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The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.
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Genoma Humano/genética , Genômica , Migração Humana/história , China , Produção Agrícola/história , Feminino , Haplótipos/genética , História Antiga , Humanos , Japão , Idioma/história , Masculino , Mongólia , Nepal , Oryza , Polimorfismo de Nucleotídeo Único/genética , Sibéria , TaiwanRESUMO
Water quality detection plays an increasingly important role in environmental protection. In this work, a novel colorimeter based on the Beer-Lambert law was designed for chemical element detection in water with high precision and miniaturized structure. As an example, the colorimeter can detect phosphorus, which was accomplished in this article to evaluate the performance. Simultaneously, a modified algorithm was applied to extend the linear measurable range. The colorimeter encompassed a near infrared laser source, a microflow cell based on microfluidic technology and a light-sensitive detector, then Micro-Electro-Mechanical System (MEMS) processing technology was used to form a stable integrated structure. Experiments were performed based on the ammonium molybdate spectrophotometric method, including the preparation of phosphorus standard solution, reducing agent, chromogenic agent and color reaction. The device can obtain a wide linear response range (0.05 mg/L up to 7.60 mg/L), a wide reliable measuring range up to 10.16 mg/L after using a novel algorithm, and a low limit of detection (0.02 mg/L). The size of flow cell in this design is 18 mm × 2.0 mm × 800 µm, obtaining a low reagent consumption of 0.004 mg ascorbic acid and 0.011 mg ammonium molybdate per determination. Achieving these advantages of miniaturized volume, high precision and low cost, the design can also be used in automated in situ detection.
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Betulinic acid (BA) is a lupane-type pentacyclic triterpene, distributed ubiquitously throughout the plant kingdom. BA and its derivatives demonstrate multiple bioactivities, particularly an antitumor effect. This review critically describes the recent research on isolation, synthesis, and derivatization of BA and its natural analogs betulin and 23-hydroxybetulinic acid. The subsequent part of the review focuses on the current knowledge of antitumor properties, combination treatments, and pharmacological mechanisms of these compounds. A 3D-QSAR analysis of 62 BA derivatives against human ovarian cancer A2780 is also included to provide information concerning the structure-cytotoxicity relationships of these compounds.
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Antineoplásicos/farmacologia , Triterpenos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Triterpenos Pentacíclicos , Relação Quantitativa Estrutura-Atividade , Triterpenos/química , Ácido BetulínicoRESUMO
There are many reports for andrographolide modification regarding antitumor effects. Transformation of the five-membered lactone ring to furan aromatic ring still results in compounds with good cytotoxicity. To determine further the importance of the five-membered lactone ring and to obtain better lead compounds, we transformed the five-membered lactone ring in andrographolide. New types of ent-labdane diterpene derivatives were made, whose cytotoxic activities were measured in vitro. Preliminary SAR was summarized and two compounds, 7 and 26, with good cytotoxic activity were obtained, which have the potential to be developed into new antitumor drugs.
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Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Diterpenos/síntese química , Diterpenos/farmacologia , Diterpenos/química , Descoberta de Drogas , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Sleep apnea syndrome (SAS) is prevalent in individuals and recently, there are many studies focus on using simple and efficient methods for SAS detection instead of polysomnography. However, not much work has been done on using nonlinear behavior of the electroencephalogram (EEG) signals. The purpose of this study is to find a novel and simpler method for detecting apnea patients and to quantify nonlinear characteristics of the sleep apnea. 30 min EEG scaling exponents that quantify power-law correlations were computed using detrended fluctuation analysis (DFA) and compared between six SAS and six healthy subjects during sleep. The mean scaling exponents were calculated every 30 s and 360 control values and 360 apnea values were obtained. These values were compared between the two groups and support vector machine (SVM) was used to classify apnea patients. Significant difference was found between EEG scaling exponents of the two groups (p < 0.001). SVM was used and obtained high and consistent recognition rate: average classification accuracy reached 95.1% corresponding to the sensitivity 93.2% and specificity 98.6%. DFA of EEG is an efficient and practicable method and is helpful clinically in diagnosis of sleep apnea.
