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Genistein:a possible solution for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2903-2905页

作者： Karolina Pierzynowska Bartosz Karaszewski Grzegorz węgrzyn Department of Molecular Biology University of GdanskGdanskPoland Gdansk Polandand Department of Adult NeurologyFaculty of MedicineMedical University of GdanskGdanskPoland

Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous *** can lead to severe nervous system dysfunction,eventually affecting multiple organs and *** hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.

关键词： organs Alzheimer death

Comprehensive lifestyle intervention vs soy protein-based meal regimen in non-alcoholic steatohepatitis

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world Journal of Gastroenterology 2019年第9期25卷 1116-1131页

作者： Peter Deibert Adhara Lazaro Denise Schaffner Aloys Berg Daniel Koenig wolfgang Kreisel manfred w.baumstark Daniel Steinmann Martin Buechert Thomas Lange Faculty of Medicine Department of MedicineInstitute of Exercise and Occupational MedicineMedical CenterUniversity of Freiburg Department of Nutrition Institute for Sports and Sports ScienceUniversity of Freiburg Faculty of Medicine Department of MedicineDivision of GastroenterologyHepatologyEndocrinology and Infectious DiseasesMedical CenterUniversity of Freiburg University Hospital of Freiburg Occupational Medicine Faculty of Medicine Department of Radiology-Medical PhysicsMedical CenterUniversity of Freiburg

BACKGROUND Non-alcoholic steatohepatitis(NASH) has become one of the leading causes of liver disease in the western world. In obese patients weight reduction is recommended. Up to now there are no specific guidelines for weight loss in order to reduce hepatic fat *** To investigate the effects of a 24-wk guided lifestyle intervention program compared to a meal replacement regimen based on soy *** Twenty-six subjects with NASH participated in a randomized single-center study. They were randomly assigned to either meal replacement group(MR-G)with soy-yogurt-honey preparation or to guided lifestyle change group(LC-G)with endurance activity and nutrition counselling. Serum alanine transaminase(ALT), aspartate transaminase(AST), lipid parameters, and adipokines were measured. Liver fat content and lipid composition were determined by magnetic resonance imaging and magnetic resonance spectroscopy. Body fat mass and lean body mass were assessed using Bod Pod? device. Pre-and post-intervention monitoring of parameters was performed. Statistical analyses were conducted with SPSS software, results were expressed as median(interquartile range).RESULTS Twenty-two subjects(MR-G, n = 11 and LC-G, n = 11) completed the study(9 women, 13 men; age 52.1(15.0) years, body mass index(BMI) 32.3(3.3) kg/m^2).In both groups a significant weight loss was achieved(MR-G:-6.4(3.6) kg, P were markedly reduced in both groups in comparable amount. There was a strong correlation between reduction in liver fat and decrease in ***, both groups showed an improvement in glycemic control and lipid profile. Changes in adipokines, particularly in adiponectin and leptin were closely related to intrahepatic lipid *** Comprehensive lifestyle intervention and meal replacement regimen have compar

关键词： Non-alcoholic steatohepatitis Meal replacement therapy Soy protein Lifestyle change weight reduction Obesity

Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension

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world Journal of Gastroenterology 2018年第38期24卷 4356-4368页

作者： Denise Schaffner Adhara Lazaro Peter Deibert Peter Hasselblatt Patrick Stoll Lisa Fauth manfred w.baumstark Irmgard Merfort Annette Schmitt-Graeff wolfgang Kreisel Institute for Exercise-und Occupational Medicine Faculty of MedicineUniversity of FreiburgFreiburg 79106Germany Department of Medicine II GastroenterologyHepatologyEndocrinologyand Infectious DiseasesFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany Anaesthesiological Practice Freiburg 79104Germany Institute of Clinical Pathology Faculty of MedicineUniversity of FreiburgFreiburg 79106Germany Department of Pharmaceutical Biology and Biotechnology University of FreiburgFreiburg 79104Germany

AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver *** In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure *** Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpres

关键词： Portal hypertension Thioacetamide Nitric oxide Liver cirrhosis Cyclic guanosine monophosphate Phosphodiesterase-5 Sildenafil Hepatic stellate cells Metabolic zonation

Glia-to-neuron reprogramming to the rescue?

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Neural Regeneration Research 2025年第5期20卷 1395-1396页

作者： Jack w.Hickmott Cindi M.Morshead Department of Surgery University of TorontoTorontoONCanada Donnelly Centre for Cellular and Biomolecular Research TorontoONCanada Institute of Biomedical Engineering University of TorontoTorontoONCanada The KITE Research Institute Toronto Rehabilitation InstituteUniversity Health NetworkTorontoONCanada

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative *** brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be *** exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

关键词： programming passing proof

Dynamic modeling of a three-dimensional braided composite thin plate considering braiding directions

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 123-138页

作者： Chentong GAO Huiyu SUN Jianping GU w.M.HUANG College of Aerospace Engineering Nanjing University of Aeronautics and Astronautics School of Mechanical and Aerospace Engineering Nanyang Technological University Jiangsu Key Laboratory of Advanced Structural Materials and Application Technology School of Materials Science and EngineeringNanjing Institute of Technology

Currently, there are a limited number of dynamic models available for braided composite plates with large overall motions, despite the incorporation of three-dimensional(3D) braided composites into rotating blade components. In this paper, a dynamic model of 3D 4-directional braided composite thin plates considering braiding directions is established. Based on Kirchhoff's plate assumptions, the displacement variables of the plate are expressed. By incorporating the braiding directions into the constitutive equation of the braided composites, the dynamic model of the plate considering braiding directions is obtained. The effects of the speeds, braiding directions, and braided angles on the responses of the plate with fixed-axis rotation and translational motion, respectively, are investigated. This paper presents a dynamic theory for calculating the deformation of 3D braided composite structures undergoing both translational and rotational motions. It also provides a simulation method for investigating the dynamic behavior of non-isotropic material plates in various applications.

关键词： Constitutive equations

Ultrastructural cellular signatures: does cellular form follow function?

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National Science Review 2019年第5期6卷 861-863页

作者： manfred Auer Molecular Biophysics and Integrated Bioimaging Division Lawrence Berkeley National Laboratory

In his watershed 1896 essay The Tall Office Building Artistically Considered,protomodern architect Louis Sullivan famously declared that ‘form follows function’.Could this concept also hold true in biology? Have cel... 详细信息

关键词： Ultrastructural cellular signatures does cellular form follow function

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

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Neural Regeneration Research 2025年第11期20卷 3063-3075页

作者： Stephen Vidman Yee Hang Ethan Ma Nolan Fullenkamp Giles w.Plant Department of Neuroscience Ohio State UniversityColumbusOHUSA

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative *** the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained *** work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as *** embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns *** barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem *** advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal *** precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed *** the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma *** of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of *** the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor ***,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support ***,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for *** to a clinical setting wi

关键词： axon regeneration central nervous system regeneration induced pluripotent stem cells neurotrauma regenerative medicine spinal cord injury stem cell therapy

一种达到最高效率的新型软切换三电平逆变器拓扑结构(英文)

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中国电机工程学报 2013年第21期33卷 1-8,187页

作者： manfred w.Gekeler HTwG康斯坦茨应用科技大学

软开关三电平逆变器（soft switching three-level inverter,S3L）于2011年首次推出。它代表了脉宽调制（pulsewidth modulation,PwM）逆变器的一种新的拓扑结构,应用于电力驱动,光伏和风力发电厂的并网逆变器,以及用于供电领域。因其... 详细信息

软开关三电平逆变器（soft switching three-level inverter,S3L）于2011年首次推出。它代表了脉宽调制（pulsewidth modulation,PwM）逆变器的一种新的拓扑结构,应用于电力驱动,光伏和风力发电厂的并网逆变器,以及用于供电领域。因其结构非常简单,所以价格相当低廉。它完全在软切换模式下运行,并且持续表现出极低的切换损耗。其结果是,效率非常高,而且可以实现特别高的切换频率。该论文对其功能进行描述,还展示一部输出电源为20~90 kVA的逆变器样品,并对测试结果作详细说明。

关键词：逆变器三电平逆变器软切换效率电力驱动并网逆变器光伏逆变器风力发电逆变器

Melanoma development: stage-dependent cancer competence of the melanocytic lineage

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Signal Transduction and Targeted Therapy 2022年第1期7卷 13-14页

作者： manfred Kunz Department of Dermatology Venereology and AllergologyUniversity Medical Center LeipzigPhilipp-Rosenthal-Str.2304155 LeipzigGermany

In a recent article in Science,Baggiolini et al.^(1) showed that the transforming ability of the BRAFM6QQE oncogene for melanoma development depends on the stage of the transformed melanocyte lineage *** neural crest cells and melanoblasts are vulnerable to malignant transformation in a zebrafish model,melanocytes only developed small patches of nevus-like cells after BRARJ6QQE expression.

关键词： expression. al. melan