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DNA extraction, playing an irreplaceable role in molecular biology as it is an essential step prior to various downstream biological analyses. Thus, the accuracy and reliability of downstream research outcomes depend largely on upstream DNA extraction methodology. However, with the advancement of downstream DNA detection techniques, the development of corresponding DNA extraction methods is lagging behind. The most innovative DNA extraction techniques are silica- or magnetic-based. Recent studies have demonstrated that plant fiber-based adsorbents (PF-BAs) have stronger DNA capturing ability than classic materials. Moreover, magnetic ionic liquid (MIL)-based DNA extraction has gathered attention lately, and extrachromosomal circular DNA (eccDNA), cell-free DNA (cfDNA), and microbial community DNA are current research hotspots. These require specific extraction methods, along with constant improvements in the way they are used. This review discusses the significance as well as the direction of innovation of DNA extraction methods to try to provide valuable references including current status and trends for DNA extraction.
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DNA , Líquidos Iônicos , Reprodutibilidade dos TestesRESUMO
Titanium oxide (TiO2) coated polyimide has broad application prospects under extreme conditions. In order to obtain a high-quality ultra-thin TiO2coating on polyimide by atomic layer deposition (ALD), the polyimide was activated byin situoxygen plasma. It was found that a large number of polar oxygen functional groups, such as carboxyl, were generated on the surface of the activated polyimide, which can significantly promote the preparation of TiO2coating by ALD. The nucleation and growth of TiO2were studied by x-ray photoelectron spectroscopy monitoring and scanning electron microscopy observation. On the polyimide activated by oxygen plasma, the size of TiO2nuclei decreased and the quantity of TiO2nuclei increased, resulting in the growth of a highly uniform and dense TiO2coating. This coating exhibited excellent resistance to atomic oxygen. When exposed to 3.5 × 1021atom cm-2atomic oxygen flux, the erosion yield of the polyimide coated with 100 ALD cycles of TiO2was as low as 3.0 × 10-25cm3/atom, which is one order less than that of the standard POLYIMIDE-ref Kapton®film.
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The polar channels formed by the curing of waterborne anticorrosive coatings compromise their water resistance, leading to coating degradation and metal corrosion. To enhance the anticorrosive performance of waterborne coatings, this study proposed a novel method of depositing ultrathin Al2O3films on the surface of waterborne epoxy coatings by atomic layer deposition, a technique that can modify the surface properties of polymer materials by depositing functional films. The Al2O3-modified coatings exhibited improved sealing and barrier properties by closing the polar channels and surface defects and cracks. The surface structure and morphology of the modified coatings were characterized by x-ray photoelectron spectroscopy and scanning electron microscopy. The hydrophilicity and corrosion resistance of the modified coatings were evaluated by water contact angle measurement, Tafel polarization curve, and electrochemical impedance spectroscopy. The results indicated that the water contact angle of the Al2O3-modified coating increased by 48° compared to the unmodified coating, and the protection efficiency of the modified coating reached 99.81%. The Al2O3-modified coating demonstrated high anticorrosive efficiency and potential applications for metal anticorrosion in harsh marine environments.
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Alzheimer's disease (AD), a prevalent cognitive disorder among the elderly, is frequently linked to the abnormal accumulation of myloid-ß (Aß), which is mainly as a result of neuronal death and inflammation. Diosmin, a flavonoid, is considered a potential drug for the treatment of AD. Our study aimed to uncover the molecular mechanism of diosmin in AD therapy. Here, rats were randomly divided into three groups: control, Aß25-35, and Aß25-35 + diosmin groups. AD model rats were induced by Aß25-35 intraventricular injection, meanwhile 50 mg/kg diosmin was orally administered for 6-week intervention. Morris water maze test assessed learning and memory abilities. Hippocampal neuronal damage was determined by HE, Nissl, and TUNEL staining. These assays indicate that diosmin improves cognitive dysfunction and reduces hippocampal neuronal loss and apoptosis. Western blot showed that diosmin reduced Bax (1.21 ± 0.12) and cleaved caspase-3 (1.27 ± 0.12) expression, and increased Bcl-2 (0.70 ± 0.06), p-PI3K (0.71 ± 0.08), and p-AKT (0.96 ± 0.10) in the hippocampus. ELISA indicated diosmin reduces IL-1ß, IL-6, and TNF-α levels, suggesting anti-inflammation effect. These results suggest that diosmin inhibits neuronal apoptosis and neuroinflammatory responses to improve cognitive dysfunction in AD rats, possibly related to upregulation of the PI3K/AKT pathway, providing a scientific basis for its use in AD treatment.
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BACKGROUND: Our study aimed to investigate the association between type D personality and adverse cardiac events in chinese patients after acute myocardial infarction (AMI). METHODS: Patients with AMI admitted to cardiac care unit (CCU) of China-Japan Friendship Hospital, Beijing, China between January 2016 and December 2017 were enrolled. 257 patients completed psychological questionnaires at enrollment. Type D personality was assessed with 14-item Type D Scale-14 (DS14). Anxiety and depression were quantified using Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression analysis was used to determine the independent predictors of in-hospital major adverse cardiac events (MACEs), while cox regression analysis was used to evaluate post-discharge endpoints. RESULTS: 54 patients (21%) were classified as Type D personality defined by the combination of a negative affectivity (NA) score ≥ 10 and a social inhibition (SI) score ≥ 10 on the DS14. Patients with Type D personality displayed significantly higher scores of anxiety (7.4 ± 3.1 vs. 4.2 ± 3.1, p < .001) and depression (7.2 ± 3.8 vs. 4.0 ± 3.4, p < .001). AMI patients with Type D personality had higher prevalence rates of anxiety (χ2 = 30.095, P < .001) and depression (χ2 = 27.082, P < .001). Type D group also displayed a significantly higher level of blood lipoprotein(a) (177.2 ± 200.7 vs. 118.1 ± 255.7 mg/L, P = .048). The incidence of in-hospital MACEs was higher in type D than in non-Type D patients (24.1% vs. 11.3%, χ2 = 5.751, P = .026). Multivariable logistic regression showed three significant independent predictors of in-hospital MACEs: age [odds ratio(OR) = 1.055; 95%CI 1.016-1.095, p = .004], type-D personality(OR 3.332; 95% CI 1.149-9.661, p = .014) and killip classification(OR 2.275, 95% CI 1.506-3.437, p < .001). The average follow-up time was 31 (23-37.5) months. Type D patients had higher incidences of post-discharge events(23.1% vs. 11.5%, p = .032). In the analysis of post-discharge events by Cox regression, χ2 of the Cox regression equation was 16.795 (P = .032). Smoking (HR 2.602; 95% CI1.266-5.347, p = .009) and type-D personality (HR 2.265; 95%CI 1.028-4.988, p = .042) were independent predictors of long-term cardiac events. Kaplan-Meier curves showed significant difference in event-free survival between type D and non-type D group (p = .043). CONCLUSIONS: Type D personality is an independent predictor of in-hospital and post-discharge cardiac events after AMI in Chinese patients.
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Infarto do Miocárdio , Personalidade Tipo D , Humanos , Assistência ao Convalescente , População do Leste Asiático , Alta do Paciente , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologiaRESUMO
BACKGROUND: ACAN heterozygous mutations can cause short stature in patients with or without advanced bone age and have recently attracted researchers' attention. Growth hormone can be used to treat short stature induced by ACAN mutations; however, few studies have focused on the underlying mechanism of this treatment. METHODS: Four patients with new mutations were reported based on clinical data and genetic tests. We investigated the expression and Gene Ontology biological process enrichment of ACAN and GH pathways based on GTEx databases through bioinformatics analyses. The effect of ACAN on the growth hormone response evaluated in ATDC5 cells with a growth hormone stimulation test. RESULTS: Four mutations were reported in this study: c.619C > A, c.1967A > G, c.1888G > A, and c.1308_1309del. All patients' heights were under -2.5 SD, with one had advanced bone age, and two had GH deficiency. Two individuals received growth hormone therapy acquired variable levels of height SD score improvement. ACAN and the GH pathway were strongly associated; ACAN does not affect GHR but regulates the response to GH. Downregulating ACAN inhibited ATDC5 cell proliferation induced by GH. CONCLUSION: ACAN is associated with the GH pathway, revealing the potential mechanism underlying GH-targeted treatment for ACAN mutation-induced short stature. GH-promoting therapies may increase patients' heights.
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Agrecanas , Nanismo , Hormônio do Crescimento Humano , Humanos , Agrecanas/genética , Regulação para Baixo , Nanismo/genética , Testes Genéticos , Hormônio do Crescimento/genética , Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/uso terapêutico , MutaçãoRESUMO
Polymeric materials, including polyethylene terephthalate (PET), are widely used in various fields because of their beneficial properties. Functional films are deposited on these materials through different approaches, such as plasma-enhanced atomic layer deposition (PEALD), to enhance their performance and prolong their life span. However, the inert and thermally fragile nature of most polymers hinders deposition. We developed a strategy for the PEALD of nanoscale Al2O3films on PET substrates. First, a PET substrate is subjected to alkali treatment, which gives it basic hydrophilicity for the subsequent dopamine modification. After 24 h of dopamine deposition, the substrate shows adequate active sites (phenolic hydroxyl groups), which can chemisorb large amounts of precursor during the initial deposition. The island growth mode was observed during the PEALD processes. We analyzed the detailed chemical components of Al2O3on alkali-treated PET and dopamine-modified PET. After 100 cycles of deposition, the Al2O3films on both samples contained much hydrogen. Benefitting from the more active sites, we observed more continuous Al2O3film on dopamine-modified PET, which exhibited excellent water vapor blocking performance. Our findings suggest that dopamine could act as a 'bridge' between polymers and PEALD functional films.
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BACKGROUND: In the present study, we attempted to develop and validate a participatory competency model for medical workers and then evaluate the current status of competency characteristics of Chinese medical workers. METHODS: The competency model was constructed in a multistage process, including literature review, expert consultation, critical incident and focus group interview. A pilot study was conducted to refine the initial model among 90 participators and the viability and reliability were evaluated by a questionnaire survey among 121 medical workers. Then, the current status of competency characteristics was measured based on the final version of competency model. RESULTS: In the pilot study, ten questionnaires were dropped for the poor quality and thus the eligible rate was 92% (138/150). KMO value was 0.785 and Bartlett test showed that the χ2 = 6464.546 (df = 903) and p value < 0.001. Then, 10 items with double loading and factor loading < 0.4 were deleted. Finally, 33 items were retained with the lowest factor loading value of 0.465. The validity and reliability of competency model were determined with Cronbach's α coefficient of 0.975 and ICC value of 0.933. Finally, a revised competency model with 5 dimensions and 31 items was obtained. The overall competencies of current medical workers were in a high level, except for emergency knowledge related competencies. Age was an independent factor affecting the competencies. CONCLUSIONS: Our competency model was a reliable and validated tool for assessing the competences of medical staffs against public health emergencies, and the overall competencies of current medical workers in China were in a high level, except for emergency knowledge related competencies.
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Competência Clínica , Saúde Pública , China , Humanos , Corpo Clínico , Projetos Piloto , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Nanoporous materials are widely explored as efficient adsorbents for the storage of gases and liquids as well as for effective low-dielectric materials in large-scale integrated circuits. These applications require fast heat transfer, while most nanoporous substances are thermal insulators. Here, the oriented growth of micrometer-sized single-crystal covalent organic frameworks (COFs) ribbons with nanoporous structures at an air-water interface is presented. The obtained COFs ribbons are interconnected into a continuous and purely crystalline thin film. Due to the robust connectivity among the COFs ribbons, the entire film can be easily transferred and reliably contacted with target supports. The measured thermal conductivity amounts to â¼5.31 ± 0.37 W m-1 K-1 at 305 K, which is so far the highest value for nanoporous materials. These findings provide a methodology to grow and assemble single-crystal COFs into large area ensembles for the exploration of functional properties and potentially lead to new devices with COFs thin films where both porosity and thermal conductivity are desired.
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Previous studies have demonstrated that miR-10b-3p is significantly downregulated in rats after cerebral ischemia injury, and this study aimed to investigate the effect of miR-10b-3p in cerebral ischemia/reperfusion (I/R) injury. The oxygen-glucose deprivation (OGD) induced SH-SY5Y cell model and middle cerebral artery occlusion model (MCAO) rats were constructed to investigate the role of miR-10b-3p and underline the regulatory mechanism of miR-10b-3p/PDCD5 axis in cerebral I/R injury. The expression of miR-10b-3p and PDCD5 was evaluated by qRT-PCR and Western blot. The binding relationship between miR-10b-3p and PDCD5 was determined by bioinformatic analysis and luciferase reporter assay. Cell proliferation was evaluated by MTT assay and Edu staining assay. The apoptosis was assessed by TUNEL staining assay and flow cytometry. MiR-10b-3p was significantly downregulated and PDCD5 was upregulated both in OGD/R induced SH-SY5Y cells and the brain tissues of MCAO/R rats. Luciferase reporter assay determined that miR-10b-3p could directly bind to the 3' UTR of PDCD5 and negatively regulate its expression. MiR-10b-3p overexpression could efficiently inhibit cell viability and proliferation, induce apoptosis of OGD/R-induced SH-SY5Y cells in vitro, and attenuate cerebral I/R injury of MCAO rats in vivo. Silencing of PDCD5 showed similar effect to miR-10b-3p mimics, while PDCD5 overexpression significantly reversed the protective effects of miR-10b-3p mimics on cerebral I/R injury. In summary, our results revealed that miR-10b-3p alleviated cerebral I/R injury partly through targeting PDCD5 and indicated that miR-10b-3p might be a potential target for ischemic stroke.
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Proteínas Reguladoras de Apoptose/metabolismo , Isquemia Encefálica , MicroRNAs , Traumatismo por Reperfusão , Animais , Apoptose/genética , Isquemia Encefálica/genética , Sobrevivência Celular , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismoRESUMO
Tuning the electrical transport behavior and reducing the Schottky barrier height of nanoelectronic devices remain a great challenge. To solve this issue, the electronic properties and Schottky barrier of the graphene/WSe2 heterostructure are investigated by the first-principles method under out-of-plane strain and an electric field. Our results show that the WSe2 monolayer and graphene could form a stable van der Waals heterostructure and the intrinsic electronic properties are well preserved. Furthermore, a transformation of a Schottky contact from the n-type to p-type occurs at d = 3.87 Å and E = +0.06 V Å-1. In addition, an ohmic contact is formed with E = -0.50, ±0.60 V Å-1. Lastly, the effective masses of electrons and holes are calculated to be 0.057m0 and -0.055m0 at the equilibrium state, respectively, indicating that the heterostructure has a high carrier mobility. Our research will provide promising approaches for the future design and development of graphene/WSe2 nano-field effect transistors.
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BACKGROUND: Electrocardiogram (ECG) is widely used to screen cardiac diseases. To date, no large population study has provided estimates of the prevalences of ECG findings in China. We aim to investigate the prevalences and associated factors of ECG abnormalities in a general population of Chinese adults. METHODS: ECG data were obtained from 34,965 participants in the 2007-2008 China National Diabetes and Metabolic Disorders Study. ECG abnormalities were classified according to the Minnesota coding (MC) criteria. Prevalences of variant ECG abnormalities were calculated. The associations between ECG abnormalities and gender, age and other risk factors for cardiovascular diseases (CVD) were analyzed by multivariate logistic regression test. RESULTS: The prevalences of major arrhythmias were 1.70, 2.37 and 1.04% in the whole population, men and women, respectively. Atrial fibrillation/flutter was found in 0.35% of men and 0.20% of women. ST depression and T abnormalities accounted for 10.96, 7.54 and 14.32% in the whole population, men and women, respectively. Independent of gender and other CVD risk factors, older age significantly increased the odds of having atrial fibrillation/flutter, complete left bundle branch block, complete right bundle branch block, sinus tachycardia, atrial/junctional/ventricular premature beats, ST depression and T abnormalities, tall R wave left, left/right atrial hypertrophy, left axis deviation and low voltage. Hypertension, overweight, obesity and hypercholesterolemia all independently increased the odds of having ST depression and T abnormalities. History of cardiovascular/cerebrovascular diseases was positively associated with major arrhythmias, ST depression and T abnormalities and tall R wave left. CONCLUSIONS: This study provides estimates of the prevalences of ECG findings in a large population of Chinese adults. Gender, age, CVD risk factors and history of cardiovascular/cerebrovascular diseases were significantly associated with ECG abnormalities.
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Arritmias Cardíacas/diagnóstico , Eletrocardiografia , Adulto , Idoso , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , China/epidemiologia , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Adulto JovemRESUMO
BACKGROUND Different blood pressure targets should be formulated for different groups of people. This study aimed to assess the effectiveness of intensive blood control in improving the carotid morphology and hemodynamics in Chinese patients with hyperhomocysteinemia-type hypertension and high risk of stroke. MATERIAL AND METHODS Chinese hypertensive patients with high risk of stroke were randomized to intensive (n=187) and standard (n=192; controls) blood pressure management groups. Systolic blood pressure (SBP) targets were 100< SBP ≤120 and 120< SBP ≤140 mmHg, respectively. All patients received folic acid 0.8 mg/d and atorvastatin 20 mg/d. Calcium antagonist was first used. If blood pressure was still uncontrolled, angiotensin-converting enzyme inhibitor or angiotensin receptor antagonist, ß-receptor blocker, and diuretics were added successively. Follow-up was 12 months. Carotid features, hemodynamics, and adverse events were examined. RESULTS There were no differences in sex, age, body mass index, blood lipids, baseline carotid parameters, and histories of smoking, diabetes, statin use, and stroke between the 2 groups. Carotid plaques after 12 months of treatment were 19.4±2.1 and 23.6±3.1 cm² for the intensive and control groups, respectively (P=0.038). Plaque scores were lower in the intensive group (1.75±0.52 vs. 2.45±0.47, P=0.023). Compared with controls, intensive management resulted in relatively higher Vd and significantly lower Vs/Vd, PI, and RI (all P<0.05). Major adverse events such as hypotension (n=5 (2.7%) vs. 3 (1.6%), P=0.020) and dizziness (n=20 (10.7%) vs. 16 (8.3%), P=0.041) were more frequent in the intensive group. CONCLUSIONS Intensive blood pressure management could be beneficial for Chinese patients with hyperhomocysteinemia-type hypertension and high risk of stroke.
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Pressão Sanguínea/efeitos dos fármacos , Hiper-Homocisteinemia/tratamento farmacológico , Hipertensão/fisiopatologia , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/uso terapêutico , Povo Asiático , Determinação da Pressão Arterial , Bloqueadores dos Canais de Cálcio/farmacologia , Artérias Carótidas/fisiologia , China , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hiper-Homocisteinemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Acidente Vascular Cerebral/fisiopatologiaRESUMO
OBJECTIVE: B-line imaging by lung ultrasound (LUS) is a new tool for evaluating subclinical pulmonary congestion. The aim of this study was to explore the prognostic value of B-line number at admission in predicting symptomatic heart failure (HF) during hospitalization in acute anterior wall STEMI patients. METHODS: This was a prospective cohort study which consecutively enrolled 96 anterior wall STEMI patients without dyspnea at admission. Pulmonary auscultation, NT-proBNP test, LUS, and echocardiography were performed within 5 hours after primary PCI. Rale occurrence, plasma NT-proBNP levels, B-line number, LVEF, E/e' were recorded, and their predictive value for HF in-hospital was analyzed. RESULTS: A total of 19 patients developed symptomatic HF. Median B-line number, NT-proBNP levels, and E/e' in the HF group were higher than those of the nonheart-failure (NHF) group (P < 0.001) while LVEF was lower (P = 0.002). There was no statistical difference in rale occurrence between the two groups. Multivariate logistic regression demonstrated that B-lines, E/e', and NT-proBNP independently predicted HF during hospitalization. According to the area under the ROC curve, the strongest predictor is B-lines (0.972), followed by NT-proBNP (0.936) and E/e' (0.928), and combining the three indicators was better than any single parameter (P = 0.048). B-line cutoff ≥18 could well predict HF event with specificity and sensitivity of 94.7% and 94.8%, respectively. CONCLUSION: Subclinical pulmonary congestion reflected by B-lines can independently predict symptomatic HF during hospitalization in patients with anterior wall STEMI, LUS will act as a complementary tool for evaluating cardiac function.
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Ecocardiografia/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Pulmão/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Idoso , Biomarcadores/sangue , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Sensibilidade e EspecificidadeRESUMO
The safety of two kinds of post-marketing enterovirus 71 (EV71) vaccine in China was evaluated in this study. Fourteen vaccination clinics were randomly assigned in a 1:1 ratio, and both children in two groups were administered according to a two-dose schedule (on a 0 and 28 day schedule). Written informed consent was obtained, and recipients in this study were observed for 30 min after inoculation in the clinic, and then followed via phone or on-site follow-up at day 3 and 30. No severe EV71-associated adverse event was reported. No significant difference was noticed between Group Sinovac and Group CAMS (χz = 0.346, p = 0.556). There was no significant difference in the occurrence of adverse events among recipients aged less than 24 months; however, the proportion of adverse events was higher in Group CAMS than in Group Sinovac among the subjects aged 24-35 months (5.3% vs. 2.5%, p < 0.001). The two kinds of EV71 vaccines showed satisfactory safety. Adverse events after vaccination were normal and acceptable.
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Enterovirus Humano A , Vacinas Virais/efeitos adversos , Pré-Escolar , China , Humanos , Lactente , Vacinas de Produtos Inativados/efeitos adversosRESUMO
BACKGROUND: Crocin has a good prospect in the treatment of Alzheimer's disease (AD), but the mechanisms underlying its neuroprotective effects remain elusive. This study aimed to investigate the neuroprotective effects of Crocin and its underlying mechanisms in AD. METHODS: AD mice were set up by injecting Aß25-35 solution into the hippocampus. Then, the AD mice were injected intraperitoneally with 40 mg/kg/day of Crocin for 14 days. Following the completion of Crocin treatment, an open-field test, Y-maze test and Morris water maze test were conducted to evaluate the impact of Crocin on spatial learning and memory deficiency in mice. The effects of Crocin on hippocampal neuron injury, proinflammatory cytokine expressions (IL-1ß, IL-6, and TNF-α), and PI3K/AKT signaling-related protein expressions were measured using hematoxylin and eosin staining, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) experiments, respectively. RESULTS: Crocin attenuated Aß25-35-induced spatial learning and memory deficiency and hippocampal neuron injury. Furthermore, the Western blot and qRT-PCR results showed that Crocin effectively suppressed inflammation and activated the PI3K/AKT pathway in Aß25-35-induced mice. CONCLUSION: Crocin restrained neuroinflammation via the activation of the PI3K/AKT pathway, thereby ameliorating the cognitive dysfunction of AD mice.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Carotenoides , Disfunção Cognitiva , Hipocampo , Doenças Neuroinflamatórias , Fármacos Neuroprotetores , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Carotenoides/farmacologia , Carotenoides/administração & dosagem , Camundongos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Peptídeos beta-Amiloides/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Modelos Animais de Doenças , Fragmentos de Peptídeos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismoRESUMO
Background: Autoimmune Poly-endocrine Syndrome Type 1 (APS-1), also known as autoimmune poly-endocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a single-gene hereditary disorder usually characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenocortical insufficiency. This syndrome is very rare in China. Methods: For our reported patient, we employed clinical and laboratory examinations along with genetic identification. For previously reported cases, we summarized findings based on meta-analysis principles. To investigate the AIRE gene's role in disease, we utilized bioinformatics analysis with existing databases and R language processing. Results: Nucleotide sequence analysis revealed two novel homozygous missense mutations (c.74C > G; c.1612C > T) in the patient's AIRE gene, confirming APS-1 diagnosis. The 3D structure of these mutation sites was described for the first time, showing that altered side chains could affect AIRE protein function. We analyzed 16 genetically diagnosed APS-1 Chinese patients, summarized the AIRE genetic spectrum, and found that exons 1, 2, 3, and 5 were most commonly affected. Hypoparathyroidism and adrenal insufficiency were the most common clinical manifestations (56%-93%), followed by hypothyroidism (31.25%), hypogonadism (12.5%), type 2 diabetes (6.25%), and type 1 diabetes (6.25%). Bioinformatics analysis indicated that AIRE mutations cause antigen presentation abnormalities in immune cells, leading to excessive endogenous and reduced exogenous antigen presentation. Conclusions: Our study summarized the clinical features of APS-1 caused by AIRE gene mutations and explored underlying mechanisms. For some patients, the prophylactic use of antimicrobial agents may be beneficial. These findings guide early genetic screening and inform potential research directions for treatment strategies.
