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The regulatory mechanisms that link WRKY gene expression to fruit ripening are largely unknown. Using transgenic approaches, we showed that a WRKY gene from wild strawberry (Fragaria vesca), FvWRKY48, may be involved in fruit softening and ripening. We showed that FvWRKY48 is localized to the nucleus and that degradation of the pectin cell wall polymer homogalacturonan, which is present in the middle lamella and tricellular junction zones of the fruit, was greater in FvWRKY48-OE (overexpressing) fruits than in empty vector (EV)-transformed fruits and less substantial in FvWRKY48-RNAi (RNA interference) fruits. Transcriptomic analysis indicated that the expression of pectate lyase A (FvPLA) was significantly downregulated in the FvWRKY48-RNAi receptacle. We determined that FvWRKY48 bound to the FvPLA promoter via a W-box element through yeast one-hybrid, electrophoretic mobility shift, and chromatin immunoprecipitation quantitative polymerase chain reaction experiments, and ß-glucosidase activity assays suggested that this binding promotes pectate lyase activity. In addition, softening and pectin degradation were more intense in FvPLA-OE fruit than in EV fruit, and the middle lamella and tricellular junction zones were denser in FvPLA-RNAi fruit than in EV fruit. We speculated that FvWRKY48 maybe increase the expression of FvPLA, resulting in pectin degradation and fruit softening.
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Fragaria , Pared Celular/genética , Pared Celular/metabolismo , Fragaria/genética , Fragaria/metabolismo , Frutas/genética , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas , Pectinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Polisacárido LiasasRESUMEN
Salvia miltiorrhiza is a renowned model medicinal plant species for which 15 SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family genes have been identified; however, the specific functions of SmSPLs have not been well characterized as of yet. For this study, the expression patterns of SmSPL6 were determined through its responses to treatments of exogenous hormones, including indole acetic acid (IAA), gibberellic acid (GA3), methyl jasmonic acid (MeJA), and abscisic acid (ABA). To characterize its functionality, we obtained SmSPL6-ovexpressed transgenic S. miltiorrhiza plants and found that overexpressed SmSPL6 promoted the accumulation of phenolic acids and repressed the biosynthesis of anthocyanin. Meanwhile, the root lengths of the SmSPL6-overexpressed lines were significantly longer than the control; however, both the fresh weights and lateral root numbers decreased. Further investigations indicated that SmSPL6 regulated the biosynthesis of phenolic acid by directly binding to the promoter regions of the enzyme genes Sm4CL9 and SmCYP98A14 and activated their expression. We concluded that SmSPL6 regulates not only the biosynthesis of phenolic acids, but also the development of roots in S. miltiorrhiza.
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Regulación de la Expresión Génica de las Plantas , Hidroxibenzoatos/metabolismo , Organogénesis de las Plantas , Proteínas de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Salvia miltiorrhiza/crecimiento & desarrollo , Proteínas de Plantas/genética , Raíces de Plantas/metabolismo , Salvia miltiorrhiza/metabolismoRESUMEN
BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis. METHODS: The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to identify differentially expressed neurotransmitter receptors. The expression pattern of gamma-aminobutyric acid type A receptor pi subunit (GABRP) in human and mouse PDAC tissues and cells was studied by immunohistochemistry and western blot analysis. The in vivo implications of GABRP in PDAC were tested by subcutaneous xenograft model and lung metastasis model. Bioinformatics analysis, transwell experiment and orthotopic xenograft model were used to identify the in vitro and in vivo effects of GABRP on macrophages in PDAC. ELISA, co-immunoprecipitation, proximity ligation assay, electrophysiology, promoter luciferase activity and quantitative real-time PCR analyses were used to identify molecular mechanism. RESULTS: GABRP expression was remarkably increased in PDAC tissues and associated with poor prognosis, contributed to tumour growth and metastasis. GABRP was correlated with macrophage infiltration in PDAC and pharmacological deletion of macrophages largely abrogated the oncogenic functions of GABRP in PDAC. Mechanistically, GABRP interacted with KCNN4 to induce Ca2+ entry, which leads to activation of nuclear factor κB signalling and ultimately facilitates macrophage infiltration by inducing CXCL5 and CCL20 expression. CONCLUSIONS: Overexpressed GABRP exhibits an immunomodulatory role in PDAC in a neurotransmitter-independent manner. Targeting GABRP or its interaction partner KCNN4 may be an effective therapeutic strategy for PDAC.
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Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Receptores de GABA-A/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/metabolismo , Macrófagos/fisiología , Ratones , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND & AIMS: Agents designed to block or alter cytokinesis can kill or stop proliferation of cancer cells. We aimed to identify cytokinesis-related proteins that are overexpressed in hepatocellular carcinoma (HCC) cells and might be targeted to slow liver tumor growth. METHODS: Using the Oncomine database, we compared the gene expression patterns in 16 cancer microarray datasets and assessed gene enrichment sets using gene ontology. We performed immunohistochemical analysis of an HCC tissue microarray and identified changes in protein levels that are associated with patient survival times. Candidate genes were overexpressed or knocked down with small hairpin RNAs in SMMC7721, MHCC97H, or HCCLM3 cell lines; we analyzed their proliferation, viability, and clone-formation ability and their growth as subcutaneous or orthotopic xenograft tumors in mice. We performed microarray analyses to identify alterations in signaling pathways and immunoblot and immunofluorescence assays to detect and localize proteins in tissues. Yeast 2-hybrid screens and mass spectrometry combined with co-immunoprecipitation experiments were used to identify binding proteins. Protein interactions were validated with co-immunoprecipitation and proximity ligation assays. Chromatin immunoprecipitation, promoter luciferase activity, and quantitative real-time polymerase chain reaction analyses were used to identify factors that regulate transcription of specific genes. RESULTS: The genes that were most frequently overexpressed in different types of cancer cells were involved in cell division processes. We identified 3 cytokinesis-regulatory proteins among the 10 genes most frequently overexpressed by all cancer cell types. Rac GTPase activating protein 1 (RACGAP1) was the cytokinesis-regulatory protein that was most highly overexpressed in multiple cancers. Increased expression of RACGAP1 in tumor tissues was associated with shorter survival times of patients with cancer. Knockdown of RACGAP1 in HCC cells induced cytokinesis failure and cell apoptosis. In microarray analyses, we found knockdown of RACGAP1 in SMMC7721 cells to reduce expression of genes regulated by yes-associated protein (YAP) and WW domain containing transcription regulator 1 (WWTR1 or TAZ). RACGAP1 reduced activation of the Hippo pathway in HCC cells by increasing activity of RhoA and polymerization of filamentous actin. Knockdown of YAP reduced phosphorylation of RACGAP1 and redistribution at the anaphase central spindle. We found transcription of the translocated promoter region, nuclear basket protein (TPR) to be regulated by YAP and coordinately expressed with RACGAP1 to promote proliferation of HCC cells. TPR redistributed upon nuclear envelope breakdown and formed complexes with RACGAP1 during mitosis. Knockdown of TPR in HCC cells reduced phosphorylation of RACGAP1 by aurora kinase B and impaired their redistribution at the central spindle during cytokinesis. STAT3 activated transcription of RACGAP in HCC cells. CONCLUSIONS: In an analysis of gene expression patterns of multiple tumor types, we found RACGAP1 to be frequently overexpressed, which is associated with shorter survival times of patients. RACGAP1 promotes proliferation of HCC cells by reducing activation of the Hippo and YAP pathways and promoting cytokinesis in coordination with TPR.
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Biomarcadores de Tumor/metabolismo , Proliferación Celular , Citocinesis , Proteínas Activadoras de GTPasa/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Células A549 , Citoesqueleto de Actina/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Femenino , Proteínas Activadoras de GTPasa/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HCT116 , Células Hep G2 , Vía de Señalización Hippo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Complejo Poro Nuclear/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Interferencia de ARN , Transducción de Señal , Factores de Tiempo , Factores de Transcripción , Carga Tumoral , Regulación hacia Arriba , Proteínas Señalizadoras YAP , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC. We found that KLK10 was significantly overexpressed in tissues of pancreatic intraepithelial neoplasia (PanIN) and PDAC from Pdx1-Cre; LSL-KrasG12D/+ mice (KC) and Pdx1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ mice (KPC) by immunohistochemical analysis. Moreover, KLK10 is extremely elevated in the PDAC tissues, especially that from the PDAC patients with lymphatic and distant metastasis. Aberrant KLK10 expression is significantly correlated with poor prognosis and shorter survival by univariable and multivariable analysis. Functionally, knockdown of KLK10 observably inhibits invasion and metastatic phenotype of PDAC cells in vitro and metastasis in vivo. In addition, blockade of KLK10 attenuates epithelial-mesenchymal transition and activation of FAK-SRC-ERK signaling, which explains the mechanism of KLK10 in promoting metastasis. Collectively, KLK10 should be considered as a promising biomarker for diagnosis and potential target for therapy in PDAC.
