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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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The rapid detection of single nucleotide polymorphisms (SNPs) in the CYP2C19 gene is crucial for precise clopidogrel usage. Quantitative real-time polymerase chain reaction (qPCR), as a powerful amplification tool, has been widely employed for CYP2C19 SNPs detection. However, traditional qPCR suffers from long amplification times and high reagent consumption. To address these challenges, this work presents a microfluidic SNPs detection device based on on-chip qPCR. The device includes a rapid thermal cycling system, an optical detection system, a control system, and a complementary silicon-glass chip for CYP2C19 SNPs detection. Compared to commercial qPCR instruments that take 1 hour for testing, this device completes the test in just 15 minutes (40 PCR cycles). The resulting linearity is similar to that found using commercial qPCR instruments but with higher amplification efficiency. Additionally, compared with other silicon-based qPCR chips, this chip is constructed by using a convenient two-step method and offers low manufacturing costs, which potentially reduces single-test costs to an acceptable level. This makes our chip promising for point-of-care testing (POCT).
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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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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
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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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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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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The laminated metal materials are widely used in military, automobile and aerospace industries, but their dynamic response mechanical behavior needs to be further clarified, especially for materials with joint interface paralleling to the loading direction. The mechanical properties of TA2/Q345 (Titanium/Steel) laminated metal of this structure were studied by using the split Hopkinson pressure bar (SHPB). To shed light on the stress-state of a laminated metal with parallel structure, the relative non-uniformity of internal stress R(t) was analyzed. The mechanism of deformation compatibility of welding interface was discussed in detail. The current experiments demonstrate that in the strain rate range of 931-2250 s-1, the discrepancies of the internal stress in specimens are less than 5%, so the stress-state equilibrium hypothesis is satisfied during the effective loading time. Therefore, it is reasonable to believe that all stress-strain responses of the material are valid and reliable. Furthermore, the four deformation stages, i.e., the elastic stage, the plastic modulus compatible deformation stage, uniform plastic deformation stage and non-uniform plastic deformation stage, of the laminated metal with parallel structure were firstly proposed under the modulating action of the welding interface. The deformation stages are helpful for better utilization of laminated materials.
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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: Alzheimer's disease (AD) is a common degenerative brain disorder with limited therapeutic options. Curcumin (Cur) exhibits neuroprotective function in many diseases. We aimed to explore the role and mechanism of Cur in AD. MATERIALS AND METHODS: Firstly, we established AD mice by injecting amyloid-ß1-42 (Aß1-42) solution into the hippocampus. Then, the AD mice received 150 mg/kg/d Cur for 10 consecutive days. The Morris water maze test was conducted to evaluate the cognitive function of the mice by hidden platform training and probe trials. To assess the spatial memory of the mice, spontaneous alternation behavior, the number of crossing the novel arm and the time spent in the novel arm during the Y-maze test was recorded. Hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNAL) assay were performed to assess the pathological damage and apoptosis of brain tissues. The number of damaged neurons was inspected by Nissl staining. Immunohistochemical staining was then performed to detect Aß1-42 deposition. The levels of tumor necrosis factor-α (TNF-a), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in serum and hippocampus, the contents of super oxide dismutase (SOD) and malondialdehyde (MDA) in brain tissues were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), RelA (p65) protein expressions and Adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation were tested using Western blot. RESULTS: Cur not only improved cognitive function and spatial memory, but also alleviated the pathological damage and apoptosis of brain tissues for AD mice. Meanwhile, upon Cur treatment, the number of damaged neurons in AD mice was decreased, the level of Aß1-42 in AD mice was significantly decreased. Furthermore, the AD mice treated with Cur exhibited lower TNF-a, IL-6, IL-1ß and MDA levels and a higher SOD content. Besides, Cur also downregulated p65 expression and upregulated AMPK phosphorylation. CONCLUSION: Cur may improve AD via suppressing the inflammatory response, oxidative stress and activating the AMPK pathway, suggesting that Cur may be a potential drug for AD.
