High fat diet (HFD) treated mouse is widely used as experimental animal model for hyperlipidemia and hyperglycemia study. Many factors contribute to establish animal model that meant to simulate high ...fat and glucose diet induced phenotypes. In the present study, four strains of experiment mouse treated by HFD were used to explore the impact of mouse strain on lipid profile, glucose level, and major inflammation cytokines. HFD fed Kunming and ICR mouse gained significantly higher body weight than control which was not shown by C57BL/6 and BALB/c mouse. All four strains fed by HFD has heavier liver and adipose tissue than control ones. Obvious fat droplets and enlarged adipose cells were observed in obese mouse of four strains. Additionally, obese mouse showed typical response to glucose and insulin load in OGTT and ITT. Serum TC, LDL-c, and TC/HDL-c ratio, but not TG, increased in all four strains. Major inflammatory cytokines and insulin level showed little changes in obese mouse as well (P<0.05) The present study could provide basic information for diet induced obesity developed by four commonly used experimental mouse strains.
Graphitic carbon nitrides (g‐C3N4) are a class of 2D polymeric materials mainly composed of carbon and nitrogen atoms. g‐C3N4 are attracting dramatically increasing interest in the areas of sensing, ...imaging, and therapy, due to their unique optical and electronic properties. Here, the luminescent properties (mainly includes photoluminescence and electrochemiluminescence), and catalytic and photoelectronic properties related to sensing and therapy applications of g‐C3N4 materials are reviewed. Furthermore, the fabrication and advantages of sensing, imaging and therapy systems based on g‐C3N4 materials are summarized. Finally, the future perspectives for developing the sensing, imaging and therapy applications of the g‐C3N4 materials are discussed.
The sensing, imaging and therapy applications of g‐C3N4 materials are summarized. The luminescent, catalytic and photoelectronic properties and mechanisms of g‐C3N4 materials related to sensing and therapy applications are introduced and discussed. The principles and advantages of the sensing, imaging and therapy systems are concluded.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Glioblastoma (GBM) is a severe malignant brain cancer with poor overall survival. Conventional intervention remains dismal to prevent recurrence and deterioration of GBM cell. Recent years have ...witnessed exciting breakthroughs in novel immune strategies, especially checkpoint inhibitors, some of which have become adjuvant setting after standard of care in melanoma. Several clinical trials of checkpoint inhibitors are ongoing in glioblastoma and other brain carcinomas. Plus, synergistic combinations of checkpoint inhibitors with conventional therapy strategies-radiotherapy, temozolomide, bevacizumab, and corticosteroids are now being exploited and applied in clinical settings. This review highlights the recent developments of checkpoints in GBM immunotherapy to provide a brief and comprehensive review of current treatment options. Furthermore, we will discuss challenges remained, such as unique immune system of central nervous system (CNS), immune-related toxicities, synergies, and adverse interactions of combination therapies.
In bridge health monitoring, in order to closely monitor the structural state changes of the bridge under heavy traffic load and other harsh environments, the monitoring system is required to give ...the change process of structural modal parameters. Due to the symmetric variables of bridge monitoring during operation, the evaluation needs to be completed by the recursive identification of modal parameters based on environmental excitation, especially the recursive recognition of the random subspace method with high recognition accuracy. We have studied the recursive identification methods of covariance-driven and data-driven random subspace categories respectively, established the corresponding recursive format, and used the model structure of the ASCE structural health monitoring benchmark problem as a numerical example to verify the reliability of the proposed method. First, based on the similar interference environment of the observation data at the same time, a reference point covariance-driven random subspace recursive algorithm (IV-RSSI/Cov) based on the auxiliary variable projection approximation tracking (IV-PAST) algorithm is established. The recursive format of the system matrix and modal parameters is obtained. Based on Givens rotation, the rank-2 update form of the row space projection matrix is established, and the recursive format of the data-driven recursive random subspace method (RSSI/Data) under the PAST algorithm is obtained. Then, based on the benchmark problem of ASCE-SHM, the response of the model structure under environmental excitation is numerically simulated, the frequency, damping ratio and vibration mode of the structure are recursively tracked, and their reliability and shortcomings are studied. After improving the recursive method, the frequency tracking accuracy has been improved, with a maximum accuracy of 99.8%.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Bacterial translocation was observed in critical illness and patients with chronic diseases such as liver cirrhosis and chronic kidney disease (CKD). Hypokalemia is a common ...complication in these diseases. Whether low potassium diet may increase intestinal permeability and result in bacterial translocation lack of evidence. The present study was aimed to investigate the potential effects of LK on intestinal permeability.
Methods
Grade 8-week-old male Bal B/C mice were randomly placed either on a normal potassium (NK) mouse chow or a low potassium (LK) diet for 28 days. Intestinal permeability and expression of tight junction proteins were compared between the two groups.
Results
Compared with the NK group, the mice in LK group had significantly lower serum potassium level, increased levels of plasmas endotoxin and plasma
d
-lactate. The bacterial translocation was higher and in occurred mainly in mesenteric lymph nodes (MLN), liver and spleen. The pathologic change of small intestine was obvious with thinner villus lamina propria, shorter crypt depth and thinner intestinal wall. Slight increases in the expression of proteins and mRNA levels of both claudin-1 and claudin-2 were observed in LK group.
Conclusions
Low potassium diet could increase intestinal permeability and thereby lead to bacterial translocation, which was suspected to result from impaired intestinal epithelial barrier and biological barrier.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Patients with brain tumor are in risk of depression or depressive symptoms, but the estimated prevalence varies between studies. The aim of this study is to get a proper summarized estimate of ...depression prevalence in brain tumor patients.
Literature search on Pubmed, PsycINFO, and Cochrane library from January 1981 through October 2016. The prevalence of depression or depressive symptoms in brain tumor patients was estimated by screening scales and analyzed using stratified meta-analysis and subgroup analysis. The prevalence of depression level or symptoms during the follow-up periods was detected by secondary analysis.
Among the 37 studies included in this meta-analysis, 25 used a cross-sectional design and 12 used longitudinal study. The pooled prevalence was 21.7% (971/4518 individuals, 95 % confidence interval (CI) 18.2%-25.2%) for overall sample. Lower prevalence was detected in studies with sample size ≥100 than <100, lower grade tumor than high grade tumor, studies using clinician-rated depression scales than self-rated or non-depression-specific ones, and in patients from UK, Germany and Italy than USA. After analyzing 6 longitudinal studies, prevalence of depression remained no change in the follow-up periods. No significant differences were observed between study designs and tumor types.
The estimated prevalence of depression or depressive symptoms among brain tumor patients was 21.7%, affected by depression assessment type, sample size, tumor grade and country. Diagnosis and treatment of co-morbid depression in brain tumor patients need to be addressed in future studies for better life quality and oncology management.
L‐theanine, originally found in green tea, elicits various physiological effects, such as promoting relaxation, improving concentration and learning ability, and providing antianxiety‐like and ...antidepressant‐like properties. This study aims to investigate the effects of L‐theanine (2 mg/kg) on monoamine levels in an animal model of depression. The effect of l‐theanine on the symptoms of depression was examined through the open‐field test, sucrose preference test, and forced swim test. The monoamine neurotransmitters that involve serotonin (5‐HT), norepinephrine (NE), and dopamine (DA) were measured in the limbic–cortical–striatal–pallidal–thalamic (LCSPT)‐circuit related brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (ST), amygdala, and hippocampus (HIP). L‐theanine ameliorated the depressive‐like behaviors in the chronic unpredictable mild stress (CUMS) rat model. In the PFC, NAC, and HIP, L‐theanine administration significantly increased the levels of 5‐HT, NE, and DA. In the ST, the levels of 5‐HT and DA were increased after the administration of L‐theanine. However, in the HIP, only the level of DA significantly changed after the treatment of L‐theanine. Taken together, these results indicated that L‐theanine has possibly antidepressant‐like effects in the CUMS rat model, which could be mediated by the monoamine neurotransmitters in the LCSPT‐circuit related brain regions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Background MicroRNAs have been proved to be successful diagnostic and prognostic markers in several cancers, including osteosarcoma. miR-195, as a tumor suppressor, has been reported to ...suppress osteosarcoma cell invasion and migration in vitro . However, its clinical value is still unclear. The aim of this study was to determine the expression pattern of miR-195 in osteosarcoma patients and to investigate its associations with tumor progression and prognosis. Methods miR-195 levels in sera from 166 osteosarcoma patients and 60 healthy controls were detected by real-time quantitative reverse transcription polymerase chain reaction. Then, the association of serum miR-195 level with clinicopathologic factors or survival of osteosarcoma patients was further evaluated. Results miR-195 levels in sera from osteosarcoma patients were significantly lower than those in healthy controls ( P < 0.001). Importantly, miR-195 could efficiently screen osteosarcoma patients from healthy controls (area under receiver operating characteristic curve = 0.892). Additionally, low miR-195 expression was more frequently occurred in osteosarcoma patients with advanced clinical stage ( P = 0.002) and positive distant metastasis ( P = 0.008). Univariate survival analysis revealed that osteosarcoma patients with low miR-195 expression had significantly shorter overall survival and disease-free survival than those with high miR-195 expression (both P < 0.001). Multivariate analysis further determined that low miR-195 expression was an independent and significant prognostic factor to predict poor overall survival ( P = 0.002) and disease-free survival ( P = 0.01). Conclusions Decreased expression of miR-195 in serum may be a novel biomarker for screening osteosarcoma and can predict poor prognosis. Detection of serum miR-195 expression may have potential applications for the diagnosis, prognosis, and treatment of osteosarcoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Pre-treatment prognostic score based on clinical stage, ECOG PS, LDH, Alb and PLR may help to identify aNSCLC patients who may benefit from immune checkpoint inhibitors (ICIs).•Among patients with ...PD-L1 expression ≥ 50%, pre-treatment prognostic score ≥ 3 tended to have a strong negative impact on survival.•irAEs may be one of the useful predictors for identifying patients who are likely to perform well on ICIs therapy.
This study aimed to explore factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer (aNSCLC) patients treated with immune checkpoint inhibitors (ICIs).
A total of 101 patients with aNSCLC receiving ICIs were included. The association between clinical factors and multiple endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) were investigated by multivariate analyses.
Multivariate logistic analyses revealed that clinical stage, lactate dehydrogena (LDH), and any grade immune-related adverse events (irAEs) were independent predictors of ORR, while LDH and ICIs treatment type were independent predictors of DCR. In Multivariate Cox analysis, Eastern Cooperative Oncology Group performance status (ECOG PS), LDH, albumin (Alb), platelet to lymphocyte ratio (PLR), and any grade irAEs were independent factors for OS. Similarly, clinical stage, LDH, Alb, and any grade irAEs were independent factors for PFS. Pre-treatment prognostic score was established based on clinical stage, ECOG PS, LDH, Alb and PLR to classify patients into three groups: the good group (0–1 score), the intermediate group (2 scores) and the poor group (3-4 scores). The immunotherapy response was significantly different in various prognostic groups. Subset analyses showed pre-treatment prognostic score ≥ 3 tended to have a strong negative impact on survival among patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 50%.
Pre-treatment prognostic score based on clinical stage, ECOG PS, LDH, Alb and PLR may help to identify aNSCLC patients who may benefit from ICIs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich ...PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair.
TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively.
Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE 2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III.
These findings indicate that, while both L-PRP and P-PRP appear to be "safe" in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to treat acutely injured tendons, it may result in the formation of excessive scar tissue due to the strong potential of P-PRP to induce inordinate cellular anabolic effects.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK