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A regiodivergent allylation of 1H-indoles highly selectively at the C3 and N1 positions with ß-acyl allylic sulfides through desulfurative C-C/C-N bond-forming reactions has been developed under mild conditions. Notably, the remarkable site-selective switch can be achieved by a delicate choice of solvents and bases. This cost-efficient method displays a broad substrate scope, good functional compatibility, and excellent site-selectivity, thus offering a divergent synthesis of indole substituted α-branched enones, which possess diverse potential opportunities for further applications and derivatization.
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Alcoholic fatty liver disease (AFLD) is an early stage of alcohol-related liver disease characterized by abnormal lipid metabolism in hepatocytes. To date, to our knowledge, there have been no effective strategies for preventing or treating alcohol-related liver disease besides alcohol abstinence. Berberine (BBR) is the main bioactive ingredient extracted from traditional Chinese medicines, such as Coptis and Scutellaria, which protect liver function and relieve liver steatosis. However, the potential role of BBR in AFLD remains unclear. Therefore, this study investigated the protective effects of BBR against Gao-binge model-induced AFLD in 6- to 8-week-old C57BL/6J male mice in vivo and ethyl alcohol (EtOH)-induced alpha mouse liver 12 (AML-12) cells in vitro. The results showed that BBR (200 mg/kg) attenuated alcoholic liver injury and suppressed lipid accumulation and metabolism disorders in vivo. Consistently, BBR effectively inhibited the expression of sterol regulatory element-binding transcription factor 1C, sterol regulatory element-binding transcription factor 2, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-CoenzymeA reductase in EtOH-stimulated AML-12 cells in vitro and promoted the expression of sirtuin 1 (SIRT1) in EtOH-fed mice and EtOH-treated AML-12 cells. Furthermore, SIRT1 silencing attenuated the hepatic steatosis alleviation potential of BBR treatment. Mechanistically, molecular docking revealed the binding effect of BBR and adenosine monophosphate-activated protein kinase (AMPK). The results of further studies showed that a decrease in AMPK activity was accompanied by a significant inhibition of SIRT1 expression. SIRT1 silencing attenuated the protective effect of BBR, whereas the inhibition of its expression had no apparent effect on AMPK phosphorylation, suggesting that SIRT1 acts downstream of AMPK in AFLD. Collectively, BBR ameliorated abnormal lipid metabolism and alleviated EtOH-induced liver injury via the AMPK/SIRT1 pathway in AFLD mice.
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Berberina , Hígado Graso , Leucemia Mieloide Aguda , Masculino , Ratones , Animales , Sirtuina 1/metabolismo , Metabolismo de los Lípidos , Berberina/farmacología , Berberina/uso terapéutico , Berberina/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BL , Hígado/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Etanol/toxicidad , Factores de Transcripción/metabolismo , Esteroles/metabolismo , Esteroles/farmacología , Leucemia Mieloide Aguda/metabolismoRESUMEN
BACKGROUND: Drawing on cognitive appraisal theory, this study investigates the effect of daily COVID-19 news on daily anxiety and protective behaviors (e.g., wearing masks and washing hands). This study proposes that such processes, leading to self-protection, are highly likely when individuals have directly experienced the Wuhan epidemic at the beginning of 2020, which is the most serious COVID-19 outbreak in history. METHODS: The positive effect of daily COVID-19 news on daily protective behaviors through daily COVID-19 anxiety was examined in this study, which was hypothesized to be accentuated by direct Wuhan epidemic experience. An online survey based on the experience sample method (ESM) was conducted during the COVID-19 epidemic in Hebei Province, China, at the beginning of 2021, in which 82 working adults participated in a daily survey for five consecutive days. Once a day during the five-day period, the participants reported their daily COVID-19 news exposure, daily COVID-19 anxiety, and daily protective behaviors. Wuhan epidemic experience was measured by the place of residence of the participants during the 2020 Wuhan epidemic through a separate general survey conducted before the ESM survey. RESULTS: Analysis of 392 day-level data confirmed the positive link between daily COVID-19 news and daily protective behaviors, mediated by daily COVID-19 anxiety (b = 0.03, SE = 0.01, p = 0.018). Furthermore, the mediated effect was significant for the participants with direct COVID-19 experience in Wuhan in 2020 (b = 0.05, SE = 0.03, p = 0.041) but not significant for those without direct experience in Wuhan (b = 0.01, SE = 0.01, p = 0.461). Thus, the results confirmed the positive moderating role of Wuhan epidemic experience. CONCLUSIONS: The analysis reveals the psychological mechanism through which COVID-19 information promotes self-protection measures to control the infectious disease and highlights the importance of direct COVID-19 experience in generating such an effect.
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Ubiquitination, a post-translational modification that attaches one or more ubiquitin (Ub) molecules to another protein, plays a crucial role in the phase-separation processes. Ubiquitination can modulate the formation of membrane-less organelles in two ways. First, a scaffold protein drives phase separation, and Ub is recruited to the condensates. Second, Ub actively phase-separates through the interactions with other proteins. Thus, the role of ubiquitination and the resulting polyUb chains ranges from bystanders to active participants in phase separation. Moreover, long polyUb chains may be the primary driving force for phase separation. We further discuss that the different roles can be determined by the lengths and linkages of polyUb chains which provide preorganized and multivalent binding platforms for other client proteins. Together, ubiquitination adds a new layer of regulation for the flow of material and information upon cellular compartmentalization of proteins.
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Poliubiquitina , Ubiquitina , Humanos , Poliubiquitina/química , Poliubiquitina/metabolismo , Ubiquitinación , Ubiquitina/metabolismoRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. DATA SOURCES: We carried out a systematic review on lncRNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lncRNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in PubMed with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lncRNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. RESULTS: LncRNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting miRNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. CONCLUSIONS: The functional lncRNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Resistencia a Medicamentos , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias PancreáticasRESUMEN
In this paper, Ti3C2Tx MXene prepared by LiF/HCl etching method was spin-coated on glass substrate and sapphire substrate as the saturable absorber (SA), and the MXene SA is combined with Yb: LuAG single crystal fiber (SCF) for the first time to achieve a 1.05 µm passively Q-switched pulsed laser output with the average power, pulse width, and repetition frequency of 1.989 W, 149.6 ns, and 365.44 kHz, respectively, which is the highest average power ever reported for passively Q-switched SCF pulsed lasers. This work enriches the research on SCF pulsed lasers and provides a feasible approach for achieving high-power all-solid-state pulsed lasers.
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Linear polyubiquitin chains regulate diverse signaling proteins, in which the chains adopt various conformations to recognize different target proteins. Thus, the structural plasticity of the chains plays an important role in controlling the binding events. Herein, paramagnetic NMR spectroscopy is employed to explore the conformational space sampled by linear diubiquitin, a minimal unit of linear polyubiquitin, in its free state. Rigorous analysis of the data suggests that, regarding the relative positions of the ubiquitin units, particular regions of conformational space are preferentially sampled by the molecule. By combining these results with further data collected for charge-reversal derivatives of linear diubiquitin, structural insights into the factors underlying the binding events of linear diubiquitin are obtained.
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Ubiquitinas/química , Espectroscopía de Resonancia por Spin del Electrón , Modelos Moleculares , Unión Proteica , Conformación Proteica , Dominios ProteicosRESUMEN
MicroRNA-142-3p (miR-142-3p) was previously investigated in various cancers, whereas, it's role in breast cancer (BC) remains far from understood. In this study, we found that miR-142-3p was markedly decreased both in cell lines and BC tumor tissues. Elevated miR-142-3p expression suppressed growth and metastasis of BC cell lines via gain-of-function assay in vitro and in vivo. Mechanistically, miR-142-3p could regulate the ras-related C3 botulinum toxin substrate 1 (RAC1) expression in protein level, which simultaneously suppressed the epithelial-to-mesenchymal transition related protein levels and the activity of PAK1 phosphorylation, respectively. In addition, rescue experiments revealed RAC1 overexpression could reverse tumor-suppressive role of miR-142-3p. Our results showed miR-142-3p could function as a tumor suppressor via targeting RAC1/PAK1 pathway in BC, suggesting a potent therapeutic target for BC treatment.
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Neoplasias de la Mama/enzimología , MicroARNs/metabolismo , Quinasas p21 Activadas/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Animales , Apoptosis , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Movimiento Celular , Proliferación Celular , Bases de Datos Genéticas , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Neovascularización Patológica , Fosforilación , Transducción de Señal , Quinasas p21 Activadas/genética , Proteína de Unión al GTP rac1/genéticaRESUMEN
BACKGROUND: Disturbed self-regulation, taste reward, as well as somatosensory and visuospatial processes were thought to drive binge eating and purging behaviors that characterize bulimia nervosa. Although studies have implicated a central role of the striatum in these dysfunctions, there have been no direct investigations on striatal functional connectivity in bulimia nervosa from a network perspective. METHODS: We calculated the functional connectivity of striatal subregions based on the resting-state functional Magnetic Resonance Imaging data of 51 bulimia nervosa patients and 53 healthy women. RESULTS: Compared with the healthy women, bulimia nervosa patients showed increased positive functional connectivity in bilateral striatal nuclei and thalamus for nearly all of the striatal subregions, and increased negative functional connectivity in bilateral primary sensorimotor cortex and occipital areas for both ventral striatum and putamen subregions. Only for the putamen subregions, we observed reduced negative functional connectivity in the prefrontal (bilateral superior and middle frontal gyri) and parietal (right inferior parietal lobe and precuneus) areas. Several striatal connectivities with occipital and primary sensorimotor cortex significantly correlated with the severity of bulimia. CONCLUSIONS: The findings indicate bulimia nervosa-related alterations in striatal functional connectivity with the dorsolateral prefrontal cortex supporting self-regulation, the subcortical striatum and thalamus involved in taste reward, as well as the visual occipital and sensorimotor regions mediating body image, which contribute to our understanding of neural circuitry of bulimia nervosa and encourage future therapeutic developments for bulimia nervosa by modulating striatal pathway.
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Mapeo Encefálico , Encéfalo/diagnóstico por imagen , Bulimia Nerviosa/diagnóstico por imagen , Conducta Alimentaria , Imagen por Resonancia Magnética , Descanso , Adolescente , Adulto , Encéfalo/fisiopatología , Bulimia Nerviosa/fisiopatología , Bulimia Nerviosa/psicología , Estudios de Casos y Controles , Femenino , Humanos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Valor Predictivo de las Pruebas , Adulto JovenRESUMEN
BACKGROUND: Consolation is a type of empathy-like behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects empathy, the relationship between stress and consolation remains understudied at the preclinical level. Here, we examined the effects of chronic emotional stress or physical stress exposure on consolation and emotional behaviors by using the socially monogamous mandarin vole (Microtus mandarinus) in both males and females. METHOD/RESULTS: Physical stress voles were exposed to 14-day social defeat stress, whereas emotional stress voles vicariously experienced the defeat of their partners. We found that physical stress, but not emotional stress, voles showed reduced grooming toward their defeated partners and increased anxiety- and despair-like behaviors. Meanwhile, physical stress voles exhibited decreased neural activity in the anterior cingulate cortex, which is centrally involved in empathy. The densities of oxytocin receptors, dopamine D2 receptors, and serotonin 1A-receptors within the anterior cingulate cortex were significantly decreased in the physical stress group compared with controls. All the behavioral and physiological changes were similar between the sexes. Finally, we found that the reduced consolation behavior and some anxiety-like syndromes in physical stress voles could be alleviated by pretreatment with an oxytocin receptor, D2 receptors, or serotonin 1A-receptor agonist within the anterior cingulate cortex, whereas injections of corresponding receptor antagonists to the control voles decreased the consolation behavior and increased some anxiety-like behaviors. CONCLUSIONS: Our results indicated that chronic physical stress exposure impaired consolation and induced anxiety-like behaviors in mandarin voles and oxytocin receptors, 5-HT1A receptors, and D2 receptors within the anterior cingulate cortex may play important roles in these processes.
