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Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. β-elemene, which is a bioactive compound extracted from a Chinese herb, Curcu...
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Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. β-elemene, which is a bioactive compound extracted from a Chinese herb, Curcuma wenyujin, has been reported to reduce resistance of chemotherapeutic drugs and induce apoptosis in tumor cells. However, the role and mechanisms of β-elemene in glioma senescence remains unknown. In the present study, we found that a low concentration of β-elemene (10 μg/mL) induced senescence in glioma cells, including reduction of cell proliferation, hypertrophic morphology, increase of senescence-associated β-galactosidase (SA-β-Gal) activity, upregulation of several senescence-associated genes such as p16, p53 and NF-κB , and downregulation of Lamin B1 . However, a high concentration of β-elemene induced apoptosis in glioma cells. Treatment with β-elemene caused a marked down-regulation of Yes-associated protein (YAP) expression in glioma cells, which is a key transcriptional co-activator in multiple cancers. Moreover, cyclin dependent kinase 6 (CDK6), which is a known downstream target of YAP, was decreased in glioma cells that treated with β-elemene. The overexpression of YAP and CDK6 significantly rescued β-elemene-induced senescence in glioma cells. Finally, β-elemene treatment also induced the senescence of glioma cells in glioma xenograft model through inactivation of YAP-CDK6 pathways, which might inhibit the glioma growth. Taken together, these results reveal a previously unknown role of β-elemene in glioma cell senescence in vitro and in vivo that is associated with YAP-CDK6 signaling pathway, which will enhance our understanding of glioma cell senescence, and provide novel strategies for the treatment of gliomas.
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Abstract The homeostasis of glutamate is mainly regulated by the excitatory amino acid transporters (EAATs), especially by EAAT2 in astrocytes. Excessive glutamate in the synaptic cleft caused by dysfunction or dysregulation of EA...
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Abstract The homeostasis of glutamate is mainly regulated by the excitatory amino acid transporters (EAATs), especially by EAAT2 in astrocytes. Excessive glutamate in the synaptic cleft caused by dysfunction or dysregulation of EAAT2 can lead to excitotoxicity, neuronal death and cognitive dysfunction. However, it remains unclear about the detailed regulation mechanism of expression and function of astrocytic EAAT2. In this study, first, we found increased neuronal death and impairment of cognitive function in YAPGFAP‐CKO mice (conditionally knock out Yes‐associated protein [YAP] in astrocytes), and identified EAAT2 as a downstream target of YAP through RNA sequencing. Second, the expression of EAAT2 was decreased in cultured YAP?/? astrocytes and the hippocampus of YAPGFAP‐CKO mice, and glutamate uptake was reduced in YAP?/? astrocytes, but increased in YAP‐upregulated astrocytes. Third, further investigation of the mechanism showed that the mRNA and protein levels of β‐catenin were decreased in YAP?/? astrocytes and increased in YAP‐upregulated astrocytes. Wnt3a activated YAP signaling and up‐regulated EAAT2 through β‐catenin. Furthermore, over‐expression or activation of β‐catenin partially restored the downregulation of EAAT2, the impairment of glutamate uptake, neuronal death and cognitive decline that caused by YAP deletion. Finally, activation of EAAT2 also rescued neuronal death and cognitive decline in YAPGFAP‐CKO mice. Taken together, our study identifies an unrecognized role of YAP signaling in the regulation of glutamate homeostasis through the β‐catenin/EAAT2 pathway in astrocytes, which may provide novel insights into the pathogenesis of brain diseases that closely related to the dysfunction or dysregulation of EAAT2, and promote the development of clinical strategy.
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Senescent astrocytes accumulate with aging and contribute to brain dysfunction and diseases such as Alzheimer's disease (AD), however, the mechanisms underlying the senescence of astrocytes during aging remain unclear. In the pres...