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Eletroencefalografia/estatística & dados numéricos , Síndromes da Apneia do Sono/diagnóstico , Máquina de Vetores de Suporte , Adulto , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Polissonografia/métodos , Polissonografia/estatística & dados numéricos , Processamento de Sinais Assistido por Computador , Análise de OndaletasRESUMO
OBJECTIVES: The present study aimed to evaluate the effectiveness of bioactive glass (BAG) in preventing dental erosion in primary teeth. METHODS: Enamel and dentin specimens (2 × 2 × 2 mm) were obtained from extracted primary teeth, which were randomly divided into the following groups based on the pretreatments (n = 12): DW (deionized water), NaF (2 % sodium fluoride), 2BAG (2 % BAG), 4BAG (4 % BAG), 6BAG (6 % BAG), and 8BAG (8 % BAG). The specimens were immersed in the respective solutions for 2 min and subjected to in vitro erosive challenges (4 × 5 min/d) for 5 d. The erosive enamel loss (EEL), erosive dentin loss (EDL), and the thickness of the demineralized organic matrix (DOM) were measured using a contact profilometer. The surface microhardness (SMH) was measured, and the percentage of SMH loss (%SMHL) was calculated. The surface morphology and mineral composition were evaluated by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. RESULTS: After the erosive challenges, the EEL, EDL, and%SMHL of the 2BAG, 4BAG, 6BAG, and 8BAG groups significantly reduced, with the greatest reduction was observed in the 6BAG (EEL: 6.5 ± 0.2 µm;%SMHL in enamel: 12.8 ± 2.6; EDL: 7.9 ± 0.3 µm; %SMHL in dentin: 22.1 ± 2.7) and 8BAG groups (EEL: 6.4 ± 0.4 µm;%SMHL in enamel: 11.0 ± 1.9; EDL: 7.8 ± 0.5 µm; %SMHL in dentin: 22.0 ± 2.5) (P < 0.05). With increasing BAG concentrations, the number of surface deposits containing Ca, P, and Si increased. CONCLUSIONS: 6BAG was the most effective for preventing dental erosion in primary teeth and showed a particularly strong potential for dentin erosion prevention. CLINICAL SIGNIFICANCE: Bioactive glass, especially at a 6 % concentration, has proven effective in reducing erosive tooth wear and surface microhardness loss while also protecting demineralized organic matrix in primary dentin.
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Esmalte Dentário , Dentina , Vidro , Dureza , Microscopia Eletrônica de Varredura , Fluoreto de Sódio , Espectrometria por Raios X , Erosão Dentária , Dente Decíduo , Erosão Dentária/prevenção & controle , Humanos , Vidro/química , Fluoreto de Sódio/uso terapêutico , Propriedades de Superfície , Cerâmica/química , Desmineralização do Dente/prevenção & controle , Teste de MateriaisRESUMO
Neural networks based on low-power artificial synapses can significantly reduce energy consumption, which is of great importance in today's era of artificial intelligence. Two-dimensional (2D) material-based floating-gate transistors (FGTs) have emerged as compelling candidates for simulating artificial synapses owing to their multilevel and nonvolatile data storage capabilities. However, the low erasing/programming speed of FGTs renders them unsuitable for low-energy-consumption artificial synapses, thereby limiting their potential in high-energy-efficient neuromorphic computing. Here, we introduce a FGT-inspired MoS2/Trap/PZT heterostructure-based polarized tunneling transistor (PTT) with a simple fabrication process and significantly enhanced erasing/programming speed. Distinct from the FGT, the PTT lacks a tunnel layer, leading to a marked improvement in its erasing/programming speed. The PTT's highest erasing/programming (operation) speed can reach â¼20 ns, which outperforms the performance of most FGTs based on 2D heterostructures. Furthermore, the PTT has been utilized as an artificial synapse, and its weight-update energy consumption can be as low as 0.0002 femtojoule (fJ), which benefits from the PTT's ultrahigh operation speed. Additionally, PTT-based artificial synapses have been employed in constructing artificial neural network simulations, achieving facial-recognition accuracy (95%). This groundbreaking work makes it possible for fabricating future high-energy-efficient neuromorphic transistors utilizing 2D materials.
