Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.439
Filtrar
1.
Circulation ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33019798

RESUMO

Background: Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP) lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules (GUG), in patients with masked hypertension. Methods: Patients with an office BP of <140/90 mmHg and daytime ambulatory BP of 135-150 mmHg systolic and/or 85-95 mmHg diastolic were randomized 1:1 to the treatment of GUG or placebo 5-10 grams twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP. Results: At baseline, office and daytime BP of the 251 participants (mean age 50.4 years, 53.4% men, mean body mass index 24.5 kg/m2, and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes mellitus, and smoking, respectively) averaged 129/82 and 135/89 mmHg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44 /3.39 and 2.91/1.60 mmHg in the GUG and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mmHg, P≤0.025) and 24-h BP (2.33/1.49 mmHg, P≤0.012), but not for the clinic and nighttime BPs (P≥0.162). The per-protocol analysis in 229 patients produced similar results. Only one adverse event (sleepiness during the day) was reported and no serious adverse event occurred. Conclusions: BP lowering treatment with Chinese traditional medicine GUG is efficacious for patients with masked hypertension. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02156024.

2.
Nat Cell Biol ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020597

RESUMO

PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified a cardiac-hypertrophy-associated piRNA (CHAPIR) that promotes pathological hypertrophy and cardiac remodelling by targeting METTL3-mediated N6-methyladenosine (m6A) methylation of Parp10 mRNA transcripts. CHAPIR deletion markedly attenuates cardiac hypertrophy and restores heart function, while administration of a CHAPIR mimic enhances the pathological hypertrophic response in pressure-overloaded mice. Mechanistically, CHAPIR-PIWIL4 complexes directly interact with METTL3 and block the m6A methylation of Parp10 mRNA transcripts, which upregulates PARP10 expression. The CHAPIR-dependent increase in PARP10 promotes the mono-ADP-ribosylation of GSK3ß and inhibits its kinase activity, which results in the accumulation of nuclear NFATC4 and the progression of pathological hypertrophy. Hence, our findings reveal that a piRNA-mediated RNA epigenetic mechanism is involved in the regulation of cardiac hypertrophy and that the CHAPIR-METTL3-PARP10-NFATC4 signalling axis could be therapeutically targeted for treating pathological hypertrophy and maladaptive cardiac remodelling.

3.
Cardiovasc Ther ; 2020: 7172052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042224

RESUMO

Background: We provide an updated meta-analysis with detailed information on a combination of TCM and routine treatment. Methods: Retrieve appropriate articles with no language restrictions on keywords until 8 July 2019 in an electronic database. All trajectories are screened according to certain criteria. The quality of certified research was also evaluated. We made a detailed record of the results of the measurement. Meta-analysis was carried out by using the Revman 5.3 software. Results: Sixty-seven RCTs were included, and 6594 subjects were analyzed. Compared with routine treatment, the total effective rate (TER) of TCM combined with routine treatment was improved, and the recovery of stroke was also significantly accelerated. Regulation of blood lipids by notably shrinking the contents of TC, TG, and LDL and enhancing the levels of HDL. The levels of serum hs-CRP, WHV, and WLV decreased significantly, indicating that the expression of thrombomodulin was decreased after the comprehensive treatment of traditional Chinese medicines (TCMs). The combination of TCM treatment could enhance the protection of neural function by decreasing the NIHSS scoring while increasing the BI scoring. Paeoniae Radix Rubra, Angeticae Sinensis Radix, etc., can effectively improve the clinical symptoms of stroke convalescent patients and promote the recovery of neurological function. ACU of Baihui, Renzhong, etc., can improve the clinical rehabilitation effect of patients. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results. Conclusion: A combination of TCM and routine treatment in the treatment of stroke could improve TER, and it is beneficial to the rehabilitation of patients in the recovery period of apoplexy. These effects can be mediated by a combination of several mechanisms. Nevertheless, due to the limitations of this study, these results should be handled with caution.