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Conducta Animal , Empatía , Giro del Cíngulo/metabolismo , Oxitocina/metabolismo , Receptor de Serotonina 5-HT1A/metabolismo , Receptores de Dopamina D2/metabolismo , Derrota Social , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Agresión , Animales , Arvicolinae , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/fisiopatología , Vivienda para Animales , Masculino , Neurotransmisores/farmacología , Transducción de Señal , Estrés Psicológico/fisiopatología , Factores de TiempoRESUMEN
The screening and identification of hyperaccumulators is the key to the phytoremediation of soils contaminated by heavy metal (HM). Arbuscular mycorrhizal fungus (AMF) can improve plant growth and tolerance to HM; therefore, AMF-assisted phytoextraction has been regarded as a potential technique for the remediation of HM-polluted soils. A greenhouse pot experiment was conducted to determine whether Sphagneticola calendulacea is a Cd-hyperaccumulator and to investigate the effect of the AMF-Funneliformis mosseae (FM) on plant growth and on the accumulation, subcellular distribution and chemical form of Cd in S. calendulacea grown in soils supplemented with different Cd levels. At 25, 50 and 100 mg Cd kg-1 level, S. calendulacea showed high Cd tolerance, the translocation factor and the bioconcentration factor exceeded 1, and accumulation of more than 100 mg Cd kg-1 was observed in the aboveground parts of the plant, meeting the requirements for a Cd-hyperaccumulator. Moreover, FM colonization significantly increased both biomasses and Cd concentration in S. calendulacea. After FM inoculation, the Cd concentrations and proportions increased in the cell walls, but exhibited no significant change in the organelles of the shoots. Meanwhile, FM symbiosis contributed to the conversion of Cd from highly toxic chemical forms (extracted by 80% ethanol and deionized water) to less toxic chemical forms (extracted by 1 M NaCl, 2% acetic acid, 0.6 M HCl) of Cd in the shoots. Overall, S. calendulacea is a typical Cd-hyperaccumulator, and FM symbiosis relieved the phytotoxicity of Cd and promoted plant growth and Cd accumulation, and thus greatly increasing the efficiency of phytoextraction for Cd-polluted soil. Our study provides a theoretical basis and application guidance for the remediation of Cd-contaminated soil by the symbiont of S. calendulacea with FM.
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Asteraceae/metabolismo , Bioacumulación , Cadmio/metabolismo , Glomeromycota/fisiología , Micorrizas/fisiología , Contaminantes del Suelo/metabolismo , Asteraceae/crecimiento & desarrollo , Asteraceae/microbiología , Biodegradación AmbientalRESUMEN
Krüppel-like factors (KLFs) are zinc-finger transcriptional factors that regulate target gene expression. Recent studies have shown that KLFs play essential roles in cancer development, whereas the function of KLF7 in glioma remains unclear. In this study, we showed that KLF7 was up-regulated in glioma tissues and its expression was inversely correlated with the patients' survival. Functional experiments demonstrated that KLF7 promoted the proliferation, migration and tumorigenesis of glioma cells. Mechanistically, KLF7 transcriptionally activated argininosuccinate lyase (ASL), which was observed highly expressed in glioma tissues. The biosynthesis of polyamine, a urea cycle metabolite, was enhanced by KLF7 in glioma cells. In addition, ASL contributed to the growth of glioma cells triggered by KLF7. Our findings demonstrate KLF7 as an oncogene and link KLF7 to ASL-mediated polyamine metabolism in glioma.