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Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Transición Epitelial-Mesenquimal/genética , Calicreínas/genética , Neoplasias Pancreáticas/genética , Regulación hacia Arriba/genética , Adenocarcinoma/patología , Animales , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Calicreínas/metabolismo , Ratones Endogámicos C57BL , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias Pancreáticas/patología , Fenotipo , Pronóstico , Transducción de Señal , Familia-src Quinasas/metabolismo , Neoplasias PancreáticasRESUMEN
OBJECTIVE: To investigate the values of urinary netrin-1 and kidney injury molecule-1 (KIM-1) in the early diagnosis of acute kidney injury (AKI) induced by neonatal asphyxia. METHODS: A total of 80 full-term neonates with asphyxia were enrolled (mild asphyxia: 34 neonates; severe asphyxia: 46 neonates). Forty normal full-term neonates were selected as the control group. Urinary samples were collected from the neonates in the three groups within 12 hours and 13-48 hours after birth. ELISA was applied to measure urinary levels of netrin-1 and KIM-1. Peripheral venous blood samples were also collected to measure serum creatinine (Scr) level. RESULTS: Compared with the control group, the asphyxia group had significantly higher urinary levels of netrin-1 and KIM-1 within 48 hours after birth and a significantly higher Scr level within 13-48 hours after birth (P<0.05). The neonates in the AKI group had significantly higher urinary levels of netrin-1 and KIM-1 and Scr level within 48 hours after birth than those in the non-AKI group (P<0.05). The areas under the receiver operating characteristic curve for urinary netrin-1 and KIM-1 levels within 12 hours after birth to predict AKI after asphyxia were 0.878 (95% CI: 0.775-0.981; P<0.01) and 0.899 (95% CI: 0.829-0.969; P<0.01), respectively. Any two indicators of urinary netrin-1 level, urinary KIM-1 level, and Scr level within 12 hours after neonatal asphyxia had a positive correlation (P<0.05). CONCLUSIONS: Urinary netrin-1 and KIM-1 levels increase significantly when neonates with asphyxia develop AKI. Urinary netrin-1 and KIM-1 can be used as indicators for the early diagnosis of AKI after asphyxia.
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Lesión Renal Aguda/diagnóstico , Asfixia Neonatal/complicaciones , Glicoproteínas de Membrana/orina , Factores de Crecimiento Nervioso/orina , Proteínas Supresoras de Tumor/orina , Lesión Renal Aguda/orina , Femenino , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Recién Nacido , Masculino , Netrina-1 , Receptores ViralesRESUMEN
OBJECTIVE: To identify and analyze the genetic relationship of four species of Gentiana (G. macrophylla, G. straminea, G. dahurica and G. crassicaulis) recorded as Gentianae Macrophyllae Radix in the Chinese Pharmacopoeia, and two other Gentiana species (G. officinalis and G. siphonantha) often used as substitutes by ISSR, in order to estimate the reasonability of G. officinalis and G. siphonantha used as substitutes from the DNA level. METHODS: Eight primers ivere screened to amplify all the samples and agarose gel electrophoresis were analyzed. NTSYSpc-2. 10E software was used to calculate similarity coefficient and draw dendrogram. Results: Nine characteristic bands were found in different species on the ISSR fingerprints and which could be used to identify five species except G. dahurica. The substitute G. officinalis firstly clustered with G. dahurica and G. siphonantha showed closer genetic relationship with G. straminea and G. dahurica. G. crassicaulis showed a far genetic relationship with the other five species. CONCLUSION: The dendrogram based on the ISSR data supports that G. officinalis and G. siphonantha can be used as substitutes of Gentianae Macrophyllae Radix.
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Gentiana/clasificación , Plantas Medicinales/clasificación , Dermatoglifia del ADN , Cartilla de ADN , ADN de Plantas/genética , Electroforesis en Gel de AgarRESUMEN
We report an electrochemically switched smart surface for controlled peptide immobilization and conformation control. This dynamic surface is based on self-assembled monolayers (SAMs) containing surface-bound trimethoxybenzene moieties, which can undergo electrochemically modulated surface activation to be stepwisely converted to two catechol derivatives. This new smart surface can be used to realize stepwise immobilization of a peptide, and more importantly, to control peptide conformation on a surface. We demonstrate herein that with one electrochemical activation step, a linear peptide containing an RGD sequence can be attached onto the SAMs. With the subsequence activation step, the attached linear RGD peptide can be converted into cyclic conformation. The SAMs bounded with linear and cyclic RGD exhibit different adhesion behaviors to fibroblasts cells. The reaction procedure can be well-monitored by cyclic voltammetry (CV), electrochemical surface enhanced Raman microscopy (EC-SERS), and X-ray photoelectron spectroscopy (XPS). It is believed this robust smart surface can find wide applications in surface immobilization of bioactive moieties.
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Proteínas Inmovilizadas/química , Oligopéptidos/química , Benceno/química , Ciclización , Electroquímica , Modelos Moleculares , Conformación Proteica , Propiedades de SuperficieRESUMEN
Bloom-induced macroalgal enrichment on the seafloor can substantially facilitate dissolved sulfide (DS) production through sulfate reduction. The reaction of DS with sedimentary reactive iron (Fe) is the main mechanism of DS consumption, which however usually could not effectively prevent DS accumulation caused by pulsed macroalgal enrichment. Here we used incubations to investigate the performance of Fe-rich red soil for buffering of DS produced from macroalgae (Ulva prolifera)-enriched sediment. Based on our results, a combination of red soil additions (6.8 kg/m2) before and immediately after pulsed macroalgal deposition (455 g/m2) can effectively cap DS within the red soil layer. The effective DS buffering is mainly due to ample Fe-oxide surface sites available for reaction with DS. Only a small loss (4 %) of buffering capacity after 18-d incubation suggests that the red soil is capable of prolonged DS buffering in macroalgae-enriched sediments.
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Sedimentos Geológicos , Hierro , Suelo , Sulfuros , Ulva , Sulfuros/análisis , Sedimentos Geológicos/química , Suelo/química , Algas Marinas , Algas ComestiblesRESUMEN
The sorption behavior of phosphorus on marine sediments in the presence of black carbon derived from fly ash (FC) was studied. For both the FC and sediment samples, the kinetic curves could be described by a two-compartment first order equation, and the isotherms fit the Freundlich and Langmuir models well. The high specific surface area with abundant acidic functional groups of FC promoted the sorption and make this process more irreversible. The effects were more significant with higher amount of FC added. After sorption, more significant increase in Ex-P, Fe/Al-P and CaP was found in the sediment with FC added, while the organic groups in FC rarely react with phosphorus to form OP. The pH of medium influenced the sorption character, and FC promoted the process significantly at pH < pHPZNPC. The sorption was endothermic with an increase in randomness. The presence of FC had little effects on the thermodynamic parameters.
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Ceniza del Carbón , Sedimentos Geológicos , Fósforo , Contaminantes Químicos del Agua , Sedimentos Geológicos/química , Fósforo/química , Fósforo/análisis , Ceniza del Carbón/química , Adsorción , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Cinética , Hollín/química , Carbono/química , TermodinámicaRESUMEN
Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.
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Aborto Espontáneo , Autofagia , Sirolimus , Serina-Treonina Quinasas TOR , Humanos , Autofagia/efectos de los fármacos , Femenino , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Embarazo , Animales , Transducción de Señal/efectos de los fármacos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Inhibidores mTOR/farmacología , Inhibidores mTOR/uso terapéuticoRESUMEN
While researchers have extensively characterized functional connectivity between brain regions, the characterization of functional homogeneity within a region of the brain connectome is in early stages of development. Several functional homogeneity measures were proposed previously, among which regional homogeneity (ReHo) was most widely used as a measure to characterize functional homogeneity of resting state fMRI (R-fMRI) signals within a small region (Zang et al., 2004). Despite a burgeoning literature on ReHo in the field of neuroimaging brain disorders, its test-retest (TRT) reliability remains unestablished. Using two sets of public R-fMRI TRT data, we systematically evaluated the ReHo's TRT reliability and further investigated the various factors influencing its reliability and found: 1) nuisance (head motion, white matter, and cerebrospinal fluid) correction of R-fMRI time series can significantly improve the TRT reliability of ReHo while additional removal of global brain signal reduces its reliability, 2) spatial smoothing of R-fMRI time series artificially enhances ReHo intensity and influences its reliability, 3) surface-based R-fMRI computation largely improves the TRT reliability of ReHo, 4) a scan duration of 5 min can achieve reliable estimates of ReHo, and 5) fast sampling rates of R-fMRI dramatically increase the reliability of ReHo. Inspired by these findings and seeking a highly reliable approach to exploratory analysis of the human functional connectome, we established an R-fMRI pipeline to conduct ReHo computations in both 3-dimensions (volume) and 2-dimensions (surface).
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Mapeo Encefálico/métodos , Encéfalo/anatomía & histología , Encéfalo/fisiología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Humanos , Reproducibilidad de los ResultadosRESUMEN
Resting-state functional MRI (R-fMRI) has emerged as a promising neuroimaging technique used to identify global hubs of the human brain functional connectome. However, most R-fMRI studies on functional hubs mainly utilize traditional R-fMRI data with relatively low sampling rates (e.g., repetition time [TR]=2 s). R-fMRI data scanned with higher sampling rates are important for the characterization of reliable functional connectomes because they can provide temporally complementary information about functional integration among brain regions and simultaneously reduce the effects of high frequency physiological noise. Here, we employed a publicly available multiband R-fMRI dataset with a sub-second sampling rate (TR=645 ms) to identify global hubs in the human voxel-wise functional networks, and further examined their test-retest (TRT) reliability over scanning time. We showed that the functional hubs of human brain networks were mainly located at the default-mode regions (e.g., medial prefrontal and parietal cortex as well as the lateral parietal and temporal cortex) and the sensorimotor and visual cortex. These hub regions were highly anatomically distance-dependent, where short-range and long-range hubs were primarily located at the primary cortex and the multimodal association cortex, respectively. We found that most functional hubs exhibited fair to good TRT reliability using intraclass correlation coefficients. Interestingly, our analysis suggested that a 6-minute scan duration was able to reliably detect these functional hubs. Further comparison analysis revealed that these results were approximately consistent with those obtained using traditional R-fMRI scans of the same subjects with TR=2500 ms, but several regions (e.g., lateral frontal cortex, paracentral lobule and anterior temporal lobe) exhibited different TRT reliability. Finally, we showed that several regions (including the medial/lateral prefrontal cortex and lateral temporal cortex) were identified as brain hubs in a high frequency band (0.2-0.3 Hz), which is beyond the frequency scope of traditional R-fMRI scans. Our results demonstrated the validity of multiband R-fMRI data to reliably detect functional hubs in the voxel-wise whole-brain networks, which motivated the acquisition of high temporal resolution R-fMRI data for the studies of human brain functional connectomes in healthy and diseased conditions.
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Mapeo Encefálico , Encéfalo/anatomía & histología , Encéfalo/fisiología , Vías Nerviosas/fisiología , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Descanso/fisiologíaRESUMEN
Based on the panel data of 30 provinces in China from 2011 to 2019, this paper uses a two-stage DEA model to measure regional innovation efficiency, then non-parametric test is used to examine the impact of innovation network structure and government R&D investment on regional innovation efficiency. The results show that, at the provincial level, innovation efficiency of regional R&D is not necessarily in direct proportion to the innovation efficiency in the commercialization stage. Commercialization efficiency is not necessarily high in provinces with high technical R&D efficiency. At the national level, the innovation efficiency gap between our country's R&D and commercialization stage is small, indicating that the development of the national innovation efficiency is more and more balanced. Innovation network structure can promote the R&D efficiency, but has no significant effect on the commercialization efficiency. Government R&D investment helps to improve the R&D efficiency, but it is not conducive to the improvement of commercialization efficiency. The interaction between innovation network structure and government R&D investment will have compound effects on regional innovation efficiency; the region with underdeveloped innovation network structure can increase the government R&D investment to make it have a higher level of R&D. This paper provides insights into how to improve innovation efficiency in different social networks and policy environments.
