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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert j.Thomas m.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William j.Flerlage mark L.Dell’Acqua Brian m.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

Arctic sea-ice extent: No record minimum in 2023 or recent years

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 52-55页

作者： Ola m.johannessen Tor I.Olaussen Nansen Scientific Society BergenNorway Nansen Environmental and Remote Sensing Center BergenNorway

Arctic sea-ice extent reaches its minimum each year in September. On 11 September 2023 the minimum was 4.969 million square kilometers(***^(2)). This was not a record low, which occurred in 2012, when the minimum was 4.175 ***^(2), 0.794 ***^(2) less than the minimum in 2023. However, the ice extent had decreased by 0.432 ***^(2) compared with 2022. Nevertheless, the summer melting in 2023 was remarkably less than expected when considering the strong heat waves in the atmosphere and ocean, with record temperatures set around the world. In general, there is a high correlation between the long-term decrease in sea-ice extent and the increasing CO_(2) in the atmosphere, where the increase of CO_(2) in recent decades explains about 80% of the decrease in sea ice in September, while the remainder is caused by natural variability.

关键词： Sea ice Arctic minimum ice Climate

A simultaneous approach for integration of thermal energy storages in industrial processes using multiperiod heat integration

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Energy Storage and Saving 2022年第2期1卷 117-128页

作者： Simon möhren Christian Schäfer jörg meyer Hartmut Krause SWK E2 Institute for Energy Technology and Energy management Hochschule Niederrhein University of Applied ScienceKrefeld47805Germany Institute of Thermal Engineering TU Bergakademie FreibergFreiberg09599Germany

In times of increasing global warming,enormous efforts are required to rapidly reduce greenhouse gas(GHG)*** to the EU’s target of climate neutrality by 2050 and the even more ambitious goal of becoming climate-neutral in Germany by 2045,it is necessary to systematically increase energy efficiency and decarbonize the industrial heat *** methods of heat integration can be used to exploit existing potentials for waste heat utilization and to integrate renewable technologies for heating and *** using a non-stationary,multiperiod approach,additional energy savings can be achieved by integrating a thermal energy storage(TES)that enables heat transportation over *** paper presents a simultaneous approach for thermal energy storage integration into multiperiod heat integration *** approach can be used to minimize energy demand,costs and CO 2 emissions and is demonstrated in two case *** case study 1,it is shown that the presented approach is capable of integrating a TES properly into a simple multiperiod heat integration problem with two *** case study 2,a simplified example from a cosmetics manufactory is *** total utility demand can be reduced by up to 44.3%due to TES integration and the energetic optimal storage size can be determined as 125 m *** savings are strongly dependent on the constellation of heat flows between the periods,on the temperature levels and on the storage *** reductions of energy demand,costs and CO 2 emissions can be achieved with TES being properly integrated into a suitable operating environment.

关键词： multiperiod heat integration Thermal energy storage Waste heat utilization Heat exchanger network Energy efficiency

Cancer drug resistance: a new perspective

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Cancer Drug Resistance 2018年第1期1卷 1-5页

作者： godefridus j.Peters Laboratory medical Oncology VU University Medical CenterCancer Center AmsterdamAmsterdam 1007 MBThe Netherlands

INTRODUCTION Cancer drug resistance has been and unfortunately still is a major problem in cancer *** any therapy(except surgery)that is being used in the treatment of cancer can result in *** there is a large group of patients that will either not respond to the applied therapy(intrinsic resistance)or will become resistant during therapy(acquired resistance).Sometimes patients can become resistant to one specific drug and remain sensitive to other drugs(one-drug resistance);another group of patients may become resistant to one drug and will be resistant to other unrelated drugs as well(multiple drug resistance,mDR).

关键词： drugs Cancer drug

Protective autophagy by thymidine causes resistance to rapamycin in colorectal cancer cells in vitro

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Cancer Drug Resistance 2021年第3期4卷 719-727页

作者： I.V.Bijnsdorp godefridus j.Peters Department of medical Oncology Amsterdam UMClocation VUMC1007 MB AmsterdamNetherlands Department of Urology Amsterdam UMClocation VUMC1007 MB AmsterdamNetherlands Department of Biochemistry Medical University of Gdansk80-210 GdanskPoland

Aim:Thynidine phosphorylase(TP)acts as a proangiogenic growth factor which may regulate mammalian Target of Rapamycin(mTOR).We investigated whether the TP substrate thymidine and overexpression of TP affected mTOR signaling by comparing Colo320(TP deficient)cells and its TP-transfected variant(Colo320TP1).methods:Drug resistance was assessed with the sulforhodamine B assay,protein expression with Western blotting,cell cycle distribution and cell death with Fluorescence-activated cell sorting analysis,and autophagy with ***:Colo320 and Colo320TP1 cells had comparable levels of sensitivity to the mTOR inhibitor *** treatment led to 13-and 50-fold resistance to rapamycin in Colo320 and Colo320TP1 cells,*** Colo320TP1 cells,the thymidine phosphorylase inhibitor(TPI)reversed the thymidine induced resistance to rapamycin,but not in Colo320 cells,indicating a role for TP in the *** increased p70/S6k-phosphorylation(downstream of mTOR)in Colo320TP1,but it was not affected in *** a mechanism behind resistance,we studied the levels of autophagy and found that,in Colo320TP1 cells,autophagy was highly induced by thymidine-rapamycin,which was decreased by *** addition,the autophagy inhibitor 3-methyl-adenine completely inhibited autophagy and its ***:Rapamycin resistance in TP-expressing cancer cells may therefore be related to thymidine-mediated autophagy activation.

关键词： Thymidine phosphorylase mTOR rapamycin thymidine thymidine phosphorylase inhibitor autophagy

Role of Akt signaling in resistance to DNA-targeted therapy

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World journal of Clinical Oncology 2016年第5期7卷 352-369页

作者： Abolfazl Avan Ravi Narayan Elisa Giovannetti godefridus j Peters Department of medical Oncology VU University Medical Center Department of Radiation Oncology VU University Medical Center

The Akt signal transduction pathway controls most hallmarks of cancer. Activation of the Akt cascade promotes a malignant phenotype and is also widely implicated in drug resistance. Therefore, the modulation of Akt activity is regarded as an attractive strategy to enhance the efficacy of cancer therapy and irradiation. This pathway consists of phosphatidylinositol 3 kinase(PI3K), mammalian target of rapamycin, and the transforming serine-threonine kinase Akt protein isoforms, also known as protein kinase B. DNA-targeted agents, such as platinum agents, taxanes, and antimetabolites, as well as radiation have had a significant impact on cancer treatment by affecting DNA replication, which is aberrantly activated in malignancies. However, the caveat is that they may also trigger the activation of repairing mechanisms, such as upstream and downstream cascade of Akt survival pathway. Thus, each target can theoretically be inhibited in view of improving the potency of conventional treatment. Akt inhibitors, e.g., mK-2206 and perifosine, or PI3K modulators, e.g., LY294002 and Wortmannin, have shown some promising results in favor of sensitizing the cancer cells to the therapy in vitro and in vivo, which have provided the rationale for incorporation of these novel agents into multimodality treatment of different malignancies. Nevertheless, despite the acceptable safety profile of some of these agents in the clinical studies, with regard to the efficacy, the results are still too preliminary. Hence, we need to wait for the upcoming data from the ongoing trials before utilizing them into the standard care of cancer patients.

关键词： Phosphatidylinositol 3 kinase/Akt Platinum Taxane Antimetabolite Radiation

Thermoelastic Analysis of Non-uniform Pressurized Functionally Graded Cylinder with Variable Thickness Using First Order Shear Deformation Theory(FSDT) and Perturbation method

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Chinese journal of mechanical Engineering 2015年第6期28卷 1149-1156页

作者： KHOSHGOFTAR m j mIRZAALI m j RAHImI G H Faculty of mechanical Engineering Tarbiat Modares University Department of mechanical Engineering Faculty of Engineering Arak University Department of mechanical Engineering Politecnico di Milano

Recently application of functionally graded materials（FGms） have attracted a great deal of interest. These materials are composed of various materials with different micro-structures which can vary spatially in FGms. Such composites with varying thickness and non-uniform pressure can be used in the aerospace engineering. Therefore, analysis of such composite is of high importance in engineering problems. Thermoelastic analysis of functionally graded cylinder with variable thickness under non-uniform pressure is considered. First order shear deformation theory and total potential energy approach is applied to obtain the governing equations of non-homogeneous cylinder. Considering the inner and outer solutions, perturbation series are applied to solve the governing equations. Outer solution for out of boundaries and more sensitive variable in inner solution at the boundaries are considered. Combining of inner and outer solution for near and far points from boundaries leads to high accurate displacement field distribution. The main aim of this paper is to show the capability of matched asymptotic solution for different non-homogeneous cylinders with different shapes and different non-uniform pressures. The results can be used to design the optimum thickness of the cylinder and also some properties such as high temperature residence by applying non-homogeneous material.

关键词： non-homogenous cylinder First order Shear Deformation Theory matched asymptotic method perturbation method functionally graded material

Frequency-dependent viscoelasticity effects on the wave attenuation performance of multi-layered periodic foundations

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Applied mathematics and mechanics(English Edition) 2024年第3期45卷 407-424页

作者： m.SAFI m.VAKILIFARD m.j.mAHmOODI Faculty of Civil Water&Environmental EngineeringShahid Beheshti UniversityTehran ***Iran Faculty of mechanical and Energy Engineering Shahid Beheshti UniversityTehran ***Iran

In this paper,layered periodic foundations(LPFs)are numerically examined for their responses to longitudinal and transverse modes in the time and frequency *** different unit-cells,i.e.,2-layer,4-layer,and 6-layer unit-cells,comprising concrete/rubber,concrete/rubber/steel/rubber,and concrete/rubber/steel/rubber/lead/rubber materials,respectively,are taken into ***,the viscoelasticity behavior of the rubber is modeled with two factors,i.e.,a frequency-independent(FI)loss factor and a linear frequency-dependent(FD)loss *** the extraction of the complex dispersion curves and the identification of the band gaps(BGs),the simulations of wave transmission in the time and frequency domains are performed using the COmSOL *** parametric studies evaluate the effects of the rubber viscoelasticity models on the dispersion curves and the wave transmission for the longitudinal and transverse *** results show that considering the rubber viscoelasticity enhances the wave attenuation ***,the transverse-mode damping is more sensitive to the viscoelasticity model than its longitudinal *** 6-layer unit-cell LPF exhibits the lowest BG,ranging from 4.8 Hz to 6.5 Hz.

关键词： layered metamaterial periodic foundation complex dispersion curve wave transmission diagram