ABSTRACT
To address the requirements of sonar imaging, such as high receiving sensitivity, a wide bandwidth, and a wide receiving angle, an AlN PMUT with an optimized ratio of 0.6 for the piezoelectric layer diameter to backside cavity diameter is proposed in this paper. A sample AlN PMUT is designed and fabricated with the SOI substrate-based bulk MEMS process. The characterization test result of the sample demonstrates a -6 dB bandwidth of approximately 500 kHz and a measured receiving sensitivity per unit area of 1.37 V/µPa/mm2, which significantly surpasses the performance of previously reported PMUTs. The -6 dB horizontal angles of the AlN PMUT at 300 kHz and 500 kHz are measured as 68.30° and 54.24°, respectively. To achieve an accurate prediction of its characteristics when being packaged and assembled in a receive array, numerical simulations with the consideration of film stress are conducted. The numerical result shows a maximum deviation of ±7% in the underwater receiving sensitivity across the frequency range of 200 kHz to 1000 kHz and a deviation of about 0.33% in the peak of underwater receiving sensitivity compared to the experimental data. By such good agreement, the simulation method reveals its capability of providing theoretical foundation for enhancing the uniformity of AlN PMUTs in future studies.
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There is a significant global upsurge in the number and proportion of older persons in the population. With this comes an increasing prevalence of age-related conditions which pose a major challenge to healthcare systems. The development of anti-ageing treatments may help meet this challenge by targeting the ageing process which is a common denominator to many health problems. Cannabis-like compounds (cannabinoids) are reported to improve quality of life and general well-being in human trials, and there is increasing preclinical research highlighting that they have anti-ageing activity. Moreover, preclinical evidence suggests that endogenous cannabinoids regulate ageing processes. Here, we review the anti-ageing effects of the cannabinoids in various model systems, including the most extensively studied nematode model, Caenorhabditis elegans. These studies highlight that the cannabinoids lengthen healthspan and lifespan, with emerging evidence that they may also hinder the development of cellular senescence. The non-psychoactive cannabinoid cannabidiol (CBD) shows particular promise, with mechanistic studies demonstrating it may work through autophagy induction and activation of antioxidative systems. Furthermore, CBD improves healthspan parameters such as diminishing age-related behavioural dysfunction in models of both healthy and accelerated ageing. Translation into mammalian systems provides an important next step. Moreover, looking beyond CBD, future studies could probe the multitude of other cannabis constituents for their anti-ageing activity.
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The lifespan of schizophrenia patients is significantly shorter than the general population. Olanzapine is one of the most commonly used antipsychotic drugs (APDs) for treating patients with psychosis, including schizophrenia and bipolar disorder. Despite their effectiveness in treating positive and negative symptoms, prolonged exposure to APDs may lead to accelerated aging and cognitive decline, among other side effects. Here we report that dysfunctional mitophagy is a fundamental mechanism underlying accelerated aging induced by olanzapine, using in vitro and in vivo (Caenorhabditis elegans) models. We showed that the aberrant mitophagy caused by olanzapine was via blocking mitophagosome-lysosome fusion. Furthermore, olanzapine can induce mitochondrial damage and hyperfragmentation of the mitochondrial network. The mitophagosome-lysosome fusion in olanzapine-induced aging models can be restored by a mitophagy inducer, urolithin A, which alleviates defective mitophagy, mitochondrial damage, and fragmentation of the mitochondrial network. Moreover, the mitophagy inducer ameliorated behavioral changes induced by olanzapine, including shortened lifespan, and impaired health span, learning, and memory. These data indicate that olanzapine impairs mitophagy, leading to the shortened lifespan, impaired health span, and cognitive deficits. Furthermore, this study suggests the potential application of mitophagy inducers as therapeutic strategies to reverse APD-induced adverse effects associated with accelerated aging.