4.
Res Sq ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33052331

RESUMO

COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) since 2012. Treatment options for CoVs are largely lacking. Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple in vitro systems, including the human embryonic stem cell-derived cardiomyocytes and ex vivo lung cultures. The FDA-approved molecule was found to inhibit multiple steps of viral replication, suggesting multiple underlying antiviral mechanisms. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and also prevented cytokine storm associated with viral infection. Additionally, clofazimine exhibited synergy when administered with remdesivir. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2, endemic MERS-CoV in the Middle East, and, possibly most importantly, emerging CoVs of the future.

5.
Nat Microbiol ; 5(11): 1439-1448, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33028965

RESUMO

SARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality1. Currently, therapeutic options for COVID-19 are limited. Historically, metal compounds have found use as antimicrobial agents, but their antiviral activities have rarely been explored. Here, we test a set of metallodrugs and related compounds, and identify ranitidine bismuth citrate, a commonly used drug for the treatment of Helicobacter pylori infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo. Ranitidine bismuth citrate exhibited low cytotoxicity and protected SARS-CoV-2-infected cells with a high selectivity index of 975. Importantly, ranitidine bismuth citrate suppressed SARS-CoV-2 replication, leading to decreased viral loads in both upper and lower respiratory tracts, and relieved virus-associated pneumonia in a golden Syrian hamster model. In vitro studies showed that ranitidine bismuth citrate and its related compounds exhibited inhibition towards both the ATPase (IC50 = 0.69 µM) and DNA-unwinding (IC50 = 0.70 µM) activities of the SARS-CoV-2 helicase via an irreversible displacement of zinc(II) ions from the enzyme by bismuth(III) ions. Our findings highlight viral helicase as a druggable target and the clinical potential of bismuth(III) drugs or other metallodrugs for the treatment of SARS-CoV-2 infection.

6.
J BUON ; 25(4): 1784-1791, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33099914

RESUMO

PURPOSE: To explore the clinical application value of color Doppler ultrasound combined with computed tomography (CT) in the diagnosis of axillary lymph node metastasis (ALNM) in breast cancer. METHODS: From January 2016 to June 2018, 189 breast cancer patients who underwent radical mastectomy in our hospital were included and retrospectively analyzed. All patients had preoperative color Doppler ultrasound and CT examination of mammary gland and axillary lymph nodes, with pathological diagnosis as the gold standard. Eighty-eight cases were divided into axillary lymph node metastasis group (metastatic group) and 101 cases formed the non-axillary lymph node metastasis group (non-metastatic group). The ultrasound and CT imaging of axillary lymph nodes were analyzed to evaluate the value of color Doppler ultrasound combined with CT in the assessment of axillary lymph node metastasis in breast cancer. RESULTS: Ultrasonographic metastatic lymph nodes showed unclear borders and eccentric thickening of the cortex. The enhancement scan showed obvious heterogeneous enhancement and disappearance of lymphatic structure. The sensitivity, accuracy, and negative predictive value of ultrasonography combined with CT were 92.05%, 90.48% and 92.78%, retrospectively, which were significantly improved compared with those in the individual tests (x2=13.41, 6.126, 8.933, p=0.001, 0.047, 0.011), with significant statistical difference. CONCLUSIONS: Color Doppler ultrasound combined with CT examination can significantly improve the detected rate of axillary lymph node metastasis in breast cancer before surgery, and provide a reliable basis for the treatment options on breast cancer patients before surgery.

7.
Clin Epigenetics ; 12(1): 150, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076962

RESUMO

BACKGROUND: miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in carcinogenesis. Given the presence of a promotor-associated CpG island for its host gene, EVL, we hypothesized that intronic miR-342-3p is a tumor suppressor co-regulated with host gene by promoter DNA methylation in B cell lymphoma. RESULTS: By bisulfite pyrosequencing-verified methylation-specific PCR (MSP), EVL/MIR342 methylation was detected in five (50%) lymphoma cell lines but not normal peripheral blood and tonsils. EVL/MIR342 methylation correlated with repression of both miR-342-3p and EVL in cell lines. In completely methylated SU-DHL-16 cells, 5-AzadC treatment resulted in promoter demethylation and re-expression of miR-342-3p and EVL. In 132 primary lymphoma samples, EVL/MIR342 was preferentially methylated in B cell lymphomas (N = 68; 68.7%) than T cell lymphoma (N = 8; 24.2%) by MSP (P < 0.0001). Moreover, EVL/MIR342 methylation was associated with lower miR-342-3p expression in 79 primary NHL (P = 0.0443). In SU-DHL-16 cells, the tumor suppressor function of miR-342-3p was demonstrated by the inhibition of cellular proliferation and increase of cell death upon over-expression of miR-342-3p. Mechanistically, overexpression of miR-342-3p resulted in a decrease of LC3-II, a biomarker of autophagy, which was pro-survival for SU-DHL-16. Pre-treatment with 3-methyladenine, an autophagy inhibitor, abrogated tumor suppression associated with miR-342-3p overexpression. By luciferase assay, MAP1LC3B, a precursor of LC3-II, was confirmed as a direct target of miR-342-3p. Finally, in SU-DHL-16 cells, overexpression of miR-342-3p downregulated the known target DNMT1, with promoter demethylation and re-expression of tumor suppressor E-cadherin. CONCLUSIONS: Intronic miR-342-3p is co-regulated with its host gene EVL by tumor-specific promoter DNA methylation in B cell lymphoma. The tumor suppressor function of miR-342-3p was mediated via inhibition of pro-survival autophagy by targeting MAP1LC3B and downregulation of DNMT1 with demethylation and re-expression of tumor suppressor genes.

8.
Genome Res ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093068

RESUMO

RNA profiling has provided increasingly detailed knowledge of gene expression patterns, yet the different regulatory architectures that drive them are not well understood. To address this, we profiled and compared transcriptional and regulatory element activities across five tissues of C. elegans, covering ~90% of cells. We find that the majority of promoters and enhancers have tissue-specific accessibility, and we discover regulatory grammars associated with ubiquitous, germline and somatic tissue-specific gene expression patterns. In addition, we find that germline-active and soma-specific promoters have distinct features. Germline-active promoters have well positioned +1 and -1 nucleosomes associated with a periodic 10-bp WW signal (W = A/T). Somatic tissue-specific promoters lack positioned nucleosomes and this signal, have wide nucleosome depleted regions, and are more enriched for core promoter elements, which differ between tissues. We observe the 10-bp periodic WW signal at ubiquitous promoters in other animals suggesting it is an ancient conserved signal. Our results demonstrate fundamental differences in regulatory architectures of germline and somatic tissue-specific genes, uncover regulatory rules for generating diverse gene expression patterns, and provide a tissue-specific resource for future studies.

9.
Mol Psychiatry ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093653

RESUMO

Sleep abnormalities are often a prominent contributor to withdrawal symptoms following chronic drug use. Notably, rapid eye movement (REM) sleep regulates emotional memory, and persistent REM sleep impairment after cocaine withdrawal negatively impacts relapse-like behaviors in rats. However, it is not understood how cocaine experience may alter REM sleep regulatory machinery, and what may serve to improve REM sleep after withdrawal. Here, we focus on the melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH), which regulate REM sleep initiation and maintenance. Using adult male Sprague-Dawley rats trained to self-administer intravenous cocaine, we did transcriptome profiling of LH MCH neurons after long-term withdrawal using RNA-sequencing, and performed functional assessment using slice electrophysiology. We found that 3 weeks after withdrawal from cocaine, LH MCH neurons exhibit a wide range of gene expression changes tapping into cell membrane signaling, intracellular signaling, and transcriptional regulations. Functionally, they show reduced membrane excitability and decreased glutamatergic receptor activity, consistent with increased expression of voltage-gated potassium channel gene Kcna1 and decreased expression of metabotropic glutamate receptor gene Grm5. Finally, chemogenetic or optogenetic stimulations of LH MCH neural activity increase REM sleep after long-term withdrawal with important differences. Whereas chemogenetic stimulation promotes both wakefulness and REM sleep, optogenetic stimulation of these neurons in sleep selectively promotes REM sleep. In summary, cocaine exposure persistently alters gene expression profiles and electrophysiological properties of LH MCH neurons. Counteracting cocaine-induced hypoactivity of these neurons selectively in sleep enhances REM sleep quality and quantity after long-term withdrawal.

11.
Medicine (Baltimore) ; 99(40): e22315, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019407

RESUMO

INTRODUCTION: chronic obstructive pulmonary disease (COPD) is 1 of the leading causes of morbidity and mortality worldwide; its economic and social burdens are substantial and increasing. Recent years, an increasing number of study has shown the promising advantage of Erchen decoction (ECD) combined with sanziyangqin decoction (SZYQD) in treating COPD. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to provide a protocol for a systematic review on ECD combined with SZYQD for COPD and provide effective evidence for further clinical use. METHODS AND ANALYSIS: We will conduct a Computerized literature searches in the following databases: PubMed, MEDLINE, EMBASE, Cochrane Library, China national information network, China biomedical literature database (CBM), Chinese Scientific Journals Database and wanfang database, from their inception to June 2020, without restrictions of language. Study selection, data collection, and evaluation of the quality of evidence will be performed by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: This study will systematically evaluate the effectiveness and safety of ECD combined with SZYQD for COPD. The results will be published in a peer-reviewed journal. CONCLUSION: This study will provide evidence from the current published RCTs of whether ERD combined with SZYQD is an effective and safe intervention for COPD. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence. In this study, no individual data from participants will be involved, so ethics approval is not required. OPEN SCIENCE FRAMEWORK(OSF)REGISTRATION NUMBER: August 19, 2020; osf.io/zxm24.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Testes de Função Respiratória
12.
Biomed Pharmacother ; 132: 110809, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049584

RESUMO

Phloretin is a natural dihydrochalcone flavonoid that is mainly distributed in apple, pear and other juicy fruit peels or root peels. Phloretin exhibits several pharmacological properties, such as antidiabetic, antioxidant, anti-inflammatory, and antitumor activities. However, the poor water solubility of phloretin limits its application in the treatment of numerous diseases. To date, the underlying mechanisms of phloretin absorption have not been investigated. In this study, the pharmacokinetics of phloretin orally administered to Sprague-Dawley (SD) rats were examined, and the absorption mechanisms of phloretin were investigated in a Caco-2 cell monolayer and single-pass intestinal perfusion in SD rat. The effects measured by basic parameters, such as compound concentration, time, temperature, paracellular pathway, in different intestinal segments were analyzed, and various inhibitors, such as the P-glycoprotein (P-gp) inhibitor verapamil, the multidrug resistance protein 2 (MRP2) inhibitor indomethacin, the breast cancer resistance protein (BCRP) inhibitor reserpine, and the closely related regulator EDTA, were evaluated to determine their effects on the absorption of phloretin. The pharmacokinetics of phloretin was studied by oral and intravenous injection in rats. The bioavailability was 8.676 %.The SPIP experiments showed that P-gp, MRP2, BCRP protein inhibitor and closely related regulator, could significantly increase the apparent permeability coefficient (Papp) of phloretin. Monolayer transport experiments in Caco-2 cells showed that P-gp, MRP2 protein inhibitor and closely related regulator EDTA, significantly increased the Papp value of phloretin. In conclusion, phloretin is a substrate of P-gp and MRP2, and its modes of transport include active transport, efflux protein transport and cell bypass.

