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1.
Nature ; 601(7891): 69-73, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34987213

RESUMEN

The 660-kilometre seismic discontinuity is the boundary between the Earth's lower mantle and transition zone and is commonly interpreted as being due to the dissociation of ringwoodite to bridgmanite plus ferropericlase (post-spinel transition)1-3. A distinct feature of the 660-kilometre discontinuity is its depression to 750 kilometres beneath subduction zones4-10. However, in situ X-ray diffraction studies using multi-anvil techniques have demonstrated negative but gentle Clapeyron slopes (that is,  the ratio between pressure and temperature changes) of the post-spinel transition that do not allow a significant depression11-13. On the other hand, conventional high-pressure experiments face difficulties in accurate phase identification due to inevitable pressure changes during heating and the persistent presence of metastable phases1,3. Here we determine the post-spinel and akimotoite-bridgmanite transition boundaries by multi-anvil experiments using in situ X-ray diffraction, with the boundaries strictly based on the definition of phase equilibrium. The post-spinel boundary has almost no temperature dependence, whereas the akimotoite-bridgmanite transition has a very steep negative boundary slope at temperatures lower than ambient mantle geotherms. The large depressions of the 660-kilometre discontinuity in cold subduction zones are thus interpreted as the akimotoite-bridgmanite transition. The steep negative boundary of the akimotoite-bridgmanite transition will cause slab stagnation (a stalling of the slab's descent) due to significant upward buoyancy14,15.

2.
Nature ; 599(7886): 605-610, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34819683

RESUMEN

Solids in nature can be generally classified into crystalline and non-crystalline states1-7, depending on whether long-range lattice periodicity is present in the material. The differentiation of the two states, however, could face fundamental challenges if the degree of long-range order in crystals is significantly reduced. Here we report a paracrystalline state of diamond that is distinct from either crystalline or amorphous diamond8-10. The paracrystalline diamond reported in this work, consisting of sub-nanometre-sized paracrystallites that possess a well-defined crystalline medium-range order up to a few atomic shells4,5,11-13, was synthesized in high-pressure high-temperature conditions (for example, 30 GPa and 1,600 K) employing face-centred cubic C60 as a precursor. The structural characteristics of the paracrystalline diamond were identified through a combination of X-ray diffraction, high-resolution transmission microscopy and advanced molecular dynamics simulation. The formation of paracrystalline diamond is a result of densely distributed nucleation sites developed in compressed C60 as well as pronounced second-nearest-neighbour short-range order in amorphous diamond due to strong sp3 bonding. The discovery of paracrystalline diamond adds an unusual diamond form to the enriched carbon family14-16, which exhibits distinguishing physical properties and can be furthered exploited to develop new materials. Furthermore, this work reveals the missing link in the length scale between amorphous and crystalline states across the structural landscape, having profound implications for recognizing complex structures arising from amorphous materials.

3.
Carcinogenesis ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008332

RESUMEN

Alkaliptosis, a form of regulated cell death, is characterized by lysosomal dysfunction and intracellular pH alkalinization. The pharmacological induction of alkaliptosis using the small molecule compound JTC801 has emerged as a promising anticancer strategy in various types of cancers, particularly pancreatic ductal adenocarcinoma (PDAC). In this study, we investigate a novel mechanism by which macropinocytosis, an endocytic process involving the uptake of extracellular material, promotes resistance to alkaliptosis in human PDAC cells. Through lipid metabolomics analysis and functional studies, we demonstrate that the inhibition of alkaliptosis by fatty acids, such as oleic acid, is not dependent on endogenous synthetic pathways but rather on exogenous uptake facilitated by macropinocytosis. Consequently, targeting macropinocytosis through pharmacological approaches (e.g., using EIPA or EHoP-016) or genetic interventions (e.g., RAC1 knockdown) effectively enhances JTC801-induced alkaliptosis in human PDAC cells. These findings provide compelling evidence that the modulation of macropinocytosis can increase the sensitivity of cancer cells to alkaliptosis inducers.

4.
Nat Mater ; 22(10): 1189-1195, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37550568

RESUMEN

Glasses, unlike crystals, are intrinsically brittle due to the absence of microstructure-controlled toughening, creating fundamental constraints for their technological applications. Consequently, strategies for toughening glasses without compromising their other advantageous properties have been long sought after but elusive. Here we report exceptional toughening in oxide glasses via paracrystallization, using aluminosilicate glass as an example. By combining experiments and computational modelling, we demonstrate the uniform formation of crystal-like medium-range order clusters pervading the glass structure as a result of paracrystallization under high-pressure and high-temperature conditions. The paracrystalline oxide glasses display superior toughness, reaching up to 1.99 ± 0.06 MPa m1/2, surpassing any other reported bulk oxide glasses, to the best of our knowledge. We attribute this exceptional toughening to the excitation of multiple shear bands caused by a stress-induced inverse transformation from the paracrystalline to amorphous states, revealing plastic deformation characteristics. This discovery presents a potent strategy for designing highly damage-tolerant glass materials and emphasizes the substantial influence of atomic-level structural variation on the properties of oxide glasses.

5.
Plant Cell ; 33(5): 1771-1789, 2021 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-33616649

RESUMEN

Oxygen deprivation caused by flooding activates acclimation responses to stress and restricts plant growth. After experiencing flooding stress, plants must restore normal growth; however, which genes are dynamically and precisely controlled by flooding stress remains largely unknown. Here, we show that the Arabidopsis thaliana ubiquitin E3 ligase SUBMERGENCE RESISTANT1 (SR1) regulates the stability of the transcription factor WRKY33 to modulate the submergence response. SR1 physically interacts with WRKY33 in vivo and in vitro and controls its ubiquitination and proteasomal degradation. Both the sr1 mutant and WRKY33 overexpressors exhibited enhanced submergence tolerance and enhanced expression of hypoxia-responsive genes. Genetic experiments showed that WRKY33 functions downstream of SR1 during the submergence response. Submergence induced the phosphorylation of WRKY33, which enhanced the activation of RAP2.2, a positive regulator of hypoxia-response genes. Phosphorylated WRKY33 and RAP2.2 were degraded by SR1 and the N-degron pathway during reoxygenation, respectively. Taken together, our findings reveal that the on-and-off module SR1-WRKY33-RAP2.2 is connected to the well-known N-degron pathway to regulate acclimation to submergence in Arabidopsis. These two different but related modulation cascades precisely balance submergence acclimation with normal plant growth.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Proteolisis , Factores de Transcripción/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Oscuridad , Epistasis Genética , Regulación de la Expresión Génica de las Plantas , Modelos Biológicos , Fosforilación , Unión Proteica , Ubiquitinación
6.
Chemphyschem ; 25(9): e202300604, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38426668

RESUMEN

We have performed in situ X-ray diffraction measurements of cubic silicon carbide (SiC) with a zinc-blende crystal structure (B3) at high pressures and temperatures using multi-anvil apparatus. The ambient volume inferred from the compression curves is smaller than that of the starting material. Using the 3rd-order Birch-Murnaghan equation of state and the Mie-Grüneisen-Debye model, we have determined the thermoelastic parameters of the B3-SiC to be K0=228±3 GPa, K0',=4.4±0.4, q=0.27±0.37, where K0, K0' and q are the isothermal bulk modulus, its pressure derivative and logarithmic volume dependence of the Grüneisen parameter, respectively. Using the 3rd-order Birch-Murnaghan EOS with the thermal expansion coefficient, the thermoelastic parameters have been found as K0=221±3 GPa, K0',=5.2±0.4, α0=0.90±0.02 ⋅ 10-5 ⋅ K-1, where α0 is the thermal expansion coefficient at room pressure and temperature. We have determined that paired B3-SiC - MgO calibrants can be used to estimate pressure and temperature simultaneously in ultrahigh-pressure experiments up to 60 GPa.

7.
Antonie Van Leeuwenhoek ; 117(1): 92, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949726

RESUMEN

Biological control is a promising approach to enhance pathogen and pest control to ensure high productivity in cash crop production. Therefore, PGPR biofertilizers are very suitable for application in the cultivation of tea plants (Camellia sinensis) and tobacco, but it is rarely reported so far. In this study, production of a consortium of three strains of PGPR were applied to tobacco and tea plants. The results demonstrated that plants treated with PGPR exhibited enhanced resistance against the bacterial pathogen Pseudomonas syringae (PstDC3000). The significant effect in improving the plant's ability to resist pathogen invasion was verified through measurements of oxygen activity, bacterial colony counts, and expression levels of resistance-related genes (NPR1, PR1, JAZ1, POD etc.). Moreover, the application of PGPR in the tea plantation showed significantly reduced population occurrences of tea green leafhoppers (Empoasca onukii Matsuda), tea thrips (Thysanoptera:Thripidae), Aleurocanthus spiniferus (Quaintanca) and alleviated anthracnose disease in tea seedlings. Therefore, PGPR biofertilizers may serve as a viable biological control method to improve tobacco and tea plant yield and quality. Our findings revealed part of the mechanism by which PGPR helped improve plant biostresses resistance, enabling better application in agricultural production.


Asunto(s)
Nicotiana , Control Biológico de Vectores , Enfermedades de las Plantas , Pseudomonas syringae , Animales , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Nicotiana/microbiología , Pseudomonas syringae/fisiología , Control Biológico de Vectores/métodos , Camellia sinensis/microbiología , Camellia sinensis/crecimiento & desarrollo , Insectos/microbiología , Thysanoptera/microbiología , Resistencia a la Enfermedad , Desarrollo de la Planta , Agentes de Control Biológico , Hemípteros/microbiología
8.
Arch Toxicol ; 98(4): 1025-1041, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38383612

RESUMEN

Activating transcription factor 4 (ATF4), a member of the ATF/cAMP response element-binding (CREB) family, plays a critical role as a stress-induced transcription factor. It orchestrates cellular responses, particularly in the management of endoplasmic reticulum stress, amino acid deprivation, and oxidative challenges. ATF4's primary function lies in regulating gene expression to ensure cell survival during stressful conditions. However, when considering its involvement in ferroptosis, characterized by severe lipid peroxidation and pronounced endoplasmic reticulum stress, the ATF4 pathway can either inhibit or promote ferroptosis. This intricate relationship underscores the complexity of cellular responses to varying stress levels. Understanding the connections between ATF4, ferroptosis, and endoplasmic reticulum stress holds promise for innovative cancer therapies, especially in addressing apoptosis-resistant cells. In this review, we provide an overview of ATF4, including its structure, modifications, and functions, and delve into its dual role in both ferroptosis and cancer.


Asunto(s)
Ferroptosis , Neoplasias , Humanos , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Regulación de la Expresión Génica , Apoptosis , Estrés del Retículo Endoplásmico , Neoplasias/tratamiento farmacológico , Neoplasias/genética
9.
Compr Rev Food Sci Food Saf ; 22(1): 587-614, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36529880

RESUMEN

Whole flaxseed (flour) as a good source of omega-3 fatty acid and phytochemicals with excellent nutritional and functional attributes has been used to enrich foods for health promotion and disease prevention. However, several limitations and contemporary challenges still impact the development of whole flaxseed (flour)-enriched products on the global market, such as naturally occurring antinutritional factors and entrapment of nutrients within food matrix. Whole flaxseed (flour) with different existing forms could variably alter the techno-functional performance of food matrix, and ultimately affect the edible qualities of fortified food products. The potential interaction mechanism between the subject and object components in fortified products has not been elucidated yet. Hence, in this paper, the physical structure and component changes of flaxseed (flour) by pretreatments coupled with their potential influences on the edible qualities of multiple fortified food products were summarized and analyzed. In addition, several typical food products, including baked, noodle, and dairy products were preferentially selected to investigate the potential influencing mechanisms of flaxseed (flour) on different substrate components. In particular, the altered balance between water absorption of flaxseed protein/gum polysaccharides and the interruption of gluten network, lipid lubrication, lipid-amylose complexes, syneresis, and so forth, were thoroughly elucidated. The overall impact of incorporating whole flaxseed (flour) on the quality and nutritional attributes of fortified food products, coupled with the possible solutions against negative influences are aimed. This paper could provide useful information for expanding the application of whole flaxseed (flour) based on the optimal edible and nutritional properties of fortified food products.


Asunto(s)
Ácidos Grasos Omega-3 , Lino , Lino/química , Proteínas , Harina/análisis , Ácidos Grasos Omega-3/química , Control de Calidad
10.
Plant J ; 105(5): 1258-1273, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33264467

RESUMEN

High salinity, one of the most widespread abiotic stresses, inhibits photosynthesis, reduces vegetation growth, blocks respiration and disrupts metabolism in plants. In order to survive their long-term lifecycle, trees, such as Populus species, recruit the abscisic acid (ABA) signaling pathway to adapt to a saline environment. However, the molecular mechanism behind the ABA-mediated salt stress response in woody plants remains elusive. We have isolated a WRKY transcription factor gene, PalWRKY77, from Populus alba var. pyramidalis (poplar), the expression of which is repressed by salt stress. PalWRKY77 decreases salt tolerance in poplar. Furthermore, PalWRKY77 negatively regulated ABA-responsive genes and relieved ABA-mediated growth inhibition, indicating that PalWRKY77 is a repressor of the ABA response. In vivo and in vitro assays revealed that PalWRKY77 targets the ABA- and salt-induced PalNAC002 and PalRD26 genes by binding to the W-boxes in their promoters. In addition, overexpression of both PalNAC002 and PalRD26 could elevate salt tolerance in transgenic poplars. These findings reveal a novel negative regulation mechanism for the ABA signaling pathway mediated by PalWRKY77 that results in more sensitivity to salt stress in poplar. This deepens our understanding of the complex responses of woody species to salt stress.


Asunto(s)
Ácido Abscísico/metabolismo , Populus/metabolismo , Regulación de la Expresión Génica de las Plantas/fisiología , Proteínas de Plantas/metabolismo , Populus/efectos de los fármacos , Estrés Salino/fisiología , Tolerancia a la Sal/fisiología , Estrés Fisiológico/fisiología , Factores de Transcripción/metabolismo
11.
Biochem Cell Biol ; 100(1): 75-84, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34678088

RESUMEN

Osteosarcoma is a malignant tumor abundant in vascular tissue, and its rich blood supply may have a significant impact on its metabolic characteristics. PDGFRß is a membrane receptor highly expressed in osteosarcoma cells and vascular wall cells, and its effect on osteosarcoma metabolism needs to be further studied. In this study, we discussed the effect and mechanism of action of PDGFRß on glucose metabolism in human osteosarcoma (HOS) cells. GSEA, Pearson's correlation test, and PPI correlation analysis indicated positive regulation of PDGFRß on aerobic glycolysis in osteosarcoma. The results of qPCR and western blot further confirmed the prediction of bioinformatics. Glucose metabolism experiments proved that PDGF/PDGFRß could effectively promote aerobic glycolysis in osteosarcoma cells. In addition, the mitochondrial membrane potential (ΔΨm) experiment proved that the metabolic change triggered by PDGFRß was not caused by mitochondrial damage. The PI3K pathway inhibitor LY294002, MEK pathway inhibitor U0126, or Warburg effect inhibitor DCA was used to perform western blot and glucose metabolism experiments, and the results showed that PDGFBB/PDGFRß mainly activated the PI3K/AKT/mTOR/c-Myc pathway to promote aerobic glycolysis in osteosarcoma HOS cells. The newly elucidated role of PDGFRß provides a novel metabolic therapeutic target for osteosarcoma.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Glucosa , Glucólisis , Humanos , Osteosarcoma/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
12.
Langmuir ; 38(43): 13139-13149, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36273338

RESUMEN

Exploring polymeric nanoplatforms combined with reactive oxygen species (ROS) responsiveness with mitochondria targeting has emerged as an effective strategy for enhanced photodynamic therapy (PDT). Amphiphilic copolymers were synthesized by reacting acrylamide thioketal (TK) linkers with amino-terminated triphenylphosphonium-polyethylene glycol and dodecylamine for encapsulating chlorin e6 (Ce6) via self-assembly. Then, anionic cladding with tumor targeting deshelled in tumor acidic microenvironments was surface-anchored by electrostatic forces (BioPEGDMA@RM). After sequential targeting to the mitochondria of cancerous cells, BioPEGDMA@RM could be light-activated with Ce6 released upon ROS cleavage of TK linkages. It was found that Ce6-loaded BioPEGDMA@RM exhibited higher cytotoxicity on CT26 cells and performed stronger ability on the production of ROS than that without TK linkers. Moreover, a minimum illumination of 3 and 5 min could be required for achieving the maximum release of Ce6 and high in vitro cytotoxicity for Ce6-loaded BioPEGDMA@RM, respectively. Furthermore, Ce6-loaded BioPEGDMA@RM showed 1.29-fold and 1.21-fold higher tumor inhibition on BALB/c nude mice and Kunming mice and stimulated immunologic reactions with more generation of IFN-γ and TNF-α and activation of CD3+, CD4+, and CD8+ T-lymphocytes and DCs than that of Ce6-loaded nanoparticles without TK bonds. This work provided an academic reference for the development of ROS-responsive drug delivery systems for advanced PDT efficiency.


Asunto(s)
Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Ratones , Animales , Especies Reactivas de Oxígeno , Ratones Desnudos , Línea Celular Tumoral , Porfirinas/química , Nanopartículas/química , Inmunoterapia , Polímeros/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Neoplasias/tratamiento farmacológico
13.
Cell Biol Int ; 46(6): 907-921, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35165984

RESUMEN

Wilms' tumor (WT) is the most common pediatric renal malignancy. PDGFRß belongs to the type III receptor tyrosine kinase family and is known to be involved in tumor metastasis and angiogenesis. Here, we studied the effect and underlying mechanism of PDGFRß on WT G401 cells. Transwell assay and wound-healing assay were used to detect the effect of PDGFRß on G401 cells invasion and migration. Western blot and immunofluorescence were used to detect the expression of EMT-related genes. The expression of PI3K/AKT/mTOR pathway proteins was detected by Western blot. The relationship between PDGFRß and aerobic glycolysis was studied by assessing the expression of glycolysis-related enzymes detected by qRT-PCR and Western blot. The activity of HK, PK, and LDH was detected by corresponding enzyme activity kits. The concentration of lactic acid and glucose was detected by Lactic Acid Assay Kit and Glucose Assay Kit-glucose oxidase method separately. To investigate the mechanism of PDGFRß in the development of WT, the changes of glucose and lactic acid were analyzed after blocking PI3K pathway, aerobic glycolysis, or PDGFRß. The key enzyme was screened by Western blot and glucose metabolism experiment after HK2, PKM2, and PDK1 were inhibited. The results showed that PDGFRß promoted the EMT process by modulating aerobic glycolysis through PI3K/AKT/mTOR pathway in which PKM2 plays a key role. Therefore, our study of the mechanism of PDGFRß in G401 cells provides a new target for the treatment of WT.


Asunto(s)
Neoplasias Renales , Tumor de Wilms , Becaplermina/metabolismo , Línea Celular Tumoral , Proliferación Celular , Niño , Transición Epitelial-Mesenquimal , Glucosa , Glucólisis , Humanos , Ácido Láctico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Tumor de Wilms/metabolismo
14.
Phys Chem Chem Phys ; 24(17): 10561-10566, 2022 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-35445232

RESUMEN

Pressure-induced sp2-to-sp3 transitions in graphite have been studied for decades by experiments and simulations. In general, pressures of 15-18 GPa are needed to initiate structural transitions in graphite at room temperature, and the high-pressure phases are usually unquenchable, as evidenced by in situ resistivity and optical transmittance measurements, X-ray diffraction (XRD), and inelastic X-ray scattering (IXS). However, our in situ Raman results show that the onset transition pressure can be as low as 9.7 GPa when using the methanol-ethanol-water (MEW) mixture as the pressure-transmitting medium (PTM), indicated by an additional GD Raman peak caused by the sp3 bonding between adjacent graphite layers. Moreover, using a combination of XRD, Raman, X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HRTEM), we show that a small amount of sp3 bonds associated with a unique feature of cross stacking are present in the recovered samples. Our findings will be useful to understand the intricate structural transitions in graphite-like materials under compression.

