RESUMO
Genetic sequencing has identified high-confidence ASD risk genes with loss-of-function mutations. How the haploinsufficiency of distinct ASD risk genes causes ASD remains to be elucidated. In this study, we examined the role of four top-ranking ASD risk genes, ADNP, KDM6B, CHD2, and MED13, in gene expression regulation. ChIP-seq analysis reveals that gene targets with the binding of these ASD risk genes at promoters are enriched in RNA processing and DNA repair. Many of these targets are found in ASD gene database (SFARI), and are involved in transcription regulation and chromatin remodeling. Common gene targets of these ASD risk genes include a network of high confidence ASD genes associated with gene expression regulation, such as CTNNB1 and SMARCA4. We further directly examined the transcriptional impact of the deficiency of these ASD risk genes. Our mRNA profiling with qPCR assays in cells with the knockdown of Adnp, Kdm6b, Chd2 or Med13 has revealed an intricate pattern of their cross-regulation, as well as their influence on the expression of other ASD genes. In addition, some synaptic genes, such as Snap25 and Nrxn1, are strongly regulated by deficiency of the four ASD risk genes, which could be through the direct binding at promoters or indirectly through the targets like Ctnnb1 or Smarca4. The identification of convergent and divergent gene targets that are regulated by multiple ASD risk genes will help to understand the molecular mechanisms underlying common and unique phenotypes associated with haploinsufficiency of ASD-associated genes.
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Transtorno do Espectro Autista , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Transtorno do Espectro Autista/genética , Regulação da Expressão Gênica/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , beta Catenina/genética , beta Catenina/metabolismo , DNA Helicases/genética , Haploinsuficiência/genética , Complexo Mediador/genética , Complexo Mediador/metabolismo , Proteínas de Ligação a DNA/genética , Regiões Promotoras Genéticas/genética , Proteínas Nucleares/genética , Proteínas do Tecido Nervoso/genéticaRESUMO
For most biological and medical applications of single-cell transcriptomics, an integrative study of multiple heterogeneous single-cell RNA sequencing (scRNA-seq) data sets is crucial. However, present approaches are unable to integrate diverse data sets from various biological conditions effectively because of the confounding effects of biological and technical differences. We introduce single-cell integration (scInt), an integration method based on accurate, robust cell-cell similarity construction and unified contrastive biological variation learning from multiple scRNA-seq data sets. scInt provides a flexible and effective approach to transfer knowledge from the already integrated reference to the query. We show that scInt outperforms 10 other cutting-edge approaches using both simulated and real data sets, particularly in the case of complex experimental designs. Application of scInt to mouse developing tracheal epithelial data shows its ability to integrate development trajectories from different developmental stages. Furthermore, scInt successfully identifies functionally distinct condition-specific cell subpopulations in single-cell heterogeneous samples from a variety of biological conditions.
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Análise de Célula Única , Análise da Expressão Gênica de Célula Única , Animais , Camundongos , Análise de Célula Única/métodos , Perfilação da Expressão Gênica/métodos , Sequenciamento do Exoma , Análise de Sequência de RNA/métodosRESUMO
BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.
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Neoplasias da Mama , Animais , Camundongos , Humanos , Feminino , Neoplasias da Mama/patologia , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Ácidos Graxos , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/genética , Proliferação de Células , Regulação Neoplásica da Expressão GênicaRESUMO
An ultra-compact and efficient acousto-optic modulator based on a thin-film lithium niobate-chalcogenide (ChG) hybrid platform was designed and realized. In this approach, π phase-shift Bragg grating has an ultra-short effective interaction length of only â¼ 300 µm and a compact footprint of 200 × 300 µm2. The strong microwave-acoustic coupling and superior photo-elastic property of the ChG allow us to achieve a half-wave voltage of Vπ = 1.08â V (4.07â V) for the π phase-shift Bragg grating (waveguide Bragg grating), corresponding to VπL = 0.03â V·cm (0.09â V·cm). This acousto-optic modulator exhibits a compact size, and low power consumption, and can be used for on-chip optical interconnects and microwave photonics.
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In Chinese criminal law, the ages of 12, 14, 16, and 18 years old play a significant role in the determination of criminal responsibility. In this study, we developed an epiphyseal grading system based on magnetic resonance image (MRI) of the hand and wrist for the Chinese Han population and explored the feasibility of employing deep learning techniques for bone age assessment based on MRI of the hand and wrist. This study selected 282 Chinese Han Chinese males aged 6.0-21.0 years old. In the course of our study, we proposed a novel deep learning model for extracting and enhancing MRI hand and wrist bone features to enhance the prediction of target MRI hand and wrist bone age and achieve precise classification of the target MRI and regression of bone age. The evaluation metric for the classification model including precision, specificity, sensitivity, and accuracy, while the evaluation metrics chosen for the regression model are MAE. The epiphyseal grading was used as a supervised method, which effectively solved the problem of unbalanced sample distribution, and the two experts showed strong consistency in the epiphyseal plate grading process. In the classification results, the accuracy in distinguishing between adults and minors was 91.1%, and the lowest accuracy in the three minor classifications (12, 14, and 16 years of age) was 94.6%, 91.1% and 96.4%, respectively. The MAE of the regression results was 1.24 years. In conclusion, the deep learning model proposed enabled the age assessment of hand and wrist bones based on MRI.
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INTRODUCTION: Fibrosing mediastinitis is a benign but fatal disorder characterized by the proliferation of fibrous tissue in the mediastinum, causing encasement of mediastinal organs and extrinsic compression of adjacent bronchovascular structures. FM-associated pulmonary hypertension (FM-PH) is a serious complication of FM, resulting from the external compression of lung vessels. Pathologic assessment is important for etiologic diagnosis and effective treatment of this disease. CASE PRESENTATION: A 59-year-old male patient presented at our hospital and was diagnosed with FM-PH. He declined surgical biopsy that is the reference standard for pathologic assessment, in consideration of the potential risks. Therefore, an endobronchial ultrasound examination was performed, which identified the subcarinal lesion. Under ultrasound guidance, four needle aspirations were carried out, followed by one cryobiopsy. Histopathological examination of transbronchial needle aspiration specimens was inconclusive, while samples from cryobiopsy suggested a diagnosis of idiopathic FM. Further immunophenotyping demonstrated the infiltration of lymphocytes, macrophages, and FOXP3-positive cells in FM-PH. CONCLUSION: Mediastinal cryobiopsy might be a novel and safe option for FM-PH patients who are unwilling or unsuitable for surgical procedure.
Assuntos
Hipertensão Pulmonar , Mediastinite , Hipertensão Arterial Pulmonar , Esclerose , Masculino , Humanos , Pessoa de Meia-Idade , Mediastino , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/complicações , Mediastinite/complicações , Mediastinite/diagnóstico , Hipertensão Arterial Pulmonar/patologiaRESUMO
PURPOSE: To report the long-term clinical outcomes of transscleral four-point fixation of Akreos intraocular lens using a closed continuous-loop suture technique. METHODS: This was a retrospective, multicenter, interventional case series. Primary outcome measures were best-corrected visual acuity, intraocular pressure, corneal endothelial cell density, and complications with a minimum of 1-year follow-up. RESULTS: One hundred and ninety-two eyes of 177 patients from two surgical hospital sites were identified. The mean best-corrected visual acuity improved from 0.88 ± 0.74 logarithm of the minimum angle of resolution (Snellen 20/152) preoperatively to 0.42 ± 0.52 logarithm of the minimum angle of resolution (Snellen 20/53) postoperatively ( P < 0.001). The mean preoperative intraocular pressure was 17.51 ± 8.67 mmHg, and the mean postoperative intraocular pressure at final follow-up was 15.08 ± 4.18 mmHg ( P = 0.001). The mean corneal endothelial cell density significantly reduced from 2,259 ± 729 cells/mm 2 to 2077 ± 659 cells/mm 2 , representing a cell loss of 5.73% ( P < 0.001). The intraocular lens was fixed well during follow-up. There were no intraoperative complications noted. Postoperative complications included transient ocular hypertension in 15 eyes (7.81%), hypotony in two eyes (1.04%), retinal detachment in one eye (0.52%), and macular edema in one eye (0.52%). CONCLUSION: The transscleral four-point fixation Akreos intraocular lens using the closed continuous-loop suture technique was effective and safe with satisfactory visual acuity with a minimum of 1-year follow-up.
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Pressão Intraocular , Implante de Lente Intraocular , Esclera , Técnicas de Sutura , Acuidade Visual , Humanos , Estudos Retrospectivos , Masculino , Feminino , Acuidade Visual/fisiologia , Esclera/cirurgia , Implante de Lente Intraocular/métodos , Idoso , Pessoa de Meia-Idade , Seguimentos , Pressão Intraocular/fisiologia , Lentes Intraoculares , Adulto , Idoso de 80 Anos ou mais , Resultado do Tratamento , Endotélio Corneano/patologia , Contagem de Células , Desenho de Prótese , Fatores de Tempo , Suturas , Complicações Pós-OperatóriasRESUMO
Syntaxin helps in catalyzing membrane fusion during exocytosis. It also forms clusters in the plasma membrane, where both its transmembrane and SNARE domains are thought to homo-oligomerize. To study syntaxin clustering in live PC12 cells, we labeled granules with neuropeptide-Y-mCherry and syntaxin clusters with syntaxin-1a green fluorescent protein (GFP). Abundant clusters appeared under total internal reflection (TIRF) illumination, and some of them associated with granules ("on-granule clusters"). Syntaxin-1a-GFP or its mutants were expressed at low levels and competed with an excess of endogenous syntaxin for inclusion into clusters. On-granule inclusion was diminished by mutations known to inhibit binding to Munc18-1 in vitro. Knock-down of Munc18-1 revealed Munc18-dependent and -independent on-granule clustering. Clustering was inhibited by mutations expected to break salt bridges between syntaxin's Hb and SNARE domains and was rescued by additional mutations expected to restore them. Most likely, syntaxin is in a closed conformation when it clusters on granules, and its SNARE and Hb domains approach to within atomic distances. Pairwise replacements of Munc18-contacting residues with alanines had only modest effects, except that the pair R114A/I115A essentially abolished on-granule clustering. In summary, an on-granule cluster arises from the specific interaction between a granule and a dense cluster of syntaxin-Munc18-1 complexes. Off-granule clusters, by contrast, were resistant to even the strongest mutations we tried and required neither Munc18-1 nor the presence of a SNARE domain. They may well form through the nonstoichiometric interactions with membrane lipids that others have observed in cell-free systems.
Assuntos
Membrana Celular/metabolismo , Proteínas Munc18/metabolismo , Proteínas Qa-SNARE/metabolismo , Proteína 25 Associada a Sinaptossoma/metabolismo , Glândulas Suprarrenais/citologia , Animais , Membrana Celular/química , Regulação da Expressão Gênica/fisiologia , Modelos Moleculares , Proteínas Munc18/genética , Mutação , Células PC12 , Ligação Proteica , Conformação Proteica , Proteínas Qa-SNARE/genética , Ratos , Proteína 25 Associada a Sinaptossoma/genéticaRESUMO
Objective: To observe the diagnostic value of four serum inflammatory biomarkers, including interleukin 6 (IL-6), interleukin 12P70 (IL-12P70), serum amyloid A (SAA), and procalcitonin (PCT), in rheumatoid arthritis (RA) and to analyze their relationship with the disease activity. Methods: The study included 60 RA patients admitted to the Department of Rheumatology at Anhui Provincial Hospital of Traditional Chinese Medicine between December 2022 and December 2023. Thirty healthy individuals from the hospital's physical examination center served as the control group. Serum levels of IL-6 and IL-12P70 were detected using flow cytometry. SAA levels were determined by immunoturbidimetry, and PCT levels were assessed by chemiluminescence. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anticyclic citrullinated peptide (ACCP) were detected using an automated biochemical analyzer. The 28-joint disease activity scores (DAS28-ESR) based on ESR were observed. Statistical analysis included t-tests, rank-sum tests, and Kruskal-Wallis H tests to compare the expression differences of the biomarkers among different groups. The diagnostic value of these biomarkers for RA was analyzed by ROC curve analysis. Spearman correlation analysis was performed to assess the relationships between the four inflammatory biomarkers and CRP, ESR, RF, ACCP, and DAS28-ESR. Results: 1) The expression levels of SAA, IL-6, and IL-12P70 in the RA group were significantly higher than those in the control group (P<0.01). 2) ROC curve analysis showed that the area under the curve (AUC) for PCT was 0.611 (95% confidence interval [CI]: 0.488-0.735, P>0.05), for SAA, it was 0.819 (95% CI: 0.733-0.906, P<0.01), for IL-6, it was 0.875 (95% CI: 0.803-0.946, P<0.01), and for IL-12P70, it was 0.832 (95% CI: 0.746-0.917, P<0.01). The combined index of IL-6, IL-12P70, SAA, and PCT had an AUC of 0.973 (95% CI: 0.942-1.000, P<0.01). This indicates that the four inflammatory biomarkers can assist in the diagnosis of rheumatoid arthritis. 3) The expression levels of PCT and SAA varied significantly among the high, moderate, and low activity RA groups (P<0.01). 4) In RA patients, CRP was positively correlated with SAA (rs =0.75, P<0.01), and IL-6 (rs =0.52, P<0.01). ESR was positively correlated with SAA (rs =0.36, P<0.01). DAS28-ESR was positively correlated with PCT (rs =0.34, P=0.01), SAA (rs =0.51, P<0.01) and IL-6 (rs =0.33, P=0.01). Conclusion: The four inflammatory biomarkers (PCT, SAA, IL-6, and IL-12P70) are closely related to rheumatoid arthritis disease activity and can serve as serum indicators to assist in the diagnosis and assessment of RA.
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Artrite Reumatoide , Biomarcadores , Interleucina-12 , Interleucina-6 , Pró-Calcitonina , Proteína Amiloide A Sérica , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/sangue , Proteína Amiloide A Sérica/metabolismo , Pró-Calcitonina/sangue , Interleucina-6/sangue , Biomarcadores/sangue , Interleucina-12/sangue , Sedimentação Sanguínea , Masculino , Feminino , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Pessoa de Meia-Idade , Curva ROCRESUMO
This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC) in delaying chondrocyte senescence of osteoarthritic(OA) rats by regulating the p53/p21 signaling pathway. Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA) combined with external rheumatic fever environmental stimuli and divided into normal(Con) group, OA model(MIA) group, OA model+rheumatic fever stimulation model(MIA-M) group, MIA-M+HQC low-dose(MIA-M+HQC-L) group, medium-dose(MIA-M+HQC-M) group, and high-dose(MIA-M+HQC-H) group, and MIA-M+glucosamine(MIA-M+GS) group. The models were successfully prepared and administered by gavage for 30 d. The pathological changes of cartilage were observed by hematoxylin-eosin(HE) and Senna O solid green(SO) staining. The expression of interleukin(IL)-1ß and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). Flow cytometry(FCM) was used to detect apoptosis and cell cycle. The mRNA expression of MMP13, ADAMTS-5, COLâ ¡, and TGF-ß was detected by RT-qPCR. The protein expression of p53/p21, p16, Bax, and Bcl-2 was detected by Western blot. The articular cartilage surface of rats in the Con group was smooth, and the tide line was smooth. The cartilage layer of MIA and MIA-M groups was obviously damaged, and the cartilage matrix was reduced. The above conditions were more severe in the MIA-M group. The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination. Compared with the MIA-M+HQC-H group, Mankin's score was higher in the HQC low-dose and medium-dose groups, and the change was not obvious in the MIA-M+GS group. Compared with the Con group, the proportion of chondrocytes G_1 was elevated in the MIA and MIA-M groups, and the proportion of the S phase and G_2 phase was significantly decreased. In addition, the apoptosis rate was increased. Compared with MIA-M, HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner. Compared with the MIA-M+HQC-H group, the effect was more significant in the HQC high-dose group than in the HQC medium-low dose, while it was not significant in the MIA-M+GS group. Compared with the Con group, IL-1ß and IL-6 were elevated in the MIA and MIA-M groups, and mRNA levels of MMP13 and ADAMTS-5 were elevated. p53, p21, p16, and Bax protein were elevated, and mRNA levels of COLâ ¡ and TGF-ß were decreased. Compared with the MIA-M group, IL-1ß and IL-6 decreased after drug interventions of HQC and GS, and mRNA levels of MMP13 and ADAMTS-5, as well as protein levels of p53, p21, Bax, and p16 decreased. In addition, Bcl-2 increased. The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups, and the difference with the MIA-M+GS group was not significant. HQC delayed MIA-induced chondrocyte senescence in OA rats, inhibited inflammatory response and extracellular matrix(ECM) degradation, and its mechanism may be related to the inhibition of the p53/p21 pathway.
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Condrócitos , Medicamentos de Ervas Chinesas , Osteoartrite , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Supressora de Tumor p53 , Animais , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Osteoartrite/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Masculino , Senescência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Cápsulas , Humanos , Apoptose/efeitos dos fármacosRESUMO
In the study of age estimation in living individuals, a lot of data needs to be analyzed by mathematical statistics, and reasonable medical statistical methods play an important role in data design and analysis. The selection of accurate and appropriate statistical methods is one of the key factors affecting the quality of research results. This paper reviews the principles and applicable principles of the commonly used medical statistical methods such as descriptive statistics, difference analysis, consistency test and multivariate statistical analysis, as well as machine learning methods such as shallow learning and deep learning in the age estimation research of living individuals, and summarizes the relevance and application prospects between medical statistical methods and machine learning methods. This paper aims to provide technical guidance for the age estimation research of living individuals to obtain more scientific and accurate results.
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Aprendizado de Máquina , Humanos , Determinação da Idade pelo Esqueleto/métodos , Análise Multivariada , Determinação da Idade pelos Dentes/métodosRESUMO
Nonalcoholic fatty liver disease is caused by an imbalance in lipid metabolism and immune response to pose a risk factor for liver fibrosis. Recent evidence indicates that M2 macrophages secrete transforming growth factor-ß1, which contributes to liver fibrosis. Galectin-12 has been demonstrated to regulate lipid metabolism and macrophage polarization. The purpose of this study is to investigate the role of galectin-12 in the development of nonalcoholic fatty liver disease and fibrosis. Liver tissue from wild-type C57BL/6 mice fed with a high-fat diet containing cholesterol and cholic acid for 4-12 weeks was used to examine galectin-12 expression and its correlation with nonalcoholic fatty liver disease. Furthermore, the effects of galectin-12 on M2 macrophages during the progression of nonalcoholic fatty liver disease were investigated by studying Kupffer cells from galectin-12 knockout mice and doxycycline-inducible Gal12-/-THP-1 cells. Ablation of galectin-12 promoted M2 polarization of Kupffer cells, as indicated by higher levels of M2 markers, such as arginase I and chitinase 3-like protein 3. Furthermore, the activation of signal transducer and activator of transcription 6 was significantly higher in Gal12-/- macrophages activated by interleukin-4, which was correlated with higher levels of transforming growth factor-ß1. Moreover, Gal12-/- macrophage-conditioned medium promoted hepatic stellate cells myofibroblast differentiation, which was indicated by higher α-smooth muscle actin expression levels compared with those treated with LacZ control medium. Finally, we demonstrated that galectin-12 knockdown negatively regulated the suppressor of cytokine signaling 3 levels. These findings suggested that galectin-12 balances M1/M2 polarization of Kupffer cells to prevent nonalcoholic fatty liver disease progression.
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Células de Kupffer , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Células de Kupffer/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fator de Crescimento Transformador beta1 , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Cirrose Hepática , Dieta Hiperlipídica/efeitos adversos , Galectinas/metabolismoRESUMO
The ability to impart multiple covarying properties into a single material represents a grand challenge in manufacturing. In the design of block copolymers (BCPs) for directed self-assembly and nanolithography, materials often balance orthogonal properties to meet constraints related to processing, structure and defectivity. Although iterative synthesis strategies deliver BCPs with attractive properties, identifying materials with all the required attributes has been difficult. Here we report a high-throughput synthesis and characterization platform for the discovery and optimization of BCPs with A-block-(B-random-C) architectures for lithographic patterning in semiconductor manufacturing. Starting from a parent BCP and using thiol-epoxy 'click' chemistry, we synthesize a library of BCPs that cover a large and complex parameter space. This allows us to readily identify feature-size-dependent BCP chemistries for 8-20-nm-pitch patterns. These blocks have similar surface energies for directed self-assembly, and control over the segregation strength to optimize the structure (favoured at higher segregation strengths) and defectivity (favoured at lower segregation strengths).
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Polímeros , Projetos de Pesquisa , Semicondutores , Compostos de SulfidrilaRESUMO
BACKGROUND: The integrative effects of prostate cancer risk factors, such as diet and endocrine status, on cancer-associated miRNA expression are poorly defined. OBJECTIVES: This study aimed to define the influence of androgens and diet (tomato and lycopene) on prostatic miRNA expression during early carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. METHODS: Wild type (WT) and TRAMP mice were fed control, tomato-containing, or lycopene-containing diets from 4 to 10 weeks of age. Mice underwent either sham (intact) or castration surgery at 8 wk, and half of the castrated mice received testosterone (2.5 mg/kg body weight/d) at 9 wk. Mice were killed at 10 wk, and dorsolateral prostate expression of 602 miRNAs was assessed. RESULTS: We detected expression of 88 miRNAs (15% of 602), all of which were present in the TRAMP, in comparison with 49 miRNAs being detectable (8%) in WT. Expression of 61 miRNAs differed by TRAMP genotype, with the majority upregulated in TRAMP. Of the 61 miRNAs, 42 were responsive to androgen status. Diet affected 41% of the miRNAs, which differed by genotype (25/61) and 48% of the androgen-sensitive miRNAs (20/42), indicating overlapping genetic and dietary influences on prostate miRNAs. Tomato and lycopene feeding influenced miRNAs previously associated with the regulation of androgen (miR-145 and let-7), MAPK (miR-106a, 204, 145/143, and 200b/c), and p53 signaling (miR-125 and miR-98) pathways. CONCLUSIONS: Expression of miRNAs in early prostate carcinogenesis is sensitive to genetic, endocrine, and diet drivers, suggesting novel mechanisms by which tomato and lycopene feeding modulate early prostate carcinogenesis.
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MicroRNAs , Neoplasias da Próstata , Solanum lycopersicum , Humanos , Masculino , Camundongos , Animais , Carotenoides/metabolismo , Licopeno/metabolismo , Testosterona/metabolismo , Próstata , Solanum lycopersicum/genética , Androgênios/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Carcinogênese , Dieta , Camundongos TransgênicosRESUMO
PURPOSE: To investigate whether patients with central serous chorioretinopathy (CSC) have increased risk of developing glaucoma. METHODS: Patients diagnosed with CSC between 1 January 2008 and 31 December 2018 were included in this study using data from the Taiwanese National Health Insurance Research Database (NHIRD). The CSC cohort was matched with a non-CSC cohort using the propensity score matching method, based on sex, age (in 10-year intervals), index date year, comorbidities, and steroid use, resulting in equal numbers of patients in both cohorts. Patients were followed up until 31 December 2019 or until they were withdrawn from the NHIRD. The incidence of glaucoma was compared between the two cohorts using the Cox regression model, and the risk of developing glaucoma was estimated using the Kaplan-Meier method. RESULTS: After adjusting for sex, age, comorbidities, and steroid use, the CSC cohort showed a significantly higher risk of developing glaucoma compared to those without CSC (adjusted HR = 3.99; 95% CI = 3.44-4.62). The cumulative incidence of glaucoma in the CSC cohort was also significantly higher than in the non-CSC cohort (log-rank test, p < 0.001). Among the glaucoma subtypes, normal tension glaucoma had the highest risk (adjusted HR = 5.79; 95% CI = 3.41-9.85), followed by primary open-angle glaucoma (adjusted HR = 2.77; 95% CI = 2.12-3.62). CONCLUSIONS: In conclusion, our study shows that CSC patients are at a higher risk of developing glaucoma, especially NTG. Awareness and regular glaucoma screenings are essential for patients with CSC.
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Coriorretinopatia Serosa Central , Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Estudos de Coortes , Coriorretinopatia Serosa Central/complicações , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/epidemiologia , Glaucoma/diagnóstico , Glaucoma/epidemiologia , Esteroides , Fatores de Risco , Estudos RetrospectivosRESUMO
Lung cancer is the leading cause of deaths from malignant neoplasms worldwide, and a satisfactory biopsy that allows for histological and other analyses is critical for its diagnosis. Guidelines have recommended endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as the reference standard for the staging of lung cancer. However, the relatively limited sample volume retrieved by needle aspiration might restrict the diagnostic capacity of EBUS-TBNA in other uncommon thoracic tumors. Transbronchial mediastinal cryobiopsy is a recently developed sampling strategy for mediastinal lesions, which demonstrates added diagnostic value to conventional needle aspiration. Here, we present a case of thoracic SMARCA4-deficient undifferentiated tumor successfully diagnosed by mediastinal cryobiopsy additional to EBUS-TBNA.
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Broncoscopia , Neoplasias Pulmonares , Humanos , Estadiamento de Neoplasias , Mediastino/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfonodos/patologia , DNA Helicases , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
BACKGROUND: Poly-D, L-lactic acid is (PDLLA) a new cosmetic filler. We reported the first case of PDLLA-related devastating complication of multiple branch retinal artery occlusion (BRAO). CASE PRESENTATION: A 23-year-old female had sudden blindness after injection of PDLLA at the glabella. After emergency intraocular pressure-lowering medicine, ocular massage, steroid pulse therapy, heparin and alprostadil infusion, and subsequent treatments including acupuncture and 40 sessions of hyperbaric oxygen therapy, her best-corrected visual acuity improved from hand motion at 30 cm to 0.3 within 2 months. CONCLUSION: Although safety of PDLLA was evaluated in animal studies and in 16,000 human cases, it could still cause rare but devastating retinal artery occlusion as in the present case. Proper and immediate therapies could still improve patient's vision and scotoma. Surgeons should keep in mind the possibility of iatrogenic filler-related retinal artery occlusion.
Assuntos
Face , Oclusão da Artéria Retiniana , Humanos , Animais , Feminino , Adulto Jovem , Adulto , Oclusão da Artéria Retiniana/induzido quimicamente , Oclusão da Artéria Retiniana/diagnóstico , Olho , Injeções , Ácido LácticoRESUMO
A six degree-of-freedom (DOF) motion control system for docking with a deep submergence rescue vehicle (DSRV) test platform was the focus of this study. The existing control methods can meet the general requirements of underwater operations, but the complex structures or multiple parameters of some methods have prevented them from widespread use. The majority of the existing methods assume the heeling effect to be negligible and ignore it, achieving motion control in only four or five DOFs. In view of the demanding requirements regarding positions and inclinations in six DOFs during the docking process, the software and hardware architectures of the DSRV platform were constructed, and then sparse filtering technology was introduced for data smoothing. Based on the adaptive control strategy and with a consideration of residual static loads, an improved S-plane control method was developed. By converting the force (moment) calculated by the controller to the body coordinate system, the complexity of thrust allocation was effectively reduced, and the challenge of thrust allocation in the case of a high inclination during dynamic positioning was solved accordingly. The automatic control of the trimming angle and heeling angle was realized with the linkage system of the ballast tank and pump valve. A PID method based on an intelligent integral was proposed, which not only dealt with the integral "saturation" problem, but also reduced the steady-state error and overshooting. Water pool experiments and sea trials were carried out in the presence of water currents for six-DOF motion control. The responsiveness and precision of the control system were verified by the pool experiment and sea trial results and could meet the control requirements in engineering practice. The reliability and operational stability of the proposed control system were also verified in a long-distance cruise.
RESUMO
To improve the energy conversion efficiency and durability of zinc-air batteries (ZABs) for large-scale implementations, here we propose an "air-breathing" strategy to significantly enlarge triple-interfaces with intensified mass transfer. By dip-coating the aerophilic perfluorochemical compounds (PFC) and amphiphilic ionomers into the self-supported electrodes, (1) the high solubility of O2 in the PFC nanoemulsions greatly increases triple-phase boundaries and facilitates the efficient supply/removal of O2 from the electrolyte; (2) the ionomers with hydrophobic and hydrophilic functionalities enable fast gas, water, and ion transport to the triple-phase boundaries; and (3) the self-supported electrode without binder ensures fast electron transfer while the firm integration prevents catalyst shedding. By applying this strategy, the ZABs show a high power density of 115 mW cm-2 and a narrow discharge/charge gap of 0.64 V at 10 mA cm-2 and a long-cycling durability (over 1000 h). This work provides a universal approach to promote gas-evolving reactions for electrochemical applications.
RESUMO
Mechanochemical (MC) remediation with zero-valent iron (ZVI) as co-milling agent enables the non-combustion and solvent-free disposal of solid halogenated organic pollutants (HOPs) via solid-phase reaction, but suffers from incomplete dechlorination (especially for less chlorinated chemicals). Herein, a reduction-oxidation coupling strategy using ZVI and peroxydisulfate as synergistic (ZVI-PDS) co-milling agents was investigated, with 2,4-dichlorophenol (2,4-DCP) as probe contaminant. By revisiting the MC destruction process of 2,4-DCP by ZVI, the contribution of both reductive and oxidative routes is confirmed, and the inefficient â¢OH generation is addressed. With ball-to-material and reagent-to-pollutant mass ratios of 30:1 and 13:1, respectively, ZVI-PDS achieves higher dechlorination ratio (86.8%) for 2,4-DCP within 5 h, outcompeting sole ZVI (40.3%) or PDS (33.9%), due to the accumulation of numerous SO4â¢-. As suggested by a two-compartment kinetic model, the optimal ZVI/PDS molar ratio of 4:1 is determined, which balances the relative contribution of reductive/oxidative routes and leads to a maximum mineralization efficiency of 77.4%. The analysis on product distribution verifies the generation of dechlorinated, ring-opening and minor coupling products (with low acute toxicity). This work validates the necessity to couple reduction with oxidation in MC destruction for solid HOPs, and may provide information on reagent formulation.