13.
Biol Psychiatry ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-33069367

RESUMO

BACKGROUND: Synaptogenesis is essential in forming new neurocircuits during development, and this is mediated in part by astrocyte-released thrombospondins (TSPs) and activation of their neuronal receptor, α2δ-1. Here, we show that this developmental synaptogenic mechanism is utilized during cocaine experience to induce spinogenesis and the generation of AMPA receptor-silent glutamatergic synapses in the adult nucleus accumbens shell (NAcSh). METHODS: Using multidisciplinary approaches including astrocyte Ca2+ imaging, genetic mouse lines, viral-mediated gene transfer, and operant behavioral procedures, we monitor the response of NAcSh astrocytes to cocaine administration and examine the role of astrocytic TSP-α2δ-1 signaling in cocaine-induced silent synapse generation as well as the behavioral impact of astrocyte-mediated synaptogenesis and silent synapse generation. RESULTS: Cocaine administration acutely increases Ca2+ events in NAcSh astrocytes, while decreasing astrocytic Ca2+ blocks cocaine-induced generation of silent synapses. Furthermore, knockout of TSP2, or pharmacological inhibition or viral-mediated knockdown of α2δ-1, prevents cocaine-induced generation of silent synapses. Moreover, disrupting TSP2-α2δ-1-mediated spinogenesis and synapse generation in NAcSh decreases cue-induced cocaine seeking after withdrawal from cocaine self-administration and cue-induced reinstatement of cocaine seeking after drug extinction. CONCLUSIONS: These results establish that silent synapses are generated by an astrocyte-mediated synaptogenic mechanism in response to cocaine experience and embed critical cue-associated memory traces that promote cocaine relapse.

14.
Behav Brain Res ; : 112968, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069740

RESUMO

ß-Amyloid (Aß) elevation, tau hyperphosphorylation, and neuroinflammation are major hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3ß (GSK-3ß) is a key protein kinase implicated in the pathogenesis of AD. Blockade of GSK-3ß is an attractive therapeutic strategy for AD. Isoorientin, a 6-C-glycosylflavone, was previously shown to be a highly selective inhibitor of GSK-3ß, while exerting neuroprotective effects in neuronal models of AD. In the present study, we evaluated the in vivo effects of isoorientin on GSK-3ß, tau phosphorylation, Aß deposition, neuroinflammatory response, long-term potentiation, and spatial memory in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice using biochemical, electrophysiological, and behavioral tests. Chronic oral administration of isoorientin to APP/PS1 mice at 8 months of age attenuated multiple AD pathogenic hallmarks in the brains, including GSK-3ß overactivation, tau hyperphosphorylation, Aß deposition, and neuroinflammation. For neuroinflammation, isoorientin treatment reduced the number of activated microglia associated with Aß-positive plaques, and in parallel reduced the levels of pro-inflammatory factors in the brains of APP/PS1 mice. Strikingly, isoorientin reversed deficits in synaptic long-term potentiation and spatial memory relevant to cognitive functions. Together, the findings suggest that isoorientin is a brain neuroprotector and may be a promising drug lead for treatment of AD and related neurodegenerative disorders.

15.
Scand J Psychol ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070330

RESUMO

In recent years, narcissism has been attracting considerable interest by researchers because of its enigmatic constructs. To enhance our understanding of narcissists' psychosocial functioning, considering the relationship between narcissism and interpersonal trust is crucial. This study aimed to investigate how narcissistic admiration and rivalry are associated with interpersonal trust. To gain a more nuanced understanding, a cross-lagged design was conducted at two time points that were six months apart. In total, 357 adolescents (Mage  = 16.33 years) completed the Narcissistic Admiration and Rivalry Questionnaire (NARQ) and the Interpersonal Trust Scale. The results showed that narcissistic admiration positively predicted interpersonal trust while narcissistic rivalry negatively predicted interpersonal trust at the second time point. However, interpersonal trust did not predict subsequent levels of narcissistic admiration and rivalry. These findings enhanced our understanding by showing that narcissistic admiration and rivalry have different effects on interpersonal trust, and that they remain relatively stable during a six-month period.

