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Quasi-two-dimensional (quasi-2D) perovskites exhibit excellent performance in light-emitting diodes (LEDs). However, the quality of perovskite films prepared via the solution method is significantly impacted by the enormous number of defects that unavoidably form at the grain boundaries and interfaces during the precursor to the crystal formation process. Here, we propose a strategy to assist perovskite crystallization and defect passivation at the buried interface through interfacial modification. The organic ammonium salt, ethylamine chloride (EACl), is added to the hole transport material and modifies the buried interface of the perovskite film. EACl introduces the nucleation sites for perovskite precursors, and promotes the crystallization process of the perovskite grains, contributing to the formation of high-quality perovskite films. At the same time, the presence of Lewis base (-NH2) groups in EACl and their lone electron pairs effectively inactivate unlocated Pb2+ ions at the buried interface, thereby reducing non-radiative recombination. In addition, chloride ions help to mitigate defects and to improve the morphology of perovskite films. Devices with this modification show a higher performance than control devices on all metrics. This work proposes a facile but efficient way for improving quasi-2D pure blue perovskite crystallization and growth.
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Translation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we data-mined human and mouse heart ribosome profiling analyses and identified a double-stranded RNA (dsRNA) structure within the GATA4 uORF that cooperates with the start codon to augment uORF translation and inhibits mORF translation. A trans-acting RNA helicase DDX3X inhibits the GATA4 uORF-dsRNA activity and modulates the translational balance of uORF and mORF. Antisense oligonucleotides (ASOs) that disrupt this dsRNA structure promote mORF translation, while ASOs that base-pair immediately downstream (i.e., forming a bimolecular double-stranded region) of either the uORF or mORF start codon enhance uORF or mORF translation, respectively. Human cardiomyocytes and mice treated with a uORF-enhancing ASO showed reduced cardiac GATA4 protein levels and increased resistance to cardiomyocyte hypertrophy. We further show the broad utility of uORF-dsRNA- or mORF-targeting ASO to regulate mORF translation for other mRNAs. This work demonstrates that the uORF-dsRNA element regulates the translation of multiple mRNAs as a generalizable translational control mechanism. Moreover, we develop a valuable strategy to alter protein expression and cellular phenotypes by targeting or generating dsRNA downstream of a uORF or mORF start codon.
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Cardiomegalia , Biossíntese de Proteínas , Humanos , Animais , Camundongos , Códon de Iniciação/genética , Regiões 5' não Traduzidas , RNA Mensageiro/genética , Fases de Leitura Aberta/genética , Cardiomegalia/genéticaRESUMO
We show that in silico design of DNA secondary structures is improved by extending the base pairing alphabet beyond A-T and G-C to include the pair between 2-amino-8-(1'-ß-d-2'-deoxyribofuranosyl)-imidazo-[1,2-a]-1,3,5-triazin-(8H)-4-one and 6-amino-3-(1'-ß-d-2'-deoxyribofuranosyl)-5-nitro-(1H)-pyridin-2-one, abbreviated as P and Z. To obtain the thermodynamic parameters needed to include P-Z pairs in the designs, we performed 47 optical melting experiments and combined the results with previous work to fit free energy and enthalpy nearest neighbor folding parameters for P-Z pairs and G-Z wobble pairs. We find G-Z pairs have stability comparable to that of A-T pairs and should therefore be included as base pairs in structure prediction and design algorithms. Additionally, we extrapolated the set of loop, terminal mismatch, and dangling end parameters to include the P and Z nucleotides. These parameters were incorporated into the RNAstructure software package for secondary structure prediction and analysis. Using the RNAstructure Design program, we solved 99 of the 100 design problems posed by Eterna using the ACGT alphabet or supplementing it with P-Z pairs. Extending the alphabet reduced the propensity of sequences to fold into off-target structures, as evaluated by the normalized ensemble defect (NED). The NED values were improved relative to those from the Eterna example solutions in 91 of 99 cases in which Eterna-player solutions were provided. P-Z-containing designs had average NED values of 0.040, significantly below the 0.074 of standard-DNA-only designs, and inclusion of the P-Z pairs decreased the time needed to converge on a design. This work provides a sample pipeline for inclusion of any expanded alphabet nucleotides into prediction and design workflows.
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Algoritmos , DNA , Pareamento de Bases , Termodinâmica , NucleotídeosRESUMO
Translation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we identified a double-stranded RNA (dsRNA) structure residing within the GATA4 uORF that augments uORF translation and inhibits mORF translation. Antisense oligonucleotides (ASOs) that disrupt this dsRNA structure promote mORF translation, while ASOs that base-pair immediately downstream (i.e., forming a bimolecular double-stranded region) of either the uORF or mORF start codon enhance uORF or mORF translation, respectively. Human cardiomyocytes and mice treated with a uORF-enhancing ASO showed reduced cardiac GATA4 protein levels and increased resistance to cardiomyocyte hypertrophy. We further show the general utility of uORF-dsRNA- or mORF- targeting ASO to regulate mORF translation for other mRNAs. Our work demonstrates a regulatory paradigm that controls translational efficiency and a useful strategy to alter protein expression and cellular phenotypes by targeting or generating dsRNA downstream of a uORF or mORF start codon. Bullet points for discoveries: dsRNA within GATA4 uORF activates uORF translation and inhibits mORF translation. ASOs that target the dsRNA can either inhibit or enhance GATA4 mORF translation. ASOs can be used to impede hypertrophy in human cardiomyocytes and mouse hearts.uORF- and mORF-targeting ASOs can be used to control translation of multiple mRNAs.
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We show that in silico design of DNA secondary structures is improved by extending the base pairing alphabet beyond A-T and G-C to include the pair between 2-amino-8-(1'-ß-D-2'-deoxyribofuranosyl)-imidazo-[1,2- a ]-1,3,5-triazin-(8 H )-4-one and 6-amino-3-(1'-ß-D-2'-deoxyribofuranosyl)-5-nitro-(1 H )-pyridin-2-one, simply P and Z. To obtain the thermodynamic parameters needed to include P-Z pairs in the designs, we performed 47 optical melting experiments and combined the results with previous work to fit a new set of free energy and enthalpy nearest neighbor folding parameters for P-Z pairs and G-Z wobble pairs. We find that G-Z pairs have stability comparable to A-T pairs and therefore should be considered quantitatively by structure prediction and design algorithms. Additionally, we extrapolated the set of loop, terminal mismatch, and dangling end parameters to include P and Z nucleotides. These parameters were incorporated into the RNAstructure software package for secondary structure prediction and analysis. Using the RNAstructure Design program, we solved 99 of the 100 design problems posed by Eterna using the ACGT alphabet or supplementing with P-Z pairs. Extending the alphabet reduced the propensity of sequences to fold into off-target structures, as evaluated by the normalized ensemble defect (NED). The NED values were improved relative to those from the Eterna example solutions in 91 of 99 cases where Eterna-player solutions were provided. P-Z-containing designs had average NED values of 0.040, significantly below the 0.074 of standard-DNA-only designs, and inclusion of the P-Z pairs decreased the time needed to converge on a design. This work provides a sample pipeline for inclusion of any expanded alphabet nucleotides into prediction and design workflows.
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Any surface immersed in sea water will suffer from marine fouling, including underwater sound absorption coatings. Traditional underwater sound absorption coatings rely heavily on the use of toxic, biocide-containing paints to combat biofouling. In this paper, an environmentally-friendly nanocomposite with integrated antifouling and underwater sound absorption properties was fabricated by adopting MWCNTs-COOH and SiO2 into PDMS at different ratios. SEM, FTIR and XPS results demonstrated MWCNTs were mixed into PDMS, and the changes in elements were also analyzed. SiO2 nanoparticles in PDMS decreased the tensile properties of the coating, while erosion resistance was enhanced. Antibacterial properties of the coatings containing MWCNTs-COOH and SiO2 at a ratio of 1:1, 1:3, and 1:5 reached 62.02%, 72.36%, and 74.69%, respectively. In the frequency range of 1500-5000 Hz, the average sound absorption coefficient of PDMS increased from 0.5 to greater than 0.8 after adding MWCNTs-COOH and SiO2, which illustrated that the addition of nanoparticles enhanced the underwater sound absorption performance of the coating. Incorporating MWCNTs-COOH and SiO2 nanoparticles into the PDMS matrix to improve its sound absorption and surface antifouling properties provides a promising idea for marine applications.
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The 5' cap and 3' poly(A) tail of mRNA are known to synergistically stimulate translation initiation via the formation of the capâ¢eIF4Eâ¢eIF4Gâ¢PABPâ¢poly(A) complex. Most mRNA sequences have an intrinsic propensity to fold into extensive intramolecular secondary structures that result in short end-to-end distances. The inherent compactness of mRNAs might stabilize the capâ¢eIF4Eâ¢eIF4Gâ¢PABPâ¢poly(A) complex and enhance cap-poly(A) translational synergy. Here, we test this hypothesis by introducing intrinsically unstructured sequences into the 5' or 3' UTRs of model mRNAs. We found that the introduction of unstructured sequences into the 3' UTR, but not the 5' UTR, decreases mRNA translation in cell-free wheat germ and yeast extracts without affecting mRNA stability. The observed reduction in protein synthesis results from the diminished ability of the poly(A) tail to stimulate translation. These results suggest that base pair formation by the 3' UTR enhances the cap-poly(A) synergy in translation initiation.
Assuntos
Regiões 3' não Traduzidas , Poli A , Biossíntese de Proteínas , Regiões 5' não Traduzidas , Fator de Iniciação Eucariótico 4G/química , Poli A/química , Proteínas de Ligação a Poli(A)/química , Capuzes de RNA/química , Sistema Livre de Células , Triticum , Saccharomyces cerevisiae , Conformação de Ácido Nucleico , Estabilidade de RNARESUMO
Background: Periodontitis is a serious health issue; however, there are few reports on periodontitis and immune related. The study sought to analyze differences in gene expression between periodontitis patients before and after treatment using bioinformatics techniques. Methods: The GSE6751 data set was screened for differentially expressed genes (DEGs) and immune-related genes using the Gene Expression Omnibus (GEO) database, a gene expression data analysis tool. Enrichment, protein-protein interaction (PPI) network construction, and immune cell correlation analyses were also performed on these genes. Results: A total of 327 DEGs in periodontitis were identified, including 149 upregulated genes, 178 downregulated genes, and 27 immune-related genes. The immune-related DEGs were mainly involved in granulocyte chemotaxis, granulocyte migration, leukocyte chemotaxis, cytokine receptor binding, Toll-like receptor (TLR) binding, the phosphatidylinositol-3-kinase and protein kinase b signaling pathway, viral protein interactions with cytokines and cytokine receptors, the Ras-proximate-1 signaling pathway, the Ras signaling pathway, natural killer cell mediated cytotoxicity, and immune response related pathways. IFNG and TLR2 were the key core genes in the constructed PPI network. Conclusions: The pathogenesis of periodontitis is closely related to changes in the expression of genes, such as PF4, ANGPT1, TNFRSF1B, IFNG and TLR2, among which IFNG and TLR2 are potential therapeutic targets for periodontitis.
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Translating ribosomes unwind mRNA secondary structures by three basepairs each elongation cycle. Despite the ribosome helicase, certain mRNA stem-loops stimulate programmed ribosomal frameshift by inhibiting translation elongation. Here, using mutagenesis, biochemical and single-molecule experiments, we examine whether high stability of three basepairs, which are unwound by the translating ribosome, is critical for inducing ribosome pauses. We find that encountering frameshift-inducing mRNA stem-loops from the E. coli dnaX mRNA and the gag-pol transcript of Human Immunodeficiency Virus (HIV) hinders A-site tRNA binding and slows down ribosome translocation by 15-20 folds. By contrast, unwinding of first three basepairs adjacent to the mRNA entry channel slows down the translating ribosome by only 2-3 folds. Rather than high thermodynamic stability, specific length and structure enable regulatory mRNA stem-loops to stall translation by forming inhibitory interactions with the ribosome. Our data provide the basis for rationalizing transcriptome-wide studies of translation and searching for novel regulatory mRNA stem-loops.
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Mudança da Fase de Leitura do Gene Ribossômico , RNA Mensageiro/química , Proteínas de Bactérias/genética , DNA Polimerase III/genética , Escherichia coli/genética , Transferência Ressonante de Energia de Fluorescência , HIV/genética , Conformação de Ácido Nucleico , RNA Bacteriano/química , RNA Bacteriano/metabolismo , RNA Mensageiro/metabolismo , RNA de Transferência/metabolismo , RNA Viral/química , RNA Viral/metabolismo , Imagem Individual de Molécula , TermodinâmicaRESUMO
Major depressive disorder (MDD) is one of the foremost causes of disability and premature death worldwide. Although the available antidepressants are effective and well tolerated, they also have many limitations. Therapeutic advances in developing a new drug's ultimate relation between MDD and chronobiology, which targets the circadian rhythm, led to a renewed focus on psychiatric disorders. In order to provide a critical analysis about antidepressant properties of agomelatine, a detailed PubMed (Medline), Scopus (Embase), Web of Science (Web of Knowledge), Cochrane Library, Google Scholar, and PsycInfo search was performed using the following keywords: melatonin analog, agomelatine, safety, efficacy, adverse effects, pharmacokinetics, pharmacodynamics, circadian rhythm, sleep disorders, neuroplasticity, MDD, bipolar disorder, anhedonia, anxiety, generalized anxiety disorder (GAD), and mood disorders. Agomelatine is a unique melatonin analog with antidepressant properties and a large therapeutic index that improves clinical safety. Published articles revealed that agomelatine is a melatonin receptors (MT1 and MT2) agonist and 5HT2C receptor antagonist. The effects receptors' on melatonin receptors enable the resynchronization of irregular circadian rhythms with beneficial effects on sleep architectures. In this way, agomelatine is accredited for its unique mode of action, which helps to exert antidepressant effects and resynchronize the sleep-wake cycle. To sum up, an agomelatine has not only antidepressant properties but also has anxiolytic effects.
Assuntos
Transtorno Depressivo Maior , Melatonina , Acetamidas , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Naftalenos , Receptores de Melatonina/uso terapêuticoRESUMO
OBJECTIVE: It has been studied that mesenchymal stem cells (MSCs)-derived exosomes could suppress tumor growth in nasopharyngeal carcinoma (NPC) and microRNA-181a (miR-181a) could mediate drug resistance in NPC. Focused on this work, the mechanism of human umbilical cord MSCs (hUC-MSCs)-derived exosomal miR-181a was explored in NPC cell progression. METHODS: NPC tissues and normal tissues were obtained from patients, and miR-181a and KDM5C expression was examined. hUC-MSCs-derived exosomes were extracted, identified and co-cultured with NPC cells (C666-1 and SUNE1). C666-1 cell progression in vitro and/or tumor growth in vivo were examined after incubation with exosomes, miR-181a or lysine-specific demethylase 5C (KDM5C). miR-181a and KDM5C expression were examined in NPC. RESULTS: miR-181a expression was reduced while KDM5C expression was elevated in NPC. hUC-MSCs-derived exosomes restrained NPC cell growth in vivo and in vitro. Depleting or restoring exosomal miR-181a promoted or delayed NPC cell progression. KDM5C silencing suppressed NPC cell progression. CONCLUSION: This study concluded that hUC-MSCs-derived exosomal miR-181a retards NPC development via negatively modulating KDM5C, serving as a candidate reference for the therapy of NPC.
Assuntos
Exossomos/genética , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Neoplasias Nasofaríngeas/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Histona Desmetilases/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Prognóstico , Células Tumorais Cultivadas , Cordão Umbilical/citologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic.
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Anticonvulsivantes/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Epilepsia/tratamento farmacológico , Propoxicaína/uso terapêutico , Animais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Eletroencefalografia , Elevação dos Membros Posteriores , Hidrogéis , Lipossomos/administração & dosagem , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Teste de Campo Aberto/efeitos dos fármacos , Propoxicaína/administração & dosagem , Propoxicaína/efeitos adversosRESUMO
The performance and microbial characteristics of ammonium-limited and nitrite-limited ANAMMOX reactors were studied in two continuously stirred tank reactors. The influent TN concentrations were controlled below 50 mg·L-1. The hydraulic retention time and water temperature were maintained at 2.0 h and 20â, respectively. Results showed that though both ANAMMOX reactors demonstrated similar TN removal loading rates[0.45-0.5 kg·(m3·d)-1] and TN removal efficiencies (around 70%), the ΔNO3-/ΔNH4+ ratio of the ammonium-limited ANAMMOX reactor showed a faster upward trend. Batch tests and high-throughput sequencing results indicated that the ammonium-limited ANAMMOX reactor had more significant functional and population heterogeneity than the nitrite-limited ANAMMOX reactor. Candidatus_Brocadia was the predominant ANAMMOX bacteria in both reactors. The relative abundance of Candidatus_Brocadia in large granules (53.9%) was significantly higher than that in flocs (19.1%) under the ammonium-limited conditions, whereas only a small difference in relative abundance of Candidatus_Brocadia was observed between the granules (28.1%) and flocs (21.3%) in the nitrite-limited ANAMMOX reactor. Nitrospira-like NOB were detected in both ANAMMOX reactors, which primarily inhabited flocs, seemingly driven by the availability of oxygen. Moreover, the ammonium-limited (i.e., excess nitrite) conditions seemingly favored the growth of Nitrospira. Building upon these results, a control strategy for optimal operation of the ammonium-limited ANAMMOX reactor was proposed based on selective floc discharge.
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AIM: To investigate the relationship between PI3K/Akt/NF-κB cellular signal pathway and the expression of P-gp and LRP in multidrug resistance (MDR) cell of nasopharyngeal carcinoma. METHOD: The PI3K, p-Akt and NF-κB/p65 as the activity of PI3K/Akt/NF-κB were detected by Western blot. The expressions of LRP and P-gp were detected by Western blot and real-time PCR. RESULT: The RIs of CNE/DDP group to DDP, 5-Fu, VCR, ADR and PTX were 35.04, 18.14, 24.13, 12.00 and 10.18, respectively. The RIs of LY-294002 group were 11.77, 5.83, 3.07, 3.86 and 3.34, and PDTC group were 11.08, 6.55, 7.66, 2.18 and 4.05. The expressions of PI3K, p-Akt and NF-κBp65, LRP and P-gp were increased and mRNA of LRP and P-gp were up-regulated in CNE/DDP. The expression of p-Akt in LY-294002 group was down-regulated. The expression of NF-κB p65 in PDTC group was decreased. The mRNA of LRP and P-gp in LY-294002 group and PDTC group were decreased. CONCLUSION: MDR of nasopharyngeal carcinoma cell can be regulated by activating PI3K/Akt/NF-κB signal pathway and then increase the expression of P-gp and LRP. The MDR of nasopharyngeal carcinoma cell can be reversed by inhibiting PI3K/Akt/NF-κB signal pathway.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirrolidinas/farmacologia , Pirrolidinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Tiocarbamatos/farmacologia , Tiocarbamatos/uso terapêutico , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo , Partículas de Ribonucleoproteínas em Forma de Abóbada/metabolismoRESUMO
A current issue about causal attribution is whether people take simple contrast-factor attributions or complex joint attributions in contrast situations. For example, a stone does not dissolve in water and a piece of salt dissolves in water. That the piece of salt dissolves in water is due to: (A) the influence of the piece of salt; (B) the influence of the water; (C) the joint influence of the piece of salt and the water. We propose a mechanism-based sufficiency account for such questions. It argues that causal attributions are guided by mechanism-based explanatory sufficiency, and people prefer a mechanism-based attribution with explanatory sufficiency. This account predicts the sufficient joint attribution (the C option), whereas the conventional covariation approach predicts the contrast-factor attribution (the A option). Two experiments investigated whether contrast situations affect causal attributions for compound causation with explicit mechanism information and simple causation without explicit mechanism information, respectively. Both experiments found that in both the presence and absence of contrast situations, the majority of participants preferred sufficient joint attributions to simple contrast-factor attributions regardless of whether explicit mechanism information was present, and contrast situations did not affect causal attributions. These findings favor the mechanism-based sufficiency account rather than the covariation approach and the complexity account. In contrast situations, the predominance of joint attributions implies that explanatory complexity affects causal attributions by the modulation of explanatory sufficiency, and people prefer mechanism-based joint attributions that provide sufficient explanations for effects. The present findings are beyond the existing approaches to causal attributions.
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Conditionals statements are a common and necessary component in natural languages. The research reported in this paper is on a fundamental question about singular conditionals. Is there an adequate account of people's truth, falsity, and credibility (probability) judgments about these conditionals when their antecedents are false? Two experiments examined people's quantitative credibility ratings and qualitative truth and falsity judgments for singular conditionals, if p then q, given false antecedent, not-p, cases. The results demonstrate that, when relevant knowledge about the conditional probability of q given p, P(q|p), is available to participants in not-p cases, they tend to make credibility ratings based on P(q|p), and to make "true" (or "false") judgments at a high (or low) level of these credibility ratings. These findings favor the Jeffrey table account of these conditionals over the other existing accounts, including that of the de Finetti table.
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Probabilidade , Feminino , Humanos , Idioma , Masculino , Resolução de ProblemasRESUMO
BACKGROUND: Astaxanthin (AST) shows a large range of beneficial effects together with anti-cancer and antioxidation properties. Human Serum Albumin (HSA) is the most abundant protein in blood plasma which plays the role of a depot and transport protein for many exogenous compounds. However, whether HSA could enhance AST-induced cytotoxic effects in human ovarian cancer cells has not been examined to date. OBJECTIVE: This study aims to explore the anticancer effect and the molecular mechanism of AST combine with HSA induced cytotoxicity in ovarian cancer SKOV3 cells. METHODS: The ovarian cancer SKOV3 cells were treated by AST combined with HSA to study the effects of cell proliferation, cell morphology, cell cycle arrest, related protein expression, nuclear transfer, cell migration, and drug-resistant. RESULTS: Our data confirmed that AST+HSA treatment enhanced the anticancer effects of AST, arrested G1 phase cell cycle and induced apoptosis in SKOV3 cells. AST+HSA induced apoptosis via mitochondrial apoptotic pathways was related to the increased ratio of Bcl-2/Bax and activation of caspase-3. Besides, exposure of cells to AST+HSA triggered the inactivation of NF-κB and activation p53 and MAPKs signaling pathways. Furthermore, AST+HSA significantly overcome the drug-resistant and inhibited the migration of SKOV3 cells. CONCLUSION: AST combined treatment with HSA considerably inhibited NF-κB expression and translocation to nucleus, thereby improving the AST-induced cytotoxic effect on SKOV3 cells. These findings may provide rationale to combine AST with HSA for the treatment of ovarian cancer.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Albumina Sérica Humana/química , Antineoplásicos/química , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Estrutura Molecular , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Xantofilas/química , Xantofilas/farmacologiaRESUMO
PURPOSE: To evaluate the treatment effect of topical doxycycline on avulsed permanent teeth compared with normal saline. METHODS: A total of 44 avulsed teeth from 38 patients (22 boys and 16 girls, aged 7-14 years) were recruited. Twenty-one teeth in group A were treated with doxycycline for 5 min before replantation while 23 teeth in group B were treated with saline solution. All participants were followed up for at least 12 months. The clinical outcome differences between 2 groups was evaluated by Mann-Whitney U test. RESULTS: In group A, 18 teeth were found pulp necrosis, 3 with infection-related resorption, 13 with ankylosis-related resorption and 6 were extracted. In group B, 16 were diagnosed with pulp necrosis, 4 with infection-related resorption, 12 with ankylosis-related resorption and 7 were extracted. No significant differences were found between the two groups on pulp survival and periodontal healing. CONCLUSIONS: Compared with treatment with normal saline, avulsed permanent teeth treated with doxycycline did not show a better clinical outcome.
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Reabsorção da Raiz , Anquilose Dental , Avulsão Dentária , Adolescente , Criança , Dentição Permanente , Doxiciclina , Feminino , Humanos , Masculino , Ligamento Periodontal , Reimplante DentárioRESUMO
Two new compounds, named (Z)-7,4'-dimethoxy-6-hydroxyaurone-4-O-ß-glucopyranoside (1) and (-)-4-O-(4-O-ß-D-glucopyranosylcaffeoyl)quinic acid (2), were isolated from the endophytic fungus Penicillium citrinum of Avicennia marina. Their structures were elucidated on the basis of spectroscopic analysis. Additionally, compound 2 exhibited potent chemoreversal activity, mainly by inhibiting P-glycoprotein efflux pump function.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Avicennia/microbiologia , Glucosídeos/isolamento & purificação , Penicillium/química , Endófitos/química , Endófitos/isolamento & purificação , Endófitos/metabolismo , Glucosídeos/química , Humanos , Células KB , Penicillium/isolamento & purificação , Penicillium/metabolismo , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Ácido Quínico/isolamento & purificaçãoRESUMO
PURPOSE: To evaluate the effect of amount of silane coupling agent on flexural strength of dental composite resins reinforced with aluminium borate whisker (ABW). METHODS: ABW was surface-treated with 0%, 1%, 2%, 3% and 4% silan coupling agent (γ-MPS), and mixed with resin matrix to synthesize 5 groups of composite resins. After heat-cured at 120 degrees centigrade for 1 h, specimens were tested in three-point flexure to measure strength according to ISO-4049. One specimen was selected randomly from each group and observed under scanning electron microscope (SEM). The data was analyzed with SAS 9.2 software package. RESULTS: The flexural strength (117.93±11.9 Mpa) of the group treated with 2% silane coupling agent was the highest, and significantly different from that of the other 4 groups (α=0.01). CONCLUSIONS: The amount of silane coupling agent has impact on the flexural strength of dental composite resins reinforced with whiskers; The flexual strength will be reduced whenever the amount is higher or lower than the threshold. Supported by Research Fund of Science and Technology Committee of Shanghai Municipality (08DZ2271100).