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Argininosuccinatoliasa/genética , Neoplasias Encefálicas/genética , Glioma/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Poliaminas/metabolismo , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Glioma/metabolismo , Glioma/patología , Humanos , Masculino , Ratones Endogámicos BALB C , Activación TranscripcionalRESUMEN
OBJECTIVES: This study aimed to evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting bowel inflammation in patients with Crohn disease (CD). METHODS: Sixteen patients who underwent intravoxel incoherent motion DW-MRI for CD and colonoscopy were recruited. Seventy-nine bowel segments were selected, and their mean D, D*, f, and apparent diffusion coefficient (ADC) values were measured. The receiver operating characteristic curve was performed to distinguish inflamed from normal bowel. RESULTS: The mean D, D*, f, and ADC values of inflamed bowel were significantly lower than those of normal bowel (P < 0.05). The area under the receiver operating characteristic curve for f (0.906) and ADC values (0.924) was greater than that for D (0.709) or D* values (0.686) for differentiating inflamed bowel from normal bowel (P < 0.05). CONCLUSIONS: Intravoxel incoherent motion DW-MRI is a feasible technique for detecting inflammation in CD patients. The ADC and f values have more potential than the D and D* values.
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Enfermedad de Crohn/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Adulto , Colonoscopía , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Inflamación/diagnóstico por imagen , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: To study the effect of macrophage stimulating protein (MSP) on the cell cycle of non-small cell lung cancer PC14 cells without expression of recepteur d'originenanta (RON) and MSP,and analyse its effect on PC14's epithelial mesenchymal transition (EMT) capacity. METHODS: Vitro culture PC14 (blank control),PC14-Mst1-pEGFP-N1 (stablely expressed MSP) and PC14-pEGFP-N1. Cell cycles were detected by flow cytometry and the gaps between cells during growth were measured by transmission electron microscope (TEM); RT-PCR and Western blot were used to figure out the shifts of EMT related gene expression in PC14-Mst1-pEGFP-N1 cells. RESULTS: Compared with the PC14 group and PC14-pEGFP-N1 group,PC14-Mst1-pEGFP-N1 population of G1/G0 phase were significantly increased while S and G2/M phase were significantly reduced;The gaps between PC14-Mst1-pEGFP-N1 cells decreased; RT-PCR and Western blot showed that mRNA and protein levels of E-cadherin of PC14-Mst1-pEGFP-N1 were significantly higher than that of PC14,but mRNA and protein levels of Vimentin were significantly lower. CONCLUSION: MSP may affect the cell cycle of PC14 and inhibit its EMT procedure by regulating the expression of related proteins including E-cadherin and Vimentin when RON was not expressed.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Ciclo Celular , Transición Epitelial-Mesenquimal , Factor de Crecimiento de Hepatocito/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas/genética , Antígenos CD/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Humanos , Péptidos y Proteínas de Señalización Intracelular , Proteínas Serina-Treonina Quinasas/genética , Vimentina/metabolismoRESUMEN
BACKGROUND: Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. METHODS: We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. RESULTS: We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. LIMITATIONS: We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. CONCLUSION: Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa.
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Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Bulimia Nerviosa/diagnóstico por imagen , Bulimia Nerviosa/fisiopatología , Conectoma , Femenino , Humanos , Imagen por Resonancia Magnética , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Escalas de Valoración Psiquiátrica , Reproducibilidad de los Resultados , Descanso , Adulto JovenRESUMEN
OBJECTIVES: To investigate the correlation between the absolute quantification of the microRNAs (miR-122, miR-451, miR-92a, miR-192) in serum during acute liver injury and the extent of liver injury on rat models of CCl4 induced acute liver injury and mice models of acetaminophen (APAP) induced acute liver injury. Furthermore, to investigate the correlation between the absolute quantification of microRNAs in serum and the drug induced liver injury pathological scoring system (DILI-PSS). METHODS: The acute liver injury model in rat by CCl4 (1.5 mL/kg), and the acute liver injury model in mice by APAP (160 mg/kg) were established. The serum at different time points on both models were collected respectively. The absolute quantification of microRNAs in serum were detected by using MiRbayTM SV miRNA Assay kit. Meanwhile, the pathological sections of liver tissue of the mice at each time point were collected to analyze the correlation between microRNAs and the degree of liver injury. RESULTS: In CCl4-induced rat acute liver injury model and APAP induced mouse acute liver injury, miR-122 and miR-192 appeared to be rising significantly, which remained the highest level at 24 h after treatment, and declined to the normal level after 72 h. In CCl4-induced rat acute liver injury model, the change of miR-92a was fluctuated and had no apparent rules, miR-451 declined gradually, but not obviously. In mice acute liver injury model induced by APAP, miR-92a and miR-451 in the progress of liver injury declined gradually, reached the lowest point at 48 h, and then recovered. The result of correlation analysis indicated that miR-122 and miR-192 presented a good positive correlation with the DILI-PSS ( r=0.741 3, P<0.05; r=0.788 3, P<0.01). CONCLUSIONS: The absolute quantification of miR-122 and miR-192 in serum has the highest level in 24 h, then decrease in 72 h, in both drug-induced and chemical liver injury. In addition, both the two microRNAs have good correlation with DILI-PSS in APAP-induced liver injury models.
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Acetaminofén/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , MicroARNs/sangre , Animales , Biomarcadores/sangre , Hígado/patología , Ratones , RatasRESUMEN
OBJECTIVES: To determine the effects of macrophage stimulating protein (Msp) on the proliferation, migration and invasion of human non-small cell lung cancer cells PC14. METHODS: The eukaryotic expression vector for st1was constructed and transfected into Msp(-)and RON(-)human non-small cell lung cancer cells PC14. The expression of st1mRNA in PC14 cells was observed by RT-PCR. The expression levels of Msp protein in PC14, PC14-st1-pEGFP-N1 and PC14-pEGFP-N1 groups as well as the expression of RON in PC14 and SKBR-3 cells were detected by Western blot. RAW264.7 (mouse monocyte macrophage) and SKBR-3 cells were cultured in the supernatant of cells(PC14, PC14-st1-pEGFP-N1and PC14-pEGFP-N1 groups)and tested with Transwell microporous membrane, through which the biologic activity of Msp was evaluated by calculating the cell number migrated. The proliferation of PC14 was measured by MTT assay. The capabilities of PC14 to migrate and invade were measured by Transwell chamber and Matrigel invasion tests, respectively. RESULTS: The expressions of mRNA and protein of Mst1 in PC14 were stable after transfection with Mst1. Msp (PC14-st1 -pEGFP-N1 group) promoted the migration of RON (+) cells (SKBR-3 and RAW264.7). Compared with PC14 and PC14-pEGFP-N1 groups, the proliferation, migration and invasion of PC14 cells in PC14-st1 -pEGFP-N1 group were inhibited significantly. CONCLUSIONS: Msp can promote the migration of RON (+) cancer cells in paracrine secretion manner and inhibit the proliferation, migration and invasion of human non-small cell lung cancer cells PC14 in an unknown way.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular , Proliferación Celular , Factor de Crecimiento de Hepatocito/genética , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas/genética , Animales , Línea Celular Tumoral , Humanos , Ratones , Células RAW 264.7 , TransfecciónRESUMEN
In this study, the embryological characters of Pterocypsela formosana (Asteraceae) were investigated with the traditional paraffin section methods. The anther has 4 sporangiates, the anther wall development follows the dicotyledonous type and comprises of an epidermis, endothelium, a middle layer and a single-layered tapetum, the tapetum belongs to glandular type. Meiosis of the microspore mother cells is of the simultaneous type, for the formation of mostly tetrahedral tetrad, the mature pollen grains are 2 celled. The ovary is bicarpellate, unilocular, one ovule and basal placenta, the ovule is unitegmic, tenuinucellate, inverted campylotropous and with developed endothelium, archesporial cell of megaspore differentiates immediately below the nucellar epidermis and functions as megasporocyte after development and belongs to tenuinucellate ovule type. The megasporocyte undergoes meitotic to form a liner tetrad, only one chalazal megaspore becomes the functional megaspore which forms female gametophyte including 7-celled and 8-nucleated after three successive mitosis, the female gametophyte is of the Polygonum type. Two polar nuclei melt into a secondary nuclei before fertilization, the chalazal antipodal cells are ephemeral and degenerate shortly after forming. Fertilization is porogamous and belongs to premitotic type of syngamy. The division of the primary endosperm nucleus is earlier than the zygote, the endosperm is of the nuclear type with the presence of haustoria, and the embryogeny belongs to asterad type chicory variant. The developed suspensor on early stage has important significance to the embryo development.