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Doença de Alzheimer , Curcumina , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeos beta-Amiloides/metabolismo , Interleucina-6/metabolismo , Interleucina-1beta/metabolismo , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo , Superóxido Dismutase/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Modelos Animais de DoençasRESUMO
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.
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Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos Transgênicos , Modelos Animais de DoençasRESUMO
van der Waals heterostructures are widely used in the field of photocatalysis due to the fact that their properties can be regulated via an external electric field, strain engineering, interface rotation, alloying, doping, etc. to promote the capacity of discrete photogenerated carriers. Herein, we fabricated an innovative heterostructure by piling monolayer GaN on isolated WSe2. Subsequently, a first principles calculation based on density functional theory was performed to verify the two-dimensional GaN/WSe2 heterostructure and explore its interface stability, electronic property, carrier mobility and photocatalytic performance. The results demonstrated that the GaN/WSe2 heterostructure has a direct Z-type band arrangement and possesses a bandgap of 1.66 eV. The built-in electric field is caused by the transfer of positive charge between the WSe2 layers to the GaN layer, directly leading to the segregation of photogenerated electron-hole pairs. The GaN/WSe2 heterostructure has high carrier mobility, which is conducive to the transmission of photogenerated carriers. Furthermore, the Gibbs free energy changes to a negative value and declines continuously during the water splitting reaction into oxygen without supplementary overpotential in a neural environment, satisfying the thermodynamic demands of water splitting. These findings verify the enhanced photocatalytic water splitting under visible light and can be used as the theoretical basis for the practical application of GaN/WSe2 heterostructures.
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BACKGROUND: The role of involved-field radiation therapy (IFRT) and intrathecal chemotherapy (IC) in leptomeningeal metastasis (LM) from solid tumors was gradually underestimated in the era of targeted therapy. This study was aimed to investigate the safety and effectiveness of concurrent IFRT and intrathecal methotrexate (MTX)/cytarabine (Ara-C) for LM, particularly for those who developed LM while receiving targeted therapy. MATERIALS AND METHODS: Enrolled patients were given induction IC first and then concurrent treatment, which consisted of IFRT (40 Gy total; 2 Gy/f) and IC (MTX 15 mg or Ara-C 50 mg, once per week). Primary endpoint was clinical response rate (RR). Secondary endpoints were safety and overall survival (OS). RESULTS: Fifty-three patients received induction intrathecal MTX (n = 27) or Ara-C (n = 26). Forty-two patients completed concurrent therapy. Total RR was 34% (18/53). The improvement rate of neurological symptoms and KPS scores were 72% (38/53) and 66% (35/53) respectively. Adverse events (AEs) rate was 28% (15/53). Eight patients (15%, 8/53) showed grade 3-4 AEs, including myelosuppression (n = 4) and radiculitis (n = 5). Median OS was 6.5 months (95% CI, 5.3-7.7 months). Median survival for 18 patients who had clinical response was 7.9 months (95% CI, 4.4-11.4 months), and 0.8 months (95% CI, 0.08-1.5 months) for 6 patients who had LM progression. The median survival in 22 patients who received prior targeted therapy was 6.3 months (95% CI, 4.5-8.1 months). CONCLUSION: Concurrent IFRT and intrathecal MTX or Ara-C was proved to be a feasible treatment option with an acceptable safety profile for LM from a common tumor entity.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metotrexato/efeitos adversos , Citarabina/efeitos adversosRESUMO
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
Ultrasound is a promising imaging method for scoliosis evaluation because it is radiation free and provide real-time images. However, it cannot provide bony details because ultrasound cannot penetrate the bony structure. Therefore, registration of real-time ultrasound images with the previous X-ray radiograph can help physicians understand the spinal deformity of patients. In this study, an improved free-from deformation registration method based on mutual registration and hierarchical adaptive grid (MRHA-FFD) was developed. The method first performed registration grid preprocessing and then optimized control points and conducted mutual registration. Finally, a Blur-aware Attention Network was adopted for image deblurring. The performance of each step was verified by ablation experiments. Comparison experiment between the proposed method and traditional registration methods was also conducted. The qualitative and quantitative results suggested that MRHA-FFD is a promising approach for registering spine ultrasound image and X-ray radiograph.
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Algoritmos , Escoliose , Humanos , Raios X , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Osso e Ossos , Imageamento Tridimensional/métodosRESUMO
The chinaberry yellow-banded longhorn beetle, Anoplophora horsfieldi Hope 1842 (Coleoptera: Cerambycidae) is an important pest on many economic tree species. In this study, the complete mitochondrial genome of A. horsfieldi was determined, which was 15,837 bp in length and contained 37 genes, including 13 protein-coding genes (PCGs), two rRNA, 22 tRNA genes, and a non-coding A + T-rich region. The phylogenetic analysis based on mitochondrial genomes showed that A. horsfieldi is sister to a clade formed by A. chinensis and A. glabripennis.
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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
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.
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Redes Neurais de Computação , NeurôniosRESUMO
DNA extraction, a vital pre-requisite for most biological studies, continues to be studied extensively. According to some studies, DNA shows a certain degree of absorbability on filter paper made of plant fiber-based adsorbent material. However, the principle underlying such specific adsorption as well as plant species associated with plant fiber-based adsorbents and optimized extraction conditions have not yet been studied. This study demonstrates the tight correlation between crystallinity and hygroscopicity in plant fiber-based adsorbents used for DNA extraction and proposes the concept of DNA adsorption on plant fiber-based adsorbents, for the first time. We also explored optimal extracting and eluting conditions and developed a novel plant fiber-based DNA extraction method that was quadruple times more powerful than current approaches. Starting with the screening of various types of earthed plant fiber-based adsorbents, we went on to mine new plant fiber-based adsorbents, bamboo paper and degreased cotton, and succeeded in increasing their efficiency of DNA extraction to 4.2 times than that of current approaches. We found a very strong correlation between the crystallinity and hygroscopicity of plant fiber-based adsorbents which showed efficiency for DNA extraction, and thus propose a principle that potentially governs such specific adsorption processes, in the hope that this information may guide related multidisciplinary research studies in the future. Nanodrop, electrophoresis and PCR were selected to demonstrate the quantity, quality, integrity and utility of the extracted DNA. Furthermore, crystallinity, hygroscopicity, pore size distribution and composition of plant fiber-based adsorbents were studied to explore their correlation in an attempt to understand the principle underlying this particular type of adsorption. The findings of this study may be further extended to the extraction of other types of nucleic acids with similar biochemical properties.
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Estruturas Vegetais , Molhabilidade , Adsorção , DNA de Plantas/genética , EletroforeseRESUMO
Objective: To investigate whether preoperative lateral anterior tibial subluxation (LATS) measured from magnetic resonance imaging (MRI) can influence tibial insertion and postoperative sagittal alignment after anterior cruciate ligament reconstructions (ACLRs). Methods: 84 patients who underwent single-bundle ACLRs were retrospectively investigated. Among them, 39 patients (LATS of <6â mm) 23 patients (LATS of ≥6â mm and <10â mm) and 22 patients (excessive LATS of ≥10â mm) were defined as group 1, 2 and 3, respectively. LATS, the position of graft insertion into tibia as ratio of anterior-posterior width (AP ratio) and the sagittal graft angle (SGA) were postoperatively assessed from MRI at 2-year follow-up. Following linear regression analyses were employed. Results: The group 3 exhibited the largest preoperative LATS and remained the most postoperative LATS. Moreover, the group 3 possessed the most posteriorly located tunnel insertion with the largest AP ratio and the most vertical graft orientation. Of all included patients, a moderate correlation was demonstrated between pre- and postoperative LATS (r = 0.635). A low correlation was observed between preoperative LATS and AP ratio (r = 0.300) and a moderate correlation was displayed between AP ratio and SGA (r = 0.656). Conclusion: For ACL injuries with excessive LATS (≥10 mm), most posteriorly located tibial insertion was found out, and worse sagittal alignment containing high residual LATS was associated with more vertical graft orientation following ACLRs.