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Hydrogen (H2) and hydrogen peroxide (H2O2) play crucial roles as energy carriers and raw materials for industrial production. However, the current techniques for H2 and H2O2 production rely on complex catalysts and involve multiple intermediate steps. In this study, we present a straightforward, environmentally friendly, and highly efficient laser-induced conversion method for overall water splitting to simultaneously generate H2 and H2O2 at ambient conditions without any catalysts. The laser direct overall water splitting approach achieves an impressive light-to-hydrogen energy conversion efficiency of 2.1%, with H2 production rates of 2.2 mmol/h and H2O2 production rates of 65 µM/h in a limited reaction area (1 mm2) within a short real reaction time (0.36 ms/h). Furthermore, we elucidate the underlying physics and chemistry behind the laser-induced water splitting to produce H2 and H2O2. The laser-induced cavitation bubbles create an optimal microenvironment for water-splitting reactions because of the transient high temperatures (104 K) surpassing the chemical barrier required. Additionally, their rapid cooling rate (1010 K/s) hinders reverse reactions and facilitates H2O2 retention. Finally, upon bubble collapse, H2 is released while H2O2 remains dissolved in the water. Moreover, a preliminary amplification experiment demonstrates the potential industrial applications of this laser chemistry. These findings highlight that laser-based production of H2 and H2O2 from water holds promise as a straightforward, environmentally friendly, and efficient approach on an industrial scale beyond conventional chemical catalysis.
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Heritability and genetic covariance/correlation quantify the marginal and shared genetic effects across traits. They offer insights on the genetic architecture of complex traits and diseases. To explore how genetic variations contribute to brain function variations, we estimated heritability and genetic correlation across cortical thickness, surface area, and volume of 33 anatomically predefined regions in left and right hemispheres, using summary statistics of genome-wide association analyses of 31,968 participants in the UK Biobank. To characterize the relationships between these regions of interest, we constructed a genetic network for these regions using recursive two-way cut-offs in similarity matrices defined by genetic correlations. The inferred genetic network matches the brain lobe mapping more closely than the network inferred from phenotypic similarities. We further studied the associations between the genetic network for brain regions and 30 complex traits through a novel composite-linkage disequilibrium score regression method. We identified seven significant pairs, which offer insights on the genetic basis for regions of interest mediated by cortical measures.
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Córtex Cerebral , Estudo de Associação Genômica Ampla , Humanos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/anatomia & histologia , Feminino , Masculino , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Redes Reguladoras de Genes/genética , Polimorfismo de Nucleotídeo Único , Idoso , Modelos GenéticosRESUMO
Wilson disease (WD) is a rare hereditary copper metabolism disorder, wherein cognitive impairment is a common clinical symptom. Chrysophanol (CHR) is an active compound with neuroprotective effects. The study aims to investigate the neuroprotective effect of CHR in WD and attempted to understand the potential mechanisms. Network pharmacology analysis was applied to predict the core target genes of CHR against cognitive impairment in WD. The rats fed with copper-laden diet for 12 weeks, and the effect of CHR on the copper content in liver and 24-h urine, the learning and memory ability, the morphological changes and the apoptosis level of neurons in hippocampal CA1 region, the expression level of Bax, Bcl-2, Cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT proteins were detected. Network pharmacology analysis showed that cell apoptosis and PI3K-AKT signaling pathway might be the main participants in CHR against cognitive impairment in WD. The experiments showed that CHR could reduce the copper content in liver, increase the copper content in 24-h urine, improve the ability of the learning and memory, alleviate the damage and apoptosis level of hippocampal neurons, down-regulate the expression of Bax, Cleaved Caspase-3, and up-regulate the expressions of Bcl-2, p-PI3K/PI3K, p-AKT/AKT. These results suggested that CHR could alleviate cognitive impairment in WD by inhibiting cell apoptosis and triggering the PI3K-AKT signaling pathway.
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Antraquinonas , Disfunção Cognitiva , Degeneração Hepatolenticular , Humanos , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Caspase 3/metabolismo , Degeneração Hepatolenticular/tratamento farmacológico , Cobre , Proteína X Associada a bcl-2 , Farmacologia em Rede , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/genética , ApoptoseRESUMO
This study investigated the protective effect of ginsenoside Rg_1(GRg_1) on oxygen and glucose deprivation/reoxygenation(OGD/R)-injured rat adrenal pheochromocytoma(PC12) cells and whether the underlying mechanism was related to the regulation of inositol-requiring enzyme 1(IRE1)-c-Jun N-terminal kinase(JNK)-C/EBP homologous protein(CHOP) signaling pathway. An OGD/R model was established in PC12 cells, and PC12 cells were randomly classified into control, model, OGD/R+GRg_1(0.1, 1, 10 µmol·L~(-1)), OGD/R+GRg_1+rapamycin(autophagy agonist), OGD/R+GRg_1+3-methyladenine(3-MA,autophagy inhibitor), OGD/R+GRg_1+tunicamycin(endoplasmic reticulum stress agonist), OGD/R+GRg_1+4-phenylbutyric acid(4-PBA, endoplasmic reticulum stress inhibitor), and OGD/R+GRg_1+3,5-dibromosalicylaldehyde(DBSA, IRE1 inhibitor) groups. Except the control group, the other groups were subjected to OGD/R treatment, i.e., oxygen and glucose deprivation for 6 h followed by reoxygenation for 6 h. Cell viability was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide(MTT) assay. Apoptosis was detected by Hoechst 33342 staining, and the fluorescence intensity of autophagosomes by the monodansylcadaverine(MDC) assay. Western blot was employed to determine the expression of autophagy-related proteins(Beclin1, LC3-â ¡, and p62) and the pathway-related proteins [IRE1, p-IRE1, JNK, p-JNK, glucose-regulated protein 78(GRP78), and CHOP]. The results showed that GRg_1 dose-dependently increased the viability of PC12 cells and down-regulated the expression of Beclin1, LC3-â ¡, p-IRE1, p-JNK, GRP78, and CHOP, compared with the model group. Furthermore, GRg_1 decreased the apoptosis rate and MDC fluorescence intensity and up-regulated the expression of p62 protein. Compared with the OGD/R+GRg_1(10 µmol·L~(-1)) group, OGD/R+GRg_1+rapamycin and OGD/R+GRg_1+tunicamycin groups showed increased apoptosis rate and MDC fluorescence intensity, up-regulated protein levels of Beclin1, LC3-â ¡, p-IRE1, p-JNK, GRP78, and CHOP, decreased relative cell survival rate, and down-regulated protein level of p62. The 3-MA, 4-PBA, and DBSA groups exerted the opposite effects. Taken together, GRg_1 may ameliorate OGD/R-induced PC12 cell injury by inhibiting autophagy via the IRE1-JNK-CHOP pathway.
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Apoptose , Ginsenosídeos , Glucose , Proteínas Serina-Treonina Quinases , Fator de Transcrição CHOP , Animais , Ratos , Células PC12 , Fator de Transcrição CHOP/metabolismo , Fator de Transcrição CHOP/genética , Glucose/metabolismo , Ginsenosídeos/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Endorribonucleases/metabolismo , Endorribonucleases/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Oxigênio/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Complexos MultienzimáticosRESUMO
BACKGROUND AND PURPOSE: Hyperphosphorylation of Tau is one of the important pathological features of Alzheimer's disease (AD). Therefore, studying the mechanisms behind Tau hyperphosphorylation is crucial in exploring the pathogenesis of neurological damage in AD. METHODS: In this study, after the establishment of rat models of AD, quantitative phosphoproteomics and proteomics were performed to identify proteins, showing that phosphorylation of microtubule associated protein 1A (MAP 1A) was lower in the model group. Western blot confirmed the changes of MAP 1A in the SD rats, APP/PS1 transgenic mice and cell AD models. To further study the molecular mechanism of recombinant MAP 1A phosphorylation affecting Tau phosphorylation, interfering siRNA-MAP 1A and protein immunoprecipitation reaction analysis were performed in AD cell models. RESULTS: Cyclin-dependent kinase 5 (CDK5) showed reduced binding to MAP 1A and increased binding to Tau, resulting in a decrease in phosphorylated MAP 1A (p-MAP 1A) and an increase in phosphorylated Tau (p-Tau), and MAP 1A silencing promoted binding of CDK5-Tau and increased Tau phosphorylation, thereby reducing the cell survival rate. CONCLUSIONS: In summary, we found that p-MAP 1A downregulation associated with p-Tau upregulation was due to their altered binding forces to CDK5, and MAP 1A could enhance autophosphorylation by competitive binding to CDK5 and antagonise Tau phosphorylation. This leads to neuronal protection and reducing tissue damage levels in AD, which can help better understand the mechanisms of AD pathogenesis.
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Doença de Alzheimer , Animais , Camundongos , Ratos , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Fosforilação , Ratos Sprague-Dawley , Proteínas tau/metabolismo , Regulação para CimaRESUMO
Epitranscriptomics, also known as "RNA epigenetics", is a type of chemical modification that regulates RNA. RNA methylation is a significant discovery after DNA and histone methylation. The dynamic reversible process of m6A involves methyltransferases (writers), m6A binding proteins (readers), as well as demethylases (erasers). We summarized the current research status of m6A RNA methylation in the neural stem cells' growth, synaptic and axonal function, brain development, learning and memory, neurodegenerative diseases, and glioblastoma. This review aims to provide a theoretical basis for studying the mechanism of m6A methylation and finding its potential therapeutic targets in nervous system diseases.
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Metiltransferases , RNA , Metilação , RNA/metabolismo , Metiltransferases/metabolismo , Sistema Nervoso/metabolismoRESUMO
BACKGROUND: The primary pathogenic factors of Alzheimer's disease (AD) have been identified as oxidative stress, inflammatory damage, and apoptosis. Chrysophanol (CHR) has a good neuroprotective effect on AD, however, the potential mechanism of CHR remains unclear. PURPOSE: In this study, we focused on the ROS/TXNIP/NLRP3 pathway to determine whether CHR regulates oxidative stress and neuroinflammation. METHODS: D-galactose and Aß25-35 combination were used to build an in vivo model of AD, and the Y-maze test was used to evaluate the learning and memory function of rats. Morphological changes of neurons in the rat hippocampus were observed using hematoxylin and eosin (HE) staining. AD cell model was established by Aß25-35 in PC12 cells. The DCFH-DA test identified reactive oxygen species (ROS). The apoptosis rate was determined using Hoechst33258 and flow cytometry. In addition, the levels of MDA, LDH, T-SOD, CAT, and GSH in serum, cell, and cell culture supernatant were detected by colorimetric method. The protein and mRNA expressions of the targets were detected by Western blot and RT-PCR. Finally, molecular docking was used to further verify the in vivo and in vitro experimental results. RESULTS: CHR could significantly improve learning and memory impairment, reduce hippocampal neuron damage, and reduce ROS production and apoptosis in AD rats. CHR could improve the survival rate, and reduce the oxidative stress and apoptosis in the AD cell model. Moreover, CHR significantly decreased the levels of MDA and LDH, and increased the activities of T-SOD, CAT, and GSH in the AD model. Mechanically, CHR significantly reduced the protein and mRNA expression of TXNIP, NLRP3, Caspase-1, IL-1ß, and IL-18, and increase TRX. CONCLUSIONS: CHR exerts neuroprotective effects on the Aß25-35-induced AD model mainly by reducing oxidative stress and neuroinflammation, and the mechanism may be related to ROS/TXNIP/NLRP3 signaling pathway.
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Doença de Alzheimer , Fármacos Neuroprotetores , Ratos , Animais , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Simulação de Acoplamento Molecular , Estresse Oxidativo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Superóxido Dismutase/metabolismo , RNA Mensageiro/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/farmacologia , Proteínas de Ciclo Celular/uso terapêuticoRESUMO
Metal coordination compound (MCC) glasses [e.g., metal-organic framework (MOF) glass, coordination polymer glass, and metal inorganic-organic complex (MIOC) glass] are emerging members of the hybrid glass family. So far, a limited number of crystalline MCCs can be converted into glasses by melt-quenching. Here, we report a universal wet-chemistry method, by which the super-sized supramolecular MIOC glasses can be synthesized from non-meltable MOFs. Alcohol and acid were used as agents to inhibit crystallization. The MIOC glasses demonstrate unique features including high transparency, shaping capability, and anisotropic network. Directional photoluminescence with a large polarization ratio (≈47 %) was observed from samples doped with organic dyes. This crystallization-suppressing approach enables fabrication of super-sized MCC glasses, which cannot be achieved by conventional vitrification methods, and thus allows for exploring new MCC glasses possessing photonic functionalities.
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Functional connectivity (FC) between brain region has been widely studied and linked with cognition and behavior of an individual. FC is usually defined as the correlation or partial correlation of fMRI blood oxygen level-dependent (BOLD) signals between two brain regions. Although FC has been effective to understand brain organization, it cannot reveal the direction of interactions. Many directed acyclic graph (DAG) based methods have been applied to study the directed interactions but their performance was limited by the small sample size while high dimensionality of the available data. By enforcing group regularization and utilizing samples from both case and control groups, we propose a joint DAG model to estimate the directed FC. We first demonstrate that the proposed model is efficient and accurate through a series of simulation studies. We then apply it to the case-control study of schizophrenia (SZ) with data collected from the MIND Clinical Imaging Consortium (MCIC). We have successfully identified decreased functional integration, disrupted hub structures and characteristic edges (CtEs) in SZ patients. Those findings have been confirmed by previous studies with some identified to be potential markers for SZ patients. A comparison of the results between the directed FC and undirected FC showed substantial differences in the selected features. In addition, we used the identified features based on directed FC for the classification of SZ patients and achieved better accuracy than using undirected FC or raw features, demonstrating the advantage of using directed FC for brain network analysis.
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Esquizofrenia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/diagnóstico por imagemRESUMO
Objectives: Huangpu Tongqiao Capsule (HPTQC) is a traditional Chinese medicine (TCM) that has been used to treat Alzheimer's disease (AD). This study was to explore the pharmacological action and molecular mechanism of HPTQC in the treatment of AD. Methods: The possible targets of HTPQC were predicted by the molecular docking technique. Intraperitoneal injection of D-galactose and bilateral injection of Aß25-35 in hippocampus induced AD rat model. Morris water maze was used to observe learning and memory function. The primary hippocampal neurons were induced by Aß25-35. Moreover, the apoptosis rate of hippocampal nerve cells was detected through AnnexinV/PI double standard staining. The mRNA and protein levels of GRP78, CHOP, Caspase 12, Caspase 9, and Caspase 3 were detected by PCR and western blot. Results: The prediction results suggest that HPTQC may act on GRP78. HPTQC significantly improved the learning and memory function, and decreased neuronal apoptosis in vivo and in vitro. In addition, HPTQC could decrease the mRNA and protein expression levels of GRP78, CHOP, Caspase12, Caspase9, and Caspase3, and the effect trend was consistent with the specific inhibitor of GRP78. Conclusions: HPTQC has a neuroprotective effect against AD by inhibiting the apoptosis pathway mediated by endoplasmic reticulum stress.
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OBJECTIVE: To investigate the efficacy and safety of Compound Chamomile and Lidocaine Hydrochloride Gel (CCLH) (Kamistadî±) applied at different time-windows on premature ejaculation (PE). METHODS: This prospective study included 72 PE patients treated by application of CCLH to the glans and penile body in our hospital from February to October 2021. According to the time of drug administration before insertion into the vagina, we randomly divided the patients into a 5-minute group (n = 39) and a 15-minute group (n = 33). Before and after 1 and 2 weeks of treatment, we compared the intravaginal ejaculation latency time (IELT), PE diagnostic tool (PEDT) score, quality of life, and adverse reactions between the two groups of patients. RESULTS: Totally 62 of the patients completed the follow-up, 35 in the 5-minute group and 27 in the 15-minute group, and all showed significant improvement in IELT (P < 0.01) and PEDT score (P < 0.05) after treatment compared with the baseline. No allergic reactions, such as redness and swelling, developed at the application site in any of the patients, and no adverse significant effect was observed on the erectile hardness in 61 of the cases. Six cases showed increased erectile hardness instead. Fifty-seven of the patients experienced no obvious penile numbness or reduced sexual satisfaction, and all could complete their sexual activities. CONCLUSION: Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows is effective on PE, with a 5-minute rapid onset of action before intercourse, and no obvious adverse effects.
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Ejaculação Precoce , Masculino , Humanos , Ejaculação Precoce/tratamento farmacológico , Ejaculação Precoce/induzido quimicamente , Lidocaína/uso terapêutico , Estudos Prospectivos , Camomila , Qualidade de VidaRESUMO
Functional network connectivity has been widely acknowledged to characterize brain functions, which can be regarded as "brain fingerprinting" to identify an individual from a pool of subjects. Both common and unique information has been shown to exist in the connectomes across individuals. However, very little is known about whether and how this information can be used to predict the individual variability of the brain. In this paper, we propose to enhance the uniqueness of individual connectome based on an autoencoder network. Specifically, we hypothesize that the common neural activities shared across individuals may reduce the individual identification. By removing contributions from shared activities, inter-subject variability can be enhanced. Our experimental results on HCP data show that the refined connectomes obtained by utilizing autoencoder with sparse dictionary learning can distinguish an individual from the remaining participants with high accuracy (up to 99.5% for the rest-rest pair). Furthermore, high-level cognitive behaviors (e.g., fluid intelligence, executive function, and language comprehension) can also be better predicted with the obtained refined connectomes. We also find that high-order association cortices contribute more to both individual discrimination and behavior prediction. In summary, our proposed framework provides a promising way to leverage functional connectivity networks for cognition and behavior study, in addition to a better understanding of brain functions.
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Variação Biológica Individual , Encéfalo , Cognição/fisiologia , Conectoma/métodos , Rede de Modo Padrão , Imageamento por Ressonância Magnética/métodos , Rede Nervosa , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiologia , Humanos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologiaRESUMO
BACKGROUND: The ratio of fPSA/tPSA in the "grey zone" of tPSA with the concentration range between 4 ng/ml and 10 ng/ml is significant for diagnosis of prostate cancer, and highly efficiency quantification of the ratio of fPSA/tPSA remain elusive mainly because of their extremely low concentration in patients' peripheral blood with high biosample complexity. METHODS: We presented an interdigitated spiral-based MXene-assisted organic electrochemical transistors (isMOECTs) biosensor for highly sensitive determination of fPSA/tPSA. The combination of MXene and the interdigitated multiple spiral architecture synergistically assisted the amplification of amperometric signal of biosensor with dual functionalizations of anti-tPSA and anti-fPSA. RESULTS: The ultrasensitivity of the biosensor was enhanced by tunable multiple spiral architecture and MXene nanomaterials; and the sensor exhibited improved detection limit of tPSA and fPSA down to 0.01 pg/ml and acceptable performance of selectivity, repeatability and stability. Moreover, the isMOECTs displayed area under the curve (AUC) value of 0.8138, confirming the potential applications of isMOECTs in clinics. CONCLUSIONS: The merits of isMOECTs biosensor demonstrated the reliability of MXene-assisted organic electrochemical transistor biosensor with multiple interdigitated spiral for ultrasensitive quantification of fPSA/tPSA, suggesting potential current and future point-of-care testing applications.
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Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Antígeno Prostático Específico/sangue , Biomarcadores/sangue , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Eletrodos , Desenho de Equipamento , Humanos , Masculino , Neoplasias da Próstata/diagnósticoRESUMO
Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid plaques and tangles that have become the fifth leading cause of death worldwide. Previous studies have found that thioredoxin interacting protein (TXNIP) expression was increased during the development of AD neurons. TXNIP separates from the TXNIP-thioredoxin complex, and the TXNIP-NLRP3 complex assembles ASC and pro-caspase-1 to form the NLRP3 inflammasome, which triggers AD inflammation and apoptosis. CB-dock was used to explore whether 21 natural flavonoids and phenols target TXNIP based on references. Docking results showed that rutin, puerarin, baicalin, luteolin and quercetin are the most potent TXNIP inhibitors, and among them, rutin as the most effective flavonoid. And rosmarinic acid is the most potent TXNIP inhibitor of phenols. These phytochemicals could be helpful to find the lead compounds in designing and developing novel agents for Alzheimer's disease.