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BACKGROUND: Accurate estimation of glomerular filtration rate (GFR) is important in clinical practice. Current models derived from regression are limited by the imprecision of GFR estimates. We hypothesized that an artificial neural network (ANN) might improve the precision of GFR estimates. STUDY DESIGN: A study of diagnostic test accuracy. SETTING & PARTICIPANTS: 1,230 patients with chronic kidney disease were enrolled, including the development cohort (n=581), internal validation cohort (n=278), and external validation cohort (n=371). INDEX TESTS: Estimated GFR (eGFR) using a new ANN model and a new regression model using age, sex, and standardized serum creatinine level derived in the development and internal validation cohort, and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2009 creatinine equation. REFERENCE TEST: Measured GFR (mGFR). OTHER MEASUREMENTS: GFR was measured using a diethylenetriaminepentaacetic acid renal dynamic imaging method. Serum creatinine was measured with an enzymatic method traceable to isotope-dilution mass spectrometry. RESULTS: In the external validation cohort, mean mGFR was 49±27 (SD) mL/min/1.73 m2 and biases (median difference between mGFR and eGFR) for the CKD-EPI, new regression, and new ANN models were 0.4, 1.5, and -0.5 mL/min/1.73 m2, respectively (P<0.001 and P=0.02 compared to CKD-EPI and P<0.001 comparing the new regression and ANN models). Precisions (IQRs for the difference) were 22.6, 14.9, and 15.6 mL/min/1.73 m2, respectively (P<0.001 for both compared to CKD-EPI and P<0.001 comparing the new ANN and new regression models). Accuracies (proportions of eGFRs not deviating >30% from mGFR) were 50.9%, 77.4%, and 78.7%, respectively (P<0.001 for both compared to CKD-EPI and P=0.5 comparing the new ANN and new regression models). LIMITATIONS: Different methods for measuring GFR were a source of systematic bias in comparisons of new models to CKD-EPI, and both the derivation and validation cohorts consisted of a group of patients who were referred to the same institution. CONCLUSIONS: An ANN model using 3 variables did not perform better than a new regression model. Whether ANN can improve GFR estimation using more variables requires further investigation.
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Taxa de Filtração Glomerular/fisiologia , Redes Neurais de Computação , Análise de Regressão , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Testes de Função Renal/estatística & dados numéricos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Accurate and precise estimates of glomerular filtration rate (GFR) are essential for clinical assessments, and many methods of estimation are available. We developed a radial basis function (RBF) network and assessed the performance of this method in the estimation of the GFRs of 207 patients with type-2 diabetes and CKD. METHODS: Standard GFR (sGFR) was determined by (99m)Tc-DTPA renal dynamic imaging and GFR was also estimated by the 6-variable MDRD equation and the 4-variable MDRD equation. RESULTS: Bland-Altman analysis indicated that estimates from the RBF network were more precise than those from the other two methods for some groups of patients. However, the median difference of RBF network estimates from sGFR was greater than those from the other two estimates, indicating greater bias. For patients with stage I/II CKD, the median absolute difference of the RBF network estimate from sGFR was significantly lower, and the P50 of the RBF network estimate (n = 56, 87.5%) was significantly higher than that of the MDRD-4 estimate (n = 49, 76.6%) (p < 0.0167), indicating that the RBF network estimate provided greater accuracy for these patients. CONCLUSIONS: In patients with type-2 diabetes mellitus, estimation of GFR by our RBF network provided better precision and accuracy for some groups of patients than the estimation by the traditional MDRD equations. However, the RBF network estimates of GFR tended to have greater bias and higher than those indicated by sGFR determined by (99m)Tc-DTPA renal dynamic imaging.
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Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Diagnóstico por Computador/métodos , Taxa de Filtração Glomerular , Redes Neurais de Computação , Algoritmos , Neuropatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To compare the clinical performances of patients in different ages with implantation of a accommodating IOLs. METHODS: It was a retrospective study. Forty-seven eyes (47 patients) were enrolled in 3 groups for phacoemulsification and a accommodating IOL implantation. According to their ages, they were divided into 3 groups: ≤ 45 years, 46 - 59 years, and ≥ 60 years. Parameters analyzed after more than 3 months postoperation were uncorrected distance, best-corrected distance, uncorrected near, and distance-corrected near visual acuities; changes of anterior chamber depth(ACD) during accommodative measured using the ultrasound biomicroscopy (UBM);changes of ACD by instilling 2% pilocarpine using the A-ultrasonic scan; and the amplitude of accommodation using the pushing-up test. RESULTS: No significant difference was observed between distance and near visual acuities of IOL groups. The mean changes of ACD measured with UBM in the group of ≤ 45 years [(0.16 ± 0.12) mm] was significantly higher than the other age groups [46 - 59 years, (0.06 ± 0.06) mm, P = 0.00; ≥ 60 years, (0.07 ± 0.05) mm, P = 0.008)]. The mean changes of ACD stimulated by pilocarpine measured with A-ultrasonic scan in the group of ≥ 60 years [(0.17 ± 0.14) mm] was significantly lower than the other age groups [≤ 45 years, (0.68 ± 0.44) mm, P = 0.00; 46 - 59 years, (0.43 ± 0.20) mm, P = 0.00]. The accommodative amplitude of the ≥ 60 years groups ((2.32 ± 0.88) D) was lower than the group of ≤ 45 years [(2.87 ± 0.52) D, P = 0.005]. CONCLUSIONS: The accommodative amplitude of patients implanted with accommodating IOLs stepped down following the increase of age. However, no statistical differences were found in distance and near visual acuities between the different age groups.
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Acomodação Ocular , Implante de Lente Intraocular , Lentes Intraoculares , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade VisualRESUMO
Medical visual question answering (Med-VQA) aims to accurately answer a clinical question presented with a medical image. Despite its enormous potential in healthcare services, the development of this technology is still in the initial stage. On the one hand, Med-VQA tasks are highly challenging due to the massive diversity of clinical questions that require different visual reasoning skills for different types of questions. On the other hand, medical images are complex in nature and very different from natural images, while current Med-VQA datasets are small-scale with a few hundred radiology images, making it difficult to train a well-performing visual feature extractor. This paper addresses above two critical issues. We propose a novel conditional reasoning mechanism with a question-conditioned reasoning component and a type-conditioned reasoning strategy to learn effective reasoning skills for different Med-VQA tasks adaptively. Further, we propose to pre-train a visual feature extractor for Med-VQA via contrastive learning on large amounts of unlabeled radiology images. The effectiveness of our proposals is validated by extensive experiments on existing Med-VQA benchmarks, which show significant improvement of our model in prediction accuracy over state-of-the-art methods. The source code and pre-training dataset are provided at https://github.com/Awenbocc/CPCR.
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Software , Extremidade SuperiorRESUMO
Objective: The aim of this study was to analyze the prevalence of vaginal flora and drug resistance in bacterial vaginitis among girls. Methods: A total of 3099 girls (0-10 years old) with vaginitis who visited the Beijing Children's Hospital from January 2020 to December 2021 were included in the present study. The clinical data, results of bacterial culture of vaginal secretions, and drug sensitivity reports of the subjects were collected and analyzed. Results: Of the 3099 girls with vaginitis, 399 girls had a positive bacterial culture of vaginal secretions. Nineteen types of bacteria were cultured from the vaginal secretions of these 399 girls, with a total of 419 strains. The top three infective bacteria were Haemophilus influenzae (127 strains, 30.31%), Staphylococcus aureus (66 strains, 15.75%), and Streptococcus agalactiae (32 strains, 7.64%). Additionally, 20 girls were simultaneously infected with two types of bacteria. Staphylococcus aureus, Group G Streptococcus, Haemophilus parainfluenzae, and Pseudomonas aeruginosa more frequently occurred in mixed infections. The number and bacterial detection rate among school-age girls were higher than those of preschool-age girls. We found seasonal variation in infection rates, and vaginitis among girls was higher in summer. Recurrence of vaginitis in girls was not related to the type of pathogenic bacteria in the infection. Drug sensitivity analyses showed that the resistance rates of clindamycin and erythromycin were generally high, 70-100%. After the coronavirus disease 2019 outbreak, the resistance rates of some antibiotics had decreased to varying degrees. Conclusion: Improving the understanding of vaginal flora and drug resistance in girls with vaginitis will facilitate the selection of highly effective and sensitive antibacterial drugs and reduce the production of drug-resistant strains.
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OBJECTIVE: Distal clavicle fracture classification directly affects the treatment decisions. It is unclear whether the classification systems implemented differ depending on surgeons' backgrounds. This study aimed to compare the interobserver agreement of four classification systems used for lateral clavicle fractures by shoulder specialists and general trauma surgeons. METHODS: Radiographs of 20 lateral clavicle fractures representing a full spectrum of adult fracture patterns were analyzed by eight experienced shoulder specialists and eight general trauma surgeons from 10 different hospitals. All cases were graded according to the Orthopedic Trauma Association (OTA), Neer, Jäger/Breitner, and Gongji classification systems. To measure observer agreement, Fleiss' kappa coefficient (κ) was applied and assessed. RESULTS: When only X-ray films were presented, both groups achieved fair agreement. However, when the 3D-CT scan images were provided, improved interobserver agreement was found in the specialist group when the OTA, Jäger/Breitner, and Gongji classification systems were used. In the generalist groups, improved agreement was found when using the Gongji classification system. In terms of interobserver reliability, the OTA, Neer, and Jäger/Breitner classification systems showed better agreement among shoulder specialists, while a slightly lower level of agreement was found using the Gongji classification system. For the OTA classification system, interobserver agreement had a mean kappa value of 0.418, ranging from 0.446 (specialist group) to 0.402 (generalist group). For the Neer classification system, interobserver agreement had a mean kappa value of 0.368, ranging from 0.402 (specialist group) to 0.390 (generalist group). For the Jäger/Breitner classification system, the inter-observer agreement had a mean kappa value of 0.380, ranging from 0.413 (specialist group) to 0.404 (generalist group). For the Gongji classification system, interobserver agreement had a mean kappa value of 0.455, ranging from 0.480 (specialist group) to 0.485 (generalist group). CONCLUSION: Generally speaking, 3D-CT scans provide a richer experience that can lead to better results in most classification systems of lateral clavicle fractures, highlighting the value of digitization and specialization in diagnosis and treatment. Competitive interobserver agreement was exhibited in the generalist group using the Gongji classification system, suggesting that the Gongji classification is suitable for general trauma surgeons who are not highly experienced in the shoulder field.
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Fraturas Ósseas , Cirurgiões , Adulto , Humanos , Clavícula/lesões , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Fraturas Ósseas/cirurgiaRESUMO
In today's information age, high performance nonvolatile memory devices have become extremely important. Despite their potential, existing devices suffer from limitations, such as low operation speed, low memory capacity, short retention time, and a complex preparation process. To overcome these limitations, advanced memory designs are required to improve speed, memory capacity, and retention time and reduce the number of preparation steps. Here, we present a nonvolatile floating-gate-like memory device based on a transistor that uses the polarization effect of ferroelectric material PZT (Pb[Zr0.2Ti0.8]O3) for regulating tunneling electrons for charging and discharging the MoS2 channel layer. The transistor is defined as a polarized tunneling transistor (PTT) and does not require a tunnel layer or a floating-gate layer. The PTT demonstrates an ultrafast programming/erasing speed of 25/20 ns and a response time of 120/105 ns, which is comparable to the ultrafast flash memories based on van der Waals heterostructures. Additionally, the PTT has a high extinction ratio of 104, a long retention time of 10 years, and a simple fabrication process. Our research provides future guidelines for the development of the next generation of ultrafast nonvolatile memory devices.
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A series of tetracyclic diterpenoids bearing the α-methylenelactone group have been synthesized and screened for their in vitro anti-tumor activities against six human cancer cell lines. The results showed that compounds 1c, 2a and 2b exhibited significant cytotoxicity superior to the positive control doxorubicin hydrochloride against MDA-MB-231, K562 and HepG2 cell lines. In particular, compound 2b was identified as the most promising anticancer agent against HepG2 cells with IC(50) value of 0.09µM.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Lactonas/química , Lactonas/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/síntese química , Humanos , Lactonas/síntese química , Neoplasias/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To evaluate the feasibility of genetic modification of mesenchymal stem cells (MSC) with Sonic Hedgehog (Shh) gene. METHODS: The pcDNA3.1-Shh eukaryotic expression plasmid was constructed and its correctness evaluated by the restriction enzyme analysis and sequencing. MSC were isolated from Wistar rats by density gradient centrifugation and purified, transfected with pcDNA3.1-Shh, blank plasmid pcDNA3.1(-) or pmaxGFP respectively by Nucleofector(TM). The protein expression of Shh in MSC was detected by Western blot after 48 hours. RESULTS: Correct construction of pcDNA3.1-Shh was identified by the methods of restriction enzyme analysis and nucleotide sequence determination. The expression of green fluorescent protein (GFP) could be observed by fluorescence microscopy after 48 hours. The expression of Shh gene was detected by Western blot. But the MSC transfected with empty plasmid expression was not detected. CONCLUSIONS: Recombinant Eukaryotic expression plasmid pcDNA3.1-Shh is successfully detected in rat MSC. It may provide experimental rationales for the future gene therapy.
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Proteínas Hedgehog/genética , Células-Tronco Mesenquimais , Transfecção , Animais , Vetores Genéticos , Plasmídeos , Ratos , Ratos WistarRESUMO
Radiofrequency ablation (RFA) is a relatively new and effective therapeutic strategy for treating lung squamous cell carcinomas (LSCCs). However, RFA is rarely used in the clinic for LSCC which still suffers from a lack of effective comprehensive treatment strategies. In the present work, we investigate iDNMT, a novel small molecular inhibitor of DNMT1 with a unique structure. In clinical LSCC specimens, endogenous DNMT1 was positively associated with methylation rates of miR-27-3p's promoter. Moreover, endogenous DNMT1 was negatively correlated with miR-27-3p expression which targets PSEN-1, the catalytic subunit of γ-secretase, which mediates the cleavage and activation of the Notch pathway. We found that DNMT1 increased activation of the Notch pathway in clinical LSCC samples while downregulating miR-27-3p expression and hypermethylation of miR-27-3p's promoter. In addition of inhibiting activation of the Notch pathway by repressing methylation of the miR-27-3p promoter, treatment of LSCC cells with iDNMT1 also enhanced the sensitivity of LSCC tumor tissues to RFA treatment. These data suggest that iDNMT-induced inhibition of DNMT-1 enhances miR-27-3p expression in LSCC to inhibit activation of the Notch pathway. Furthermore, the combination of iDNMT and RFA may be a promising therapeutic strategy for LSCC.
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The NF-kappaB pathway regulates the expression of over 150 target genes, e.g., cytokines, chemokines, leukocyte adhesion molecules and inducible effector enzymes. Consequently, it plays a crucial role in innate and adaptive immune responses, inflammatory response, stress responses, apoptosis and so on. IkappaB kinase (IKK) is the key of this pathway, and it owns a special structure which consists of catalytic subunit and regulatory subunit. Naturally, the activation of IKK needs the interaction of the two subunits and phosphorylation by its upstream kinases. Actually, there are two methods of activation of the NF-kappaB pathway, and both of the methods need the IKK complex. Given to the crucial role of IKK, researchers have isolated and synthesized amounts of IKK inhibitors, and these provide a great convenience to develop novel anti-inflammatory and anti-tumor drugs.
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Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/metabolismo , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Ativação Enzimática , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Quinase I-kappa B/química , Quinase I-kappa B/fisiologia , Fosforilação , Transdução de SinaisRESUMO
OBJECTIVE: To analyze the cause of flexible open-loop anterior chamber intraocular lenses (AC-IOL) extraction and to evaluate the safety of these lenses implantation. METHODS: This retrospective study comprised 28 patients (28 eyes) who had received open-loop AC-IOL extraction from 1999 to 2009 in our hospital. Several factors of these patients were analyzed, including the type of AC-IOL, primary disease, the intraocular duration of AC-IOL, the cause of AC-IOL extraction and therapeutic result. RESULTS: All of the AC-IOL used were modern flexible open-loop AC-IOL. Twenty one patients were implanted AC-IOL because of ocular trauma; the average intraocular duration of the AC-IOL was (6.1 ± 3.1) years. In the causes of AC-IOL extraction, bullous keratopathy was the most common cause, accounted for 42.9% (12/28); secondary glaucoma, retinal detachment and lens dislocation accounted for 32.1% (9/28), 17.9% (5/28) and 7.1% (2/28), respectively. In the 12 cases with bullous keratopathy, 6 cases just received AC-IOL extraction and the others received penetrate corneal transplantation. Six cases with secondary glaucoma received AC-IOL extraction combined with trabeculectomy. CONCLUSIONS: Bullous keratopathy and secondary glaucoma are the two most common causes for open-loop AC-IOL extraction. The patients who will receive AC-IOL implantation need an adequate selection and must be followed properly.
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Câmara Anterior/cirurgia , Remoção de Dispositivo , Lentes Intraoculares/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Attributed graph clustering aims to discover node groups by utilizing both graph structure and node features. Recent studies mostly adopt graph neural networks to learn node embeddings, then apply traditional clustering methods to obtain clusters. However, they usually suffer from the following issues: (1) they adopt original graph structure which is unfavorable for clustering due to its noise and sparsity problems; (2) they mainly utilize non-clustering driven losses that cannot well capture the global cluster structure, thus the learned embeddings are not sufficient for the downstream clustering task. In this paper, we propose a spectral embedding network for attributed graph clustering (SENet), which improves graph structure by leveraging the information of shared neighbors, and learns node embeddings with the help of a spectral clustering loss. By combining the original graph structure and shared neighbor based similarity, both the first-order and second-order proximities are encoded into the improved graph structure, thus alleviating the noise and sparsity issues. To make the spectral loss well adapt to attributed graphs, we integrate both structure and feature information into kernel matrix via a higher-order graph convolution. Experiments on benchmark attributed graphs show that SENet achieves superior performance over state-of-the-art methods.