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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

Effect of inorganic and organic fertilizers on productivity of groundnut(Arachis hypogaea L.)varieties in East Hararghe,Eastern Ethiopia

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Oil Crop Science 2022年第3期7卷 112-121页

作者： Getachew Bekele Nigussie Dechassa Tamado tana Department of Plant Sciences Bedele College of Agriculture and Forestry Mettu UniversityEthiopia School of Plant Sciences College of Agriculture and Environmental SciencesHaramaya UniversityEthiopia

Groundnut(Arachis hypogaea L.)is a high economic value oil crop commonly grown in low-land semi-arid areas of *** crop production is constrained by low soil fertility;however,the nutrient management practice has been given low *** study was therefore conducted during the main cropping season of 2015/2016 at Babile and Fedis sites of East Hararghe,Ethiopia to evaluate the growth,nodulation,and yield response of groundnut varieties to the application of combined mineral nitrogen,phosphorus,and vermicompost fertilizers,and *** consisted of a factorial combination of three varieties(Ba-ha-Gudo,Ba-ha-jidu,and Roba);three fertilizers combinations(0:0 kg N:POhawith no VC,46:46 kg N:POhawith no VC,and 46:46 kg N:POhawith 2.5 t VC ha);and three rates of Zn(0,5,and 10 kg Zn ha)in a randomized complete block design at both *** growth,nodulation,yield components,and yield data were subjected to analysis by *** result revealed that plant height was significantly affected by variety and fertilizers combination,the number of branches plant-1affected by the interaction of variety and fertilizers combination while canopy spread and nodulation parameters were affected by the interaction of variety,fertilizers combination,and Zn *** plant-1and hundred seed weight,dry biomass,pod and seed yields,and seed oil content were significantly affected by the interaction of variety,fertilizers combination,and Zn *** highest dry biomass(7.26 t ha),pod(3.13 t ha),seed(2.16 t ha)yields and seed oil content(51.3%),net benefit($1704.2 ha)with a marginal rate of return of 242%were obtained from variety Ba-ha Gudo received the combined application of 46:46 kg N:POhaand 2.5 t VC hawith 5 kg Zn ***,it can be concluded that the Ba-ha Gudo variety is preferably produced using the combined application of 46:46 kg N:POhaand 2.5 t VC hawith 5kg Zn hafor high productivity in the study sites and similar agro-ecologies.

关键词： Fertilizers combination Oil content Vermicompost Zinc

multivariate adaptive regression splines analysis for 3D slope stability in anisotropic and heterogenous clay

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journal of Rock mechanics and Geotechnical Engineering 2023年第4期15卷 1052-1064页

作者： jim Shiau Van qui Lai Suraparb Keawsawasvong School of Civil Engineering and Surveying University of Southern QueenslandToowoombaQueensland4350Australia Faculty of Civil Engineering Ho Chi Minh City University of Technology(HCMUT)268 Ly Thuong Kiet StreetDistrict 10Ho Chi Minh CityViet Nam Vietnam National University Ho Chi minh City(VNU-HCm) Linh Trung WardThu Duc DistrictHo Chi Minh CityViet Nam Department of Civil Engineering Thammasat School of EngineeringThammasat UniversityPathumthaniBangkok12120Thailand

Little research can be found in relation to the stability of anisotropic and heterogenous soils in three *** this paper,we propose a study on the three-dimensional(3D)undrained slopes in anisotropic and heterogenous clay using advanced upper and lower bounds finite element limit analysis(FELA).The obtained stability solutions are normalized,and presented by a stability number that is a function of three geometrical ratios and two material ratios,*** ratio,length ratio,slope angle,shear strength gradient ratio and anisotropic strength *** results are compared with experimental data in the literature,and charts are presented to cover a wide range of design *** the multivariate adaptive regression splines(mARS)analysis,the respective influence and sensitivity of each design parameter on the stability number and the failure mechanism are *** empirical equation is also developed to effectively estimate the stability number.

关键词： 3D undrained slope Limit analysis Anisotropy Heterogeneity

Effect of martensitic transformation on nano/ultrafine-grained structure in 304 austenitic stainless steel

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journal of Iron and Steel Research International 2017年第12期24卷 1231-1237页

作者： Na Gong Hui-bin Wu Gang Niu jia-ming Cao Da Zhang tana Instituted Engineering Technology University of Science and Technology BeijingBeiking 100083China Collaborative Innovation Center of Steel Technology University of Science and Technology BeijingBeijing 100083China Sinohydro Renewable Energy Co. Ltd.Beijing 100083China

304 austenitic stainless steel was cold rolled in the range of 20%-80%reductions and then annealed at 700-900°C for 60 sto obtain nano/ultrafine-grained（NG/UFG）*** electron microscopy,electron backscatter diffraction and X-ray diffraction were used to characterize the resulting *** results showed that with the increase of cold reduction,the content of martensite was *** steel performed work hardening during cold-working owing to the occurrence of strain induced martensite which nucleated in single shear *** rolling broke up the lath-type martensite into dislocation-cell type martensite because of the formation of slip *** annealed at 800-960°C for 60 swere of NG/UFG structure with different percentage of nanocrystalline（60-100 nm）and ultrafine（100-500 nm）grains,submicron size（500-1000 nm）grains and micron size（〉1000 nm）*** value of the Gibbs free energy exhibited that the reversion mechanism of the reversion process was shear controlled by the annealing *** a certain annealing time during the reversion process,austenite nucleated first on dislocation-cell type martensite and the grains grew up subsequently and eventually to be micrometer/submicrometer grains,while the nucleation of austenite on lath-type martensite occurred later resulting in nanocrystalline/ultrafine *** existence of the NG/UFG structure led to a higher strength and toughness during tensile test.