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A Q345 steel butt-welded joint was manufactured using laser-arc hybrid welding (LAHW) technology, and its microstructure, microhardness, and residual stress (RS) distribution were measured. Using ABAQUS software, a sequentially coupled thermo-metallurgical-mechanical finite element method was employed to model the welding RS distribution in the LAHW joint made of Q345 steel. The effects of solid-state phase transformation (SSPT) and transverse restraint on the welding RS distribution were explored. The results show that a large number of martensite phase transformations occurred in the fusion zone and heat-affected zone of the LAHW joint. Furthermore, the SSPT had a significant effect on the magnitude and distribution of RS in the LAHW joint made of Q345 steel, which must be taken into account in numerical simulations. Transverse restraints markedly increased the transverse RS on the upper surface, with a comparatively minor impact on the longitudinal RS distribution. After the transverse restraint was released, both the longitudinal and transverse RS distributions in the LAHW joint reverted to a level akin to that of the welded joint under free conditions.
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With the introduction of neuron coverage as a testing criterion for deep neural networks (DNNs), covering more neurons to detect more internal logic of DNNs became the main goal of many research studies. While some works had made progress, some new challenges for testing methods based on neuron coverage had been proposed, mainly as establishing better neuron selection and activation strategies influenced not only obtaining higher neuron coverage, but also more testing efficiency, validating testing results automatically, labeling generated test cases to extricate manual work, and so on. In this article, we put forward Test4Deep, an effective white-box testing DNN approach based on neuron coverage. It is based on a differential testing framework to automatically verify inconsistent DNNs' behavior. We designed a strategy that can track inactive neurons and constantly triggered them in each iteration to maximize neuron coverage. Furthermore, we devised an optimization function that guided the DNN under testing to deviate predictions between the original input and generated test data and dominated unobservable generation perturbations to avoid manually checking test oracles. We conducted comparative experiments with two state-of-the-art white-box testing methods DLFuzz and DeepXplore. Empirical results on three popular datasets with nine DNNs demonstrated that compared to DLFuzz and DeepXplore, Test4Deep, on average, exceeded by 32.87% and 35.69% in neuron coverage, while reducing 58.37% and 53.24% testing time, respectively. In the meantime, Test4Deep also produced 58.37% and 53.24% more test cases with 23.81% and 98.40% fewer perturbations. Even compared with the two highest neuron coverage strategies of DLFuzz, Test4Deep still enhanced neuron coverage by 4.34% and 23.23% and achieved 94.48% and 85.67% higher generation time efficiency. Furthermore, Test4Deep could improve the accuracy and robustness of DNNs by merging generated test cases and retraining.
Assuntos
Redes Neurais de Computação , NeurôniosRESUMO
Alzheimer's disease (AD) is the most common form of dementia, and ginsenoside Rg2 (Rg2) is proven to inhibit AD's progression. This study investigates the potential benefits of Rg2 treatment on 3xTg-AD mice. Following 6 weeks of gavage treatment, Rg2-treated 3xTg-AD mice exhibited improved spatial recognition memory behaviors, regional cerebral blood flow, and histopathological injury of the hippocampus, which were observed through a Y-maze test, laser Doppler flowmetry, and hematoxylin-eosin staining. Additionally, Rg2 treatment caused a decrease in the levels of amyloid beta 25-35, TNF-α, IL-1ß, and IL-6, as measured by enzyme-linked immunosorbent assay, as well as a reduction in mRNA levels of IL-1ß and IL-6 in 3xTg-AD mouse brains using quantitative real-time PCR. In particular, NeuN and CD31 levels were inhibited and GFAP level was elevated in 3xTg-AD mice that were observed through immunofluorescence, and these levels were all antagonized by Rg2, suggesting the effects of Rg2 on neurovascular damage, astrocyte activation, and neuronal loss. Furthermore, Western blot and qRT-PCR assays showed that Rg2 blocked the expression of ICAM-1 and VCAM-1 in 3xTg-AD mice. By Western blot, the ratios of p-ERK/ERK and p-MAPK/MAPK in 3xTg-AD mice were upregulated by Rg2 treatment, suggesting the neuroprotective effects of Rg2 may be related to the MAPK-ERK pathway. In summary, this study demonstrated the potential of Rg2 to improve AD and provided a scientific basis for research on the biological mechanism of AD and the development of Rg2.