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Senescent astrocytes accumulate with aging and contribute to brain dysfunction and diseases such as Alzheimer's disease (AD), however, the mechanisms underlying the senescence of astrocytes during aging remain unclear. In the present study, we found that Yes-associated Protein (YAP) was downregulated and inactivated in hippocampal astrocytes of aging mice and AD model mice, as well as in D-galactose and paraquat-induced senescent astrocytes, in a Hippo pathway-dependent manner. Conditional knockout of YAP in astrocytes significantly promoted premature senescence of astrocytes, including reduction of cell proliferation, hypertrophic morphology, increase in senescence-associated β-galactosidase activity, and upregulation of several senescence-associated genes such as p16, p53 and NF-κB, and downregulation of Lamin B1. Further exploration of the underlying mechanism revealed that the expression of cyclin-dependent kinase 6 (CDK6) was decreased in YAP knockout astrocytes in vivo and in vitro, and ectopic overexpression of CDK6 partially rescued YAP knockout-induced senescence of astrocytes. Finally, activation of YAP signaling by XMU-MP-1 (an inhibitor of Hippo kinase MST1/2) partially rescued the senescence of astrocytes and improved the cognitive function of AD model mice and aging mice. Taken together, our studies identified unrecognized functions of YAP-CDK6 pathway in preventing astrocytic senescence in vitro and in vivo, which may provide further insights and new targets for delaying brain aging and aging-related neurodegenerative diseases such as AD.
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The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and ...
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The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets.The clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed.Overall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy.WMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.
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In this article, combining the phase synchronization method (PSM) and high harmonic operation (HHO), a novel parity-time (PT)-symmetric wireless power transfer (WPT) system with reduced switching frequency and improved step-down c...
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In this article, combining the phase synchronization method (PSM) and high harmonic operation (HHO), a novel parity-time (PT)-symmetric wireless power transfer (WPT) system with reduced switching frequency and improved step-down conversion ratio is proposed, where the power transferred to receiver side is carried by the
$n$
th harmonic. We demonstrate that constant current (CC) and constant voltage (CV) independent of coupling coefficient and load resistance can also be obtained without wireless communication and additional dc–dc converters. Here, a new implementation of a negative resistor based on the
$n$
th harmonic operation is proposed, which is a necessary condition of a PT-based system. In contrast to the standard PT-based system with the same resonant frequency, the switching frequency is reduced to 1/
$n$
due to the use of the
$n$
th harmonic, thereby realizing low switching losses and high system efficiency. Besides, an inherently improved step-down conversion ratio can be obtained. A prototype with a 6-A charging current and a 36-V charging voltage is built to verify the feasibility of the proposed method.
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Abstract Background Laparoscopic liver resection (LLR) has been proposed as a safe and feasible treatment option for colorectal liver metastasis (CRLM). However, the short-term and oncologic outcomes of LLR versus open liver resec...
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Abstract Background Laparoscopic liver resection (LLR) has been proposed as a safe and feasible treatment option for colorectal liver metastasis (CRLM). However, the short-term and oncologic outcomes of LLR versus open liver resection (OLR) for CRLM have not been adequately assessed. Thus, we herein provide an updated systematic review comparing short-term and oncologic outcomes of CRLM patients undergoing LLR versus OLR. Methods A systematic literature search was performed in the Pubmed, Embase, and Cochrane Library databases (until November 2, 2016) with a limitation to the publications in English. Quality assessment was performed based on the modification of the Newcastle-Ottawa Scale. Dichotomous data were calculated by odds ratio (OR), and continuous data were calculated by weighted mean difference (WMD) with 95% confidence intervals (CIs). Results A total of 28 studies enrolling 4591 patients with CRLM were included. With respect to short-term outcomes, patients in LLR group showed significantly reduced blood loss (WMD: ?143.64; 95% CI: ?180.56 to ?106.73; I 2 ?=?86%; P ? 2 ?=?0%; P ? 2 ?=?82%; P ? 2 ?=?38%; P ? 2 ?=?35%; P ? 2 ?=?37%; P ?=?0.03). Conclusions LLR should be the standard approach for selected patients with CRLM, and further research should focus on determining which patients would benefit most from LLR.
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Background:Cap-assisted endoscopic sclerotherapy is a new interventional therapy for internal hemorrhoids and rectal prolapse under colonoscopy. The proper length of the endoscopic injection needle is the core for performing cap-a...
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Background:Cap-assisted endoscopic sclerotherapy is a new interventional therapy for internal hemorrhoids and rectal prolapse under colonoscopy. The proper length of the endoscopic injection needle is the core for performing cap-assisted endoscopic sclerotherapy well with more benefits and less complications. However, no data are currently available to guide endoscopists to consider the length of injection needle before cap-assisted endoscopic sclerotherapy. This study is designed to evaluate the efficacy and safety of cap-assisted endoscopic sclerotherapy with long or short injection needle in the treatment of internal hemorrhoids.Methods:This is a nationwide multi-center, prospective, single-blind and randomized controlled trial. Patients with grade I-II internal hemorrhoids who have failed to conservative treatments and grade III internal hemorrhoids who are not suitable for surgery or refuse surgery will be included. Participants will be randomized 1:1 into either long or short injection needle group. The primary outcome is the recurrence rate of internal hemorrhoids 24?weeks after cap-assisted endoscopic sclerotherapy. The secondary outcomes are as follows: (1) symptom severity score, (2) three-level EuroQoL five dimensions health scale scores, (3) occurrence of adverse events and severe adverse events, and (4) patients’ attitudes toward cap-assisted endoscopic sclerotherapy. Data collection will be conducted before and during operation, the 1st day, 1st week, 2nd week, and 24th week after cap-assisted endoscopic sclerotherapy.Discussion:The outcome of this study is expected to provide a practical clinical protocol of cap-assisted endoscopic sclerotherapy for patients with internal hemorrhoids and promote the use of this new endoscopic technique.Trial registration:ClinicalTrials.gov, NCT03917056. Registered on 12 April 2019.
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Background To identify gender differences in factors associated with the health literacy of hospitalized older patients with chronic diseases. Methods A total of 471 hospitalized older patients with chronic diseases in four hospit...
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Background To identify gender differences in factors associated with the health literacy of hospitalized older patients with chronic diseases. Methods A total of 471 hospitalized older patients with chronic diseases in four hospitals were investigated from May 2019 to June 2020. The self-developed demographic information questionnaire, the “Health Literacy Scale for Patients with Chronic Diseases” and the “Self-Efficacy for Managing Chronic Diseases 6-item Scale” were applied in this study. Multiple linear regression was used to assess the factors influencing health literacy among older patients with chronic diseases by gender. Results The factors influencing health literacy differed by gender. Male health literacy was related to education background, number of children, monthly income, duration of chronic disease and chronic disease self-efficacy. For females, health literacy was associated with age, education background, monthly income, duration of chronic disease and chronic disease treatment. Conclusion Healthcare providers should focus on the above-mentioned factors that could help identify those with low health literacy differ base on gender. Gender-specific strategies should be developed to improve the health literacy of older patients with chronic diseases and strengthen their chronic disease management.
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In electric power transmission, 110kV XLPE cables have been given a wide usage recently. Specific samples are selected as specimens of accelerated thermal aging tests and are tested at different temperatures. Once the value of the...
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In electric power transmission, 110kV XLPE cables have been given a wide usage recently. Specific samples are selected as specimens of accelerated thermal aging tests and are tested at different temperatures. Once the value of the specimen elongation at break decreases to 50% of the initial value, the cable at this condition is no longer suitable to be tested. The data obtained in this condition are the standard of judgment as a test failure and are used for calculation of the residual life. The Arrhenius equation is used to calculate the residual life of the tested 110kV XLPE cables based on the data obtained from the experiments. The calculation shows that the whole service life of a cable at different periods is consistent. Furthermore, the calculations prove that the method used to assess the cables' residual life is robust and reliable. The result of the experiment provide both theoretical and practical basis to replace 110kV XLPE cables preventively.
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In this work, we reported a kind of low floating fiber, high-performance composites which were prepared by means of mixing polypropylene and polybutylene-1/glass fiber masterbatch. The polybutylene-1/glass fiber masterbatch prepar...
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In this work, we reported a kind of low floating fiber, high-performance composites which were prepared by means of mixing polypropylene and polybutylene-1/glass fiber masterbatch. The polybutylene-1/glass fiber masterbatch prepared by coating method made the surface of glass fiber covered by a thin resin, and the as-prepared composites displayed significantly higher shear thinning, higher interface bonding strength, and lower crystallization temperature. The results of scanning electron microscope and atomic force microscope showed that the coating process could effectively hinder the exposure of glass fiber. And, the composites at the PB-1 content of 10 wt% showed higher flexural strength (142.0 MPa) and tensile strength (69.6 MPa) than those for PP (41.3 MPa and 31.4 MPa, respectively). Moreover, the behavior of possible stacking arrangements inside the composites was inferred in this study.
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