15.
Zhonghua Nan Ke Xue ; 28(6): 516-523, 2022 Jun.
Artículo en Zh | MEDLINE | ID: mdl-37477469

RESUMEN

OBJECTIVE: To investigate the correlation between the characteristics of resting-state brain function and the types of traditional Chinese medicine (TCM) syndrome in premature ejaculation (PE) patients with heart-kidney disharmony, and the pathogenesis of abnormal ejaculation of the patients. METHODS: We enrolled 33 PE patients with heart-kidney disharmony and 32 healthy controls matched in general demographic data, evaluated the severity of the main and concurrent symptoms of PE using the PE Diagnostic Tool (PEDT) and TCM Syndrome Scale (TCMSS), and obtained the brain structural and functional MRI data. We processed the collected data and calculated the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF) and regional homogeneity (Reho) of the brain with the DPABI software. Using the REST software package, we compared the significantly different brain areas between the PE and control groups by two-sample t-test and corrected the results for multiple comparisons by AlphaSim, followed by Pearson correlation analysis of ALFF, fALFF and Reho in abnormal brain areas and the PEDT and CMSS scores of the patients. RESULTS: The PE patients showed decreased ALFF values in the bilateral inferior temporal gyrus, left middle frontal gyrus and left orbital part of the inferior frontal gyrus, and increased ALFF values in the bilateral hippocampus, thalamus and precuneus, right inferior occipital gyrus, right calcarine and left inferior parietal, with positive correlations of the ALFF values of the left thalamus with the scores on PEDT (r = 0.35, P < 0.05) and TCMSS (r = 0.44, P < 0.05). The fALFF values of the patients were also decreased in the left temporal pole of the middle temporal gyrus and left anterior cingulate gyrus, but increased in the left inferior temporal gyrus. The Reho values of the patients were decreased as well in the right inferior temporal gyrus, left middle frontal gyrus, right dorsolateral superior frontal gyrus, right middle occipital gyrus, right middle occipital gyrus and right precuneus, but increased in the left temporal pole of the middle temporal gyrus, left middle frontal gyrus and left superior frontal gyrus, with negative correlations between the Reho value of the right superior parietal gyrus and TCMSS scores (r = -0.35, P < 0.05). CONCLUSION: Abnormal brain regions were found in PE patients with heart-kidney disharmony, with might be the pathologically associated with PE symptoms and heart-kidney disharmony of the patients.


Asunto(s)
Mapeo Encefálico , Eyaculación Prematura , Masculino , Humanos , Mapeo Encefálico/métodos , Medicina Tradicional China , Encéfalo , Imagen por Resonancia Magnética/métodos , Síndrome , Riñón
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(8): 936-941, 2022 Aug 15.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-36036134

RESUMEN

OBJECTIVES: To study the association between hepatocyte growth factor (HGF) and treatment response in mice with hypoxic pulmonary arterial hypertension (HPAH) and the possibility of HGF as a new targeted drug for HPAH. METHODS: After successful modeling, the HPAH model mice were randomly divided into two groups: HPAH group and HGF treatment group (tail vein injection of recombinant mouse HGF 1 mg/kg), with 10 mice in each group. Ten normal mice were used as the control group. After 5 weeks, echocardiography was used to measure tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio; the Griess method was used to measure the content of nitric oxide in serum; ELISA was used to measure the serum level of endothelin-1; transmission electron microscopy was used to observe changes in the ultrastructure of pulmonary artery. RESULTS: Compared with the HGF treatment and normal control groups, the HPAH group had significantly higher tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio (P<0.05). The transmission electron microscopy showed that the HPAH group had massive destruction of vascular endothelial cells and disordered arrangement of the elastic membrane of arteriolar intima with rupture and loss. The structure of vascular endothelial cells was almost complete and the structure of arterial intima elastic membrane was almost normal in the HGF treatment group. Compared with the normal control and HGF treatment groups, the HPAH group had significantly higher serum levels of nitric oxide and endothelin-1 (P<0.05). CONCLUSIONS: Increasing serum HGF level can alleviate the impact of HPAH on the cardiovascular system of mice, possibly by repairing endothelial cell injury, improving vascular remodeling, and restoring the normal vasomotor function of pulmonary vessels.