关键词： 304 austenitic stainless steel Nano/ultrafine-grained structure Reversion mechanism Lath-type martensite Dislocation-cell type martensite martensitic transformation

Development of a miniaturized 3D organoid culture platform for ultra-high-throughput screening

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journal of molecular Cell Biology 2020年第8期12卷 630-643页

作者： Yuhong Du Xingnan Li Qiankun Niu Xiulei mo min qui Tingxuan ma Calvin j.Kuo Haian Fu Department of Pharmacology and Chemical Biology and Emory Chemical Biology Discovery Center Emory University School of MedicineAtlantaGAUSA Department of medicine Division of HematologyStanford University School of MedicineStanfordCAUSA

The recent advent of robust methods to grow human tissues as 3D organoids allows us to recapitulate the 3D architecture of tumors in an in vitro setting and offers a new orthogonal approach for drug ***,organoid culturing with extracellular matrix to support 3D architecture has been challenging for high-throughput screening(HTS)-based drug discovery due to technical *** genetically engineered human colon organoids as a model system,here we report our effort to miniaturize such 3D organoid culture with extracellular matrix support in high-density plates to enable *** first established organoid culturing in a 384-well plate format and validated its application in a cell viability HTS assay by screening a 2036-compound *** further miniaturized the 3D organoid culturing in a 1536-well ultra-HTS format and demonstrated its robust performance for large-scale primary compound *** miniaturized organoid culturing method may be adapted to other types of *** leveraging the power of 3D organoid culture in a high-density plate format,we provide a physiologically relevant screening platform to model tumors to accelerate organoid-based research and drug discovery.

关键词： human colon organoids KRAS^G12D 3D culture 384-well plate high-throughput screening(HTS) 1536-well plate ultra-HTS(uHTS)

Complete clinical response of liver metastasis after chemotherapy:To resect or not?

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World journal of Gastrointestinal Oncology 2011年第7期3卷 107-110页

作者： jose m Ramia-Angel Roberto De la Plaza jose E quiones HPB Surgical Unit Department of Surgery Universitary Hospital of Guadalajara

This paper aims to update the therapeutical strategies in liver metastasis with complete clinical response(CCR) after chemotherapy and to determine if surgery is always necessary after *** aim of chemotherapy is to achieve a good clinical response rather than CCR of liver *** CCR of liver metastasis after chemotherapy cannot be considered synonymous with a *** resection of the hepatic segment where there was hepatic metastases with CCR after chemotherapy theoretically prevents recurrence,improves survival and makes it possible to conf irm whether there has been a complete pathological ***,the medical literature about this topic is scarce and sometimes contradictory.

关键词： metastasis Liver Clinical response Chemotherapy Surgery

Extremely thin but very robust:Surprising cryptogam trait combinations at the end of the leaf economics spectrum

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Plant Diversity 2024年第5期46卷 621-629页

作者： tana Wuyun Lu Zhang Tiina Tosens Bin Liu Kristiina mark joséÁngel morales-Sanchez jesamine jöneva Rikisahedew Vivian Kuusk Ülo Niinemets Institute of Agricultural and Environmental Sciences Estonian University of Life SciencesKreutzwaldi 1Tartu 51014Estonia College of Landscape and Architecture Zhejiang A&F University666 Wusu StreetHangzhou 311300China Estonian Academy of Sciences Kohtu 6Tallinn 10130Estonia

Leaf economics spectrum(LES)describes the fundamental trade-offs between leaf structural,chemical,and physiological ***,structurally robust thick leaves with high leaf dry mass per unit area(LmA)exhibit lower photosynthetic capacity per dry mass(Amass).Paradoxically,“soft and thinleaved”mosses and spikemosses have very low Amass,but due to minute-size foliage elements,their LmA and its components,leaf thickness(LT)and density(LD),have not been systematically ***,we characterized LES and associated traits in cryptogams in unprecedented details,covering five evolutionarily different *** found that mosses and spikemosses had the lowest LmA and LT values ever measured for terrestrial *** a broad range of species from different lineages,Amass and LD were negatively *** contrast,Amass was only related to LmA when LmA was greater than 14 g cm^(-2).In fact,low Amass reflected high LD and cell wall thickness in the studied *** conclude that evolutionarily old plant lineages attained poorly differentiated,ultrathin mesophyll by increasing *** plant lineages,LD,not LmA,is the trait that represents the trade-off between leaf robustness and physiology in the LES.

关键词： Investment strategy Leaf density Leaf structural traits LmA estimation bias Non-seed plants Trait trade-offs

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