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CH4 serves as an important greenhouse gas, yet limited knowledge is available in global and regional CH4 cycling, particularly in widely distributed karst terrain. In this study, we investigated an upland in Puding Karst Ecosystem Research Station, and explored CH4 concentration and/or flux in atmosphere, soil and cave using a closed static chamber method and an eddy covariance system. Meanwhile, we monitored atmospheric temperature, precipitation, temperature and wind velocity in the cave entrance. The results demonstrated that atmospheric CH4 and actual soil CH4 fluxes in the source area of eddy covariance system were -0.19 ± 8.64 nmols-1m-2 and -0.16 nmols-1m-2 respectively. The CH4 concentrations in Shawan Cave exhibited 10 â¼ 100-fold lower than that of the external atmosphere. CH4 oxidation rate dominated by methane-oxidizing bacteria was 1.98 nmols-1m-2 in Shawan Cave when it combined with temperature difference between cave and external atmosphere. Therefore, CH4 sink in global karst subterranean spaces was estimated at 106.2 Tg CH4 yr-1. We supplemented an understanding of CH4 cycling paths and fluxes in karst terrain, as well as CH4 sinks in karst subterranean space. Further works require to establish a karst ecosystem observation network to conduct long-term integrated studies on CH4 fluxes regarding atmosphere, soils, plants and caves.
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Atmósfera , Cuevas , Metano , Suelo , Metano/análisis , Metano/metabolismo , Atmósfera/química , Suelo/química , Monitoreo del Ambiente/métodos , Microbiología del Suelo , Contaminantes Atmosféricos/análisisRESUMEN
The quantification of intracranial gefitinib (GEF) exposure is limited owing to the sensitivity of analytical equipment. Although mass spectrometry (MS) is the preferred method because of its high sensitivity, the equipment is not available in many laboratories, especially in developing Asian countries. In this paper, we developed a highly sensitive high performance liquid chromatography-diode array detector (HPLC-DAD) method for the assay of GEF in human cerebrospinal fluid (CSF) and plasma. GEF was extracted from CSF and plasma by solid-phase extraction and liquid-liquid extraction, respectively. The chromatographic separation was performed on a C18 column with gradient elution of 0.1% triethylamine solution and acetonitrile, then finally detected at 344 nm. This method was validated and proved to be highly sensitive with a lower limit of quantitation value of 0.11 ng/mL in CSF and 11 ng/mL in plasma. The blood-brain barrier penetration ratio of GEF ranged from 1.48 to 2.41%. This method provides a reliable MS-independent solution for the quantitation of GEF in patients' CSF and plasma.
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Barrera Hematoencefálica/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Quinazolinas/sangre , Quinazolinas/líquido cefalorraquídeo , Neoplasias Encefálicas/tratamiento farmacológico , Gefitinib , Humanos , Modelos Lineales , Quinazolinas/farmacocinética , Quinazolinas/uso terapéutico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Extracción en Fase SólidaRESUMEN
PURPOSE: This research was designed to elucidate the anti-inflammatory impacts of liquiritin on lipopolysaccharide (LPS)-activated human corneal epithelial cells (HCECs). METHODS: The Cell Counting kit-8 (CCK-8) assay was adopted to assess cell viability. The enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α. Transcriptome analysis was conducted to identify the genes that exhibited differential expression between different treatment. The model group included cells treated with LPS (10 µg/mL), the treatment group comprised cells treated with liquiritin (80 µM) and LPS (10 µg/mL), and the control group consisted of untreated cells. To further validate the expression levels of the selected genes, including CSF2, CXCL1, CXCL2, CXCL8, IL1A, IL1B, IL24, IL6, and LTB, quantitative real-time PCR was performed. The expression of proteins related to the Akt/NF-κB signaling pathway was assessed through western blot analysis. NF-κB nuclear translocation was evaluated through immunofluorescence staining. RESULTS: The secretion of IL-6, IL-8, and TNF-α in LPS-induced HCECs was significantly downregulated by liquiritin. Based on the transcriptome analysis, the mRNA expression of pro-inflammatory cytokines, namely IL-6, IL-8, IL-1ß, IL-24, TNF-α, and IL-1α was overproduced by LPS stimulation, and suppressed after liquiritin treatment. Furthermore, the Western blot results revealed a remarkable reduction in the phosphorylation degrees of NF-κB p65, IκB, and Akt upon treatment with liquiritin. Additionally, immunofluorescence analysis confirmed liquiritin's inhibition of LPS-induced p65 nuclear translocation. CONCLUSIONS: Collectively, these findings imply that liquiritin suppresses the expression of proinflammatory cytokines, and the anti-inflammatory impacts of liquiritin may be caused by its repression of the Akt/NF-κB signaling pathway in LPS-induced HCECs. These data indicate that liquiritin could provide a potential therapeutic application for inflammation-associated corneal diseases.
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Supervivencia Celular , Citocinas , Ensayo de Inmunoadsorción Enzimática , Epitelio Corneal , Flavanonas , Glucósidos , Lipopolisacáridos , Humanos , Lipopolisacáridos/toxicidad , Flavanonas/farmacología , Epitelio Corneal/metabolismo , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/patología , Glucósidos/farmacología , Citocinas/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Reacción en Cadena en Tiempo Real de la Polimerasa , Western Blotting , Transducción de Señal , Inflamación/metabolismo , FN-kappa B/metabolismo , Regulación de la Expresión GénicaRESUMEN
In this work, novel monoclinic tungsten oxide (WO3)-encapsulated phosphate-rich porous sodium alginate (PASA) microspherical hydrogel beads were prepared for efficient U(VI) capture. These macroporous and hollow beads were systematically characterized through XRD, FTIR, EDX-mapping, and SEM-EDS techniques. The O and P atoms in the PO and monoclinic WO3 offered inner-spherical complexation with U(VI). The in situ growth of WO3 played a significant role inside the phosphate-rich biopolymeric network to improve its chemical stability, specific surface area, adsorption capacity, and sorption rate. The phytic acid (PA) served for heteroatom doping and crosslinking. The encapsulated WO3 mass ratio was optimized in different composites, and WO3/PASA3 (the microspherical beads with a mass ratio of 30.0 % w/w) exhibited remarkable maximum sorption capacity qm (336.42 mg/g) computed through the best-fit Langmuir model (R2 ≈ 0.99) and rapid sorption equilibrium, teq (150 min). The isothermal sorption studies were conducted at different temperatures (298, 303, and 308 K) and thermodynamic parameters concluded that the process of U(VI) sorption using WO3/PASA3 is endothermic and feasible having ΔHo (8.19 kJ/mol), ΔGo (-20.75, -21.38, and - 21.86 kJ/mol) and proceeds with a minute increase in randomness ΔSo (0.09 kJ/mol.K). Tungsten oxide (WO3)-encapsulated phosphate-rich porous microspherical beads could be promising material for uranium removal.
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Alginatos , Óxidos , Tungsteno , Uranio , Alginatos/química , Adsorción , Fosfatos , Porosidad , Termodinámica , Cinética , Uranio/química , Concentración de Iones de HidrógenoRESUMEN
Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.
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Mapeo Encefálico/métodos , Encéfalo/anatomía & histología , Encéfalo/fisiología , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Algoritmos , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Factores Sexuales , Adulto JovenRESUMEN
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive deficits and dementia. AD entails predominant pathological characteristics including amyloid beta (Aß) plaque formation, neurofibrillary entanglements, and brain atrophy, which gradually result in cognitive dysfunctions. Studies showed that these pathological changes are found in a myriad of brain structures, including the claustrum (CLA), a nucleus that penetrates deeply into the brain and is extensively interconnected to various brain structures. The CLA modulates many aspects of cognitive functions, with attention, executive function, visuospatial ability, language, and memory in particular. It is also implicated in multiple neuropsychiatric disorders, of which one worthy of particular attention is AD-related cognitive impairments. To inspire novel AD treatment strategies, this review has summarized the CLA functionality in discriminative cognitive dysfunctions in AD. And then propose an array of potential mechanisms that might contribute to the cognitive impairments caused by an abnormal CLA physiology. We advocate that the CLA might be a new promising therapeutic target in combination with existing anti-AD drugs and brain stimulation approaches for future AD treatment.
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OBJECTIVE: To explore the reproducibility and stability of brain functional area in the response of language tasks during Chinese word processing with functional magnetic resonance imaging (fMRI) by follow-up scanning so as to provide rationales for clinical preoperative localization and the mechanisms of recovery from aphasia. METHODS: The fMRI data were collected by scanning semantic and phonologic judgments in 15 healthy volunteers. Each subject was scanned twice by the same fMRI procedure of both language tasks with an interval of 1 month. By analyzing the effective overlapping average activation maps, the reproducibility of inter-subject imaging result for two language tasks were estimated by selecting the main language areas, such as Broca's area and Wernicke's area as the region of interest (ROI). By individually calculating the spatial distance of ROI centroid coordinates in the same activating range before and after test, the inter-subject stability in between-session was calculated quantitatively. RESULTS: Both language tasks activated more than one language-related brain areas in cerebral hemispheres. Both language tasks induced significant BOLD response in Broca's and Wernicke's areas with a tendency of left lateralization. The number of subjects in terms of the activation of both language tasks in Broca's and Wernicke's areas accounted over a half of the total subjects. As compared with the phonologic judgment task, the semantic judgment task showed better reproducibility in Broca's area. In the same spatial distance of ROI centroid coordinates, the stability of Broca's area was higher than that of Wernicke's area while the stability of semantic judgment in Broca's area higher than that of phonologic judgment. CONCLUSION: Such main language domains as Broca's and Wernicke's areas can be effectively activated by both semantic and phonologic judgments. By comparison, semantic judgment in Broca's area shows a higher level of reproducibility and stability. Thus it is applicable for clinical preoperative localization and the mechanisms of recovery from aphasia.
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Corteza Cerebral/fisiología , Lóbulo Frontal/fisiología , Imagen por Resonancia Magnética/métodos , Lóbulo Temporal/fisiología , Adulto , Femenino , Humanos , Lenguaje , Lingüística , Masculino , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: Developmental dyslexia (DD) is a specific impairment during the acquisition of reading skills and may have a lifelong negative impact on individuals. Reliable estimates of the prevalence of DD serve as the basis for evidence-based health resource allocation and policy making. However, the prevalence of DD in primary school children varies largely across studies. Moreover, it is unclear whether there are differences in prevalence in different genders and writing systems. Hence, the present study aims to conduct a systematic review and meta-analysis to assess the global prevalence of DD and to explore related factors. METHODS: We will undertake a comprehensive literature search in 14 databases, including EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure and Cochrane, from their inception to June 2021. Cross-sectional and longitudinal studies that describe the prevalence of DD will be eligible. The quality of the included observational studies will be assessed using the Strengthening the Reporting of Observational Studies in Epidemiology statement. The risk of bias will be determined by sensitivity analysis to identify publication bias. RESULTS: One meta-analysis will be conducted to estimate the prevalence of DD in primary school children. Heterogeneity will be assessed in terms of the properties of subjects (e.g., gender, grade and writing system) and method of diagnosis in the included primary studies. Subgroup analyses will also be performed for population and secondary outcomes. CONCLUSION: The results will synthesize the prevalence of DD and provide information for policy-makers and public health specialists.
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Dislexia , Niño , Humanos , Masculino , Femenino , Prevalencia , Estudios Transversales , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto , Dislexia/diagnóstico , Dislexia/epidemiología , Instituciones AcadémicasRESUMEN
OBJECTIVE: To investigate the mechanism underlying the regulation of the invasion and metastasis of oral squamous cell carcinoma (OSCC) by long-chain noncoding RNA (lncRNA) PCGEM1 through the transforming growth factor (TGF) ß2/Smad2 signaling pathways. METHODS: A total of 60 OSCC cases were collected. Cancer tissues and normal tissues more than 2 cm away from cancer tissues were also collected. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-148a and lncRNA PCGEM1 in OSCC, adjacent normal tissues, oral mucosa epithelial cells, KB, BcaCD885, SCC-4, CAL27, and SCC-15. The relationship between the expression of lncRNA PCGEM1 and miR-148a and the clinicopathological information of patients was analyzed. The lncRNA PCGEM1-silenced cell line KB-siPCGEM1 and negative control (KB-NC) group were constructed, and KB was used as the blank control group. The effects of lncRNA PCGEM1 on the proliferation, invasion, and migration of KB cells were determined via MTT, Transwell, and scratch assays. The bioinformatics website starBase was used to predict the complementary binding microRNA (miRNA) of lncRNA PCGEM1. Furthermore, the genes that the miRNA could target and bind were predicted in accordance with the website www.microRNA.org. Western blotting analysis was used to detect the expression of TGF ß2/Smad2 signaling pathway proteins. RESULTS: qRT-PCR results showed that the expression level of lncRNA PCGEM1 and miR-148a in OSCC tissues was higher than that in normal tissues (P<0.05). The expression of lncRNA PCGEM1 and miR-148a in the cancer tissues of patients with different TNM grades, lymph node metastasis, and tissue differentiation was statistically significant (P<0.05). Compared with those in the blank control group and the KB-NC group, OD492 nm value was significantly decreased and cell mobility was significantly reduced in the KB-siPCGEM1 group (P<0.05). Bioinformatics predictions showed that lncRNA PCGEM1 could bind to miR-148a in a complementary manner and that miR-148a had a targeted binding site with TGF ß2. qRT-PCR and Western blotting analysis results showed that the expression levels of miR-148a, TGF ß2, and p-Smad2 in the KB-siPCGEM1 group were significantly lower than those in the blank control and KB-NC groups (P<0.05), and no statistically significant difference between the blank control group and the KB-NC group was observed (P>0.05). CONCLUSIONS: LncRNA PCGEM1 is highly expressed in OSCC. The high expression of lncRNA PCGEM1 may enhance the TGF ß2/Smad2 signaling pathway by upregulating miR-148a, thus promoting the development of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , ARN Largo no Codificante , Carcinoma de Células Escamosas/genética , Proliferación Celular , Células Epiteliales , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias de la Boca/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/fisiología , Transducción de Señal , Proteína Smad2 , Factor de Crecimiento Transformador beta2RESUMEN
In the Dempster-Shafer theory (DST) of evidence, the alarm evidence updating-based method can effectively deal with the uncertainty of the monitored process variable so as to significantly reduce the false alarm rates (FAR) and missed alarm rates (MAR) of the industrial alarm system. But the price of the decrease of FAR and MAR is the increase of the averaged alarm delay (AAD). In order to obtain better comprehensive performance, besides the accuracy indices (FAR and MAR), the sensitivity index (AAD) should be considered simultaneously in the alarm system parameter optimization design. In the framework of DST, firstly, this paper defines the static and dynamical performance indices in the alarm evidence space which are compatible with FAR/MAR/AAD in the process variable space. But the former can measure the performance of the DST-based alarm systems more naturally and elaborately than the latter; secondly, a systematic parameter optimization design procedure for the alarm system is investigated by using these new indices and the tradeoff among them. Finally, two typical numerical experiments and an industrial case are provided to illustrate the effectiveness of the static and dynamical indices for improving the comprehensive performance of the DST-based alarm systems.
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High-dose erlotinib is effective for non-small cell lung cancer patients with brain metastases. The aim of the present study was to investigate whether aspirin could increase the anti-proliferative and anti-metastatic effects of regular erlotinib treatment. The data demonstrated that combining aspirin with erlotinib significantly induced apoptosis and inhibited tumor cell proliferation in several human cancer types. Furthermore, aspirin plus erlotinib significantly induced the activation of E-cadherin and suppression of p38. The data also indicated that the p38/E-cadherin pathway may be involved in the apoptosis caused by the combination of aspirin and erlotinib. As p38 and E-cadherin also serve a key role in epithelial-to-mesenchymal transition (EMT) and cancer metastasis, we hypothesized that the combination of aspirin and erlotinib may significantly inhibit tumor metastasis. First, aspirin plus erlotinib achieved potent inhibition of cancer cell migration and invasion, which are crucial for cancer metastasis. Next, the results demonstrated that aspirin plus erlotinib inhibited angiogenesis by suppressing endothelial cell migration and invasion. Moreover, it was confirmed that aspirin plus erlotinib exerted synergistic anti-angiogenic effects. Finally, the synergistic anti-proliferative and anti-metastatic effects of the combination of aspirin with erlotinib were further validated in an A549 xenograft model in vivo. In conclusion, aspirin plus erlotinib may be an effective combination regimen for patients with metastatic cancer.
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Claustro , Giro del Cíngulo , Corteza Cerebral , Ganglios Basales , Actividad Motora , Vías NerviosasRESUMEN
This event-related functional MRI study examined the neural correlates for Chinese writing, by comparing the writing of logographic characters and that of pinyin, a phonetic notation system for Chinese characters. The temporal profile of the activations indicated that the middle frontal gyrus, superior parietal lobule, and posterior inferior temporal gyrus reflected more central processes for writing. Although pinyin writing elicited greater activity overall than character writing, the critical finding is that the two types of symbols recruited essentially the same brain regions. The results were compared with studies in Japanese showing dissociation between logographic kanji and phonetic kana writing and frequency of use was suggested to be an important factor in accounting for result differences across the two writing systems.
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Encéfalo/fisiología , Escritura Manual , Adolescente , Adulto , Corteza Cerebral/fisiología , China , Señales (Psicología) , Interpretación Estadística de Datos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Lenguaje , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Fonética , Desempeño Psicomotor/fisiología , Lóbulo Temporal/fisiologíaRESUMEN
In this study, 4 male Qigong masters (aged 60 +/- 12) who had Qigong practicing experience for more than 30 years were tested. By using the technique of fMRI, the change of brain function under the state of Qigong was observed through the peripheral pain stimulation generated by potassium penetrating method. The fMRI examination was running on a GE signa VH/3.0 T MRI machine and block design was used. The test was repeated several times, which was carried out before and 15 min after Qigong practicing. The heart and respiration rate of these 4 Qigong masters were monitored during the whole test. SPM2 was used for the data analysis, and the result showed that before Qigong practicing, besides SI and SII-insula regions, many other Brodmann areas, the cigulate cortex, the thalamus, and the cerebellum were all activated, while 15 min after that, the activated areas were decreased obviously, which were mainly at the SII-insula region and some other Brodmann areas. Since the SII-insula region was activated in both of these two states, further analysis of the response curve was focused on it. Its response amplitude under the state of Qigong (3.5%) was greater than that before Qigong (1.2%). Our result indicated that the main manifestation of brain functional change under Qigong was functional suppressing, but in some particular regions such as SII-insula region in our study, the response amplitude was increased. Further study of the exact physiological mechanism of Qigong is needed.
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Encéfalo/fisiopatología , Ejercicios Respiratorios , Umbral del Dolor/fisiología , Dolor/fisiopatología , Anciano , Encéfalo/patología , Mapeo Encefálico , Cerebelo/patología , Cerebelo/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dolor/patología , Respiración , Tálamo/patología , Tálamo/fisiopatologíaRESUMEN
OBJECTIVE: To investigate the roles the different functional activation areas in whole human brain related to movement play during motor preparation (CUE) and execution (GO). METHODS: Event-related functional MRI technique was used on 12 right-handed healthy subjects to record the brain activation in a manner of delayed sequential finger movement. Activation maps and time-signal intensity curves were generated. RESULTS: Bilateral anterior parts of supplementary motor area (Pre-SMA), bilateral posterior parietal cortex (PPC), and bilateral anterior premotor cortex (PMC) were strongly activated during the preparation period, while bilateral SMA proper, and contralateral primary motor cortex (M1) were strongly activated during the execution period, Cerebellar cortex was activated during both periods. The time-signal intensity curves based on single voxel indicated that above-mentioned brain areas were activated during both periods to different degrees; however, the characteristics of distribution in every area were different. CONCLUSION: The brain areas related to movement are activated differently during preparation period and execution period, areas close to M1 participate in the motor execution process mainly, and the areas away from M1 are concerned with motor preparation process chiefly.
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Encéfalo/fisiología , Imagen por Resonancia Magnética , Corteza Motora/fisiología , Desempeño Psicomotor/fisiología , Adulto , Mapeo Encefálico , Corteza Cerebelosa/fisiología , Femenino , Lateralidad Funcional , Humanos , MasculinoRESUMEN
OBJECTIVE: To detect the differences in subcortical structures between patients with paroxysmal kinesigenic dyskinesia (PKD) and normal subjects during movement preparation and execution. METHODS: The PKD patients performed a movement task, in which a CUE signal (preparation) indicated the movement sequence prior to the appearance of an imperative GO signal (execution). Event-related functional magnetic resonance imaging (fMRI) and 3dDeconvolve program of AFNI were used to estimate the hemodynamic response function and to generate activation maps. RESULT: During movement preparation, the activated brain areas in PKD patients were less than those of normal subject, and there was no activation in basal ganglia in PKD patients. During execution, the activation was also less in PKD patients except in bilateral M1. CONCLUSION: During intermission, abnormalities of the brain still exist in PKD patients when during preparing or performing movement. The movement circuit in the brain displays an unusual state. The attack may be caused by reducing of inhibition in brain areas.
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Corea/fisiopatología , Imagen por Resonancia Magnética , Corteza Motora/fisiopatología , Movimiento/fisiología , Adulto , Humanos , MasculinoRESUMEN
Platinum compounds, such as cisplatin, carboplatin, oxaliplatin and nedaplatin, are widely used to treat a number of solid malignancies. Nedaplatin is a second-generation platinum complex, based on its pronounced anti-cancer activities against several solid tumors being equivalent to that of cisplatin, but with lower nephrotoxicity. In this context, the present study aimed to investigate the potential anti-cancer effect by combining nedaplatin with ABT-737. It was found that nedaplatin greatly increased ABT-737-mediated apoptosis in A549 and 95-D cells, accompanied by enhanced cleavage of poly(ADP-ribose) polymerase and caspase-3. In addition, this enhancement was also paralleled by cytochrome c release and dissipation of mitochondrial membrane potential. Additional mechanistic investigations revealed that nedaplatin plus ABT-737 exerted a synergistic effect on cancer cells through their ability to accelerate the degradation of Mcl-1. The present study has revealed nedaplatin as a pertinent sensitizer to ABT-737, which opens up new avenues for this promising BH3-mimetic molecule in the clinic.
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Previous research has found heroin addicts to be impulsive. This study employed functional magnetic resonance imaging technology to investigate the differences between heroin addicts and normal controls in neural activity associated with cognitive regulation of behavior. Twenty-one Chinese men participated in this study, 11 of whom were newly admitted heroin-addicted patients and 10 of whom were healthy volunteers. In the experimental task, the subjects were required to first identify the correct directions of arrowheads and then give the opposite answers. Behaviorally, the heroin-dependent patients took a much shorter time to complete the more demanding second part of the task but committed more errors than the normal controls. This pattern of behavior, characteristic of people who are disinhibited and who tend to be impulsive, was consistent with previous reports of impulsivity observed in people who have abused heroin. The neural activity of the patients that was associated with performing the experimental task of cognitive regulation was different to that of the normal controls in terms of the pattern of prefrontal activation, the attenuation of activity in the anterior cingulate, and the additional recruitment of the right inferior parietal region. This study is the first that seeks to understand the neural activity associated with impulsive behavior in people who abuse heroin. The pattern of imaging data obtained resembled the pattern of data observed in immature brains attempting to exercise cognitive control of behavior. Further theoretical and clinical implications of the findings are discussed.
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Mapeo Encefálico , Encéfalo/fisiología , Cognición/fisiología , Dependencia de Heroína/fisiopatología , Neuronas/fisiología , Adulto , Encéfalo/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Conducta Impulsiva/fisiopatología , Imagen por Resonancia Magnética , Masculino , Tiempo de ReacciónRESUMEN
Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.
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Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Corteza Cerebral/fisiopatología , Imagen por Resonancia Magnética , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Ganglios Basales/efectos de los fármacos , Ganglios Basales/fisiopatología , Estudios de Casos y Controles , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Cerebelo/efectos de los fármacos , Cerebelo/fisiopatología , Corteza Cerebral/efectos de los fármacos , Niño , Humanos , Pruebas de Inteligencia , Masculino , Metilfenidato/farmacología , Metilfenidato/uso terapéutico , Corteza Prefrontal/fisiopatologíaRESUMEN
OBJECTIVE: To explore the heterogeneity of aging brain. METHODS: Blood oxygenation level dependent functional magnetic resonance imaging was performed on 10 subjects meeting the standards of successful aging (SA), 9 subjects meeting the standards of usual aging (UA), and 9 subjects meeting the criteria of mild cognitive impairment (MCI), all age, and sex-matched, under stimulation of verbal fluent test (VFT). The activation level of different regions of interest (ROI), laterality index, and the activation level of occipital lobe were analyzed. RESULTS: The achievement in VFT of the SA group was greater than that of the UA group, and much greater than that of the MCI group with significant differences between any 2 groups (all P < 0.05) except in the task of "names of vegetables". The activation volume of the SA group was greater than that of the UA group, and much greater than that of the MCI group. The main activated regions of the SA and UA groups included left precuneus, anterior cingulate gyrus, middle frontal gyrus, superior frontal gyrus and inferior parietal lobule, and bilateral occipital lobes. The main activated regions of the MCI group included the bilateral prefrontal lobe. The intensity of activation was not significantly different between the SA and UA groups, however, was significantly different between the SA and MCI groups and between the UA and MCI groups. The laterality index (LI) was 0.46 in the SA group, significantly higher than those of the UA group (-0.12) and MCI group (-0.06) (both P < 0.01), however, without a significant difference between the UA group and MCI group. The activation of left prefrontal lobe in the SA group was more obvious than that in the UA group, and much more obvious than that in the MCI group with a significant difference between the UA and MCI groups as well (all P < 0.01). The activation volume of the left dorsal lateral prefrontal cortex (DLPFC) in the SA group was 787 voxels, significantly greater than that in the UA group (292 voxels) and MCI group (0 voxel) (all P < 0.01). CONCLUSION: Heterogeneity exists in the course of aging, associated with complicated brain mechanism. The activation level of DLPFC and LI may be used as sensitive indexes in evaluation of the brain function of the elderly.