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Doença de Alzheimer/tratamento farmacológico , Flavonoides/farmacologia , Fenóis/farmacologia , Doença de Alzheimer/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Desenho de Fármacos , Desenvolvimento de Medicamentos , Humanos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Simulação de Acoplamento MolecularRESUMO
Recently, functional network connectivity (FNC) has been extended from static to dynamic analysis to explore the time-varying functional organization of brain networks. Nowadays, a majority of dynamic FNC (dFNC) analysis frameworks identified recurring FNC patterns with linear correlations based on the amplitude of fMRI time series. However, the brain is a complex dynamical system and phase synchronization provides more informative measures. This paper proposes a novel framework for the prediction/classification of behaviors and cognitions based on the dFNCs derived from phase locking value. When applying to the analysis of fMRI data from Human Connectome Project (HCP), four dFNC states are identified for the study of sleep quality. State 1 exhibits most intense phase synchronization across the whole brain. States 2 and 3 have low and weak connections, respectively. State 4 exhibits strong phase synchronization in intra and inter-connections of somatomotor, visual and cognitive control networks. Through the two-sample t-test, we reveal that for the group with bad sleep quality, state 4 shows decreased phase synchronization within and between networks such as subcortical, auditory, somatomotor and visual, but increased phase synchronization within cognitive control network, and between this network and somatomotor/visual/default-mode/cerebellar networks. The networks with increased phase synchronization in state 4 behave oppositely in state 2. Group differences are absent in state 3, and weak in state 1. We establish a prediction model by linear regression of FNC against sleep quality, and adopt a support vector machine approach for the classification. We compare the performance between conventional FNC and PLV-based dFNC with cross-validation. Results show that the PLV-based dFNC significantly outperforms the conventional FNC in terms of both predictive power and classification accuracy. We also observe that combining static and dynamic features does not significantly improve the classification over using dFNC features alone. Overall, the proposed approach provides a novel means to assess dFNC, which can be used as brain fingerprints to facilitate prediction and classification.
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Córtex Cerebral/fisiologia , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Modelos Teóricos , Rede Nervosa/fisiologia , Sono/fisiologia , Máquina de Vetores de Suporte , Adulto , Córtex Cerebral/diagnóstico por imagem , Conjuntos de Dados como Assunto , Humanos , Rede Nervosa/diagnóstico por imagemRESUMO
OBJECTIVE: PBRM1, located on 3p21, functions as a tumor suppressor and somatic mutation of PBRM1 is frequent in clear cell renal cell carcinoma (ccRCC). This study aims to determine the influence of PBRM1 expression on the prognosis of patients with mRCC receiving tyrosine kinase inhibitor (TKI) treatment. METHODS: We identified 116 mRCC patients who were administered sunitinib or sorafenib as first-line therapy, between January 2006 and December 2016 at our institution. PBRM1 expression was assessed by immunohistochemistry. The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS), log-rank test was used to compare the survival outcomes between patients with low and high PBRM1 expression levels, and the Cox proportional hazard regression model was used to estimate the prognostic value. Prognostic accuracy was determined using Harrell concordance index, and nomograms were built to evaluate the prognosis of mRCC. RESULTS: Patients with low PBRM1 expression had significantly shorter median PFS (9 vs 26 months, P < 0.001) and OS (21 vs 44 months, P < 0.001) than those with high expression. Multivariate analysis showed that PBRM1 expression was an independent predictor of PFS (HR 1.975, P = 0.013) and OS (HR 2.282, P = 0.007). The model built by the addition of PBRM1 improved the C-index of PFS and OS to 0.72 and 0.82, respectively. CONCLUSIONS: The expression of PBRM1 could be a significant prognostic factor for mRCC patients treated with targeted therapy, and it increases the prognostic accuracy of the established prognostic model.