16.
J Biotechnol ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007350

RESUMO

Deracemization of D,L-phosphinothricin (D,L-PPT) is one of the most promising routes for preparation of optically pure L-PPT. In this work, an efficient multi-enzyme redox cascade was developed for deracemization ofPPT, which includes oxidative reaction and reductive reaction. The oxidative reaction catalyzing oxidative deamination of D-PPT to 2-oxo-4-[(hydroxy)(-methyl)phosphinyl]butyric acid (PPO) was performed by a D-amino acid oxidase and a catalase for removing H2O2. The reductive reaction catalyzing amination of PPO to L-PPT is achieved by a glufosinate dehydrogenase and a glucose dehydrogenase for cofactor regeneration. To avoid the inhibitory effect of glucose on the oxidative reaction, a "two stages in one-pot" strategy was developed to combine these two reactions in deracemization process. By using this strategy, the L-PPT was obtained with a high yield (89 %) and > 99 % enantiomeric excess at substrate loading of 300 mM in absence of addition of extra NADP+. These encouraging results demonstrated that the developed enzyme cascade deracemization process exhibits great potential and economical competitiveness for manufacture of L-PPT from D,L-PPT.

17.
J Bioinform Comput Biol ; : 2050032, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938283

RESUMO

Gleason score (GS) is a powerful prognostic factor in prostate cancer (PCa). A GS-7 tumor typically has the primary Gleason (architectural) pattern and secondary prevalent one being graded with 3 and 4 (or 4 and 3), respectively. Due to the well-known intratumoral multifocal occurrence of different patterns, a biological sample from a GS-7 tumor used in a molecular experiment will be uncertain regarding the actually represented pattern if no special attention is given to specimen preparation. In this study, by an integrative analysis of several published gene expression datasets, one of which is the profiling of the paired GP-3 (Gleason pattern 3) and GP-4 (Gleason pattern 4) specimens of 13 GS-7 tumors, we demonstrate that such an uncertainty can be frequently observed in the published data. More specifically, our results suggest that the GS-7 specimens used to generate the frequently-cited The Cancer Genome Atlas (TCGA) data and the Gene Expression Omnibus (GEO) dataset GSE21032 which largely are individual GP-3 or GP-4 specimens rather than the "intermediate" specimens of GP-3 and GP-4. This indicates a pitfall in the existing molecular research of prostate tumors relevant to GS and in GS-related molecular biomarker identification using the previously documented data.

18.
Br J Psychol ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940352

RESUMO

Multiple facial cues such as facial expression and face gender simultaneously influence facial trustworthiness judgement in adults. The current work was to examine the effect of multiple facial cues on trustworthiness judgement across age groups. Eight-, 10-year-olds, and adults detect trustworthiness from happy and neutral adult faces (female and male faces) in Experiment 1. Experiment 2 included both adult and child faces wearing happy, angry, and neutral expressions. Nine-, 11-, 13-year-olds, and adults had to rate facial trustworthiness with a 7-point Likert scale. The results of Experiments 1 and 2 revealed that facial expression and face gender independently affected facial trustworthiness judgement in children aged 10 and below but simultaneously affected judgement in children aged 11 and above, adolescents, and adults. There was no own-age bias in children and adults. The results showed that children younger than 10 could not process multiple facial cues in the same manner as in older children and adults when judging trustworthiness. The current findings provide evidence for the stable-feature account, but not for the own-age bias account or the expertise account.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32881664

RESUMO

OBJECTIVE: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. MATERIALS AND METHODS: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. RESULTS: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. CONCLUSIONS: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

20.
Inorg Chem ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32885961

RESUMO

Nonlinear-optical (NLO) crystals, which can regulate the laser wavelength through a cascading second-harmonic-generation technique, have been widely utilized in the field of optoelectronics. In this work, we grew the NLO borate crystal Rb3YB6O12 (RYBO) using the spontaneous crystallization method. RYBO crystallizes in a chiral trigonal space group of R32 with a new type of structural arrangement built from Y-O short chains and B5O10 groups. It is significantly different from the known structure of chemical analogues Rb3REB6O12 (RE = Nd, Eu) not only in the halved unit cell parameter but also in the Y-O connection manner. The NLO response of RYBO is about 0.8KDP, 8-fold larger than that of KB5O8·4H2O with the same B5O10 groups because of the coexistence of two NLO-active units of the distorted YO6 octahedra and B5O10 anions. Thanks to the short ultraviolet (UV) cutoff, RYBO may have potential NLO applications in the UV and even deep-UV spectral regions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA