A graphene oxide-assisted protein immobilization paper-tip immunosensor with smartphone and naked eye readout for the detection of okadaic acid.

BACKGROUND: Okadaic acid (OA), as a diarrhetic shellfish poisoning, can increase the risk of acute carcinogenic or teratogenic effects for the ingestion of OA contaminated shellfish. At present, much effort has been made to graft immunoassay onto a paper substrate to make paper-based sensors for rapid and simple detection of shellfish toxin. However, the complicated washing steps and low protein fixation efficiency on the paper substrate need to be further addressed. RESULTS: A novel paper-tip immunosensor for detecting OA was developed combined with smartphone and naked eye readout. The trapezoid paper tip was consisted of quantitative and qualitative detection zones. To improve the OA antigen immobilization efficiency on the paper substrate, graphene oxide (GO)-assisted protein immobilization method was introduced. Meanwhile, Au nanoparticles composite probe combined with the lateral flow washing was developed to simplify the washing step. The OA antigen-immobilized zone, as the detection zone Ⅰ, was used for quantitative assay by smartphone imaging. The paper-tip front, as the detection zone Ⅱ, which could qualitatively differentiate OA pollution level within 45 min using the naked eye. The competitive immunoassay on the paper tip exhibited a wide linear range for detecting OA (0.02-50 ng∙mL-1) with low detection limit of 0.02 ng∙mL-1. The recovery of OA in spiked shellfish samples was in the range of 90.3 %-113.%. SIGNIFICANCE: These results demonstrated that the proposed paper-tip immunosensor could provide a simple, low-cost and high-sensitivity test for OA detection without the need for additional large-scale equipment or expertise. We anticipate that this paper-tip immunosensor will be a flexible and versatile tool for on-site detecting the pollution of marine products.

Discriminative feature analysis of dairy products based on machine learning algorithms and Raman spectroscopy.

Discriminant analysis of similar food samples is an important aspect of achieving food quality control. The effective combination of Raman spectroscopy and machine learning algorithms has become an extremely attractive approach to develop intelligent discrimination techniques. Feature spectral analysis can help researchers gain a deeper understanding of the data patterns in food quality discrimination. Herein, this work takes the discrimination of three brands of dairy products as an example to investigate the Raman spectral feature based on the support vector machines (SVM), extreme learning machines (ELM) and convolutional neural network (CNN) algorithms. The results show that there are certain differences in the optimal spectral feature interval corresponding to different machine learning algorithms. Selecting the appropriate spectral feature interval can maintain high recognition accuracy and improve the computational efficiency of the algorithm. For example, the SVM algorithm has a recognition accuracy of 100% in the 890-980 cm-1, 1410-1500 cm-1 fusion spectral range, which takes about 200 s. The ELM algorithm also has a recognition accuracy of 100% in the 890-980 cm-1, 1410-1500 cm-1 fusion spectral range, which takes less than 0.3 s. The CNN algorithm has a recognition accuracy of 100% in the 890-980 cm-1, 1050-1180 cm-1, 1410-1500 cm-1 fusion spectral range, which takes about 80 s. In addition, by analyzing the distribution of spectral feature intervals based on Euclidean distance, the distribution of experimental samples based on feature spectra is visually displayed. Through the spectral feature analysis process of similar samples, a set of analysis strategies is provided to deeply reveal the data foundation of classification algorithms, which can provide reference for the analysis of relevant discriminative research patterns.

A capillary-based centrifugal indicator equipped with in situ pathogenic bacteria culture for fast antimicrobial susceptibility testing.

Antimicrobial resistance has become a major global health threat due to the misuse and overuse of antibiotics. Rapid, affordable, and high-efficiency antimicrobial susceptibility testing (AST) is among the effective means to solve this problem. Herein, we developed a capillary-based centrifugal indicator (CBCI) equipped with an in situ culture of pathogenic bacteria for fast AST. The bacterial incubation and growth were performed by macro-incubation, which seamlessly integrated the capillary indicator. Through simple centrifugation, all the bacterial cells were confined at the nanoliter-level capillary column. The packed capillary column height could linearly reflect the bacterial count, and the minimum inhibitory concentration (MIC) was determined based on the difference in the column height between the drug-added groups and the control group. The AST results could easily be determined by the naked eye or smartphone imaging. Thus, the CBCI realized the combination of macro-bacterial incubation and early micro assessment, which accelerated the phenotypic AST without complex microscopic counting or fluorescent labelling. The whole operation process was simple and easy to use. AST results could be determined for E. coli ATCC strains within 3.5 h, and the output results for clinical samples were consistent with the hospital reports. We expect this AST platform to become a useful tool in limiting antimicrobial resistance, especially in remote/resource-limited areas or in underdeveloped countries.

Designing of a functional paper-tip substrate for sensitive surface-enhanced Raman spectroscopy (SERS) detection.

A simple and flexible fabrication method of paper SERS substrate was developed by nanoparticles (NPs) droplet self-assembly at the paper tip with a temperature gradient (PTTG). We turned the drawback of the coffee ring effect into an effective way of preparing paper SERS substrate. When the NPs droplets were continuously dripped onto the PTTG, NPs were densely and uniformly distributed at the paper-tip front based on the combination of gravity and the coffee ring effect, which could achieve 91.2-fold improvement of SERS performance compared to a flat filter paper. Meanwhile, the analytes could also be enriched at the paper-tip front, which could achieve 9.3-fold signal enhancement compared to the paper-tip tail. Thus, the PTTG realized an excellent signal amplification for SERS detection. The paper-tip SERS substrate combined with a portable Raman spectrometer yielded an excellent analytical enhancement factor of 1.15 × 105 with the detection limit of 10 nM Rhodamine 6G (R6G). The whole fabrication procedure was completed within 2 h, and the paper-tip substrate showed a satisfactory substrate-to-substrate reproducibility with a relative standard deviation (RSD) of 5.13% (n = 10). It was successfully applied for quantitatively detecting real samples of oxytetracycline and malachite green with recoveries of 83.84-105.25% (n = 3). Meanwhile, we further evaluated the SERS performance of the PTTG using a laboratory-based Raman spectrometer, and it could realize the detection as low as 10 pM R6G. The proposed paper-tip substrate would offer a promising potential application for the on-site SERS analysis of food safety and environmental health.

Integrated Microfluidic Chip for Rapid Antimicrobial Susceptibility Testing Directly from Positive Blood Cultures.

Rapid and accurate antimicrobial prescriptions are critical for bloodstream infection (BSI) patients, as they can guide drug use and decrease mortality significantly. The traditional antimicrobial susceptibility testing (AST) for BSI is time-consuming and tedious, taking 2-3 days. Avoiding lengthy monoclonal cultures and shortening the drug sensitivity incubation time are keys to accelerating the AST. Here, we introduced a bacteria separation integrated AST (BSI-AST) chip, which could extract bacteria directly from positive blood cultures (PBCs) within 10 min and quickly give susceptibility information within 3 h. The integrated chip includes a bacteria separation chamber, multiple AST chambers, and connection channels. The separator gel was first preloaded into the bacteria separation chamber, enabling the swift separation of bacteria cells from PBCs through on-chip centrifugation. Then, the bacteria suspension was distributed in the AST chambers with preloaded antibiotics through a quick vacuum-assisted aliquoting strategy. Through centrifuge-assisted on-chip enrichment, detectable growth of the phenotype under different antibiotics could be easily observed in the taper tips of AST chambers within a few hours. As a proof of concept, direct AST from artificial PBCs with Escherichia coli against 18 antibiotics was performed on the BSI-AST chip, and the whole process from bacteria extraction to AST result output was less than 3.5 h. Moreover, the integrated chip was successfully applied to the diagnosis of clinical PBCs, showing 93.3% categorical agreement with clinical standard methods. The reliable and fast pathogen characterization of the integrated chip suggested its great potential application in clinical diagnosis.

Mechanical rotational chair-assisted multiple canalith repositioning procedures for benign paroxysmal positional vertigo: enhanced vertigo relief, comparable adverse effects, and decreased incidence of residual dizziness.

Objectives: This retrospective study aimed to assess the effectiveness and adverse effects of mechanical rotational chair-assisted multiple canalith repositioning procedures (CRPs) to treat benign paroxysmal positional vertigo (BPPV). Materials and methods: A retrospective analysis of 1,273 BPPV patients was conducted, with 241 patients included in the final study. The participants diagnosed with BPPV, unresolved by a single previous CRP, were categorized into either the single or multiple CRP groups. In both groups, on days 1, 4, and 7 after the initial treatment, the participants were re-evaluated after a single CRP; if positional vertigo was resolved, the treatment was regarded as successful. The remission rate, adverse effects (such as canal switch (CS), falls, and vomiting), residual dizziness (RD) rate, and RD duration were compared between the two groups. Results: The resolution rates for the single and multiple CRP groups were significantly different on days 1 and 4 (55.7% vs. 85.1%, 75.5% vs. 91.9%; P < 0.05) but not on day 7 (93.3% vs. 94.8%; P > 0.05). There were no significant differences between the single and multiple CRP groups in terms of CS and falls (3.8% vs. 5.2%, 10.3% vs. 8.9%; P > 0.05). However, there was a significant difference in the incidence of vomiting (6.6% vs. 14.8%; P < 0.05). RD such as head heaviness, imbalance, and non-specific dizziness is more common in the single CRP group than in the multiple CRP group (34.9% vs. 20.7%, 42.5% vs. 26.7%, 47.2% vs. 32.6%; P < 0.05). The incidence and duration of RD were notably diminished in the group undergoing multiple CRPs compared to the single CRP group, with incidence rates of 41.5% and 57.5%, respectively (P < 0.05). Conclusion: For patients with BPPV, multiple CRPs offer greater benefits than a single CRP.

Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia: A case report.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of neurogenetic diseases of the corticospinal tract, accompanied by distinct spasticity and weakness of the lower extremities. Mutations in the spastic paraplegia type 4 (SPG4) gene, encoding the spastin protein, are the major cause of the disease. This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene. CASE SUMMARY: A 44-year-old male was admitted to our hospital for long-term right lower limb weakness, leg stiffness, and unstable walking. His symptoms gradually worsened, while no obvious muscle atrophy in the lower limbs was found. Neurological examinations revealed that the muscle strength of the lower limbs was normal, and knee reflex hyperreflexia and bilateral positive Babinski signs were detected. Members of his family also had the same symptoms. Using mutation analysis, a novel heterozygous duplication mutation, c.1053dupA, p. (Gln352Thrfs*15), was identified in the SPG4 gene in this family. CONCLUSION: A Chinese family with HSP had a novel mutation of the SPG4 gene, which is autosomal dominant and inherited as pure HSP. The age of onset, sex distribution, and clinical manifestations of all existing living patients in this family were analyzed. The findings may extend the current knowledge on the existing mutations in the SPG4 gene.

Bent-Capillary-Centrifugal-Driven Monodisperse Droplet Generator with Its Application for Digital LAMP Assay.

We developed a bent-capillary-centrifugal-driven (BCCD) monodisperse droplet generator, which could achieve a perfect combination of driving and segmentation for the dispersed phase only using a rotating bent capillary immersed in the continuous phase (mineral oil). The sample could flow continuously to the bent-capillary outlet to form the droplet precursors, which were segmented into homogeneous droplets in the continuous phase. Through the investigation of influence factors on droplet size and stability, we found that the droplet size could be conveniently controlled by the rotational speed of the bent capillary. The droplet volumes could be adjusted with the range from 34 pL to 1 µL, and the coefficient variations (CVs) were less than 3%. Meanwhile, the BCCD droplet generator could realize the controllable droplet output with a high-efficiency sample utilization of 99.75 ± 1.15%, which offered a significant advantage in reducing the waste of precious samples in the droplet generation process. We validated this system with a digital loop-mediated isothermal amplification (dLAMP) assay for the absolute quantification of Mycobacterium tuberculosis complex nucleic acids. The results demonstrated that the BCCD droplet generator was easy to build, was of low cost, and was convenient to operate, as well as avoided sample loss and cross-contamination by coupling with a 96-well plate. Overall, the present platform, as a simple chip-free droplet generator, will provide an especially valuable droplet generation solution for biochemical applications based on droplets.

Target-induced gold nanoparticles colorimetric sensing coupled with aptamer for rapid and high-sensitivity detecting kanamycin.

Herein we report a novel colorimetric sensing strategy for the detection of kanamycin (kana) based on target-induced gold nanoparticles (AuNPs) coupled with aptamers. Aptamer-functionalized AuNPs, as the colorimetric probe, showed a distinct red shift with addition of kana, which avoiding the tedious and unnecessary additive-induced process. To study the interaction between kana and AuNPs and the effects of the specific aptamer adsorption, a series of experiments including UV-vis absorbance and surface enhanced Raman spectroscopy (SERS) were performed. Based on the results, a new alternative view is proposed that kana can directly induce the aggregation of aptamer-wrapped AuNPs, attributed to the co-adsorption of kana and aptamer on the surface of AuNPs. The proposed colorimetric sensing exhibited high selectivity and sensitivity for kanamycin assay with a wide linear range from 10.0 nM to 4.0 µM, and the limit of detection (LOD) reached 4.0 nM. Moreover, the whole detection process could be completed within 5 min, and it also achieved excellent performance in real samples detection with recoveries in the range of 86.22-109.89%. The results indicate that target-induced AuNPs colorimetric sensing coupled with aptamers for the direct detection of kana is simple, rapid and high-sensitivity, has the promising potential applications in the fields of food safety and environmental monitoring.

SLC20A2-related primary familial brain calcification with purely acute psychiatric symptoms: a case report.

BACKGROUND: Primary familial brain calcification (PFBC) is a rare inherited neurological disorder characterized by bilateral basal ganglia calcification with a series of motor and nonmotor symptoms. Mutations in the SLC20A2 gene, encoding the PiT2 protein, are the major cause of the disease. Here, we report a Chinese PFBC family carrying a SLC20A2 gene mutation, and the proband presented with purely acute psychiatric symptoms, which has been rarely reported in this disease. CASE PRESENTATION: A 38-year-old woman was hospitalized due to disorganized speech; disordered thought contents; disorganized behaviour; emotional instability and lability; and grandiose words, actions and facial expressions. Brain computerized tomography (CT) revealed calcification in the basal ganglia; cerebellar dentate nuclei; and subcortical, periventricular, and deep white matter regions in she and her family members. Through mutation analysis, a heterozygous truncating mutation, c.1723G > T, p.(Glu575*), was identified in the SLC20A2 gene in this family. Thus, this patient was diagnosed with genetically confirmed PFBC, and she responded well to a low dose of antipsychotic drugs. The penetrance of the disease in this family was only 33%, which was significantly lower than that in most families carrying SLC20A2 gene mutations. CONCLUSIONS: Patients with SLC20A2-related PFBC might present with psychiatric symptoms alone, and the penetrance of the disease may be quite low, which adds to the clinical heterogeneity of the disease.

Aptamer-based signal amplification strategies coupled with microchips for high-sensitivity bioanalytical applications: A review.

With their advantages in specificity, high stability and easy screening, aptamers are becoming increasingly popular recognition elements for biosensor platforms. At the same time, microchips as the new analytical detection platforms have achieved significant growth in the past decades. At present, with the intersection of aptamer and microfluidic technology, aptamer-based high-sensitivity bioanalysis on microchips exhibits a great application potential in biomedical science and environmental fields. In this review, we highlight the recent progress in high-sensitivity bioanalytical applications based on aptamer signal amplification strategies on microchips. Furthermore, the main challenges in the practical application are discussed, and the development in the future is prospected.

A smartphone-assisted microarray immunosensor coupled with GO-based multi-stage signal amplification strategy for high-sensitivity detection of okadaic acid.

Okadaic acid (OA) is one of the main virulence factors of diarrheal shellfish toxins (DSP), which can cause acute carcinogenic or teratogenic effects after ingestion of contaminated shellfish. Therefore, high-sensitivity and fast detection of OA is a key to preventing the occurrence of safety accidents. In this paper, we effectively established a smartphone-assisted microarray immunosensor combined with an indirect competitive ELISA (iELISA) for quantitative colorimetric detection of OA. To further improve the detection sensitivity and match the smartphone imaging, a novel graphene oxide (GO) composite probe was developed to realize the multi-stage signal amplification. The system exhibited a wide linear range for the detection of OA (0.02-33.6 ng ·mL-1) with low detection limit of 0.02 ng ·mL-1. The recovery of OA in spiked shellfish samples was in the range of 80%-103.5%, which indicates the good applicability of this biosensor. The whole detection system has advantages of simplicity, low cost, high sensitivity and portability, which is expected to be a powerful alternative tool for on-site detecting and early warning of the pollution of marine products.

Prevalence and outcome of young stroke patients with middle cerebral artery stenosis.

BACKGROUND: Etiologies of acute ischemic stroke in young adults are heterogeneous. Middle cerebral artery (MCA) stenosis is a common finding in Asians which may be an important cause of stroke in young adults. However, studies of stroke in young Asian populations are rare. Our study was to investigate the prevalence and outcome of young stroke patients with MCA stenosis in Chinese populations. METHODS: Young patients with MCA territory infarction between January 2013 and September 2018 were retrospectively recruited. Subjects were defined as stenosis group (MCA stenosis ≥50%) and no-stenosis group (MCA stenosis<50% or no stenosis) by their MCA stenosis. For patients in stenosis group, they were categorized as uni-MCA stenosis subgroup and multiple stenosis subgroup. Demographic data, risk factors, imaging feature and complications were compared between groups. Prevalence of MCA stenosis and risk factor score (score ≥ 2 or 3) in different age groups were investigated. Modified Rankin Scale (mRS) was used for evaluating functional outcome at discharge (unfavorable outcome: 3-6). Binary logistic regression was performed to determine independent risk factors of unfavorable outcome. RESULTS: Two hundred forty-nine young stroke patients were included in our study and 110 (44.2%) patients were defined as stenosis group. 55 (50%) patients were categorized as uni-MCA stenosis subgroup and 55 (50%) were multiple stenosis subgroup. The most common traditional vascular risk factors included hypertension, hyperlipemia, smoking, hyperhomocysteinemia and alcohol consumption. Prevalence of risk factor score ≥ 2 or 3 increased with age, but not incidence of MCA stenosis. By TOAST classification, the most common etiologies were large-artery atherosclerosis (41.0%) and small vessel disease (33.7%). Compared with no-stenosis group, patients in stenosis group were more likely to have large territorial infarct, develop complications and have unfavorable outcome. No significant difference was found between patients in uni-MCA stenosis and multiple stenosis subgroups except history of stroke/TIA, risk factor score ≥ 3 and silent infarct. By logistic regression, hypertension (OR = 3.561; 95%CI, 1.494 to 8.492; p = 0.004), NIHSS scores at admission (OR = 1.438; 95%CI, 1.276 to 1.620; p = 0,000) and infarct size (p = 0.015) independently predicted unfavorable outcome. CONCLUSIONS: Forty-four point two percent young Chinese adults with MCA territory infarction had MCA stenosis. Prevalence of MCA stenosis did not increase with age. Patients with MCA stenosis had worse clinical outcome, however, only hypertension, NIHSS scores at admission and infarct size were independent predictors.

mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

It is growingly concerned about methamphetamine (MA)-induced lung toxicity. IMP1 is identified as a key molecule for cell life processes, but the role of IMP1 in MA-induced senescence remains unclear. The purpose of this study was to investigate whether chronic exposure to MA can cause autophagy and senescence of the lungs, whether there are interactions between Mammalian target of rapamycin (mTOR) and IMP1 and whether IMP1 is involved in pulmonary senescence promoted by mTOR-autophagy. The rats were randomly divided into control group and MA group, following by H&E staining, immunohistochemistry staining and Western blot. The alveolar epithelial cells were proceeded by ß-galactosidase staining, cell cycle detection, transfection and co-immunoprecipitation. Long-term exposure to MA led to the thickening of alveolar septum and more compact lungs. MA promoted the conversion of LC3-I to LC3-II and inhibited the activation of mTOR to induce autophagy. Bioinformatics and co-immunoprecipitation results presented the interactions between IMP1 and mTOR. MA induced cell senescence by decreasing IMP1, up-regulating p21 and p53, arresting cell cycle and increasing SA-ß-gal. Overexpression of IMP1 reduced p21 and SA-ß-gal to inhibit the senescence of alveolar epithelial cells. These results demonstrated that mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

RUNX3-dependent oxidative epithelial-to-mesenchymal transition in methamphetamine-induced chronic lung injury.

Lung toxicity is the main cause of the death from methamphetamine (MA) abuse, but its mechanism has remained unclear. The purpose of our study was to investigate if MA can induce epithelial-to-mesenchymal transition (EMT) and if RUNX3 is involved in oxidative EMT in MA-induced chronic lung injury. The rats were divided into the control group and MA group. Extracted lungs were used for morphological measurements and Western blot. The alveolar epithelial cells were cultured or transfected and then treated with MA or/and N-acetyl cysteine (NAC) followed by flow cytometry, Western blot, and immunohistochemistry. Chronic exposure to MA resulted in the lower growth ratio of weight, increased right ventricular index, thickened alveolar walls, and reduced number of alveolar sacs. Long-term administration with MA caused oxidative stress and pulmonary EMT. NAC increased RUNX3 and alleviated EMT. However, after knockdown of RUNX3, reactive oxygen species (ROS) levels were significantly upregulated, indicating that RUNX3 was closely related to oxidative stress. Knockdown of RUNX3 aggravated MA-induced EMT by activating RUNX3-dependent TGF-ß signaling. Therefore, RUNX3 may be the key to oxidative EMT in methamphetamine-induced chronic lung injury.

Resveratrol protects the integrity of alveolar epithelial barrier via SIRT1/PTEN/p-Akt pathway in methamphetamine-induced chronic lung injury.

OBJECTIVES: SIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)-induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA-induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p-Akt pathway. MATERIALS AND METHODS: The rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio-informatics prediction. RESULTS: Chronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA-induced apoptosis was associated with SIRT1-related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO-1 and E-cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA-induced higher permeability of alveolar epithelium. CONCLUSIONS: MA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA-induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p-Akt pathway.

Identifying the pulsed neuron networks' structures by a nonlinear Granger causality method.

BACKGROUND: It is a crucial task of brain science researches to explore functional connective maps of Biological Neural Networks (BNN). The maps help to deeply study the dominant relationship between the structures of the BNNs and their network functions. RESULTS: In this study, the ideas of linear Granger causality modeling and causality identification are extended to those of nonlinear Granger causality modeling and network structure identification. We employed Radial Basis Functions to fit the nonlinear multivariate dynamical responses of BNNs with neuronal pulse firing. By introducing the contributions from presynaptic neurons and detecting whether the predictions for postsynaptic neurons' pulse firing signals are improved or not, we can reveal the information flows distribution of BNNs. Thus, the functional connections from presynaptic neurons can be identified from the obtained network information flows. To verify the effectiveness of the proposed method, the Nonlinear Granger Causality Identification Method (NGCIM) is applied to the network structure discovery processes of Spiking Neural Networks (SNN). SNN is a simulation model based on an Integrate-and-Fire mechanism. By network simulations, the multi-channel neuronal pulse sequence data of the SNNs can be used to reversely identify the synaptic connections and strengths of the SNNs. CONCLUSIONS: The identification results show: for 2-6 nodes small-scale neural networks, 20 nodes medium-scale neural networks, and 100 nodes large-scale neural networks, the identification accuracy of NGCIM with the Gaussian kernel function was 100%, 99.64%, 98.64%, 98.37%, 98.31%, 84.87% and 80.56%, respectively. The identification accuracies were significantly higher than those of a traditional Linear Granger Causality Identification Method with the same network sizes. Thus, with an accumulation of the data obtained by the existing measurement methods, such as Electroencephalography, functional Magnetic Resonance Imaging, and Multi-Electrode Array, the NGCIM can be a promising network modeling method to infer the functional connective maps of BNNs.

Chronic toxicity of methamphetamine: Oxidative remodeling of pulmonary arteries.

Methamphetamine (MA) has a high uptake in lung, but the precise mechanism of MA-induced lung toxicity remains unclear. The aim of this study is to investigate the role of MA abuse in remodeling of pulmonary arteries and to explore the possible correlation of the association of the remodeling with the redox imbalance in pulmonary arterial smooth muscle cells (PASMCs). Wistar rats were randomly divided into control group and MA group for the experimental study. We employed H&E staining, western blot, immunofluorescence, knockdown, flow in our experimental approach. Our studies shows that chronic exposure to MA led to weight loss, increased pulmonary arterial pressure, hypertrophy of right ventricle and remodeling of pulmonary arterial wall of rats. Our cell culture study with PASMCs indicates that MA significantly induced the imbalance between proliferation and apoptosis by upregulating the level of PCNA, Bcl-2 and reduction in the expression of BAX and Caspase 3. MA markedly prevented the nuclear translocation of Nrf2 to inhibit antioxidation. The knockdown of Nrf2 expression using siRNA significantly elevated the expression of SOD2/GCS and the production of ROS in PASMCs and even scaled up the amount of PASMCs induced by MA. Linear regression analysis showed that knockdown of Nrf2 promoted the positive correlation of relative ROS level with proliferation of PASMCs. Therefore, chronic exposure to MA induces pulmonary arterial remodeling by Nrf2-mediated imbalance of redox system to aggravate oxidative stress, and Nrf2 is a possible target for the treatment of MA-lung toxicity.

Late delayed radiation-induced cerebral Arteriopathy by high-resolution magnetic resonance imaging: a case report.

BACKGROUND: Radiation therapy can cause cerebral arteriopahty, resulting in ischemic stroke. We document late-delayed cerebral arteriopathy by high-resolution magnetic resonance imaging (HR-MRI) in a middle aged man who had cranial irradiation 19 years earlier. CASE PRESENTATION: A 45-year-old man was diagnosed with frontal lobe glioma 19 years ago and was treated with radiation after surgical resection. He was admitted to our hospital with an acute cerebral infarction in November 8, 2017. Traditional MRI examination and HR-MRI (sagittal, reconstruction of coronal and axial) were performed at admission. He was treated with prednisone (30 mg/day) and clinical symptoms disappeared after 3 months by telephone follow-up. Our patient complained of dizziness and blurred vision and traditional MRI examination indicated acute ischemic stroke in temporal lobe and occipital lobe and microbleeds. In order to define the exact mechanism of stroke, blood tests, auto-immune screening and thrombophilia were performed and results were normal. Electrocardiography and echocardiography were negative and cardiogenic cerebral embolism was excluded. In cerebrospinal fluid (CSF) examination, level of albumin and IgG were elevated. HR-MRI showed vessel wall thickening in T1-weighted imaging, narrow lumen in proton density imaging and vessel wall concentric enhancement in contrast-enhanced T1- weighted imaging. Combined with radiotherapy history, the patient was diagnosed with radioactive vasculitis. CONCLUSION: Radiation-induced cerebrovascular damages could be a lasting progress, which we cannot ignore. HR-MRI can provide sensitive and accurate diagnostic assessment of radiation-induced arteritis and may be a useful tool for the screening of causes of cryptogenic stroke.