Subject(s)
Antipsychotic Agents , Animals , Humans , Olanzapine/pharmacology , Antipsychotic Agents/adverse effects , Aging , Mitophagy , Mitochondria , Caenorhabditis elegansABSTRACT
Oxidative stress is a common characteristic of psychiatric, neurological, and neurodegenerative disorders. Therefore, compounds that are neuroprotective and reduce oxidative stress may be of interest as novel therapeutics. Phenolic, flavonoid and anthocyanin content, ORAC and DPPH free radical scavenging, and Cu2+ and Fe2+ chelating capacities were examined in variations (fresh/capsule) of Queen Garnet plum (QGP, Prunus salicina), black pepper (Piper nigrum) clove (Syzygium aromaticum), elderberry (Sambucus nigra), lemon balm (Melissa officinalis) and sage (Salvia officinalis), plus two blends (Astralagus membranaceus-lemon balm-rich, WC and R8). The ability of samples to prevent and treat H2O2-induced oxidative stress in SH-SY5Y cells was investigated. Pre-treatment with WC, elderberry, QGP, and clove prevented the oxidative stress-induced reduction in cell viability, demonstrating a neuroprotective effect. Elderberry increased cell viability following oxidative stress induction, demonstrating treatment effects. Clove had the highest phenolic and flavonoid content, DPPH, and Cu2+ chelating capacities, whereas QGP and elderberry were highest in anthocyanins. Black pepper had the highest ORAC and Fe2+ chelating capacity. These findings demonstrate that plant extracts can prevent and treat oxidative stress-induced apoptosis of neuron-like cells in vitro. Further research into phytochemicals as novel therapeutics for oxidative stress in the brain is needed.
Subject(s)
Melissa , Neuroblastoma , Neuroprotective Agents , Sambucus , Humans , Antioxidants/pharmacology , Neuroprotective Agents/pharmacology , Anthocyanins , Hydrogen Peroxide , Flavonoids/pharmacologyABSTRACT
The decreasing-width, increasing-aspect-ratio RDL presents significant challenges to the design for reliability (DFR) of an advanced package. Therefore, this paper proposes an ML-based RDL modeling and simulation method. In the method, RDL was divided into blocks and subdivided into pixels of metal percentage, and the RDL was digitalized as tensors. Then, an ANN-based surrogate model was built and trained using a subset of tensors to predict the equivalent material properties of each block. Lastly, all blocks were transformed into elements for simulations. For validation, line bending simulations were conducted on an RDL, with the reaction force as an accuracy indicator. The results show that neglecting layout impact caused critical errors as the substrate thinned. According to the method, the reaction force error was 2.81% and the layout impact could be accurately considered with 200 × 200 elements. For application, the TCT maximum temperature state simulation was conducted on a CPU chip. The simulation indicated that for an advanced package, the maximum stress was more likely to occur in RDL rather than in bumps; both RDL and bumps were critically impacted by layouts, and RDL stress was also impacted by vias/bumps. The proposed method precisely concerned layout impacts with few resources, presenting an opportunity for efficient improvement.