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Eficiencia , Gobierno , China , Inversiones en Salud , Desarrollo EconómicoRESUMEN
The dried root of Codonopsis pilosula (Franch.) Nannf., referred to as Dangshen in Chinese, is a famous traditional Chinese medicine. Polysaccharides, lobetyolin, and atractylenolide III are the major bioactive components contributing to its medicinal properties. Here, we investigated the dynamic changes of the main substances in annual Dangshen harvested at 12 time points from 20 May to 20 November 2020 (from early summer to early winter). Although the root biomass increased continuously, the crude polysaccharides content increased and then declined as the temperature fell, and so did the content of soluble proteins. However, the content of total phenolics and flavonoids showed an opposite trend, indicating that the carbon flux was changed between primary metabolism and secondary metabolism as the temperature and growth stages changed. The changes in the contents of lobetyolin and atractylenolide III indicated that autumn might be a suitable harvest time for Dangshen. The antioxidant capacity in Dangshen might be correlated with vitamin C. Furthermore, we analyzed the expression profiles of a few enzyme genes involved in the polysaccharide biosynthesis pathways at different growth stages, showing that CpUGpase and CPPs exhibited a highly positive correlation. These results might lay a foundation for choosing cultivars using gene expression levels as markers.
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Development of potential cancer treatment strategies by using an exogenous reactive oxygen species (ROS)-generating agent (prooxidant) or redox intervention, has attracted much interest. One effective ROS generation method is to construct a prooxidant system by polyphenolic compounds and Cu(II) ions. This work demonstrates that Cu(II) and the stilbene-chroman hybrid with a catechol moiety could synergistically induce pBR322 plasmid DNA damage, as well as cell cycle arrest and apoptosis of HepG2 cells. Additionally, an interesting acid/base-promoted prooxidant reaction was found. The detailed chemical mechanisms for the reaction of the hybrid with Cu(II) in acid, neutral and base solutions are proposed based on UV/Vis spectral changes and identification of the related oxidative intermediates and products.
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Antineoplásicos/química , Catecoles/química , Cromanos/química , Cobre/química , Oxidantes/química , Estilbenos/química , Desequilibrio Ácido-Base , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Cobre/farmacología , ADN/química , Fragmentación del ADN/efectos de los fármacos , Células Hep G2 , Humanos , Oxidantes/farmacología , Plásmidos/química , Especies Reactivas de Oxígeno/química , Análisis EspectralRESUMEN
In the past decade, there was a great deal of interest and excitement in developing more active antioxidants and cancer chemoprevention agents than resveratrol, a naturally occurring stilbene. In this work, eight resveratrol-directed 4-mercaptostilbenes were constructed based on the inspiration that thiophenol should be a stronger radical scavenger than phenol, and their reaction rates with galvinoxyl (GO(.)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH(.)) radicals in methanol and ethyl acetate were measured by using stopped-flow UV/Vis spectroscopy at 25 °C. Kinetic analysis demonstrates that 4-mercaptostilbenes are extraordinary radical scavengers, and the substitution of the 4-SH group for the 4-OH group in the stilbene scaffold is an important strategy to improve the radical-scavenging activity of resveratrol. Surprisingly, in methanol, some of the 4-mercaptostilbenes are 10(4)-times more active than resveratrol, dozens of times to hundreds of times more effective than known antioxidants (α-tocopherol, ascorbic acid, quercetin, and trolox). The detailed radical-scavenging mechanisms were discussed based on acidified-kinetic analysis. Addition of acetic acid remarkably reduced the GO(.) and DPPH(.) radical-scavenging rates of the 4-mercaptostilbenes in methanol, a solvent that supports ionization, suggesting that the reactions proceed mainly through a sequential proton loss electron transfer mechanism. In contrast, an interesting acid-promoted kinetics was observed for the reactions of the 4-mercaptostilbenes with DPPH(.) in ethyl acetate, a solvent that weakly supports ionization. The increased ratio in rates is closely correlated with the electron-rich environment in the molecules, suggesting that the acceleration could benefit from the contribution of the electron transfer from the 4-mercaptostilbenes and DPPH(.). However, the addition of acetic acid had no influence on the GO(.)-scavenging rates of the 4-mercaptostilbenes in ethyl acetate, due to the occurrence of the direct hydrogen atom transfer. Our results show that the radical-scavenging activity and mechanisms of 4-mercaptostilbenes depends significantly on the molecular structure and acidity, the nature of the attacking radical, and the ionizing capacity of the solvent.
Asunto(s)
Antioxidantes/química , Depuradores de Radicales Libres/química , Estilbenos/química , Compuestos de Sulfhidrilo/química , Compuestos de Bifenilo , Cromanos/química , Metanol/química , Estructura Molecular , Picratos , Resveratrol , Solventes/química , Estilbenos/síntesis química , Tocoferoles/químicaRESUMEN
In this paper, the kinetics and thermodynamics of Adenosine 5'-monophosphate (AMP) sorption on the sediments obtained from the Yangtze River Estuary and adjacent areas were studied, in combination with the effects of the sediments' properties and media conditions. The kinetics curves could be described by a two-compartment first-order equation, and the equilibrium isotherms fitted well with the modified Langmuir and Freundlich models. The analysis of organic phosphorus (OP) fractions changes after sorption indicated that the contents of exchangeable or loosely sorbed PO increased most significantly. Higher organic matter (OM) of the sediments were favorable for the sorption ability. It was also found that the content of OP and OM in the sediments showed an obvious positive correlation, indicating that organic matter rather than Fe/Al oxides played an important role in the migration of OP in the Yangtze River estuary and its adjacent area. Temperature, salinity and pH of the media influenced the sorption of AMP significantly. Increase of temperature was of benefit to the sorption of AMP, which was a spontaneous and exothermic process according to the calculations of the thermodynamic parameters. The sorption capacity was higher at a moderate salinity in the range of our study. With the pH changing from 3 to 10, the sorption capacity exhibited as a "U-trend" curve.
Asunto(s)
Sedimentos Geológicos , Contaminantes Químicos del Agua , Adenosina , Adenosina Monofosfato , Adsorción , Sedimentos Geológicos/química , Compuestos Organofosforados , Fósforo/química , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: Early scar pregnancy (CSP) in the lower uterine segment after cesarean section is a type of ectopic pregnancy that can cause major complications if left untreated. Transabdominal ultrasound is a common procedure but is influenced by external factors. Thus, intracavitary ultrasound may have better diagnostic efficiency for CSP. AIM: To assess the value of intracavitary ultrasound for diagnosing CSP in the lower uterine segment after cesarean section. METHODS: Patients diagnosed with CSP in our hospital from October 2019 to April 2021 were recruited. Transabdominal and intracavitary ultrasound examinations were performed to compare the diagnostic differences for CSP and its types. RESULTS: Sixty-three patients were diagnosed during the study period. The diagnostic accuracy for CSP was higher in intracavitary ultrasound (96.83%) than in transabdominal ultrasound (84.13%) (P < 0.05). The missed diagnosis and misdiagnosis rates did not differ among the ultrasound types (intra: 0.00% and 3.17%; trans: 4.76% and 11.11%, respectively; P > 0.05). For the diagnostic rates for the CSP types, the rates for gestational sac (100.00% vs 90.48%), heterogeneous mass (93.75% vs 75.00%), and part of the uterine cavity (80.00% vs 60.00%) were higher in intracavitary ultrasound than in transabdominal ultrasound, but the difference was not statistically significant (P > 0.05). For gestational sac CSP patients, intracavitary ultrasound showed that the gestational sac was located in the lower uterine segment scar with abundant peripheral blood flow; the distance between the gestational sac and the serosal layer was 2.42 ± 0.50 cm. Intracavitary ultrasound for heterogeneous mass CSP patients indicated that the mass mainly occurred in the lower anterior uterine wall, protruding into the bladder, and was surrounded by abundant internal and peripheral blood flow; the distance between the mass and serosal layer was 1.79 ± 0.30 cm. For CSP type partly located in the uterine cavity, the gestational sac was partly located in the lower uterine cavity and partly in the scar with abundant internal and peripheral blood flow; the distance between the gestational sac and the serosal layer was 2.29 ± 0.28 cm. CONCLUSION: Intracavitary ultrasound had a higher diagnostic accuracy and application value for diagnosing CSP than transabdominal ultrasound, with reduced risk of missed diagnoses and misdiagnosis, thereby preventing delayed treatment.