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Carcinoma de Células Renais/tratamento farmacológico , Proteínas de Ligação a DNA/metabolismo , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Fatores de Transcrição/metabolismo , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Sorafenibe/uso terapêutico , Sunitinibe/uso terapêutico , Resultado do TratamentoRESUMO
Huangpu Tongqiao Capsules(HPTQC), with the functions of invigorating Qi and kidney, eliminating phlegm and removing blood stasis, have the effect of treating Alzheimer's disease(AD), but its mechanism needs further exploration. To explore the relationship between the therapeutic mechanism of HPTQC on Alzheimer's disease and EGFR-PLCγ signal pathway, 40 healthy male SD rats were selected and divided into 4 groups randomly: sham operation group(sham), model group(model), HPTQC group(HPTQC), and nimodipine group(NMP). AD rat model was established by intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-ß peptide(25-35). After 28 days of administration, Morris water maze test and HE staining showed that the learning and memory ability of AD rats were significantly decreased(P<0.01), and hippocampal neurons were obviously da-maged. However, HPTQC could improve the learning and memory ability of AD rats(P<0.05) and reduce the damage of hippocampal neurons. Immunofluorescence test results showed that the expression levels of EGFR and p-Tau in hippocampal CA1 region of AD rats were significantly increased(P<0.01), and HPTQC could reduce the expression of EGFR and p-Tau in hippocampus of AD rats(P<0.01). Western blot results showed that the protein expression levels of EGFR, PLCγ, IP3 R and p-Tau in hippocampus of AD rats were significantly increased(P<0.01), and HPTQC could reduce the protein expression of EGFR, PLCγ, IP3 R and p-Tau in AD rats(P<0.05). RT-PCR results showed that the mRNA levels of EGFR, PLCγ, IP3 R and Tau in hippocampus of AD rats were significantly increased(P<0.01), and HPTQC could reduce the mRNA levels of EGFR, PLCγ, IP3 R and Tau in AD rats(P<0.05). The results indicate that HPTQC can improve the learning and memory ability of AD rats, and its mechanism of action may be related to regulating EGFR-PLCγ signal pathway.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Animais , Cápsulas , Modelos Animais de Doenças , Receptores ErbB , Hipocampo , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Brain functional connectome analysis is commonly based on population-wise inference. However, in this way precious information provided at the individual subject level may be overlooked. Recently, several studies have shown that individual differences contribute strongly to the functional connectivity patterns. In particular, functional connectomes have been proven to offer a fingerprint measure, which can reliably identify a given individual from a pool of participants. In this work, we propose to refine the standard measure of individual functional connectomes using dictionary learning. More specifically, we rely on the assumption that each functional connectivity is dominated by stable group and individual factors. By subtracting population-wise contributions from connectivity patterns facilitated by dictionary representation, intersubject variability should be increased within the group. We validate our approach using several types of analyses. For example, we observe that refined connectivity profiles significantly increase subject-specific identifiability across functional magnetic resonance imaging (fMRI) session combinations. Besides, refined connectomes can also improve the prediction power for cognitive behaviors. In accordance with results from the literature, we find that individual distinctiveness is closely linked with differences in neurocognitive activity within the brain. In summary, our results indicate that individual connectivity analysis benefits from the group-wise inferences and refined connectomes are indeed desirable for brain mapping.
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Encéfalo/fisiologia , Conectoma , Rede Nervosa/fisiologia , Adolescente , Envelhecimento/fisiologia , Algoritmos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Criança , Cognição/fisiologia , Feminino , Humanos , Individualidade , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo , Rede Nervosa/diagnóstico por imagem , Reprodutibilidade dos Testes , Adulto JovemRESUMO
X-ray phase-contrast imaging can substantially enhance image contrast for weakly absorbing samples. The fabrication of dedicated optics remains a major barrier, especially in high-energy regions (i.e. over 50â keV). Here, the authors perform X-ray phase-contrast imaging by using engineered porous materials as random absorption masks, which provides an alternative solution to extend X-ray phase-contrast imaging into previously challenging higher energy regions. The authors have measured various samples to demonstrate the feasibility of the proposed engineering materials. This technique could potentially be useful for studying samples across a wide range of applications and disciplines.