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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.
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Gastos en Salud , Seguro de Salud , Humanos , Estudios Transversales , ChinaRESUMEN
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.
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Péptidos beta-Amiloides/toxicidad , Caenorhabditis elegans/crecimiento & desarrollo , Cannabidiol/farmacología , Longevidad , Neuroblastoma/tratamiento farmacológico , Proyección Neuronal , Receptor Cannabinoide CB1/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Animales Modificados Genéticamente/genética , Animales Modificados Genéticamente/crecimiento & desarrollo , Anticonvulsivantes/farmacología , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Neuroblastoma/metabolismo , Neuroblastoma/patología , Neuronas/citología , Neuronas/metabolismo , Fármacos Neuroprotectores , Fosforilación , Receptor Cannabinoide CB1/genética , Factor de Transcripción STAT3/genéticaRESUMEN
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.
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Proteínas Adaptadoras Transductoras de Señales/genética , Regulación hacia Abajo/genética , Proteína Ligando Fas/genética , Guanilato-Quinasas/genética , Degeneración del Disco Intervertebral/genética , Núcleo Pulposo/metabolismo , ARN Largo no Codificante/genética , Proteínas Adaptadoras Transductoras de Señales/sangre , Adulto , Anciano , Células Cultivadas , Proteína Ligando Fas/metabolismo , Femenino , Silenciador del Gen , Guanilato-Quinasas/sangre , Humanos , Degeneración del Disco Intervertebral/sangre , Masculino , Persona de Mediana Edad , Núcleo Pulposo/patología , ARN Largo no Codificante/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética , TransfecciónRESUMEN
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.
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Long persistence phosphors with high emitting intensity are promising materials for safety signage and energy storage applications. Herein, an improved persistent luminescence of Y3Al2Ga3O12 phosphor by co-doping Ce3+, Yb3+, and B3+ is achieved using conventional solid-state reaction. On one hand, the incorporation of H3BO3 can improve the crystallinity; on the other hand, B3+ can replace Al3+/Ga3+ in tetrahedral sites in the host lattice, causing lattice contraction and modifying the trap depth and density. It is found that adding B3+ forms a much deeper trap with â¼1.10 eV depth. In addition, the density of the electron trap can also be dramatically increased compared to the sample without B3+. The charging process for persistent luminescence is demonstrated by comparing the photoluminescence excitation spectrum with the thermoluminescence excitation spectrum. The persistence luminescence mechanism is given by a visual energy level diagram on the basis of the vacuum referred binding energy scheme of Y3Al2Ga3O12.
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Grapes are an important economic crop and are widely cultivated around the world. Most grapes are grown in arid or semi-arid regions, and droughts take a heavy toll in grape and wine production areas. Developing effective drought-resistant cultivation measures is a priority for viticulture. Melatonin, an indoleamine, mediates many physiological processes in plants. Herein, we examined whether exogenously applied melatonin could improve the resistance of wine grape seedlings grown from cuttings to polyethylene glycol-induced water-deficient stress. The application of 10% polyethylene glycol (PEG) markedly inhibited the growth of cuttings, caused oxidative stress and damage from H2 O2 and O2â-, and reduced the potential efficiency of Photosystem II and the amount of chlorophyll. Application of melatonin partially alleviated the oxidative injury to cuttings, slowed the decline in the potential efficiency of Photosystem II, and limited the effects on leaf thickness, spongy tissue, and stoma size after application of PEG. Melatonin treatment also helped preserve the internal lamellar system of chloroplasts and alleviated the ultrastructural damage induced by drought stress. This ameliorating effect may be ascribed to the enhanced activity of antioxidant enzymes, increased levels of nonenzymatic antioxidants, and increased amount of osmoprotectants (free proline). We conclude that the application of melatonin to wine grapes is effective in reducing drought stress.
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Antioxidantes/metabolismo , Cloroplastos/efectos de los fármacos , Melatonina/farmacología , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo , Vitis/efectos de los fármacos , Vitis/metabolismo , Cloroplastos/ultraestructura , Microscopía Electrónica de Transmisión , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta/ultraestructuraRESUMEN
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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Caenorhabditis elegans , Cannabinoides , Envejecimiento Saludable , Longevidad , Animales , Caenorhabditis elegans/efectos de los fármacos , Cannabinoides/farmacología , Longevidad/efectos de los fármacos , Envejecimiento Saludable/efectos de los fármacos , Envejecimiento Saludable/fisiología , Humanos , Cannabidiol/farmacología , Envejecimiento/fisiología , Envejecimiento/efectos de los fármacos , Modelos AnimalesRESUMEN
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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The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case-control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (ORMet allele vs. Thr allele=1.17, 95 % CI 0.97-1.42, P OR=0.102; ORMetMet vs. ThrThr =1.32, 95 % CI 0.93-1.87, P OR=0.121; ORThrMet vs. ThrThr =1.17, 95 % CI 0.94-1.45, P OR=0.150; ORMetMet + ThrMet vs. ThrThr =1.20, 95 % CI 0.96-1.51, P OR=0.114; ORMetMet vs. ThrThr + ThrMet =1.37, 95 % CI 0.98-1.93, P OR=0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case-control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.
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Neoplasias Colorrectales/etiología , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético/genética , Estudios de Casos y Controles , Humanos , Factores de RiesgoRESUMEN
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.
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Enfermedad de Alzheimer , Cannabidiol , Animales , Humanos , Cannabidiol/farmacología , Astrocitos/metabolismo , Astrocitos/patología , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/farmacología , Caenorhabditis elegans/metabolismo , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/farmacologíaRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Síndrome de la Vena Cava Superior , Masculino , Humanos , Anciano , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Antígeno B7-H1 , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Estudios de Factibilidad , Síndrome de la Vena Cava Superior/patología , Células Asesinas NaturalesRESUMEN
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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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.
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Hospitalización , Seguro de Salud , Humanos , Estudios Transversales , Encuestas y Cuestionarios , Costos y Análisis de CostoRESUMEN
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.
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Antipsicóticos , Animales , Humanos , Olanzapina/farmacología , Antipsicóticos/efectos adversos , Envejecimiento , Mitofagia , Mitocondrias , Caenorhabditis elegansRESUMEN
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.
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Melissa , Neuroblastoma , Fármacos Neuroprotectores , Sambucus , Humanos , Antioxidantes/farmacología , Fármacos Neuroprotectores/farmacología , Antocianinas , Peróxido de Hidrógeno , Flavonoides/farmacologíaRESUMEN
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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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.
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Cannabidiol , Neuroblastoma , Animales , Autofagia/fisiología , Caenorhabditis elegans/genética , Cannabidiol/farmacología , Humanos , Longevidad/fisiología , Neuronas , Sirtuina 1RESUMEN
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.
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Procesamiento de Imagen Asistido por Computador , Neoplasias Pulmonares , Algoritmos , Atención , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Redes Neurales de la ComputaciónRESUMEN
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.
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Programas InformáticosRESUMEN
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.