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Lymphoma is the third most common cancer diagnosed in children, and T-cell lymphoma has the worst prognosis based on clinical observations. To date, a lymphoma model with uniform penetrance has not yet been developed. In this study, we generated a p53 deficient mouse model by targeting embryonic stem cells derived from a C57BL/6J mouse strain. Homozygous p53 deficient mice exhibited a higher rate of spontaneous tumorigenesis, with a high spontaneous occurrence rate (93.3%) of malignant lymphoma. Because tumor models with high phenotypic consistency are currently needed, we generated a lymphoma model by a single intraperitoneal injection of 37.5 or 75 mg/kg N-methyl-N-nitrosourea to p53 deficient mice. Lymphoma and retinal degeneration occurred in 100% of p53+/- mice administered with higher concentrations of N-methyl-N-nitrosourea, a much greater response than those of previously reported models. The main anatomic sites of lymphoma were the thymus, spleen, bone marrow, and lymph nodes. Both induced and spontaneous lymphomas in the thymus and spleen stained positive for CD3 antigen, and flow cytometry detected positive CD4 and/or CD8 cells. Based on our observations and previous data, we hypothesize that mice with a B6 background are prone to lymphomagenesis. [ABSTRACT FROM AUTHOR]

Burgeoning evidence has shown that neighborhood environments are related to depressive symptoms in the older population. Older adults living in residential care homes may be more vulnerable to environmental characteristics. The current study sought to understand how institutionalized older adults relate to environmental factors and residential satisfaction in terms of depressive symptoms. Data were collected from a cross-sectional national survey of 1,429 Chinese elders living in residential care homes. The findings reveal that 46.1% of the older Chinese residents living in residential care homes suffered from mild to severe depression. In addition, the current study finds that both environmental factors (e.g., geographic position, air quality, and transportation) and residential satisfaction are negatively associated with depressive symptoms. The findings support that residential satisfaction partially mediate the relationship between exterior environmental characteristics and depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Real-time polymerase chain reaction (PCR) has become an increasingly important technique for gene expression profiling because it can provide insights into complex biological and pathological processes and be used to predict disease or treatment outcomes. Although normalized data are necessary for an accurate estimation of mRNA expression levels, several pieces of evidence suggest that the expression of so-called housekeeping genes is not stable. This study aimed to validate reference genes for the normalization of real-time PCR in an N-methyl-N-nitrosourea (MNU)-induced T-cell lymphoma mouse model.Methods: T-cell lymphomas were generated in p53-deficient mice by treatment with 37.5 mg/kg MNU. Thymus and spleen were identified as the primary target organs with the highest incidences of lymphomas. We analyzed the RNA expression levels of eight potential endogenous reference genes (Gapdh, Rn18s, Actb, Hprt, B2M, Rplp0, Gusb, Ctbp1). The expression stabilities of these reference genes were tested at different time points after MNU treatment using geNorm and NormFinder algorithms.Results: A total of 65% of MNU-treated mice developed T-cell lymphomas, with the spleen and thymus as the major target organs. All candidate reference genes were amplified efficiently by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Gene stability evaluation after MNU treatment and during lymphomagenesis revealed that Ctbp1 and Rplp0 were the most stably expressed genes in the thymus and spleen, respectively. RT-PCR of thymus RNA using two additional sets of primer confirmed that Ctbp1 was the most stable of all the candidate reference genes.Conclusions: We provided suitable endogenous controls for gene expression studies in the T-cell lymphoma model. [ABSTRACT FROM AUTHOR]

An accurate description of the motion of bullets in ballistic gelatin penetration can only be given if a corresponding mathematical model is derived. In this paper, change of the effective wetted area of the bullet is studied well with the increase of angle of yaw in the penetration process. By introducing an area detached ratio and the influence of slenderness, a novel framework is proposed for drag and lift coefficients. Further, a new motion model of rifle bullet is established based on the new frameworks and validated by comparison with the results from experiment data and FEA. The comparative analysis shows that results of the new motion model have a better fit with experiment data than that of the traditional models in previous literatures and the proposed framework for drag and lift coefficients is better than the traditional ones in literatures by comparison with the numerical results. In addition, the calculation of the new motion model is in great accordance with FEA in terms of penetration depth, deflection path, yaw angle, velocity, lift force and drag force at different initial conditions. Benefitting from the motion model based on the new frameworks for drag and lift coefficients, the behavior of rifle bullet in gelatin penetration can be characterized accurately, the prediction of the distribution of energy deposited along the penetration trajectory and the potential for incapacitation of rifle bullets may become possible. [ABSTRACT FROM AUTHOR]

This study aims to explore the molecular mechanism and potential active ingredients of Danhe granules in improving the blood lipid level of hypercholesterolemia by intestinal TICE (transintestinal cholesterol excretion) through in vivo experimental research, network pharmacology methods, and molecular docking. The diet‐induced hypercholesterolemia rat model evaluated the effects of Danhe granules on fecal cholesterol levels and intestinal TICE‐related protein expression in rats. Based on the experimental results, the network pharmacology method was used to predict the potential active ingredients, and the binding strength between the potential active ingredients and key targets was further confirmed by molecular docking. Danhe granules increased LDLR, ABCG5, ABCB1, and LXRα which can promote the uptake of cholesterol by intestinal cells and the excretion of cholesterol into the intestine, and then reduce the levels of serum LDL‐C and TC and increase the level of fecal TC, so as to achieve the effect of treating hypercholesterolemia. The results of network pharmacology and molecular docking showed that 19 active ingredients had good binding activity with the targets. These may be the active ingredients of Danhe granules for the treatment of hypercholesterolemia. This study revealed the molecular mechanism of Danhe granules in the treatment of hypercholesterolemia via TICE, and preliminarily clarified the potential effective ingredients. It provides new ideas for the treatment of hypercholesterolemia and the development of new drugs. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether Activated 5'AMP-activated protein kinase (AMPK) activation enhances Fusarium solani (F. solani) fungicidal capacity of neutrophils. Methods: The expression of AMPK and phosphorylated-AMPK (p-AMPK) proteins was tested using Western Blot. Plate counting studied the effects of the fungicidal capacity of neutrophils enhanced by AMPK activation. Phagocytized spores by neutrophils were assessed by immunostaining and inhibited hyphal growth images were captured by JULI Stage real-time cell history recorder. Flow cytometry assay tested Reactive Oxygen Species (ROS) production and the percentage of apoptosis neutrophils. ROS Assay Kit also tested ROS production at different time points. The F. solani keratitis murine model was established, and slit-lamp microscopy captured corneal photographs. Results: Our experiments were divided into the following groups. Neutrophils (N), neutrophils+spores (N+S), neutrophils+spores+ 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) (N+S+A), neutrophils+spores+Compound C (N+S+C). AMPK activator AICAR significantly increased the expression of p-AMPK in neutrophils. The plate counting experiment showed that the number of colonies in the N+S+A was significantly less than in the N+S group. Immunostaining results showed phagocytized spores were significantly increased in the N+S+A group compared with the N+S group. Captured photographs by a real-time cell history recorder camera showed F. solani hyphal growth in the N+S+A group was significantly inhibited than in the N+S group. ROS release in the N+S+A group was significantly higher in the N+S+A group than in other groups. The percentage of apoptosis neutrophils in the N+S+A group was decreased than in the N+S group. Captured photographs by slit-lamp showed that AICAR eye drop treatment alleviated the severity and decreased clinical score at 12 and 24 hours post-infection (h.p.i) Conclusion: AMPK activation enhances the efficacy of neutrophils in killing F. solani in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Purpose: In wound ballistics, skin has obvious blocking effect in the biological target penetration of projectiles. An analytical description of skin mechanical properties under compression can set the basis for the numerical simulation and the evaluation of blocking effect. Methods: In this study, an improved three-parameter solid visco-elastic model was proposed to describe the skin creep phenomenon. And then combined with Maxwell and Ogden model, a new nonlinear skin constitutive model, consisting of hyper-elastic unit, creep unit and relaxation unit in parallel, was established. Here, we examine the material properties of freshly harvested porcine skin in compression at strain rates from 0.01/s to 4000/s. Results: The model is verified by comparison with the experimental results by our test and that in the literature at different strain rates. Conclusions: It shows that calculated results of the constitutive model agree well with the experiment data at extremely low to high strain rates, which is useful for the description of the heterogeneous, nonlinear viscoelastic, relaxation and creep mechanical response of skin under compression. [ABSTRACT FROM AUTHOR]

Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (*****35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively. [ABSTRACT FROM AUTHOR]