS: Our results suggest that hormones may play a key role in regulating tobacco stigma exsertion induced by corolla shortening.
Assuntos
Nicotiana , Transcriptoma , Nicotiana/genética , Revelação , Ácidos Indolacéticos/metabolismo , Hormônios/metabolismo , Flores/metabolismoRESUMO
Cytoarchitectural staining is of great importance in disease diagnosis and cell biology research. This study developed user-friendly multifunctional red-emissive carbon dots (R-CDs) for rapid cell nucleus staining via targeting nuclear proteins. R-CDs, simply prepared by electrochemical treatment of 1,2,4-benzenetriamine, exhibit strong emission at 635 nm when excited at 507 nm. The R-CDs can rapidly stain the nucleus of human SH-SY5Y, HepG2, and HUH-7 cells with a high signal-to-noise ratio owing to fluorescence enhancement after entering the nucleus. Compared to conventional cytosolic dyes such as Hoechst and DAPI, R-CDs are cheaper, more highly dispersed in water, and more stable (requiring no stringent storage conditions). The R-CDs show stable optical properties with insignificant photobleaching over 7 days and salt resistance up to 2 M of NaCl. More importantly, R-CDs, possessing a positive charge, allow rapid staining of live cells (3 min) and dead cells (10 s) in saline. According to kinetic variation, R-CDs can distinguish live cells from dead cells. Staining exhibits high efficiency in onion epidermal cells, Aspergillus niger, Caenorhabditis elegans, and human spermatozoa. The mechanism for efficient staining is based on their fast accumulation in the nucleus due to their small size and positive charge and strong interaction with nuclear proteins at amino acid residues of histidine and arginine, resulting in fluorescence enhancement by dozens of times. The developed R-CDs do not bind to DNA and would not cause genetic damage and will find various safe applications in biological and medical fields.
Assuntos
Carbono , Núcleo Celular , Pontos Quânticos , Humanos , Carbono/química , Núcleo Celular/química , Núcleo Celular/metabolismo , Pontos Quânticos/química , Animais , Proteínas Nucleares/metabolismo , Proteínas Nucleares/análise , Corantes Fluorescentes/química , Coloração e Rotulagem , Caenorhabditis elegans/química , Cebolas/química , Cebolas/citologiaRESUMO
Chemical equilibrium stands as a fundamental principle governing the dynamics of chemical systems. However, it may become intricate when it refers to nanomaterials because of their unique properties. Here, we invesitigated concave gold nanocubes (CGNs) subjected to an akaline Au3+/H2O2 solution, which exhibit both etching and growth in a monotonic solution. When CGNs were subjected to an increasingly alkaline Au3+/H2O2 solution, their dimensions increased from 107 to 199 nm and then decreased to 125 nm. Transmission electron microscopy (TEM) demonstrated that their morphology undergoes intricate alternations from concave to mutibranch and finally to concave again. Real-time ultraviolet-visible spectroscopy and time-dependent TEM also demonstrated reduction first and then oxidation in one solution. Among the nanomaterials, the obtained carpenterworm-like gold nanoparticles revealed the best catalytic performance in p-nitrophenol reduction by NaBH4, with a chemical rate that continues to increase until the reaction reaches completion. Growth leading to atomic dislocation, distortion, and exposure on nanoparticles and the redox of H2O2 plausibly account for the further etching due to the Ostwald ripening effect. Our study may spur more interest in the tuning of the properties, engineering, investigation, and design of new kinds of nanomaterials.
RESUMO
A novel axially chiral all-hydrocarbon cyclo[7] (1,3-(4,6-dimethyl)benzene (CDMB-7) was designed and synthesized using atroposelective[2 + 5] cyclization through Suzuki-Miyaura coupling. CDMB-7 adopts an irregular bowl-like shape with C2 symmetry and exhibits two diastereoisomers in its crystallographic structure. The conformational isomers of CDMB-7 racemates remain stable at high temperatures (393 K). High-performance liquid chromatography (HPLC) confirmed that a single chiral isomer will spontaneously undergo racemization within 30 min at room temperature. This finding opens up possibilities for achieving adaptive chirality in all-hydrocarbon cyclo[7] m-benzene macrocycles.
RESUMO
Structurally novel 2-azaspiro[4.5]deca-1,6,9-trien-8-ones were synthesized from N-(2-propyn-1-yl) amides and 1,3,5-trimethoxybenzenes by a tandem method consisting of a Tf2O-promoted amide activation and a TfOH-promoted Friedel-Crafts ipso-cyclization. The method offered the first example of using N-(2-propyn-1-yl) amides as substrates in both Tf2O-promoted secondary amide activation and the synthesis of azaspiro[4.5]deca-6,9-diene-8-ones.
Assuntos
Amidas , Trientina , Estrutura Molecular , CiclizaçãoRESUMO
Intermetallic electrides have recently shown their priority as catalyst components in ammonia synthesis and CO2 activation. However, their function mechanism has been elusive since its inception, which hinders the further development of such catalysts. In this work, ternary intermetallic electrides La-TM-Si (TM = Co, Fe, and Mn) were synthesized as hosts of ruthenium (Ru) particles for ammonia synthesis catalysis. Although they have the same crystal structure and possess low work functions commonly, the promotion effects on Ru particles rather differ from each other. The catalytic activity follows the sequence of Ru/LaCoSi > Ru/LaFeSi > Ru/LaMnSi. Furthermore, Ru/LaCoSi exhibits much better catalytic durability than the other two. A combination of experiments and first-principles calculations shows that apparent N2 activation energy on each catalyst is much lower than that over conventional Ru-based catalysts, which suggests that N2 dissociation can be conspicuously promoted by the concerted actions of the specific electronic structure and atomic configuration of intermetallic electride-supported catalysts. The NHx formations proceeded on La are energetically favored, which makes it possible to bypass the scaling relations based on only Ru as the active site. The rate-determining step of Ru/La-TM-Si was identified to be NH2 formation. The transition metal (TM) in La-TM-Si electrides has a significant influence on the metal-support interaction of Ru and La-TM-Si. These findings provide a guide for the development of new and effective catalyst hosts for ammonia synthesis and other hydrogenation reactions.
RESUMO
2-Propynamides have been never used as substrates in classic and Tf2O-promoted Bischler-Napieralski reactions. In this article, a novel tandem synthesis of benzo[a]acridines is developed from N-aryl-2-propynamides and alkynes consisting of a Tf2O-promoted intermolecular Bischler-Napieralski reaction and a TfOH-promoted intramolecular Friedel-Crafts reaction.
RESUMO
A TfOH-promoted tandem synthesis of 1,3-disubstituted naphthalenes is developed via a directed-aldol reaction and a Friedel-Crafts reaction. Two new C-C bonds and one new benzene ring are created efficiently in one pot due to the discovery of a TfOH-promoted highly chemoselective directed-aldol reaction between two different ketones with α-hydrogens.
RESUMO
An efficient method for the synthesis of 6-alkynyl phenanthridines was developed. The method offered the first example to use 2-propynamides as substrates in the Bischler-Napieralski reaction and to create alkynylnitrilium triflates as new active intermediates in organic synthesis.
Assuntos
FenantridinasRESUMO
A general and efficient synthesis of fully substituted 4-aminodixazoles was developed based on the strategies of amide activation and umpolung reaction. In this method, 1,4,2-dioxazol-5-ones were introduced as a rare type of umpolung reagent bearing a nucleophilic N-atom that could be used well together with the activating agent Tf2O. Because 1,4,2-dioxazol-5-ones played triple roles as an umpolung reagent, a substrate, and a weak base, the method proceeded smoothly under extremely convenient conditions.
RESUMO
PTEN/AKT signaling cascade is frequently activated in various cancers, including lung cancer. The downstream effector of this signaling cascade is poorly understood. ß-Thymosin 10 (TMSB10) functions as an oncogene or tumor suppressors in cancers, whereas its significance in lung cancer remains unknown. In this study, we showed that the activation of PTEN/AKT signaling promoted the expression of TMSB10. Based on the TCGA database, TMSB10 was upregulated in lung cancer tissues and its overexpression was correlated with poor prognosis of lung cancer patients. Functional experiments demonstrated that TMSB10 knockdown suppressed, while its overexpression promoted the proliferation, growth, and migration of lung cancer cells. Apoptosis and epithelial-mesenchymal transition were also regulated by TMSB10. We therefore suggest that TMSB10 is a novel oncogene for lung cancer. Targeting TMSB10 may benefit lung cancer patients with activated PTEN/AKT signaling.
Assuntos
Neoplasias Pulmonares/patologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Timosina/fisiologia , Regulação para Cima , Apoptose/fisiologia , Transição Epitelial-Mesenquimal/genética , Técnicas de Silenciamento de Genes , Humanos , Prognóstico , Transdução de Sinais , Análise de Sobrevida , Timosina/genéticaRESUMO
CK2, a serine/threonine (Ser/Thr) kinase present in eukaryotic cells, is known to have a vast number of substrates. We have recently shown that it localizes to nuclei and at pores between hyphal compartments in Magnaporthe oryzae We performed a pulldown proteomics analysis of M. oryzae CK2 catalytic subunit MoCKa to detect interacting proteins. The MoCKa pulldown was enriched for septum and nucleolus proteins and intrinsically disordered proteins (IDPs) containing a CK2 phosphorylation motif that is proposed to destabilize and unfold α-helices. This points to a function for CK2 phosphorylation and corresponding phosphatase dephosphorylation in the formation of functional protein-protein aggregates and protein-RNA/DNA binding. To test this as widely as possible, we used secondary data downloaded from databases from a large range of M. oryzae experiments, as well as data for a relatively closely related plant-pathogenic fungus, Fusarium graminearum We found that CKa expression was strongly positively correlated with Ser/Thr phosphatases, as well as with disaggregases (HSP104, YDJ1, and SSA1) and an autophagy-indicating protein (ATG8). The latter points to increased protein aggregate formation at high levels of CKa expression. Our results suggest a general role for CK2 in chaperoning aggregation and disaggregation of IDPs and their binding to proteins, DNA, and RNA.IMPORTANCE CK2 is a eukaryotic conserved kinase enzyme complex that phosphorylates proteins. CK2 is known to phosphorylate a large number of proteins and is constitutively active, and thus a "normal" role for a kinase in a signaling cascade might not be the case for CK2. Previous results on localization and indications from the literature point to a function for CK2 phosphorylation in shaping and folding of proteins, especially intrinsically disordered proteins, which constitute about 30% of eukaryotic proteins. We used pulldown of interacting proteins and data downloaded from a large range of transcriptomic experiments in M. oryzae and complemented these with data downloaded from a large range of transcriptomic experiments in Fusarium graminearum We found support for a general role for CK2 in aggregation and disaggregation of IDPs and their binding to proteins, DNA, and RNA-interactions that could explain the importance of CK2 in eukaryotic cell function and disease.
Assuntos
Caseína Quinase II/genética , Proteínas Fúngicas/genética , Proteínas Intrinsicamente Desordenadas/genética , Magnaporthe/genética , Chaperonas Moleculares/genética , Caseína Quinase II/metabolismo , Domínio Catalítico , Proteínas Fúngicas/metabolismo , Proteínas Intrinsicamente Desordenadas/metabolismo , Magnaporthe/metabolismo , Chaperonas Moleculares/metabolismo , ProteômicaRESUMO
The copper-catalyzed decarboxylative selenation of aromatic carboxylic acids with diselenide is reported. This transformation tolerated a diverse set of functional groups on the substrates, including pentafluorobenzoic acid and heteroaromatic acids, delivering diaryl and methyl aryl selenides in good to excellent yields. Mechanistic studies indicated that the copper catalyst is essential in the activation of the Se-Se bond and the decarboxylation of aromatic acids. The utility of the products has been demonstrated in the facile synthesis of 10H-phenoselenazine and 11-methyldibenzo-(b,f)-1,4-selenazepine.
RESUMO
BACKGROUND: Alexithymia is characterised by difficulties identifying and describing emotions. Few studies have investigated how alexithymia influences decision-making under different conditions (ambiguity and risk). This study aimed to examine whether alexithymia contributes to impairment in decision-making. METHOD: This study included 42 participants with high scores in the Chinese version of Toronto Alexithymia Scale (alexithymia group), and 44 matched subjects with low scores (control group). Decision-making was measured using the Iowa Gambling Task (IGT) and the Game of Dice Task (GDT). RESULTS: The main findings of this study revealed selective deficits in IGT performance for the alexithymia group, while GDT performance was unimpaired when compared with the control group. In IGT, total netscores were lower for the alexithymia group compared to the control group, particularly with regard to block 5. Moreover, the alexithymia individuals selected significantly more adverse cards than the controls, indicating significant decision-making impairments. CONCLUSION: Alexithymia selectively influences decision-making under ambiguity.
Assuntos
Sintomas Afetivos/psicologia , Tomada de Decisões , Jogo de Azar/psicologia , Análise e Desempenho de Tarefas , Adulto , Povo Asiático/psicologia , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Assunção de RiscosRESUMO
Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine protein kinase and belongs to the extracellular signal-regulated kinases/microtubule-associated protein kinase families (Erks/MAPKs). Previous studies have indicated that abnormal expressions of NLK played critical roles in various types of human cancers. Recent studies suggested that NLK expression was significantly upregulated in the hepatocellular carcinoma (HCC) specimens. However, the clinical significance of NLK expression in HCC remains largely unknown. In this study, we focused on the clinical significance of NLK in HCC and found that high expression of NLK was significantly associated with Edmondson-Steiner grade (P = 0.002), tumor size (P = 0.022), and no. of tumor nodules (P < 0.001), and NLK was positively correlated with proliferation marker Ki-67 (P < 0.01). Univariate analysis suggested that NLK expression was associated with poor prognosis (P < 0.001). Multivariate analysis indicated that NLK expression was an independent prognostic indicator for HCC (P = 0.0370). In conclusion, NLK overexpression is associated with poor overall survival in patients with HCC, it might be an independent poor prognostic marker for HCC.
Assuntos
Biomarcadores Tumorais/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Neoplasias Hepáticas/genética , Prognóstico , Proteínas Serina-Treonina Quinases/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/genéticaRESUMO
BACKGROUND: p21-activated protein kinase (PAK) 6 is a serine-threonine kinase belonging to the PAK family. Previous studies have indicated that abnormal expressions of PAK1, PAK2, and PAK5 played critical roles in hepatocellular carcinoma (HCC). Recent studies suggested that deregulation of PAK6 expression played an important role in oncogenesis. To explore the potential roles of PAK6 in HCC, expression of PAK6 was detected in human HCC specimens. METHODS: Immunohistochemistry and Western blot analysis were performed for PAK6 in 121 HCC samples. The data were correlated with clinicopathologic features. The univariate and multivariate survival analyses were also performed to determine their clinical prognostic significance. RESULTS: PAK6 was overexpressed in HCC as compared with the adjacent noncancerous liver tissues. High expression of PAK6 was associated with Edmondson-Steiner grade (P = 0.006) and number of tumor nodules (P < 0.001), and PAK6 was positively correlated with proliferation marker Ki-67 (P < 0.01). Univariate analysis suggested that PAK6 expression was associated with poor prognosis (P < 0.001). Multivariate analysis indicated that PAK6 and Ki-67 protein expressions were independent prognostic markers for HCC (P = 0.0245 and 0.0331, respectively). CONCLUSIONS: Our results suggest that PAK6 overexpression is involved in the pathogenesis of HCC; it may be an independent poor prognostic factor for HCC.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Fígado/enzimologia , Quinases Ativadas por p21/biossíntese , Quinases Ativadas por p21/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , China/epidemiologia , Feminino , Humanos , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Quinases Ativadas por p21/metabolismoRESUMO
Accurate estimation of pandemic likelihood in every US state of interest and at any time. Coronavirus disease 2019 (COVID-19) is an infectious illness with a high potential for global dissemination and low rates of fatality and morbidity, placing some strains on national public health systems. This research intends to benchmark a novel technique, that enables hazard assessment, based on available clinical data, and dynamically observed patient numbers while taking into account pertinent territorial and temporal mapping. Multicentre, population-based, and biostatistical strategies have been utilized to process raw/unfiltered medical survey data. The expansion of extreme value statistics from the univariate to the bivariate situation meets with numerous challenges. First, the univariate extreme value types theorem cannot be directly extended to the bivariate (2D) case,-not to mention challenges with system dimensionality higher than 2D. Assessing outbreak risks of future outbreaks in any nation/region of interest. Existing bio-statistical approaches do not always have the benefits of effectively handling large regional dimensionality and cross-correlation between various regional observations. These methods deal with temporal observations of multi-regional phenomena. Apply contemporary, novel statistical/reliability techniques directly to raw/unfiltered clinical data. The current study outlines a novel bio-system hazard assessment technique that is particularly suited for multi-regional environmental, bio, and public health systems, observed over a representative period. With the use of the Gaidai multivariate hazard assessment approach, epidemic outbreak spatiotemporal risks may be properly assessed. Based on raw/unfiltered clinical survey data, the Gaidai multivariate hazard assessment approach may be applied to a variety of public health applications. The study's primary finding was an assessment of the risks of epidemic outbreaks, along with a matching confidence range. Future global COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-COV2) epidemic risks have been examined in the current study; however, COVID-19/SARS-COV2 infection transmission mechanisms have not been discussed.
RESUMO
High expression of programmed cell death protein 1 (PD-1), a typical immune checkpoint, results in dysfunction of T cells in tumor microenvironment. Antibodies and inhibitors against PD-1 or its ligand (PD-L1) have been widely used in various malignant tumors. However, the mechanisms by which PD-1 is regulated are not fully understood. Here, we report a mechanism of PD-1 degradation triggered by d-mannose and the universality of this mechanism in anti-tumor immunity. We show that d-mannose inactivates GSK3ß via promoting phosphorylation of GSK3ß at Ser9, thereby leading to TFE3 translocation to nucleus and subsequent PD-1 proteolysis induced by enhanced lysosome biogenesis. Notably, combination of d-mannose and PD-1 blockade exhibits remarkable tumor growth suppression attributed to elevated cytotoxicity activity of T cells in vivo. Furthermore, d-mannose treatment dramatically improves the therapeutic efficacy of MEK inhibitor (MEKi) trametinib in vivo. Our findings unveil a universally unrecognized anti-tumor mechanism of d-mannose by destabilizing PD-1 and provide strategies to enhance the efficacy of both immune checkpoint blockade (ICB) and MEKi -based therapies.
Assuntos
Lisossomos , Manose , Receptor de Morte Celular Programada 1 , Linfócitos T , Receptor de Morte Celular Programada 1/metabolismo , Lisossomos/metabolismo , Animais , Humanos , Camundongos , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Manose/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Inibidores de Checkpoint Imunológico/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Pirimidinonas/farmacologia , Fosforilação , Piridonas/farmacologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Camundongos Endogâmicos C57BL , Proteólise , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismoRESUMO
In this study, we aimed to synthesis of Fe-doping green fluorescent carbon dots (G-CDs) through the co-electrolysis of chrysoidine G and potassium ferrocyanide for Cr(VI) detection. The use of potassium ferrocyanide improves the quantum yield and sensing performance of G-CDs toward Cr(VI). The G-CDs have a maximum excitation wavelength of 308 nm and an emission wavelength of 510 nm. Comprehensive analyses including Raman, FT-IR, and XPS provided insights into the chemical structure and composition of the G-CDs. Under optimal conditions, G-CDs demonstrated concentration-dependent quenching upon interaction with Cr(VI). A linear relationship within the range of 0.25-100 µM was established with a calibration equation of ΔF/F0 = 0.005 + 0.015CCr(VI), yielding an R2 value of 0.996 and a limit of detection of 0.15 µM. The applicability of the G-CDs method was demonstrated by successful Cr(VI) detection in water samples with recovery rates ranging from 98.8 % to 100.1 % and relative standard deviation within 3.0 %. The fluorescence lifetime and Zeta potential measurements confirmed that the mechanism was via a static quenching process, while redox reaction, nanoparticle aggregation, and surface charge variation also played significant roles.
RESUMO
The effective differentiation and detection of multiple tea polyphenols are often challenging due to their subtle structural similarities. Although post-column derivatization HPLC strategies are commonly employed to distinguish multiple targets, the short physical distance between chromatographic column and detector limits reaction time, thereby reducing the derivatization efficiency. Dopamine (DA) reacts rapidly with resorcinol to form fluorescent azamonardine products, making fast fluorometric derivatization of tea polyphenols containing resorcinol motifs possible. In this study, a DA-driven rapid and post-column fluorescence derivatization method has been applied to sensitively detect eight tea polyphenols. This method is based on fluorescence derivatization and possesses low background interference, high sensitivity, and excellent reproducibility. Moreover, the practical application of this proposed fluorometric derivatization platform was further validated by simultaneous identification of multiple tea polyphenols in different tea samples. This work has great potential to become an alternative to the National Standard method for tea polyphenols determination.