RESUMEN
Antiferromagnetic spintronics1-16 is a rapidly growing field in condensed-matter physics and information technology with potential applications for high-density and ultrafast information devices. However, the practical application of these devices has been largely limited by small electrical outputs at room temperature. Here we describe a room-temperature exchange-bias effect between a collinear antiferromagnet, MnPt, and a non-collinear antiferromagnet, Mn3Pt, which together are similar to a ferromagnet-antiferromagnet exchange-bias system. We use this exotic effect to build all-antiferromagnetic tunnel junctions with large nonvolatile room-temperature magnetoresistance values that reach a maximum of about 100%. Atomistic spin dynamics simulations reveal that uncompensated localized spins at the interface of MnPt produce the exchange bias. First-principles calculations indicate that the remarkable tunnelling magnetoresistance originates from the spin polarization of Mn3Pt in the momentum space. All-antiferromagnetic tunnel junction devices, with nearly vanishing stray fields and strongly enhanced spin dynamics up to the terahertz level, could be important for next-generation highly integrated and ultrafast memory devices7,9,16.
RESUMEN
Lipid droplets (LDs) stored during seed development are mobilized and provide essential energy and lipids to support seedling growth upon germination. Triacylglycerols (TAGs) are the main neutral lipids stored in LDs. The lipase SUGAR DEPENDENT 1 (SDP1), which hydrolyzes TAGs in Arabidopsis thaliana, is localized on peroxisomes and traffics to the LD surface through peroxisomal extension, but the underlying mechanism remains elusive. Here, we report a previously unknown function of a plant-unique endosomal sorting complex required for transport (ESCRT) component FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING 1 (FREE1) in regulating peroxisome/SDP1-mediated LD turnover in Arabidopsis. We showed that LD degradation was impaired in germinating free1 mutant; moreover, the tubulation of SDP1- or PEROXIN 11e (PEX11e)-marked peroxisomes and the migration of SDP1-positive peroxisomes to the LD surface were altered in the free1 mutant. Electron tomography analysis showed that peroxisomes failed to form tubules to engulf LDs in free1, unlike in the wild-type. FREE1 interacted directly with both PEX11e and SDP1, suggesting that these interactions may regulate peroxisomal extension and trafficking of the lipase SDP1 to LDs. Taken together, our results demonstrate a pivotal role for FREE1 in LD degradation in germinating seedlings via regulating peroxisomal tubulation and SDP1 targeting.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Plantones/metabolismo , Peroxisomas/metabolismo , Proteínas de Arabidopsis/metabolismo , Gotas Lipídicas/metabolismo , Lipasa/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Lípidos , Hidrolasas de Éster Carboxílico/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMEN
Prostate cancer (PCa) is the most prevalent malignant tumor of the genitourinary system, and metastatic disease has a significant impact on the prognosis of PCa patients. As a result, knowing the processes of PCa development can help patients achieve better outcomes. Here, we investigated the expression and function of ORC6 in PCa. Our findings indicated that ORC6 was elevated in advanced PCa tissues. Patients with PCa who exhibited high levels of ORC6 had a poor prognosis. Following that, we investigated the function of ORC6 in PCa progression using a variety of functional experiments both in vivo and in vitro, and discovered that ORC6 knockdown inhibited PCa cell proliferation, growth, and migration. Furthermore, RNA-seq was employed to examine the molecular mechanism of PCa progression. The results revealed that ORC6 might promote the expression of PLK1, a serine/threonine kinase in PCa cells. We also discovered that ORC6 as a novel miR-361-5p substrate using database analysis, and miR-361-5p was found to lower ORC6 expression. Additionally, RNA immunoprecipitation (RIP) and luciferase reporter tests revealed that the transcription factor E2F1 could regulate ORC6 expression in PCa cells. PLK1 overexpression or miR-361-5p inhibitor treatment effectively removed the inhibitory effects caused by ORC6 silencing. Notably, our data showed that therapeutically targeting the miR-361-5p/ORC6/PLK1 axis may be a viable therapy option for PCa.