Asunto(s)
Factor de Crecimiento de Hepatocito , Hipertensión Arterial Pulmonar , Animales , Peso Corporal , Células Endoteliales , Endotelina-1 , Factor de Crecimiento de Hepatocito/uso terapéutico , Hipertrofia Ventricular Derecha , Hipoxia , Ratones , Óxido Nítrico , Hipertensión Arterial Pulmonar/tratamiento farmacológico
17.
New Phytol ; 230(3): 1095-1109, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33492673

RESUMEN

It is critically important for plants to control the trade-off between normal growth and pathogen immunity. However, the underlying molecular mechanism remains largely unknown. Here we report such a mechanism controlled by WRKY70 and its partner CHYR1 in Arabidopsis. We found that both levels of the WRKY70 target gene SARD1 and the phosphorylated forms of WRKY70 were increased in WRKY70OE plants upon Pst DC3000 infection. Mechanistically, phosphorylation of WRKY70 at Thr22 and Ser34 occurs, which then activates SARD1 expression through binding to a WT box. Phosphorylated WRKY70 is degraded by 26S proteasome via CHYR1 when resuming normal growth after infection. In addition, nonphosphorylated WRKY70 represses SARD1 expression by binding to both W (inhibitory activity site) and WT (active activity site) boxes. The binding of WRKY70 to alternative cis-elements of SARD1 through a phosphorylation-mediated switch controlled by CHYR1 contributes to modulating the balance between immunity and growth.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas , Inmunidad de la Planta , Pseudomonas syringae/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
18.
New Phytol ; 229(1): 106-125, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33098101

RESUMEN

Tolerance of hypoxia is essential for most plants, but the underlying mechanisms are largely unknown. Here we show that adaptation to submergence induced hypoxia in Arabidopsis involves up-regulation of RAP2.2 through interactive action of WRKY33 and WRKY12. WRKY33- or WRKY12-overexpressing plants showed enhanced resistance to hypoxia. Y2H, BiFC, Co-IP and pull-down experiments confirmed the interaction of WRKY33 with WRKY12. Genetic experiments showed that RAP2.2 acts downstream of WRKY33/WRKY12. WRKY33 and WRKY12 can bind to and activate RAP2.2 individually. Genetic and molecular experiments demonstrate that the two WRKYs can synergistically enhance activation towards RAP2.2 to increase hypoxia tolerance. WRKY33 expression is increased in RAP2.2-overexpressing plants, indicating a feedback regulation by RAP2.2 during submergence process, which was corroborated by EMSA, ChIP, dual-LUC and genetic experiments. Our results show that a regulatory cascade module involving WRKY33, WRKY12 and RAP2.2 plays a key role in submergence induced hypoxia response of Arabidopsis and illuminate functions of WRKYs in hypoxia tolerance.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Hipoxia , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Unión al ADN , Inundaciones , Regulación de la Expresión Génica de las Plantas , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
19.
Inorg Chem ; 60(20): 15215-15222, 2021 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-34612630

RESUMEN

High-quality hafnium disilicide (HfSi2) has been successfully synthesized using a high-pressure and high-temperature (HPHT) method at 3 GPa and 1573 K in a DS6 × 10 MN cubic press. The modest synthesis temperature is aided by significant decreases in both liquidus and solidus temperatures at high pressure for the Si-rich portion of the Hf-Si binary system. The in situ high-pressure X-ray diffraction study yielded a bulk modulus of B0 = 124.4 ± 0.8 GPa with a fixed B0' = 4.0 for HfSi2, which exhibits a dramatically anisotropic compressibility, with a and c axes nearly twice as incompressible as the b axis. The bulk HfSi2 as synthesized has a Vickers hardness of 6.9 ± 0.1 GPa and high thermal stability of 1163 K in air, indicating its hard and refractory ceramic properties. The core-level XPS data of Hf 4f and Si 2p have been collected on the bulk samples of HfSi2, HfSi, and Hf, as well as Si powder to examine the Hf-Si bonding in hafnium silicides. The Hf 4f7/2 binding energies are 15.0 and 14.8 eV for bulk HfSi2 and HfSi, respectively.

20.
Biopolymers ; 110(8): e23282, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30977898

RESUMEN

How to characterize short protein sequences to make an effective connection to their functions is an unsolved problem. Here we propose to map the physicochemical properties of each amino acid onto unit spheres so that each protein sequence can be represented quantitatively. We demonstrate the usefulness of this representation by applying it to the prediction of cell penetrating peptides. We show that its combination with traditional composition features yields the best performance across different datasets, among several methods compared. For the convenience of users, a web server has been established for automatic calculations of the proposed features at http://biophy.dzu.edu.cn/SNumD/.


Asunto(s)
Algoritmos , Proteínas/química , Secuencia de Aminoácidos , Análisis de Secuencia de Proteína/métodos , Interfaz Usuario-Computador
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