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A 67-year-old male patient presented with extensive-stage small cell lung cancer with the primary lesion located in the right upper lung, accompanied by multiple metastases to the pleura and abdominal cavity with enlarged mediastinal lymph nodes. A combination therapy approach was used to target the patient's multiple systemic metastases after localized radiotherapy. The approach involved adoptive transfer of programmed death ligand 1 (PD-L1) enhanced exogenous natural killer (NK) cells, along with antiangiogenic treatment. Allogeneic cord blood NK cells were infused back into the patient over two consecutive days. On the first day, the treatment was followed by a dose of 1200 mg of atezolizumab. Subsequently, the patient received a daily dose of 10 mg of anlotinib administered orally for 14 days. This was followed by a 7-day break, and each cycle lasted 21 days. After delivering localized radiation to the primary lesion in the right lung and metastatic mediastinal lymph nodes, complete remission was achieved in the local lesion, effectively avoiding the risk of superior vena cava syndrome. Following six cycles of combined therapy, most of the metastatic lesions had disappeared, and the remaining metastatic lesions had significantly reduced in size. The recent therapeutic effect resulted in partial remission. The combination therapy of immune checkpoint inhibitor PD-L1-enhanced exogenous adoptive transfer NK cells, along with antiangiogenic targeted treatment, demonstrated a satisfactory short-term effect, with disappearance of most of the metastases and noticeable shrinkage in the remaining metastatic lesions.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Small Cell Lung Carcinoma , Superior Vena Cava Syndrome , Male , Humans , Aged , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/pathology , B7-H1 Antigen , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Feasibility Studies , Superior Vena Cava Syndrome/pathology , Killer Cells, NaturalABSTRACT
BACKGROUND: This study aimed to explore the factors that affect insured's perceptions of convenience of the basic medical insurance (PCBMI) in Harbin, China and to diagnose the key problems to further propose corresponding measures. The findings provide evidence-based support for the reform of convenience of the basic medical insurance system (BMIS) and the cultivation of public literacy. METHODS: We adopted a mixed methods design composing a multivariate regression model using the data from a cross-sectional questionnaire survey (n = 1045) of residents who were enrolled for BMIS in Harbin to identify the factors influencing the PCBMI. A quota sampling method was further adopted. Semi-structured interviews were then conducted with 30 important information providers selected by convenience sampling. Interpretative phenomenological analysis was employed to summarize and analyze the key problems. RESULTS: Overall, approximately 51% of respondents reported poor PCBMI. The logistic regression model showed that insured without outpatient experience within two weeks (OR = 2.522, 95% CI = 1.267-5.024), had poorer levels of understanding of basic medical insurance information (OR = 2.336, 95% CI = 1.612-3.386), lived in rural areas (OR = 1.819, 95% CI = 1.036-3.195), had low levels of annual out-of-pocket medical expenses (OR = 1.488, 95% CI = 1.129-1.961), and were more likely to give the PCBMI a worse evaluation than their counterparts. The results of the qualitative analysis showed that the key problem areas of the PCBMI were the design of the BMIS, the cognitive biases of the insured, publicity information about the BMIS, and the health system environment. CONCLUSIONS: This study found that in addition to the design of BMIS, the cognition of the insured, the BMIS information publicity and the health system environment are also the key problems hindering PCBMI. While optimizing system design and implementation, Chinese policymakers need to focus on the insured with low PCBMI characteristics. Moreover, it is necessary to focus on exploring effective BMIS information publicity methods, supporting public policy literacy and improving the health system environment.
Subject(s)
Health Expenditures , Insurance, Health , Humans , Cross-Sectional Studies , ChinaABSTRACT
Background: The perceptions of the benefits of the basic medical insurance system among the insured not only reflect the system's performance but also the public's basic medical insurance policy literacy, valuable information for countries that have entered the stage of deepening reform. This study aims to examine the factors that affect the perceptions of the benefits of the basic medical insurance system in China, diagnose the key problems, and propose corresponding measures for improvement. Methods: A mixed method design was used. Data for the quantitative study were obtained from a cross-sectional questionnaire survey (n = 1,045) of residents of Harbin who had enrolled for basic medical insurance system. A quota sampling method was further adopted. A multivariate logistic regression model was then employed to identify the factors influencing the perceptions of the benefits of the basic medical insurance system, followed by semi-structured interviews with 30 conveniently selected key informants. Interpretative phenomenological analysis was used to analyze the interview data. Results: Approximately 44% of insured persons reported low perceptions of benefits. The logistic regression model showed that low perceptions of the benefits of the basic medical insurance system was positively correlated with the experience of daily drug purchases (OR = 1.967), perceptions of recognition with basic medical insurance system (OR = 1.948), perceptions of the financial burden of participation costs (OR = 1.887), perceptions of the convenience of using basic medical insurance for medical treatment (OR = 1.770), perceptions of the financial burden of daily drug purchases costs (OR = 1.721), perceptions of the financial burden of hospitalization costs (OR = 1.570), and type of basic medical insurance system (OR = 1.456). The results of the qualitative analysis showed that the key problem areas of perceptions of the benefits of the basic medical insurance system were: (I) system design of basic medical insurance; (II) intuitive cognition of the insured; (III) rational cognition of the insured; and (IV) the system environment. Conclusions: Improving the perceptions of the benefits of the basic medical insurance system of the insured requires joint efforts in improving system design and implementation, exploring effective publicity methods of basic medical insurance system information, supporting public policy literacy, and promoting the health system environment.
Subject(s)
Hospitalization , Insurance, Health , Humans , Cross-Sectional Studies , Surveys and Questionnaires , Costs and Cost AnalysisABSTRACT
Introduction: As aging is the leading risk factor for Alzheimer's disease (AD), ablation of senescent cells is a promising therapeutic approach to prevent AD. It is known that astrocytes lose their ability to maintain a healthy brain environment when aging. Studies have recently shown that cannabidiol (CBD) provides a promising therapeutic avenue for AD; however, if or how CBD prevents astrocyte aging is not known. Materials and Methods: In this study, human astrocytes were employed to measure amyloid-beta (Aß)-induced senescence features, including senescence-associated ß-galactosidase (SA-ß-gal), p16INK4A, p21WAF1, and p53. The effects of CBD on the production of mitochondrial dysfunction and mitophagy pathway were measured by Western blot and fluorescence assay. Caenorhabditis elegans was used as in vivo AD model to investigate the effects of CBD on life span and health span. All experimental procedures were approved by the Human Research Ethics Committee, University of Wollongong, Australia. Results: In human astrocytes, we show that treatment with Aß, an endogenous pathogenic agent of AD, results in an increase in the percentage of SA-ß-gal-positive cells and induces mitochondrial reactive oxygen species (ROS). However, CBD treatment protects from Aß-induced senescence. Furthermore, the anti-senescence and anti-apoptotic activities of CBD were observed to be mediated through the protective effect of Parkin-dependent mitophagy. In C. elegans, we used the transgenic GRU102 strain, which expresses the human Aß peptide, and found that CBD treatment extended life span, improved pumping rate, and decreased mitochondrial ROS. Conclusion and Significance: Our results demonstrate that CBD prevents the human astrocyte senescence induced by Aß by a mechanism involving the Parkin-mediated mitophagy pathway. Our findings support the new therapeutic avenues of CBD for the treatment of AD patients.
Subject(s)
Alzheimer Disease , Cannabidiol , Animals , Humans , Cannabidiol/pharmacology , Astrocytes/metabolism , Astrocytes/pathology , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/pharmacology , Caenorhabditis elegans/metabolism , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/pharmacologyABSTRACT
A high abundance of tumor-infiltrating lymphocytes (TILs) has a positive impact on the prognosis of patients with lung adenocarcinoma (LUAD). We aimed to develop and validate an artificial intelligence-driven pathological scoring system for assessing TILs on H&E-stained whole-slide images of LUAD. Deep learning-based methods were applied to calculate the densities of lymphocytes in cancer epithelium (DLCE) and cancer stroma (DLCS), and a risk score (WELL score) was built through linear weighting of DLCE and DLCS. Association between WELL score and patient outcome was explored in 793 patients with stage I-III LUAD in four cohorts. WELL score was an independent prognostic factor for overall survival and disease-free survival in the discovery cohort and validation cohorts. The prognostic prediction model-integrated WELL score demonstrated better discrimination performance than the clinicopathologic model in the four cohorts. This artificial intelligence-based workflow and scoring system could promote risk stratification for patients with resectable LUAD.
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Automatic tissue segmentation in whole-slide images (WSIs) is a critical task in hematoxylin and eosin- (H&E-) stained histopathological images for accurate diagnosis and risk stratification of lung cancer. Patch classification and stitching the classification results can fast conduct tissue segmentation of WSIs. However, due to the tumour heterogeneity, large intraclass variability and small interclass variability make the classification task challenging. In this paper, we propose a novel bilinear convolutional neural network- (Bilinear-CNN-) based model with a bilinear convolutional module and a soft attention module to tackle this problem. This method investigates the intraclass semantic correspondence and focuses on the more distinguishable features that make feature output variations relatively large between interclass. The performance of the Bilinear-CNN-based model is compared with other state-of-the-art methods on the histopathological classification dataset, which consists of 107.7 k patches of lung cancer. We further evaluate our proposed algorithm on an additional dataset from colorectal cancer. Extensive experiments show that the performance of our proposed method is superior to that of previous state-of-the-art ones and the interpretability of our proposed method is demonstrated by Grad-CAM.
Subject(s)
Image Processing, Computer-Assisted , Lung Neoplasms , Algorithms , Attention , Humans , Image Processing, Computer-Assisted/methods , Lung Neoplasms/diagnostic imaging , Neural Networks, ComputerABSTRACT
Autophagy is a catabolic process to eliminate defective cellular molecules via lysosome-mediated degradation. Dysfunctional autophagy is associated with accelerated aging, whereas stimulation of autophagy could have potent anti-aging effects. We report that cannabidiol (CBD), a natural compound from Cannabis sativa, extends lifespan and rescues age-associated physiological declines in C. elegans. CBD promoted autophagic flux in nerve-ring neurons visualized by a tandem-tagged LGG-1 reporter during aging in C. elegans. Similarly, CBD activated autophagic flux in hippocampal and SH-SY5Y neurons. Furthermore, CBD-mediated lifespan extension was dependent on autophagy genes (bec-1, vps-34, and sqst-1) confirmed by RNAi knockdown experiments. C. elegans neurons have previously been shown to accumulate aberrant morphologies, such as beading and blebbing, with increasing age. Interestingly, CBD treatment slowed the development of these features in anterior and posterior touch receptor neurons (TRN) during aging. RNAi knockdown experiments indicated that CBD-mediated age-associated morphological changes in TRNs require bec-1 and sqst-1, not vps-34. Further investigation demonstrated that CBD-induced lifespan extension and increased neuronal health require sir-2.1/SIRT1. These findings collectively indicate the anti-aging benefits of CBD treatment, in both in vitro and in vivo models, and its potential to improve neuronal health and longevity.
Subject(s)
Cannabidiol , Neuroblastoma , Animals , Autophagy/physiology , Caenorhabditis elegans/genetics , Cannabidiol/pharmacology , Humans , Longevity/physiology , Neurons , Sirtuin 1ABSTRACT
Histopathological tissue classification is a simpler way to achieve semantic segmentation for the whole slide images, which can alleviate the requirement of pixel-level dense annotations. Existing works mostly leverage the popular CNN classification backbones in computer vision to achieve histopathological tissue classification. In this paper, we propose a super lightweight plug-and-play module, named Pyramidal Deep-Broad Learning (PDBL), for any well-trained classification backbone to improve the classification performance without a re-training burden. For each patch, we construct a multi-resolution image pyramid to obtain the pyramidal contextual information. For each level in the pyramid, we extract the multi-scale deep-broad features by our proposed Deep-Broad block (DB-block). We equip PDBL in three popular classification backbones, ShuffLeNetV2, EfficientNetb0, and ResNet50 to evaluate the effectiveness and efficiency of our proposed module on two datasets (Kather Multiclass Dataset and the LC25000 Dataset). Experimental results demonstrate the proposed PDBL can steadily improve the tissue-level classification performance for any CNN backbones, especially for the lightweight models when given a small among of training samples (less than 10%). It greatly saves the computational resources and annotation efforts. The source code is available at: https://github.com/linjiatai/PDBL.
Subject(s)
SoftwareABSTRACT
PURPOSE: Explore the longitudinal CT-based radiomics to demonstrate the changing trend of radiotherapy response and to determine at which point after the onset of treatment radiomics exhibit the greatest change for stage III NSCLC patients. METHODS AND MATERIALS: Ten stage III NSCLC patients in line with inclusion criteria were enrolled retrospectively, each of whom received radiotherapy or concurrent chemo-radiotherapy and performed eight series of follow-up CT imaging. Longitudinal radiomics were extracted on region of interest from the eight registered images, then two steps were conducted to select significant features as indicators of tumor change: 1) stable features were selected by Kendall rank correlation; 2) texture feature types with a steadily changing trend were retained and intensity features with stable change trends were selected to represent the large number of them. Next, the trend and rate of tumor change were analyzed using the Delta method and Curve-fitting method. Finally, the statistics in the distribution of stable features in patients were calculated. RESULTS: 675 stable features were selected from a total number of 1371 radiomics features, then 12 texture features types were retained and three intensity features were chosen to represent their own category. Among the final selected feature types, it was found that the two time points were weeks 1 and 3 with the higher rate of change. One patient had very few stable tumor features out of a total of 101 features, and the rate of change of features of another patient was conspicuously higher than the average level with number of 301 features. CONCLUSION: The longitudinal CT radiomics could demonstrate the change trend of tumor and at which point exhibit the greatest change during radiotherapy, and potentially be used for treatment decisions concerning adaptive radiotherapy.
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AIM: The study is aimed at investigating the curative effect of acupuncture on simple obesity and its influence on serum levels of prostaglandin E and leptin in Sprague-Dawley (SD) rats. METHODS: In the study, there are 50 male SD rats. We took 10 as healthy controls and fed 40 with a diet of high fat for 8 weeks. After the 40 rat model was established successfully, we fed 10 rats in the model group with a normal diet and treated 10 rats in the acupuncture group by acupuncture. During the experiment, the body fat and body length of rats were measured weekly, and Lee's index was calculated. After the treatment, the levels of leptin, prostaglandin E, C-reactive protein (CRP), triacylglycerol (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were detected, and the liver fat morphology was observed by electron microscope. RESULTS: Acupuncture significantly downregulated the serum levels of CRP, TG, CHO, LDL, leptin, and prostaglandin E and upregulated the serum levels of HDL in rats with simple obesity. CONCLUSION: On basis of these results, it was found that acupuncture could boost fat metabolism and weight loss by inhibiting the production of leptin and prostaglandin E.
Subject(s)
Acupuncture Therapy , Leptin/blood , Obesity/blood , Obesity/therapy , Prostaglandins E/blood , Adipose Tissue/pathology , Animals , C-Reactive Protein/metabolism , Computational Biology , Disease Models, Animal , Lipids/blood , Liver/pathology , Male , Obesity/pathology , Rats , Rats, Sprague-Dawley , Weight LossABSTRACT
OBJECTIVE: To analyze the role of circMYC in cervical cancer. METHODS: Protein and RNA expression was detected by RT-qPCR and western blotting. Transwell, CCK8, and colony formation assays were used for measuring metastasis, cell viability, and proliferation, respectively. Lactate production, glucose uptake, and ATP generation were examined to evaluate cell glycolysis. Interactions between circMYC, miR-577, and MET were determined by RNA pull-down and immunoprecipitation, and dual-luciferase reporter assays. Xenografts were established in mice to evaluate the functions of circMYC in vivo. RESULTS: circMYC was overexpressed in tumor tissue, which was related to poor prognosis. CircMYC knockdown reduced proliferation, colony formation, metastasis, and glycolysis in cervical cancer cells as well as inhibiting tumor growth in vivo. Mechanistically, circMYC targeted miR-577, and the effects of circMYC knockdown could be reversed by miR-577 inhibition. Moreover, miR-577 downregulated the expression of MET. Therefore, the oncogenic role of circMYC in cervical cancer was achieved by sponging miR-577 and maintaining MET expression. CONCLUSION: circMYC promotes cervical cancer progression through regulation of the miR-577/MET axis. circMYC may thus be a potential target for diagnosing and treating cervical cancer.
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Cannabidiol (CBD), a phytocannabinoid from the Cannabis sativa plant, exhibits a broad spectrum of potential therapeutic properties for neurodegenerative diseases. An accumulation of amyloid-ß (Aß) protein is one of the most important neuropathology in neurodegenerative diseases like Alzheimer's disease (AD). Data on the effect of CBD on the amelioration of Aß-induced neurite degeneration and its consequences of life and health spans is sparse. This study aimed to investigate the effects of CBD on neurite outgrowth in cells and lifespan and health span in Caenorhabditis elegans (C. elegans). In human SH-SY5Y neuronal cells, CBD prevented neurite lesion induced by Aß1-42 and increased the expression of fatty acid amide hydrolase (FAAH) and cannabinoid receptor 1 (CB1R). Furthermore, CBD both protected the reduction of dendritic spine density and rescued the activity of synaptic Ca2+ /calmodulin-dependent protein kinase II (CaMKII) from Aß1-42 toxicity in primary hippocampal neurons. In C. elegans, we used the transgenic CL2355 strain of C. elegans, which expresses the human Aß peptide throughout the nervous system and found that CBD treatment extended lifespan and improved health span. The neuroprotective effect of CBD was further explored by observing the dopaminergic neurons using transgenic dat-1: GFP strains using the confocal microscope. This study shows that CBD prevents the neurite degeneration induced by Aß, by a mechanism involving CB1R activation, and extends lifespan and improves health span in Aß-overexpressing worms. Our findings support the potential therapeutic approach of CBD for the treatment of AD patients.
Subject(s)
Amyloid beta-Peptides/toxicity , Caenorhabditis elegans/growth & development , Cannabidiol/pharmacology , Longevity , Neuroblastoma/drug therapy , Neuronal Outgrowth , Receptor, Cannabinoid, CB1/metabolism , STAT3 Transcription Factor/metabolism , Animals , Animals, Genetically Modified/genetics , Animals, Genetically Modified/growth & development , Anticonvulsants/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/genetics , Disease Models, Animal , Mice , Mice, Inbred C57BL , Neuroblastoma/metabolism , Neuroblastoma/pathology , Neurons/cytology , Neurons/metabolism , Neuroprotective Agents , Phosphorylation , Receptor, Cannabinoid, CB1/genetics , STAT3 Transcription Factor/geneticsABSTRACT
BACKGROUND: It is known that Fas ligand (FasL) is involved in the development of intervertebral disc degeneration (IDD). A recent study reported that lncRNA MAGI2-AS3 up-regulated the expression of FasL to promote breast cancer. Therefore, we investigated the roles that lncRNA MAGI2-AS3 might play in IDD. METHODS: A total of 66 IDD patients (IDD group) and 58 healthy volunteers (Control group) were recruited in this study. Quantitative real-time PCR (qRT-PCR) and western blot were used to investigate gene expression levels. Cell transfections were carried out to analyze gene interactions. The diagnostic value of lncRNA MAGI2-AS3 for IDD was assessed by ROC curve analysis. RESULTS: The expression levels of plasma lncRNA MAGI2-AS3 were lower in IDD patients compared to that in the control group. Down-regulation of lncRNA MAGI2-AS3 effectively distinguished IDD patients from the control group. The expression levels of plasma lncRNA MAGI2-AS3 were significantly increased after the treatments. Over-expression of lncRNA MAGI2-AS3 inhibited the expression of FasL, while the silencing of lncRNA MAGI2-AS3 promoted the expression of FasL in nucleus pulposus (NP) cells. CONCLUSIONS: Therefore, lncRNA MAGI2-AS3 is down-regulated in IDD and participates in the regulation of FasL expression in nucleus pulposus (NP) cells.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Down-Regulation/genetics , Fas Ligand Protein/genetics , Guanylate Kinases/genetics , Intervertebral Disc Degeneration/genetics , Nucleus Pulposus/metabolism , RNA, Long Noncoding/genetics , Adaptor Proteins, Signal Transducing/blood , Adult , Aged , Cells, Cultured , Fas Ligand Protein/metabolism , Female , Gene Silencing , Guanylate Kinases/blood , Humans , Intervertebral Disc Degeneration/blood , Male , Middle Aged , Nucleus Pulposus/pathology , RNA, Long Noncoding/blood , Real-Time Polymerase Chain Reaction , Signal Transduction/genetics , TransfectionABSTRACT
The Sr3SiO5:Eu2+ phosphor has attracted considerable attention for applications in white LEDs owing to its highly efficient yellow emission under violet-blue excitation. We report herein an enhancement of yellow persistent luminescence in Sr3SiO5:Eu2+ through Ge incorporation. The strongest persistent luminescence intensity is observed for Sr3(Si1- xGe x)O5:Eu2+ with x = 0.005 with a peak emission wavelength at â¼580 nm and a persistent time of â¼7000 s at the 0.32 mcd/m2 threshold value after UV radiation. A combination of thermoluminescence measurements and density functional theory (DFT) calculations reveals that the afterglow enhancement is due to a significant increase in the number of oxygen vacancies that act as electron trapping centers with appropriate trap depths. This investigation is anticipated to encourage more exploration of GeSi substitution to design and improve Si-containing persistent phosphors with superior functionalities.
ABSTRACT
OBJECTIVE: To compare the clinical effects of closed reduction and internal fixation with limited transtarsal sinus incision in the treatment of Sanders type II calcaneal fractures. METHODS: From June 2015 to February 2018, 60 patients with Sanders type II calcaneal fractures were treated by minimally invasive method. According to the different treatment methods, they were divided into two groups: closed prying reduction and internal fixation with hollow nails(group A) and limited transtarsal sinus incision internal fixation (group B). There were 34 cases in group A, including 22 males and 12 females, aged 21 to 60(38.90±3.25) years old, 14 cases of Sanders type IIA, 14 cases of Sanders type IIB and 6 cases of Sanders type IIC. There were 20 cases in group B, including 14 males and 6 females, aged 20 to 59(39.20±2.96) years old, 8 cases of Sanders type IIA, 9 cases of Sanders type IIB and 3 cases of Sanders type IIC. Calcaneal height, calcaneal width, Gissane angle and Bohler angle were measured before and after operation. The complications, hospitalization time and cost were compared. Functional evaluation was performed by AOFAS score system one year after operation. RESULTS: Fifty-four cases were followed up for 6 to 16(11.40±2.55) months and 6 cases were lost. All the wounds healed in grade A without complications such as skin infection and necrosis. There were 1 case of nerve injury in group A, 2 cases of tendon entrapment, 2 cases of nerve injury in group B, there was no significant difference(P>0.05). There was no significant difference in calcaneal width, height, Bohlers angle and Gissane angle between group A and group B (P>0.05). There was no significant difference in AOFAS score between group A and group B(89.2±4.7 vs 88.7±4.8, P>0.05). The hospitalization expenditure and length of stay in group A were(5 021.25±1 047.19) yuan, (6.31±4.75) d, and those in group B were(13 591.35±1 975.21) yuan, (9.65±3.42) d, respectively, with significant difference(P<0.05). CONCLUSIONS: Closed reduction and internal fixation is as effective as transtarsal sinus incision reduction and internal fixation for Sanders typeIIfracture. It has the advantages of less trauma and fewer complications. Closed reduction and hollow nail fixation group can significantly shorten hospitalization time, reduce hospitalization costs, and is more economical. It is worth recommending, but attention should be paid to avoid choosing to comminute serious calcaneal fracture.