Asunto(s)
Proteínas de Ciclo Celular , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , MicroARNs , Quinasa Tipo Polo 1 , Neoplasias de la Próstata , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas , Animales , Humanos , Masculino , Ratones , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Complejo de Reconocimiento del Origen/genética , Complejo de Reconocimiento del Origen/metabolismo , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismoRESUMEN
Cu2S likely plays an important role in the sharp resistivity transition of LK-99. Nevertheless, this immediately arouses an intriguing question of whether the extraordinary room-temperature colossal magnetoresistance in the initial reports, which has been less focused, originates from Cu2S as well. To resolve this issue, we have systematically investigated the electrical transport and magnetotransport properties of near-stoichiometric Cu2S pellets and thin films. Neither Cu2S nor LK-99 containing Cu2S in this study was found to exhibit the remarkable magnetoresistance effect implied by Lee et al. This implies that Cu2S could not account for all of the intriguing transport properties of the initially reported LK-99, and the initially reported LK-99 samples might contain magnetic impurities. Moreover, based on the crystal-structure-sensitive electrical properties of Cu2S, we have constructed a piezoelectric-strain-controlled device and obtained a giant and reversible resistance modulation of 2 orders of magnitude at room temperature, yielding a huge gauge factor of 160,000.
RESUMEN
An iodine-mediated method for the synthesis of 6-alkylthio-1,3,5-triazine-2,4-diamines by the reaction of N-alkylpyridinium salts and NH4SCN in air is reported. Twenty-seven compounds were obtained under the standard conditions. Pyridinium salts work as benzyl-group transfer reagents to promote the formation of the CBn-SSCN bond and thereby the construction of the triazine skeleton. A plausible mechanism is proposed based on the experimental results and literature survey.
RESUMEN
The endomembrane system consists of various membrane-bound organelles including the endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN), endosomes, and the lysosome/vacuole. Membrane trafficking between distinct compartments is mainly achieved by vesicular transport. As the endomembrane compartments and the machineries regulating the membrane trafficking are largely conserved across all eukaryotes, our current knowledge on organelle biogenesis and endomembrane trafficking in plants has mainly been shaped by corresponding studies in mammals and yeast. However, unique perspectives have emerged from plant cell biology research through the characterization of plant-specific regulators as well as the development and application of the state-of-the-art microscopical techniques. In this review, we summarize our current knowledge on the plant endomembrane system, with a focus on several distinct pathways: ER-to-Golgi transport, protein sorting at the TGN, endosomal sorting on multivesicular bodies, vacuolar trafficking/vacuole biogenesis, and the autophagy pathway. We also give an update on advanced imaging techniques for the plant cell biology research.
Asunto(s)
Endosomas , Plantas , Plantas/metabolismo , Endosomas/metabolismo , Vacuolas/metabolismo , Cuerpos Multivesiculares/metabolismo , Transporte de Proteínas , Aparato de Golgi/metabolismo , Red trans-Golgi/metabolismoRESUMEN
BACKGROUND: In China, the recommended treatment regimens for HIV-infected individuals were tenofovir in combination with lamivudine or emtricitabine as NRTIs, efavirenz or rilpivirine as NNRTIs, lopinavir/ritonavir as protease inhibitors, and raltegravir or dolutegravir as INSTIs. The development of drug resistance increases the risk of viral rebound, opportunistic infections, and ultimately treatment failure such that the early detection of resistance is ideal. This study was developed to explore primary drug resistance characteristics and genotypic distributions in newly diagnosed antiretroviral therapy (ART)-naïve HIV-1 patients in Nanjing with the goal of establishing a basis for their individualized treatment in the clinic. METHODS: Samples of serum were collected from newly diagnosed ART-naïve HIV patients from the Second Hospital of Nanjing between May 2021 and May 2022. The HIV-1 integrase (IN), protease (PR), and reverse transcriptase (RT) gene coding sequences were amplified from these samples, sequenced, and assessed for drug resistance-related mutations. RESULTS: Major integrase resistance-related mutations were detected in 4/360 amplified samples, with 5 other patient samples exhibiting accessory resistance mutations. The overall prevalence of PR and RT inhibitor-related transmitted drug resistance mutations (TDRMs) in this patient population was 16.99% (61/359). The most common mutations were non-nucleoside reverse transcriptase inhibitor-related mutations (51/359; 14.21%), followed by those associated with nucleoside reverse transcriptase inhibitors (7/359; 1.95%) and protease inhibitors (7/359; 1.95%). Dual-resistant strains were also observed in a subset of patients. CONCLUSIONS: In summary, this study is the first to have surveyed the prevalence of integrase inhibitor resistance-related mutations and other drug resistance-related mutations among newly diagnosed ART-naïve HIV-positive patients in Nanjing, China. These results highlight the need for further molecular surveillance-based monitoring of the HIV epidemic in Nanjing.
Asunto(s)
Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa/uso terapéutico , Tenofovir , Inhibidores de Proteasas , Mutación , Farmacorresistencia Viral/genéticaRESUMEN
Organic donor-acceptor complexes as new organic semiconductor class have attracted wide attention, due to their potential applications in functional optoelectronics. Herein, we present two new charge transfer cocrystals of di-cyanodiazafluorene -perylene (DCPE) and di-cyanodiazaflfluorene-pyrene (DCPY) through a rational cocrystal-engineering strategy. Although they are both 1 : 1 mixed stacking cocrystals with similar chemical structures, the DCPE cocrystal possesses a non-centrosymmetric space group and narrower band gap compared to DCPY cocrystal, because of the non-covalent bonding variation. The electrostatic potential accumulated in the lateral facets leads to highly twisted DCPE nanobelts, and the small band gap causes near infrared fluorescence. Meanwhile, the DCPY crystals with centrosymmetric space groups and weaker intermolecular interactions exhibited an untwisted morphology and red emission. This study will be helpful for the design and understanding of functional cocrystal materials that can be used in flexible micro/nano-mechanics, mechanical energy, and optical devices.
RESUMEN
Rural domestic sewage has the characteristics of large and scattered discharge, as well as complex components; thus, how to effectively and efficiently manage rural domestic sewage is a big challenge for policy makers. Current decentralized domestic sewage treatment facilities (DDSTF) involve different treatment processes and power drive modes; at the same time, the treatment effect is also affected by a variety of local factors. However, there is a lack of research to explore the implementation performance of the DDSTF from a comprehensive perspective. In this study, we took Nantong City, China, as a case study and conducted field investigations of 79 DDSTFs in seven counties from July 2021 to September 2022. We then made an in-depth analysis of the implementation performances of the DDSTF from an internal and external perspective. The results indicate that low temperature will reduce the DDSTF's treatment capacity, and the operation and maintenance mode affect the treatment effect of the facilities significantly. In addition, the non-standardized design for small-capacity facilities commonly results in lower compliance rates. Based on the results, we suggest that improving the quality of design and construction and adopting specialized operations are important ways to improve the treatment efficiency of rural DDSTF.
Asunto(s)
Población Rural , Aguas del Alcantarillado , Humanos , China , CiudadesRESUMEN
Glycosyltransferase (GT) enzymes promote the formation of glycosidic bonds between a sugar molecule and a diversity of substrates. Heptosyltransferase II (HepII) is a GT involved in the lipopolysaccharide (LPS) biosynthetic pathway that transfers the seven-carbon sugar (l-glycero-d-manno-heptose, Hep) onto a lipid-anchored glycopolymer (heptosylated Kdo2-Lipid A, Hep-Kdo2-Lipid A, or HLA). LPS plays a key role in Gram-negative bacterial sepsis, biofilm formation, and host colonization, and as such, LPS biosynthetic enzymes are targets for novel antimicrobial therapeutics. Three heptosyltransferases are involved in the inner-core LPS biosynthesis, with Escherichia coli HepII being the last to be quantitatively characterized in vivo. HepII shares modest sequence similarity with heptosyltransferase I (HepI) while maintaining a high degree of structural homology. Here, we report the first kinetic and biophysical characterization of HepII and demonstrate the properties of HepII that are shared with HepI, including sugar donor promiscuity and sugar acceptor-induced secondary structural changes, which results in significant thermal stabilization. HepII also has an increased catalytic efficiency and a significantly tighter binding affinity for both of its substrates compared to HepI. A structural model of the HepII ternary complex, refined by molecular dynamics simulations, was developed to probe the potentially important substrate-protein contacts. Ligand binding-induced changes in Trp fluorescence in HepII enabled the determination of substrate dissociation constants. Combined, these efforts meaningfully enhance our understanding of the heptosyltransferase family of enzymes and will aid in future efforts to design novel, potent, and specific inhibitors for this family of enzymes.
Asunto(s)
Escherichia coli , Glicosiltransferasas , Lípido A , Catálisis , Escherichia coli/enzimología , Glicosiltransferasas/metabolismo , Heptosas/química , Lípido A/metabolismo , Lipopolisacáridos , Simulación de Dinámica MolecularRESUMEN
A three starting material four component reaction (3SM-4CR) is developed for the synthesis of α,ß-unsaturated ketones and ß-amino ketones in good yields. The reaction employs tetramethylethylenediamine (TMEDA) as a methylene and terminal olefin source, and Selectfluor as a mild oxidant. TMEDA worked as a dual synthon to provide two carbons in this metal-free transformation process. The scope and versatility of the methods have been demonstrated with 23 examples. A Selectfluor-promoted oxidative reaction mechanism is proposed based on the results of the experimental studies.
RESUMEN
Materials that exhibit simultaneous order in their electric and magnetic ground states hold promise for use in next-generation memory devices in which electric fields control magnetism. Such materials are exceedingly rare, however, owing to competing requirements for displacive ferroelectricity and magnetism. Despite the recent identification of several new multiferroic materials and magnetoelectric coupling mechanisms, known single-phase multiferroics remain limited by antiferromagnetic or weak ferromagnetic alignments, by a lack of coupling between the order parameters, or by having properties that emerge only well below room temperature, precluding device applications. Here we present a methodology for constructing single-phase multiferroic materials in which ferroelectricity and strong magnetic ordering are coupled near room temperature. Starting with hexagonal LuFeO3-the geometric ferroelectric with the greatest known planar rumpling-we introduce individual monolayers of FeO during growth to construct formula-unit-thick syntactic layers of ferrimagnetic LuFe2O4 (refs 17, 18) within the LuFeO3 matrix, that is, (LuFeO3)m/(LuFe2O4)1 superlattices. The severe rumpling imposed by the neighbouring LuFeO3 drives the ferrimagnetic LuFe2O4 into a simultaneously ferroelectric state, while also reducing the LuFe2O4 spin frustration. This increases the magnetic transition temperature substantially-from 240 kelvin for LuFe2O4 (ref. 18) to 281 kelvin for (LuFeO3)9/(LuFe2O4)1. Moreover, the ferroelectric order couples to the ferrimagnetism, enabling direct electric-field control of magnetism at 200 kelvin. Our results demonstrate a design methodology for creating higher-temperature magnetoelectric multiferroics by exploiting a combination of geometric frustration, lattice distortions and epitaxial engineering.
RESUMEN
BACKGROUND: Endoscopic combined intrarenal surgery (ECIRS) is well established as a minimally invasive procedure for the treatment of multiple urolithiasis. The position is the key to the perfect combination of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). Galdakao-modified supine Valdivia (GMSV) and prone split-leg positions are widely used. However, both positions have their own advantages and disadvantages. This study aimed to evaluate the effect of ECIRS in the treatment of multiple urolithiasis in the modified prone split-leg position. PATIENTS AND METHODS: A total of 96 patients with multiple urolithiasis underwent ECIRS in modified prone split-leg position from September 2017 to January 2021. Relevant demographic and clinical data were analysed retrospectively. Clinical outcomes, such as the stone free rate, complications and postoperative hospital stay were evaluated. The chi-square test was used to compare categorical variables and Student's t test was applied for continuous variables of the treatment groups. RESULTS: The mean renal stone size was 32.5 ± 10.7 mm and renal stone surface area was 712.2 ± 264.8 mm2. The mean ureteral stones size was 24.8 ± 12.3 mm. The mean surgical time was 82.2 ± 38.3 min. The incidence of complications was 16.7%, and they were mainly grade 1 and grade 2. No complications occurred above grade 3. The stone was completely removed in 75 (78.1%) patients in a single operation. The risk factors affecting the stone-free rate of ECIRS were analysed, and only the number of involved calyces by stone was found to be significant (p = 0.01). CONCLUSION: ECIRS is safe and effective in the treatment of multiple renal calculi or multiple renal calculi with ipsilateral ureteral calculi in the modified prone split-leg position. The modification of the prone split-leg position makes the retrograde operation more convenient, which is conducive to the combination of RIRS and PCNL.
Asunto(s)
Cálculos Renales/cirugía , Nefrolitotomía Percutánea/métodos , Posicionamiento del Paciente/métodos , Anciano , Femenino , Humanos , Cálculos Renales/patología , Masculino , Persona de Mediana Edad , Nefrolitotomía Percutánea/efectos adversos , Tempo Operativo , Estudios RetrospectivosRESUMEN
Excessive manganese (Mn) exposure can cause nerve damage and mitochondrial dysfunction, which may involve defects in mitochondrial dynamics. Resveratrol (RSV) exerts a wide range of beneficial effects via activation of sirtuin 1 (SIRT1) and thus may positively impact Mn-induced mitochondrial damage through the regulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) by SIRT1. In this study, we investigated the molecular mechanisms by which RSV alleviates the nerve injury and mitochondrial fragmentation caused by Mn in C57 BL/6 mice. Our results demonstrated that RSV activated the deacetylase activity of SIRT1 and protected against the surge of mitochondrial reactive oxygen species, the loss of mitochondrial membrane potential, and the attenuation of ATP caused by Mn. RSV, therefore, inhibits mitochondrial fragmentation and safeguards neural cells. Increased deacetylase activity led to a reduction in the acetylation of PGC-1α, which directly regulates DRP1 expression by binding to the DRP1 promoter. The resultant attenuation of DRP1-mediated mitochondrial fragmentation in RSV-pretreated mice was abolished by the addition of the SIRT1 inhibitor EX527. Taken together, these findings indicate that RSV alleviates Mn-induced mitochondrial dysfunction mediated by DRP1 by modulating the SIRT1/PGC-1α signaling pathway.
Asunto(s)
Manganeso , Sirtuina 1 , Animales , Manganeso/toxicidad , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Resveratrol , Transducción de Señal , Sirtuina 1/genética , Sirtuina 1/metabolismoRESUMEN
Cold stress at the booting stage leads to a lower seed setting rate and seriously threatens the production of rice (Oryza sativa L.), which has become a major yield-limiting factor in higher-altitude and -latitude regions. Because cold tolerance at the booting stage (CTB) is a complex trait and is controlled by multiple loci, only a few genes have been reported so far. In this study, a function of OsMKKK70 (Mitogen Activated Protein Kinase Kinase Kinase 70) in response to CTB was characterized. OsMKKK70 expression was rapidly induced by cold stress at the booting stage. OsMKKK70 overexpression (OsMKKK70-OE) plants were more sensitive to cold stress at the booting stage with a lower seed setting and pollen fertility, but there was no significant difference between the osmkkk70 mutant and WT. Considering the effect of functional redundancy, we further tested the CTB response of osmkkk62/70 and osmkkk55/62/70, the double and triple mutants of OsMKKK70 with its closest homologs OsMKKK62 and OsMKKK55, and found that osmkkk62/70 and osmkkk55/62/70 displayed significantly increased CTB with a higher seed setting and pollen fertility, indicating that OsMKKK70 negatively regulates rice CTB. Moreover, under the low-temperature (LT) condition, the osmkkk62/70 mutant had slightly higher Gibberellin (GA) contents, increased expression of GA biosynthesis genes, and lower protein level of OsSLR1 in anthers than those in WT. By contrast, OsMKKK70-OE anther had a lower GA biosynthesis than that of WT. Together, these findings suggest that OsMKKK70 negatively regulates rice CTB by fine-tuning GA levels in anthers.
Asunto(s)
Oryza , Oryza/genética , Frío , Respuesta al Choque por Frío , Tolerancia a MedicamentosRESUMEN
Cuticular wax plays crucial roles in protecting plants from environmental stresses, particularly drought stress. Many enzyme-encoding genes and transcription factors involved in wax biosynthesis have been identified, but the underlying posttranslational regulatory mechanisms are poorly understood. Here, we demonstrate that DROUGHT HYPERSENSITIVE (DHS), encoding a Really Interesting New Gene (RING)-type protein, is a critical regulator of wax biosynthesis in rice (Oryza sativa). The cuticular wax contents were significantly reduced in DHS overexpression plants but increased in dhs mutants compared with the wild type, which resulted in a response opposite that of drought stress. DHS exhibited E3 ubiquitin ligase activity and interacted with the homeodomain-leucine zipper IV protein ROC4. Analysis of ROC4 overexpression plants and roc4 mutants indicated that ROC4 positively regulates cuticular wax biosynthesis and the drought stress response. ROC4 is ubiquitinated in vivo and subjected to ubiquitin/26S proteasome-mediated degradation. ROC4 degradation was promoted by DHS but delayed in dhs mutants. ROC4 acts downstream of DHS, and Os-BDG is a direct downstream target of the DHS-ROC4 cascade. These results suggest a mechanism whereby DHS negatively regulates wax biosynthesis by promoting the degradation of ROC4, and they suggest that DHS and ROC4 are valuable targets for the engineering of drought-tolerant rice cultivars.
Asunto(s)
Vías Biosintéticas , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteolisis , Factores de Transcripción/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ceras/metabolismo , Adaptación Fisiológica , Sequías , Mutación/genética , Oryza/genética , Fenotipo , Epidermis de la Planta/metabolismo , Epidermis de la Planta/ultraestructura , Plantas Modificadas Genéticamente , Complejo de la Endopetidasa Proteasomal/metabolismo , Unión Proteica , Estabilidad Proteica , Estrés Fisiológico , Ubiquitina/metabolismoRESUMEN
AIMS: Renal cell cancers typically exhibit high metastasis and recurrence, and this is thought to be due to renal cancer stem cells (CSCs). Meanwhile, aberrant activation of Sonic hedgehog (Shh) signaling is linked with CSCs. Resveratrol has direct or indirect impacts on the pathological activities of CSCs. However, the effects of resveratrol on renal CSCs remain to be elucidated. METHODS: We cultured renal CSCs in serum-free medium. Western blotting was used to analyze the expression levels of related proteins. The mRNA changes were detected by qRT-PCR after resveratrol treatment. The CD133+ cells were quantified by flow cytometry analysis. Immunofluorescence staining images showed the changes in CD44 and Smoothened expression in the cell spheres. RESULTS: Renal CSCs were enriched by tumorsphere formation assays of ACHN and 786-O cells. Resveratrol treatments markedly decreased the size and number of cell spheres and downregulated the expression of the Shh pathway-related proteins and CSCs markers. Moreover, we observed that resveratrol inhibited cell proliferation and induced cell apoptosis, while purmorphamine upregulated the Shh pathway and weakened the effects of resveratrol on renal CSCs. CONCLUSIONS: These results suggested that resveratrol is a potential novel therapeutic agent that targets inactivation of renal CSCs by affecting the function of the Shh pathway.
Asunto(s)
Proteínas Hedgehog , Neoplasias , Células Madre Neoplásicas/efectos de los fármacos , Resveratrol , Transducción de Señal , Proliferación Celular , Células Cultivadas , Humanos , Resveratrol/farmacologíaRESUMEN
In this work, amino acids (AAs) including serine (S), histidine (H) and glutamic acid (E)-conjugated poly(3-thiophene acetate acid) (P3TAA) were synthesized to promote the catalytic hydrolysis and in situ electrochemical detection of organophosphorus pesticides (OPs). The hydrolysis of OPs followed the mechanism of proton transfer relay composed of AAs of S, H, E, called the "catalytic triad", found in biomimetic hydrolases. P3TAA was used as a carrier to attach S, H, E, and these AA sites have the hydrolysis activity of Ops; the polymer P3TAA-AAs behaved like biomimetic enzymes. After the hydrolysis of OPs (e.g., methyl paraoxon, ethyl paraoxon and methyl parathion), p-nitrophenol (PNP) was generated, which can be detected electrochemically. Herein, an electrochemical method using P3TAA-conjugated S, H, E-modified electrodes for the determination of OPs was developed. OPs can be quantified by the electrochemical responses of PNP. This technique was selective toward OPs with the p-nitrophenol group. The detection limit of OPs (methyl paraoxon, methyl parathion and ethyl paraoxon) reached 0.5 µM. This detection technique was successfully applied to the detection of OPs in real samples with high detection accuracy.
RESUMEN
Grain size and leaf angle are key agronomic traits that determine final yields in rice. However, the underlying molecular mechanisms are not well understood. Here we demonstrate that the Oryza sativa Mitogen Activated Protein Kinase Kinase Kinase OsMKKK70 regulates grain size and leaf angle in rice. Overexpressing OsMKKK70 caused plants to produce longer seeds. The osmkkk62/70 double mutant and the osmkkk55/62/70 triple mutant displayed significantly smaller seeds and a more erect leaf angle compared to the wild type, indicating that OsMKKK70 functions redundantly with its homologs OsMKKK62 and OsMKKK55. Biochemical analysis demonstrated that OsMKKK70 is an active kinase and that OsMKKK70 interacts with OsMKK4 and promotes OsMAPK6 phosphorylation. In addition, the osmkkk62/70 double mutant showed reduced sensitivity to Brassinosteroids (BRs). Finally, overexpressing constitutively active OsMKK4, OsMAPK6, and OsWRKY53 can partially complement the smaller seed size, erect leaf, and BR hyposensitivity of the osmkkk62/70 double mutant. Taken together, these findings suggest that OsMKKK70 might regulate grain size and leaf angle in rice by activating OsMAPK6 and that OsMKKK70, OsMKK4, OsMAPK6, and OsWRKY53 function in a common signaling pathway that controls grain shape and leaf angle.
Asunto(s)
Oryza , Brasinoesteroides/metabolismo , Grano Comestible/metabolismo , Regulación de la Expresión Génica de las Plantas , Oryza/genética , Oryza/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Gastric cancer (GC) is a malignant tumour originating from the gastric mucosa epithelium that seriously threatens human health. DCLK1, miR-15b and lncRNA SNHG1 play potential roles in the occurrence of GC, but the mechanism remains unclear. METHODS: Gene expression of DCLK1, miR-15b and lncRNA SNHG1 was investigated by qRT-PCR. Protein expression was detected by Western blotting. Migration and invasion of gastric cancer cells was tested by a Transwell assay and wound healing assay. Cell proliferation was measured by an MTT assay. Finally, the correctness of the prediction results was confirmed by a dual-luciferase reporter assay. RESULTS: The expression of DCLK1, Notch1, and SNHG1 was increased in GC tissues, while the expression of miR-15b was decreased. Overexpression of lncRNA SNHG1 promoted the expression of DCLK1 and Nothc1 in GC cells. Moreover, miR-15b targeted DCLK1 to regulate Notch1 expression and inhibited the EMT process in GC cells. SNHG1 enhanced the effects of DCLK1/Notch1 on the EMT process through regulating miR-15b expression. CONCLUSION: SNHG1 enhances the EMT process in GC cells through DCLK1-mediated Notch1 pathway, which can be a potential target for treating GC.