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Asteraceae/embriología , Meiosis , ReproducciónRESUMEN
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by restricted, repetitive behavioral patterns and deficits in social interactions. The prevalence of ASD has continued to rise in recent years. However, the etiology and pathophysiology of ASD remain largely unknown. Currently, the diagnosis of ASD relies on behavior measures, and there is a lack of reliable and objective biomarkers. In addition, there are still no effective pharmacologic therapies for the core symptoms of ASD. Extracellular vesicles (EVs) are lipid bilayer nanovesicles secreted by almost all types of cells. EVs play a vital role in cell-cell communications and are known to bear various biological functions. Emerging evidence demonstrated that EVs are involved in many physiological and pathological processes throughout the body and the content in EVs can reflect the status of the originating cells. EVs have demonstrated the potential of broad applications for the diagnosis and treatment of various brain diseases, suggesting that EVs may have also played a role in the pathological process of ASD. Besides, EVs can be utilized as therapeutic agents for their endogenous substances and biological functions. Additionally, EVs can serve as drug delivery tools as nano-sized vesicles with inherent targeting ability. Here, we discuss the potential of EVs to be considered as promising diagnostic biomarkers and their potential therapeutic applications for ASD.
Asunto(s)
Trastorno del Espectro Autista , Biomarcadores , Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/terapia , Trastorno del Espectro Autista/metabolismo , Biomarcadores/metabolismoRESUMEN
CONTEXT: In order to study the relationship between the sensitivity and pressure of energetic materials, six kinds of energetic materials were selected as the research object. The crystal structure, electronic, and phonon properties under hydrostatic pressure of 0 ~ 45 GPa were calculated by first principles. The calculation results show that the lattice parameters and band gap values of these six energetic materials decrease with the increase of pressure. The peak of the density of states decreases and moves to the low energy direction, and the electrons become more active. Meanwhile, the effect of pressure on the sensitivity of the energetic materials is analyzed based on the multi-phonon up-pumping theory. The number of doorway modes and integral of projected phonon density of states under high pressure is calculated. The results show that both of them increase with the increase of pressure. And the smaller the value of the band gap, the larger the number of doorway modes and integral of projected phonon density of states, and the more sensitive the energetic material is. METHODS: All calculations are performed using the Materials Studio software based on density functional theory. The Perdew-Burke-Ernzerhof (PBE) functional of the generalized gradient approximation (GGA) is used to calculate the exchange correlation function, and the Grimme dispersion correction method is used to deal with the weak intermolecular interaction. The structure of the compound was optimized by BFGS algorithm. The linear response is used to calculate the phonon properties of energetic materials. The plane wave cutoff energy was set to 830 eV. The K-point grids of TATB, FOX-7, TNX, RDX, TNT, and HMX were chosen as 2 × 2 × 2, 2 × 2 × 1, 2 × 1 × 1, 1 × 1 × 1, 1 × 2 × 1, and 2 × 1 × 2.