Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Chem Biodivers ; 19(6): e202200207, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35419971

RESUMO

Two new austocystin analogs, austocystin P (1) and austocystin Q (2), along with fourteen known compounds (3-16) were isolated from the fermentation extract of Aspergillus sp. WHUF05236. The planar structures of 1 and 2 were elucidated through 1D, 2D NMR and MS analyses. Their absolute configurations were determined by the time-dependent density functional (TDDFT)-ECD calculation. Compounds 3, 11, and 12 exhibited antimicrobial activities against Helicobacter pylori with MIC values ranging from 20.00 to 43.47 µM. Compounds 3, 6, and 7 showed cytotoxicities against the human colon cancer cell lines Hct-116 with IC50 values of 101.79, 65.46, and 36.72 µM, respectively.


Assuntos
Aspergillus , Fungos , Aspergillus/química , Fungos/química , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular
2.
Gastroenterology ; 158(3): 550-561, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31711921

RESUMO

BACKGROUND & AIMS: Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC). METHODS: In a phase 2, proof-of-concept, double-blind, parallel-group study, adult outpatients with modified Mayo Clinic scores (MCSs) (stool frequency, rectal bleeding, and endoscopy findings) of 4-9, endoscopic subscores of 2 or more, and rectal bleeding subscores of 1 or more were randomly assigned to groups given once-daily etrasimod 1 mg (n = 52), etrasimod 2 mg (n = 50), or placebo (n = 54) for 12 weeks. The study was performed from October 15, 2015, through February 14, 2018, at 87 centers in 17 countries. The primary endpoint was an increase in the mean improvement in modified MCS from baseline to week 12. Secondary endpoints included the proportion of patients with endoscopic improvement (subscores of 1 or less) from baseline to week 12. Exploratory endpoints, including clinical remission, are reported in the article, although the study was statistically powered to draw conclusions only on the primary endpoint. RESULTS: At week 12, the etrasimod 2 mg group met the primary and all secondary endpoints. Etrasimod 2 mg led to a significantly greater increase in mean improvement in modified MCS from baseline than placebo (difference from placebo, 0.99 points; 90% confidence interval, 0.30-1.68; P = .009), and etrasimod 1 mg led to an increase in mean improvement from baseline in modified MCS of 0.43 points more than placebo (90% confidence interval, reduction of 0.24 to increase of 1.11; nominal P = .15). Endoscopic improvement occurred in 41.8% of patients receiving etrasimod 2 mg vs 17.8% receiving placebo (P = .003). Most adverse events were mild to moderate. Three patients had a transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously all patients had evidence of atrioventricular block before etrasimod exposure. CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, etrasimod 2 mg was more effective than placebo in producing clinical and endoscopic improvements. Further clinical development is warranted. Clinicaltrials.gov, Number: NCT02447302.


Assuntos
Acetatos/administração & dosagem , Bloqueio Atrioventricular/epidemiologia , Colite Ulcerativa/tratamento farmacológico , Hemorragia Gastrointestinal/prevenção & controle , Indóis/administração & dosagem , Acetatos/efeitos adversos , Adulto , Doenças Assintomáticas/epidemiologia , Bloqueio Atrioventricular/induzido quimicamente , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Colonoscopia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Indóis/efeitos adversos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Placebos/efeitos adversos , Estudo de Prova de Conceito , Reto , Índice de Gravidade de Doença , Receptores de Esfingosina-1-Fosfato/imunologia , Receptores de Esfingosina-1-Fosfato/metabolismo , Resultado do Tratamento
3.
J Phys Chem A ; 124(28): 5824-5831, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32579357

RESUMO

In this study, we present a new hybrid functional denoted as xOPBE, which is optimized at the 6-311+G(2d,p) basis set and designed with a specific aim of providing accurate 13C chemical shifts. By mixing the Hartree-Fock exchange into the OPBE functional, xOPBE provides a significantly improved overall performance as compared to its parent OPBE functional, while OPBE was shown previously as an excellent functional for 13C chemical shifts. Even in the case of the 1-adamantyl cation, for which OPBE completely fails in reproducing the experimental results, xOPBE still performs very well with similar accuracy as the standard CCSD(T) method with a large basis set. Our results also demonstrate that xOPBE not only can improve quantitatively the description of the correct assignments given by OPBE but also can revert OPBE's incorrect assignments qualitatively. Thus, we would like to recommend the use of xOPBE for routine evaluations of 13C chemical shifts.

4.
Eur Respir J ; 54(4)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31391223

RESUMO

PURPOSE: This phase 2 study was designed to assess the efficacy, safety and tolerability of immediate-release orally administered ralinepag, a selective, non-prostanoid prostacyclin receptor agonist with a 24-h terminal half-life, compared to placebo in adult patients with symptomatic pulmonary arterial hypertension (PAH). METHODS: 61 PAH patients who were receiving standard care, including mono or dual PAH-targeted background therapy were randomised 2:1 to ralinepag (n=40) or placebo (n=21). The starting dose of ralinepag was 10 µg twice daily. Dosage was then up-titrated as tolerated over the course of the 9-week dose-titration period, to a maximum total daily dose of 600 µg (300 µg twice daily). The primary efficacy end-point was the absolute change in pulmonary vascular resistance (PVR) from baseline to week 22. Additional end-points included percentage change in PVR from baseline, other haemodynamic parameters, 6-min walk distance (6MWD) and safety and tolerability. RESULTS: Ralinepag significantly decreased PVR by 163.9 dyn·s·cm-5 compared to an increase of 0.7 dyn·s·cm-5 with placebo (p=0.02); the least-squares mean change from baseline PVR was -29.8% compared with placebo (p=0.03). 6MWD increased from baseline by 36.2 m with ralinepag and 29.4 m with placebo (p=0.90). Serious adverse events occurred in 10% of ralinepag patients and 29% of placebo patients. Study discontinuations occurred in 13% of ralinepag patients and 10% of placebo patients. SUMMARY: Ralinepag reduced PVR compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy.


Assuntos
Acetatos/uso terapêutico , Carbamatos/uso terapêutico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Ativadores de Enzimas/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Receptores de Epoprostenol/agonistas , Resistência Vascular , Teste de Caminhada , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Arterial Pulmonar/fisiopatologia , Guanilil Ciclase Solúvel , Adulto Jovem
6.
Int J Mol Sci ; 15(2): 2761-72, 2014 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-24552875

RESUMO

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Animais , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Transplante Heterólogo , Verapamil/química , Verapamil/toxicidade , Vincristina/química , Vincristina/toxicidade
7.
Int J Mol Sci ; 15(5): 7199-212, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24776763

RESUMO

Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (P(eff)) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations. Theophylline (high permeability) and ranitidine (low permeability) were also applied to access the permeability of NCE as reference compounds. The bioavailability after intragastrical and intravenous administration was measured in beagle dogs. The solubility of NCE in tested phosphate buffers was quite low with the maximum solubility of 81.73 µg/mL at pH 1.0. The intrinsic dissolution ratio of NCE was 1 × 10⁻4 mg·min⁻¹·cm⁻². The P(eff) value of NCE in all intestinal segments was more proximate to the high-permeability reference theophylline. Therefore, NCE was classified as class II drug according to Biopharmaceutics Classification System due to its low solubility and high intestinal permeability. In addition, concentration-dependent permeability was not observed in all the segments, indicating that there might be passive transportation for NCE. The absolute oral bioavailability of NCE in beagle dogs was 26.75%. Therefore, dissolution promotion will be crucial for oral formulation development and intravenous administration route will also be suggested for further NCE formulation development. All the data would provide a reference for biopharmaceutics classification research of other novel drug candidates.


Assuntos
Absorção Intestinal , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Administração Intravenosa , Administração Oral , Animais , Disponibilidade Biológica , Biofarmácia , Cães , Mucosa Intestinal/metabolismo , Masculino , Neoplasias/tratamento farmacológico , Permeabilidade , Inibidores de Proteínas Quinases/administração & dosagem , Ratos , Ratos Sprague-Dawley , Solubilidade
8.
J Crohns Colitis ; 18(6): 885-894, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38245818

RESUMO

BACKGROUND AND AIMS: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis [UC]. This post-hoc analysis of the phase 2 OASIS trial [NCT02447302] evaluated its efficacy for endoscopic improvement-histologic remission [EIHR] and assessed correlation between faecal calprotectin [FCP] and C-reactive protein [CRP] levels with efficacy outcomes. METHODS: In total, 156 adults with moderately to severely active UC received once-daily etrasimod (1 mg [n = 52]; 2 mg [n = 50]) or placebo [n = 54] for 12 weeks. Clinical, endoscopic, and histologic variables were evaluated at baseline and Week 12. EIHR was defined as achievement of endoscopic improvement [endoscopic subscore ≤ 1, without friability] and histologic remission [Geboes score < 2.0]. Outcomes included the relationships between FCP and CRP concentration and clinical, endoscopic, and histologic variables. RESULTS: Achievement of EIHR was significantly higher in patients who received etrasimod 2 mg versus placebo [19.5% vs 4.1%; Mantel-Haenszel estimated difference, 15.4%; p = 0.010]. In the etrasimod 2 mg group, median FCP and CRP levels at Week 12 were significantly lower in patients who achieved clinical remission, endoscopic improvement, histologic remission, and EIHR versus patients who did not [all p < 0.05]. An FCP concentration cutoff of 250 µg/g achieved optimum sensitivity and specificity for efficacy, including EIHR [0.857 and 0.786, respectively; κ coefficient, 0.3584]. Higher proportions of patients with FCP ≤ 250 µg/g achieved efficacy outcomes at Week 12 versus patients with FCP > 250 µg/g. CONCLUSIONS: Etrasimod was effective for inducing EIHR in patients with UC. FCP and CRP may be useful, noninvasive biomarkers to monitor treatment response. CLINICALTRIALS.GOV NUMBER: NCT02447302.


Assuntos
Proteína C-Reativa , Colite Ulcerativa , Fezes , Complexo Antígeno L1 Leucocitário , Humanos , Complexo Antígeno L1 Leucocitário/análise , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Masculino , Feminino , Fezes/química , Adulto , Pessoa de Meia-Idade , Indução de Remissão/métodos , Colonoscopia , Método Duplo-Cego , Resultado do Tratamento , Biomarcadores/análise , Índice de Gravidade de Doença , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Moduladores do Receptor de Esfingosina 1 Fosfato/administração & dosagem
9.
Clin Pharmacol Drug Dev ; 13(5): 534-548, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38345530

RESUMO

Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator in development for immune-mediated inflammatory diseases (IMIDs). Here, we report the human safety, pharmacokinetics, and pharmacodynamics of etrasimod obtained from both a single ascending dose (SAD; 0.1-5 mg) study and a multiple ascending dose (MAD; 0.35-3 mg once daily) study. Overall, 99 healthy volunteers (SAD n = 40, MAD n = 59) completed the 2 studies. Evaluated single and multiple doses were well tolerated up to 3 mg without severe adverse events (AEs). Gastrointestinal disorders were the most common etrasimod-related AEs. Over the evaluated single- and multiple-dose ranges, dose-proportional and marginally greater-than-dose-proportional etrasimod plasma exposure were observed, respectively. At steady state, etrasimod oral clearance and half-life mean values ranged from 1.0 to 1.2 L/h and 29.7 to 36.4 hours, respectively. Dose-dependent total peripheral lymphocyte reductions occurred following etrasimod single and multiple dosing. Etrasimod multiple dosing resulted in reductions from baseline in total lymphocyte counts ranging from 41.1% to 68.8% after 21 days. Lymphocyte counts returned to normal range within 7 days following treatment discontinuation. Heart rate lowering from pretreatment baseline on etrasimod dosing was typically mild, with mean reductions seen after the first dose of up to 19.5 bpm (5 mg dose). The favorable safety, pharmacokinetic, and pharmacodynamic properties of etrasimod in humans supported its further development and warranted its investigation for treatment of IMIDs.


Assuntos
Relação Dose-Resposta a Droga , Voluntários Saudáveis , Humanos , Adulto , Masculino , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Meia-Vida , Administração Oral , Método Duplo-Cego , Moduladores do Receptor de Esfingosina 1 Fosfato/administração & dosagem , Moduladores do Receptor de Esfingosina 1 Fosfato/farmacocinética , Moduladores do Receptor de Esfingosina 1 Fosfato/efeitos adversos , Moduladores do Receptor de Esfingosina 1 Fosfato/farmacologia , Esquema de Medicação , Receptores de Esfingosina-1-Fosfato , Adolescente , Área Sob a Curva
10.
Front Psychol ; 14: 1260084, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38078244

RESUMO

Retrieval practice can enhance learning but is rarely used in self-regulated learning. Although explicit retrieval practice guidance (RPG)-which helps students use retrieval correctly-can improve learning outcomes, however, task difficulty and differences in academic self-efficacy (ASE) may influence retrieval practice decisions and learning performance, which were not considered in previous researches. The purpose of this study was to explore whether RPG produces different effects due to task difficulty and ASE. In Experiment 1, participants studied tasks with varying difficulty levels, some of which were guided. Results showed that RPG could enhance learning through increased retrieval practice, and participants engaged in more retrieval for difficult tasks. In Experiment 2, participants with different degrees of ASE learned tasks under guidance. Participants with high ASE persisted better on different tasks. Hence, task difficulty can affect retrieval practice decisions, and ASE increases persistence in retrieval practice. The implications of the findings for students' use of RPG are discussed in this article.

11.
Mar Life Sci Technol ; 5(2): 232-241, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37275544

RESUMO

Metabolites of microorganisms have long been considered as potential sources for drug discovery. In this study, five new depsidone derivatives, talaronins A-E (1-5) and three new xanthone derivatives, talaronins F-H (6-8), together with 16 known compounds (9-24), were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362. The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher's method. Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring. A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin. The antimicrobial activity assay indicated that compounds 5, 9, 10, and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration (MIC) values in the range of 2.42-36.04 µmol/L. While secalonic acid D (19) demonstrated significant antimicrobial activity against four strains of H. pylori with MIC values in the range of 0.20 to 1.57 µmol/L. Furthermore, secalonic acid D (19) exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC50 values of 0.15 and 0.19 µmol/L, respectively. The structure-activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H. pylori. The depsidone derivatives are promising leads to inhibit H. pylori and provide an avenue for further development of novel antibiotics. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00170-5.

12.
Front Psychiatry ; 13: 937841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046157

RESUMO

Secondary Vocational School Students are particularly susceptible to online game addiction due to adolescent characteristics and superimposed pressures of academic and employment. Based on the theoretical framework of self-identity and self-esteem, the present research conducted a questionnaire survey using samples of secondary vocational school students to investigate the relationship between pathological online game use (POGU), self-esteem and self-identity. The results showed that 15.56% of secondary vocational students' level of POGU met the diagnostic criteria, and POGU and self-esteem appeared significant differences in gender and family types. Moreover, lower self-esteem and self-identity were associated with higher POGU and self-esteem played a partial mediating role in the relationship between self-identity and POGU. We briefly discussed practical implications of our findings and the future research.

13.
Front Plant Sci ; 13: 945553, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903234

RESUMO

Brassica napus as both oilseed and vegetable, is widely cultivated in China. The purple leaf of B. napus is rich in anthocyanins and can provide valuable nutrients. Although several high-anthocyanin cultivars have been reported, the molecular mechanism underlying anthocyanin biosynthesis in B. napus remains lesser-known. Therefore, in this study, we conducted integrative metabolome and transcriptome analyses in three B. napus cultivars with different leaf colors. Overall, 39 flavonoids were identified (including 35 anthocyanins), and 22 anthocyanins were differentially accumulated in the leaves, contributing to the different leaf colors. Cyanidin-3,5,3'-O-triglucoside was confirmed as the main contributor of the purple leaf phenotype. Meanwhile, other anthocyanins may play important roles in deepening the color of B. napus leaves. A total of 5,069 differentially expressed genes (DEGs) and 32 overlapping DEGs were identified by RNA-sequencing; hence, the correlation between anthocyanin content and DEG expression levels was explored. Two structural genes (DFR and ANS), three GSTs (homologous to TT19), and 68 differentially expressed transcription factors (TFs), especially MYB-related TFs and WRKY44, were identified in three B. napus varieties characterized by different leaf color, thereby indicating that these genes may contribute to anthocyanin biosynthesis, transport, or accumulation in B. napus leaves. The findings of study provide important insights that may contribute to gaining a better understanding of the transcriptional regulation of anthocyanin metabolism in B. napus.

14.
Front Psychol ; 12: 736922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34975627

RESUMO

Cue labels are useful during multimedia learning. According to spatial contiguity principle, people learn more when related words and pictures are displayed spatially near one another. Well-arranged labels of multimedia material can greatly facilitate learning. This study used eye tracking to examine the joint influence of label size (large vs. small) and color (included vs. not) on multimedia learning. The results revealed that larger labels led to better retention test performance and a higher AOI glance count, but no cueing effect was found for color. Cues have a certain attention-leading function that promotes the learner remembering the content. These findings suggest that salient labels that provide explanatory information can guide learners' attention and facilitate learning, though a combination of label size and color salience did not demonstrate a superior cueing effect.

15.
Front Public Health ; 9: 728762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513793

RESUMO

People constantly talk to one another about the past, and in so doing, they recount certain details while remaining silent about others. Collaborative or conversational remembering plays an important role in establishing shared representations of the past (e.g., the 911 attacks, Covid-19). According to the socially shared retrieval-induced forgetting (SS-RIF) effect, a listener will forget about relevant but unpracticed information during communication, due to intentional or unintentional selective retrieval of data by the speaker. The SS-RIF paradigm has been applied to explain how collective memory is shaped within the context of conversation/discourse. This study sought to determine if SS-RIF occurred only during face-to-face communication, or whether shared memories could be developed through other types of conversation quite common in modern society. We also investigated whether a level of social interaction in the real-world presence of others is a necessary condition for inducing SS-RIF, and if listeners experience different degrees of SS-RIF due to different levels of perceived social presence. We observed the SS-RIF phenomenon in listeners both in real life and video; the degree of forgetting was the same for the two conditions. These results indicate that social presence may not be associated with SS-RIF. Public silence affects the formation of collective memory regardless of the face-to-face presence of others, and thus physical presence is not necessary to induce SS-RIF.


Assuntos
COVID-19 , Relações Interpessoais , Comunicação , Humanos , SARS-CoV-2 , Estudantes
16.
Front Psychol ; 12: 755804, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795620

RESUMO

Do students learn better with texts that are slightly harder-to-read (i.e., disfluent)? Previous research has yielded conflicting findings. The present study identified the boundary condition that determines when disfluent texts benefit learning. We used eye-tracking to examine the joint influence of text legibility (fluent vs. disfluent) and signaling (signaling vs. non-signaling) on multimedia learning. The results revealed that both disfluent text and signaling led to better transfer test performance, and there was also an interaction between them. Specifically, the disfluent text led to better learning outcomes with or without signaling; however, in the fluent text condition, only signaling facilitated learning. Eye movement analyses indicated that signaling guided learners to pay more attention to important content in the learning materials. The current results suggest that signaling can enhance individuals' perceived fluency or familiarity to the material and guide the attention during multimedia learning, and the positive impact of disfluency on multimedia learning seems to be more stable and ubiquitous. We discuss these under the framework of disfluency effect and attention-guiding effect.

17.
J Crohns Colitis ; 15(6): 950-959, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-33475734

RESUMO

BACKGROUND AND AIMS: Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator. In a phase 2, randomised, double-blind, placebo-controlled trial in adults with moderately-to-severely active ulcerative colitis [OASIS], etrasimod 2 mg provided significant benefit versus placebo and was generally well tolerated. This open-label extension [OLE] evaluated safety and efficacy of etrasimod for up to 52 weeks. METHODS: In OASIS, 156 patients received etrasimod 1 mg, etrasimod 2 mg, or placebo, once daily for 12 weeks. After completing OASIS, patients could enrol in the OLE and receive etrasimod 2 mg for an additional 34-40 weeks. RESULTS: In all, 118 patients enrolled in the OLE; 112 patients received etrasimod 2 mg at any point and were evaluated for safety and efficacy. A total of 92 [82%] patients who received etrasimod 2 mg in the OLE completed the study. Treatment-emergent adverse events occurred in 60% [67/112] of patients receiving etrasimod 2 mg at any time, most commonly worsening ulcerative colitis and anaemia; 94% of adverse events were mild/moderate. At end of treatment, 64% of patients met the criteria for clinical response, 33% for clinical remission, and 43% for endoscopic improvement. Week 12 clinical response, clinical remission, or endoscopic improvement was maintained to end of treatment in 85%, 60%, or 69% of patients, respectively. Steroid-free clinical remission occurred in 22% of overall patients. CONCLUSIONS: In this long-term extension study, etrasimod 2 mg demonstrated a favourable safety profile. Most patients with clinical response, clinical remission, or endoscopic improvement at Week 12 maintained that status to end of treatment.


Assuntos
Acetatos , Colite Ulcerativa , Indóis , Efeitos Adversos de Longa Duração , Indução de Remissão/métodos , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Adulto , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Relação Dose-Resposta Imunológica , Monitoramento de Medicamentos/métodos , Redução da Medicação/métodos , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/estatística & dados numéricos , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Efeitos Adversos de Longa Duração/induzido quimicamente , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/prevenção & controle , Masculino , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , Resultado do Tratamento
18.
Front Pharmacol ; 11: 577017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33424590

RESUMO

As a typical traditional Chinese medicine, Bu-Yin-Qian-Zheng Formula (BYQZF) has been shown to have neuroprotective effects in patients with Parkinson's disease (PD), particularly by ameliorating mitochondrial dysfunction and regulating expression of the parkin protein. However, the underlying mechanisms by which BYQZF affects mitochondrial function through parkin are unclear. Accordingly, in this study, we evaluated the mechanisms by which BYQZF ameliorates mitochondrial dysfunction through parkin in PD. We constructed a parkin-knockdown cell model and performed fluorescence microscopy to observe transfected SH-SY5Y cells. Quantitative real-time reverse transcription polymerase chain reaction and western blotting were conducted to detect the mRNA and protein expression levels of parkin. Additionally, we evaluated the cell survival rates, ATP levels, mitochondrial membrane potential (ΔΨm), mitochondrial morphology, parkin protein expression, PINK1 protein expression, and mitochondrial fusion and fission protein expression after treatment with MPP+ and BYQZF. Our results showed that cell survival rates, ATP levels, ΔΨm, mitochondrial morphology, parkin protein levels, PINK1 protein levels, and mitochondrial fusion protein levels were reduced after MPP+ treatment. In contrast, mitochondrial fission protein levels were increased after MPP+ treatment. Moreover, after transient transfection with a negative control plasmid, the above indices were significantly increased by BYQZF. However, there were no obvious differences in these indices after transient transfection with a parkin-knockdown plasmid. Our findings suggest that BYQZF has protective effects on mitochondrial function in MPP+-induced SH-SY5Y cells via parkin-dependent regulation of mitochondrial dynamics.

19.
Zootaxa ; 4544(1): 144-150, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30647281

RESUMO

Cucujus costatus Zhao Zhang, new species is described from Guangdong, China. This new species can be easily recognized by the longitudinal elevated carinae on elytra and its strongly convex eyes. Additional records for C. kempi Grouvelle, 1913 and C. elongatus Lee Pütz, 2008 are added. A key to the known Chinese species of Cucujus Fabricius is given.


Assuntos
Besouros , Distribuição Animal , Estruturas Animais , Animais , China
20.
Nanoscale Res Lett ; 14(1): 264, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31376019

RESUMO

Rational design of cage-like structure is an effective method for the improvement of the capacitive performance of transition metal hydroxides. In this work, cubic Ni(OH)2 nanocages (Ni(OH)2 NCs) were constructed through a coordinating etching and precipitating (CEP) route. Ni(OH)2 NCs possess abundant active sites, sufficient diffusion channels, and accelerated electron transfer rate, which are beneficial for electrochemical kinetics. As a positive electrode for supercapacitors, the Ni(OH)2 NCs/Ni foam (NF) electrode presents a high specific capacitance of 539.8 F g-1 at 1 A g-1, which is much larger than that of broken Ni(OH)2 NCs/NF (Ni(OH)2 BNCs/NF, 87.3 F g-1 at 1 A g-1). In addition, the Ni(OH)2 NCs/NF electrode still retains 96.9% of its initial specific capacitance after 2000 cycles. The asymmetric supercapacitor (ASC) devices were assembled using Ni(OH)2 NCs/NF and activated carbon (AC)/NF as positive and negative electrodes, respectively. The ASC exhibits a higher energy density of 23.3 Wh kg-1 at a power density of 800 W kg-1 compared to Ni(OH)2 BNCs/NF (3 Wh kg-1 at 880 W kg-1). These results demonstrate that the Ni(OH)2 NCs/NF electrode presents potential applications in the field of energy storage. The design of cage-like structure paves an effective way to achieve high-performance electrode materials.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA