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1.
Curr Issues Mol Biol ; 46(5): 3752-3762, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38785502

RESUMO

Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient embryological research. In this study, we established optimal superovulation and fertilized-egg transfer conditions, including optimal hormone injection concentration (≥150 IU/kg of PMSG and hCG) and culture medium (mR1ECM), to obtain high-quality zygotes and establish in vitro fertilization conditions for rats. Next, sgRNA with optimal targeting activity was selected by performing PCR analysis and the T7E1 assay, and the CRISPR/Cas9 system was used to construct a rat model for muscular dystrophy by inducing a deficiency in the fukutin gene without any off-target effect detected. The production of fukutin knockout rats was phenotypically confirmed by observing a drop-in body weight to one-third of that of the control group. In summary, we succeeded in constructing the first muscular dystrophy disease rat model using the CRISPR/CAS9 system for increasing future prospects of producing various animal disease models and encouraging disease research using rats.

2.
Lancet Rheumatol ; 6(2): e105-e114, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38267097

RESUMO

BACKGROUND: Social determinants of health are consistently associated with systemic lupus erythematosus (SLE) outcomes. However, social determinants of health are typically measured with conventional socioeconomic status factors such as income or education. We assessed the association of economic insecurities (ie, food, housing, health care, and financial insecurity) with patient-reported outcomes in a cohort of patients with SLE. METHODS: In this cross-sectional analysis, data were derived from the California Lupus Epidemiology Study based in the San Francisco Bay Area, CA, USA. Participants were recruited between Feb 25, 2015, and Jan 10, 2018, from rheumatology clinics. Inclusion criteria were Bay Area residency; oral fluency in English, Spanish, Cantonese, or Mandarin; 18 years or older; ability to provide informed consent; and a physician confirmed SLE diagnosis. Food, housing, health care, and financial economic insecurities were assessed by validated screening tools. Patient-reported outcomes were obtained using PROMIS, Quality of Life in Neurological Disorders (known as Neuro-QoL) Cognitive Function short form, Patient Health Questionnaire (PHQ)-8, and General Anxiety Disorder (GAD)-7 instruments. Poverty was defined as household income of 125% or less of the federal poverty limit. Lower education was defined as less than college-graduate education. The association of economic insecurities with patient-reported outcomes was assessed by multivariable linear regression models adjusting for demographics, SLE disease characteristics, and comorbidities. We tested for interactions of insecurities with poverty and education. FINDINGS: The final cohort included 252 participants. Mean age was 49·7 (SD 13·4) years, 228 (90%) of 252 were women and 24 (10%) were men. 80 (32%) individuals self-identified as Asian, 26 (10%) as Black, 101 (40%) as White, eight (3%) as mixed race, and 37 (15%) as other race; 59 (23%) self-identified as Hispanic. 135 (54%) individuals had at least one insecurity. Insecurities were highly prevalent, and more common in those with poverty and lower education. Adjusted multivariate analyses revealed that participants with any insecurity had significantly worse scores across all measured patient-reported outcomes. For physical function, no insecurity had an adjusted mean score of 48·9 (95% CI 47·5-50·3) and any insecurity had 45·7 (44·3-47·0; p=0·0017). For pain interference, no insecurity was 52·0 (50·5-53·5) and any insecurity was 54·4 (53·0-55·8; p=0·031). For fatigue, no insecurity was 50·5 (48·8-52·3) and any insecurity was 54·9 (53·3-56·5; p=0·0005). For sleep disturbance, no insecurity was 49·9 (48·3-51·6) and any insecurity was 52·9 (51·4-54·5; p=0·012). For cognitive function, no insecurity was 49·3 (47·7-50·9) and any insecurity was 45·6 (44·1-47·0; p=0·0011). For PHQ-8, no insecurity was 4·4 (3·6-5·1) and any insecurity was 6·1 (5·4-6·8; p=0·0013). For GAD-7, no insecurity was 3·3 (2·6-4·1) and any insecurity was 5·2 (4·5-5·9; p=0·0008). Individuals with more insecurities had worse patient-reported outcomes. There were no statistically significant interactions between insecurities and poverty or education. INTERPRETATION: Having any economic insecurity was associated with worse outcomes for people with SLE regardless of poverty or education. The findings of this study provide insight into the relationship between economic insecurities and SLE outcomes and underscore the need to assess whether interventions that directly address these insecurities can reduce health disparities in SLE. FUNDING: US Centers for Disease Control, Rheumatology Research Foundation, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.


Assuntos
Transtornos de Ansiedade , Lúpus Eritematoso Sistêmico , Qualidade de Vida , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Lúpus Eritematoso Sistêmico/epidemiologia , São Francisco/epidemiologia
3.
Lab Anim Res ; 39(1): 24, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37872597

RESUMO

BACKGROUND: The importance of animal welfare is being recognized worldwide. Recently, the increasing demand for enhanced laboratory animal welfare has led to clinically featured transformations of animal research institutes. This study aims to describe the process and findings of veterinary medical check-ups and its influence on laboratory dogs and pigs welfare. Regular medical checkups were conducted by the attending veterinarian twice a year to ensure the health and welfare of dogs and pigs in our animal research institute. Based on the findings from the medical checkup, we assessed the current health of dogs and pigs,providing reasonable treatments to prevent the risk of complications. RESULTS: Blood tests and physical examinations revealed clinically relevant findings. Some of these findings were due to insufficient postoperative care after invasive surgical experiments and the remaining were predictable side effects after surgical experiments. However, one finding involved severe gum bleeding due to retained deciduous teeth. This animal was euthanized because it was judged to reach the humane endpoint. Majority of the dogs and pigs at our animal research institute were considered to be healthy, based on the comprehensive results of the medical checkups. CONCLUSIONS: Regular medical checkups by the attending veterinarian established enhanced animal welfare, ensuring the accuracy and reproducibility of animal studies. This pioneering veterinary animal care program can serve as a potential advanced guideline for animal research institutes to improve dogs and pigs welfare.

4.
Multivariate Behav Res ; 58(6): 1090-1105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36952487

RESUMO

Meta-analysis using individual participant data (IPD) is an important methodology in intervention research because it (a) increases accuracy and precision of estimates, (b) allows researchers to investigate mediators and moderators of treatment effects, and (c) makes use of extant data. IPD meta-analysis can be conducted either via a one-step approach that uses data from all studies simultaneously, or a two-step approach, which aggregates data for each study and then combines them in a traditional meta-analysis model. Unfortunately, there are no evidence-based guidelines for how best to approach IPD meta-analysis for count outcomes with many zeroes, such as alcohol use. We used simulation to compare the performance of four hurdle models (3 one-step and 1 two-step models) for zero-inflated count IPD, under realistic data conditions. Overall, all models yielded adequate coverage and bias for the treatment effect in the count portion of the model, across all data conditions. However, in the zero portion, the treatment effect was underestimated in most models and data conditions, especially when there were fewer studies. The performance of both one- and two-step approaches depended on the formulation of the treatment effects, suggesting a need to carefully consider model assumptions and specifications when using IPD.


Assuntos
Modelos Estatísticos , Humanos , Simulação por Computador , Viés
5.
Multivariate Behav Res ; 58(3): 543-559, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35263213

RESUMO

There are several approaches to incorporating uncertainty in power analysis. We review these approaches and highlight the Bayesian-classical hybrid approach that has been implemented in the R package hybridpower. Calculating Bayesian-classical hybrid power circumvents the problem of local optimality in which calculated power is valid if and only if the specified inputs are perfectly correct. hybridpower can compute classical and Bayesian-classical hybrid power for popular testing procedures including the t-test, correlation, simple linear regression, one-way ANOVA (with equal or unequal variances), and the sign test. Using several examples, we demonstrate features of hybridpower and illustrate how to elicit subjective priors, how to determine sample size from the Bayesian-classical approach, and how this approach is distinct from related methods. hybridpower can conduct power analysis for the classical approach, and more importantly, the novel Bayesian-classical hybrid approach that returns more realistic calculations by taking into account local optimality that the classical approach ignores. For users unfamiliar with R, we provide a limited number of RShiny applications based on hybridpower to promote the accessibility of this novel approach to power analysis. We end with a discussion on future developments in hybridpower.


Assuntos
Projetos de Pesquisa , Teorema de Bayes , Tamanho da Amostra , Modelos Lineares , Incerteza
6.
Molecules ; 27(12)2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35744907

RESUMO

Inflammation is a severe topic in the immune system and play a role as pro-inflammatory mediators. In response to such inflammatory substances, immune cells release cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Lipopolysaccharide (LPS) is known as an endotoxin in the outer membrane of Gram-negative bacteria, and it catalyzes inflammation by stimulating the secretion of inflammatory-mediated cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by stimulated immune cells. Among the pathways involved in inflammation, nuclear factor kappa (NF-кB) and mitogen-activated protein kinases (MAPKs) are important. NF-kB is a diploid composed of p65 and IkBα and stimulates the pro- gene. MAPKs is a family consisting of the extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38, JNK and p38 play a role as proinflammatory mediators. Thus, we aim to determine the scutellarein (SCU) effect on LPS stimulated RAW264.7 cells. Furthermore, since scutellarein has been shown to inhibit the SARS coronavirus helicase and has been used in Chinese medicine to treat inflammatory disorders like COVID-19, it would be required to examine scutellarein's anti-inflammatory mechanism. We identified inflammation-inducing substances using western blot with RAW264.7 cells and SCU. And we discovered that was reduced by treatment with SCU in p-p65 and p-IκBα. Also, we found that p-JNK and p-ERK were also decreased but there was no effect in p-p38. In addition, we have confirmed that the iNOS was also decreased after treatment but there is no change in the expression of COX-2. Therefore, this study shows that SCU can be used as a compound to treat inflammation.


Assuntos
COVID-19 , NF-kappa B , Animais , Apigenina , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/efeitos adversos , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Transdução de Sinais
7.
Int J Mol Sci ; 23(10)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35628252

RESUMO

Inflammation is a multifaceted response of the immune system at the site of injury or infection caused by pathogens or stress via immune cells. Due to the adverse effects of chemical drugs, plant-based compounds are gaining interest in current research. Prunetinoside or prunetin-5-O-glucoside (PUG) is a plant-based active compound, which possesses anti-inflammatory effects on immune cells. In this study, we investigate the effect of PUG on mouse macrophage RAW264.7 cells with or without stimulation of lipopolysaccharide (LPS). Cytotoxicity results showed that PUG is non-cytotoxic to the cells and it reversed the cytotoxicity in LPS-stimulated cells. The levels of nitric oxide (NO) and interleukin-6 (IL-6) were determined using a NO detection kit and IL-6 ELISA kit, respectively, and showed a significant decrease in NO and IL-6 in PUG-treated cells. Western blot and qRT-PCR were performed for the expression of two important pro-inflammatory cytokines, COX2 and iNOS, and found that their expression was downregulated in a dose-dependent manner. Other pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNFα, had reduced mRNA expression after PUG treatment. Furthermore, a Western blot was performed to calculate the expression of NF-κB and MAPK pathway proteins. The results show that PUG administration dramatically reduced the phosphorylation of p-Iκbα, p-NF-κB 65, and p-JNK. Remarkably, after PUG treatment, p-P38 and p-ERK remain unchanged. Furthermore, docking studies revealed that PUG is covalently linked to NF-κB and suppresses inflammation. In conclusion, PUG exerted the anti-inflammatory mechanism by barring the NF-κB pathway and activating JNK. Thus, prunetinoside could be adopted as a therapeutic compound for inflammatory-related conditions.


Assuntos
Cumarínicos , Macrófagos , NF-kappa B , Animais , Anti-Inflamatórios/uso terapêutico , Cumarínicos/farmacologia , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7
8.
Genes (Basel) ; 13(5)2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35627138

RESUMO

Glycosylphosphatidylinositol-anchored sperm hyaluronidases (HYAL) assist sperm penetration through the cumulus-oocyte complex (COC), but their role in mammalian fertilization remains unclear. Previously, we demonstrated that sperm from HYAL 5 and 7 double-knockout (dKO) mice produced significantly less offspring than sperm from wild-type mice due to defective COC dispersal. However, the HYAL6 gene remained active in the sperm from the dKO mice, indicating that they were not entirely infertile. This study explored the role of HYAL6 in fertilization by analyzing HYAL6-mutant mice. In this mouse model, HYAL5 and HYAL7 were present in the HYAL6-knockout sperm, and they could disperse hyaluronic acid. We found that HYAL6 was present on the surface of sperm. However, male mice lacking the HYAL6 gene had normal fertility, testicular integrity, and sperm characteristics. Furthermore, in vitro fertilization assays demonstrated that HYAL6-deficient epididymal sperm functioned normally. Therefore, HYAL6 is dispensable for fertilization.


Assuntos
Moléculas de Adesão Celular , Hialuronoglucosaminidase , Animais , Moléculas de Adesão Celular/genética , Fertilidade/genética , Hialuronoglucosaminidase/genética , Masculino , Mamíferos , Camundongos , Oócitos , Interações Espermatozoide-Óvulo/genética
9.
Med Ultrason ; 24(3): 305-313, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35437523

RESUMO

AIMS: To develop a decision tree model using US features to differentiate testicular torsion and other conditions of acute scrotum and to investigate predictive parameters of unsalvageable testis in testicular torsion. MATERIALS AND METHODS: Scrotal US was reviewed in patients aged <30 years who presented with acute scrotum from 2014 to 2020. US findings of whirlpool sign, testicular volume ratio, heterogeneous echotexture, testicular vascularity, epididymis enlargement and/or hyperemia, and avascular nodule were evaluated and compared. A decision tree model was created using the conditional inference tree analysis and the accuracy was calculated. Univariate logistic regression analysis was performed to find out the predictive US features of unsalvageable testes. RESULTS: Total of 381 patients (13.2±7.2 years old; range, 1 day-30 years) were included. Thirty-four patients were diagnosed with testicular torsion, and the others with orchitis or epididymo-orchitis (n=59), epididymitis (n=264), and appendage torsion (n=24). In the conditional inference tree analysis, whirlpool sign, avascular nodule, and increased testicular vascularity were the most significant discriminators (p<0.001), and the whirlpool sign was the first discriminator. The overall accuracy of the conditional inference tree was 91.1% (95% confidence interval [CI], 87.8-93.7%). Heterogeneous echotexture (odds ratio [OR], 74.99; 95% CI, 2.75-2046.26; p=0.01) and symptom-to-operation time >24 h (OR, 49.28; 95% CI, 1.92-1262.03; p=0.02) were significant predictors of unsalvageable testis. CONCLUSIONS: Conditional inference tree analysis showed that the whirlpool sign of the spermatic cord, avascular nodule, and altered testicular vascularity were significant discriminators. Heterogeneous echotexture and symptom-to-operation delay were important prognostic factors for unsalvageable testis.


Assuntos
Epididimite , Orquite , Torção do Cordão Espermático , Adolescente , Adulto , Criança , Humanos , Masculino , Escroto , Torção do Cordão Espermático/diagnóstico por imagem , Testículo/diagnóstico por imagem , Adulto Jovem
10.
Adv Sci (Weinh) ; 8(9): 2002768, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33977043

RESUMO

Monolayer MoS2 is a promising semiconductor to overcome the physical dimension limits of microelectronic devices. Understanding the thermochemical stability of MoS2 is essential since these devices generate heat and are susceptible to oxidative environments. Herein, the promoting effect of molybdenum oxides (MoO x ) particles on the thermal oxidation of MoS2 monolayers is shown by employing operando X-ray absorption spectroscopy, ex situ scanning electron microscopy and X-ray photoelectron spectroscopy. The study demonstrates that chemical vapor deposition-grown MoS2 monolayers contain intrinsic MoO x and are quickly oxidized at 100 °C (3 vol% O2/He), in contrast to previously reported oxidation thresholds (e.g., 250 °C, t ≤ 1 h in the air). Otherwise, removing MoO x increases the thermal oxidation onset temperature of monolayer MoS2 to 300 °C. These results indicate that MoO x promote oxidation. An oxide-free lattice is critical to the long-term stability of monolayer MoS2 in state-of-the-art 2D electronic, optical, and catalytic applications.

11.
Adv Sci (Weinh) ; 8(3): 2002876, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33552867

RESUMO

Transmission electron microscopy (TEM) is arguably the most important tool for atomic-scale material characterization. A significant portion of the energy of transmitted electrons is transferred to the material under study through inelastic scattering, causing inadvertent damage via ionization, radiolysis, and heating. In particular, heat generation complicates TEM observations as the local temperature can affect material properties. Here, the heat generation due to electron irradiation is quantified using both top-down and bottom-up approaches: direct temperature measurements using nanowatt calorimeters as well as the quantification of energy loss due to inelastic scattering events using electron energy loss spectroscopy. Combining both techniques, a microscopic model is developed for beam-induced heating and to identify the primary electron-to-heat conversion mechanism to be associated with valence electrons. Building on these results, the model provides guidelines to estimate temperature rise for general materials with reasonable accuracy. This study extends the ability to quantify thermal impact on materials down to the atomic scale.

12.
Nat Microbiol ; 6(3): 277-288, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33432149

RESUMO

The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1-5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.


Assuntos
Bifidobacterium bifidum/fisiologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Probióticos/uso terapêutico , Carga Tumoral/efeitos dos fármacos , Animais , Bifidobacterium bifidum/classificação , Bifidobacterium bifidum/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/microbiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Combinada , Microbioma Gastrointestinal , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/microbiologia , Neoplasias Pulmonares/patologia , Metaboloma/efeitos dos fármacos , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Probióticos/administração & dosagem , Especificidade da Espécie , Transcriptoma/efeitos dos fármacos , Triptofano/metabolismo
13.
Adv Mater ; 32(37): e2003020, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32743836

RESUMO

Forming pits on molybdenum disulfide (MoS2 ) monolayers is desirable for (opto)electrical, catalytic, and biological applications. Thermal oxidation is a potentially scalable method to generate pits on monolayer MoS2 , and pits are assumed to preferentially form around undercoordinated sites, such as sulfur vacancies. However, studies on thermal oxidation of MoS2 monolayers have not considered the effect of adventitious carbon (C) that is ubiquitous and interacts with oxygen at elevated temperatures. Herein, the effect of adventitious C on the pit formation on MoS2 monolayers during thermal oxidation is studied. The in situ environmental transmission electron microscopy measurements herein show that pit formation is preferentially initiated at the interface between adventitious C nanoparticles and MoS2 , rather than only sulfur vacancies. Density functional theory (DFT) calculations reveal that the C/MoS2 interface favors the sequential adsorption of oxygen atoms with facile kinetics. These results illustrate the important role of adventitious C on pit formation on monolayer MoS2 .

14.
Sci Rep ; 10(1): 643, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959763

RESUMO

Immune checkpoint blockade is promising for treating non-small-cell lung cancer (NSCLC). We used multipanel markers to predict the response to immune checkpoint inhibitors (ICIs) by characterizing gene expression signatures or individual genes in patients who showed durable clinical benefit to ICIs. Twenty-one patients with NSCLC treated with single-agent anti-programmed cell death protein (PD)-1 antibody were analyzed and their clinicopathological characteristics and response to ICIs were characterized. Nine (43%) showed a durable clinical benefit (DCB), while the remaining 12 (57%) patients showed non-durable benefit (NDB). The M1 and peripheral T cell signatures showed the best performance for discriminating DCB from NDB (sensitivity, specificity, accuracy = 0.89, 1.0, 0.95, respectively). Progression-free survival (PFS) was significantly longer in patients with high M1 signature or high peripheral T cell signature scores. CD137 and PSMB9 mRNA expression was higher in the DCB group than in the NDB group. Patients with high PSMB9 expression showed longer PFS. M1 signature, peripheral T cell signature and high mRNA expression level of CD137 and PSMB9 showed better predictive performance than known biomarkers, such as PD-L1 immunohistochemistry, tumor mutation burden, or tumor-infiltrating lymphocytes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/imunologia , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Feminino , Previsões , Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Resultado do Tratamento , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
15.
Sci Adv ; 5(11): eaav3097, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31723597

RESUMO

Skin-like sensory devices should be stretchable and self-healable to meet the demands for future electronic skin applications. Despite recent notable advances in skin-inspired electronic materials, it remains challenging to confer these desired functionalities to an active semiconductor. Here, we report a strain-sensitive, stretchable, and autonomously self-healable semiconducting film achieved through blending of a polymer semiconductor and a self-healable elastomer, both of which are dynamically cross-linked by metal coordination. We observed that by controlling the percolation threshold of the polymer semiconductor, the blend film became strain sensitive, with a gauge factor of 5.75 × 105 at 100% strain in a stretchable transistor. The blend film is also highly stretchable (fracture strain, >1300%) and autonomously self-healable at room temperature. We proceed to demonstrate a fully integrated 5 × 5 stretchable active-matrix transistor sensor array capable of detecting strain distribution through surface deformation.

16.
J Clin Med ; 8(11)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31684051

RESUMO

Persistently activated STAT3 is a promising target for a new class of anticancer drug development and cancer therapy, as it is associated with tumor initiation, progression, malignancy, drug resistance, cancer stem cell properties, and recurrence. Here, we discovered 3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (ODZ10117) as a small-molecule inhibitor of STAT3 to be used in STAT3-targeted cancer therapy. ODZ10117 targeted the SH2 domain of STAT3 regardless of other STAT family proteins and upstream regulators of STAT3, leading to inhibition of the tyrosine phosphorylation, dimerization, nuclear translocation, and transcriptional activity of STAT3. The inhibitory effect of ODZ10117 on STAT3 was stronger than the known STAT3 inhibitors such as S3I-201, STA-21, and nifuroxazide. ODZ10117 suppressed the migration and invasion, induced apoptosis, reduced tumor growth and lung metastasis, and extended the survival rate in both in vitro and in vivo models of breast cancer. Overall, we demonstrated that ODZ10117 is a novel STAT3 inhibitor and may be a promising agent for the development of anticancer drugs.

17.
ACS Appl Mater Interfaces ; 11(50): 46651-46657, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31697463

RESUMO

Obtaining a catalyst with high activity and thermal stability is essential for high-performance energy conversion devices operating at an elevated temperature. Herein, the design and fabrication of a heterogeneous catalyst with an ultrathin CeO2 overlayer via atomic layer deposition (ALD) on Pt electrodes for low-temperature solid oxide fuel cells (LT-SOFCs) is reported. The cell with a CeO2-overcoated (five ALD cycles) Pt cathode shows lower activation resistance by 50% after a 10 h operation and higher thermal stability by a factor of 2 compared with the cell with a Pt-only cathode, which is known to be the best single catalyst at 450 °C. Eventually, a thin-film SOFC with a highly active and stable CeO2-overcoated cathode based on an anodized aluminum oxide (AAO) substrate demonstrates a high peak power density of 800 mW cm-2 at 500 °C, which is the highest performance ever reported for an AAO-based SOFC at this temperature.

18.
Psychol Methods ; 24(5): 590-605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30816728

RESUMO

Power analysis serves as the gold standard for evaluating study feasibility and justifying sample size. However, mainstream power analysis is often oversimplified, poorly reflecting complex reality during data analysis. This article highlights the complexities inherent in power analysis, especially when uncertainties present in data analysis are realistically taken into account. We introduce a Bayesian-classical hybrid approach to power analysis, which formally incorporates three sources of uncertainty into power estimates: (a) epistemic uncertainty regarding the unknown values of the effect size of interest, (b) sampling variability, and (c) uncertainty due to model approximation (i.e., models fit data imperfectly; Box, 1979; MacCallum, 2003). To illustrate the nature of estimated power from the Bayesian-classical hybrid method, we juxtapose its power estimates with those obtained from traditional (i.e., classical or frequentist) and Bayesian approaches. We employ an example in lexical processing (e.g., Yap & Seow, 2014) to illustrate underlying concepts and provide accompanying R and Rcpp code for computing power via the Bayesian-classical hybrid method. In general, power estimates become more realistic and much more varied after uncertainties are incorporated into their computation. As such, sample sizes should be determined by assurance (i.e., the mean of the power distribution) and the extent of variability in power estimates (e.g., interval width between 20th and 80th percentiles of the power distribution). We discuss advantages and challenges of incorporating the three stated sources of uncertainty into power analysis and, more broadly, research design. Finally, we conclude with future research directions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Teorema de Bayes , Modelos Estatísticos , Psicologia/métodos , Incerteza , Humanos
20.
Cogn Neurosci ; 10(2): 66-76, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30663513

RESUMO

We composed an R-based script for Image-based Bayesian random-effect meta-analysis of previous fMRI studies. It meta-analyzes second-level test results of the studies and calculates Bayes Factors indicating whether the effect in each voxel is significantly different from zero. We compared results from Bayesian and classical meta-analyses by examining the overlap between the result from each method and that created by NeuroSynth as the target. As an example, we analyzed previous fMRI studies focusing on working memory extracted from NeuroSynth. The result from our Bayesian method showed a greater overlap than the classical method. In addition, Bayes Factors proved a better way to examine whether the evidence supported hypotheses than p-values. Given these, Bayesian meta-analysis provides neuroscientists with an alternative meta-analysis method for fMRI studies given the improved overlap with the NeuroSynth result and the practical and epistemological value of Bayes Factors that can directly test the presence of an effect.


Assuntos
Encéfalo/fisiologia , Neuroimagem Funcional/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Memória de Curto Prazo/fisiologia , Metanálise como Assunto , Neurociências/métodos , Teorema de Bayes , Humanos
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