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Brain-penetrating neurotrophic factor mimetics: HER-096 as a disease-modifying therapy for Parkinson’s disease

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Neural Regeneration Research 2025年第4期20卷 1094-1095页

作者： Natalia Kulesskaya Kira m.Holmström Henri j.Huttunen Herantis Pharma Plc EspooFinland

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying *** for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,*** that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

关键词： diseases treatment therapeutic

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

Biochar and Compost Increase Crop Yields but the Effect is Short Term on Sandplain Soils of Western Australia

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Pedosphere 2015年第5期25卷 720-728页

作者： David j.m.HALL Richard W.bell Department of Agriculture and Food School of veterinary and Life Sciences Murdoch University

Sandplain soils on the south coast of Western Australia have low inherent fertility, which is mainly due to poor nutrient retention caused by insufficient clay and organic colloidal material. Previous research has shown the benefits in nutrient levels and retention from adding clay to sandplain soils; however, there is almost no information on the addition of organic amendments. A field experiment was established at the Esperance Downs Research Station, Western Australian, in may 2010, to assess the effects of wheat straw(WS) and chicken manure(Cm) biochars and compost with and without phosphorus(P) addition on soil properties and crop production over five growing seasons. The five seasons alternated between winter and summer crops. The Cm and WS biochar and compost treatments significantly increased crop yields and P uptake in 3, 2 and 1 of the five seasons, respectively. The yield increases(P more than 8%. By the end of the third season, no differences in crop yields were found that could be attributed to the organic amendments. The addition of P increased crop yields in each winter cropping season. Phosphorus addition explained more than 30%of the variation in crop yields. Despite marginal P levels and summer drought conditions, arbuscular mycorrhizal root colonisation was not affected by the organic amendments. There were no significant interactions between the organic amendments and P addition in terms of crop yields, P uptake or P uptake efficiency. We conclude that much of the effect of the organic amendments was due to direct nutrient addition which dissipated over time.

关键词： mycorrhizal root colonisation nutrient retention organic amendments P addition P uptake

Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

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Neural Regeneration Research 2025年第6期20卷 1565-1581页

作者： moawiah m.Naffaa Department of Psychology and Neuroscience Duke UniversityDurhamNCUSA Department of Cell Biology Duke University School of MedicineDurhamNCUSA

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased

关键词： network adaptability neurogenesis neuronal communication olfactory bulb olfactory learning olfactory memory synaptic plasticity

SBL-jP-0004:A promising dual inhibitor of jAK2 and PI3KCD against gastric cancer

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Oncology Research 2025年第1期33卷 235-243页

作者： HASSAN m.OTIFI Department of Pathology College of MedicineKing Khalid UniversityAbha62521Saudi Arabia

Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional *** phosphoinositide 3-kinase and PI3K and janus kinase(jAK)signal transducer and activator of transcription(jAK-STAT)pathways play pivotal roles in GC progression,making them attractive targets for therapeutic ***:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-jP-0004 as a potential dual inhibitor of jAK2 and PI3KCD *** and SNU-5 GC cells were used for in vitro ***:SBL-jP-0004 exhibited a robust binding affinity for jAK2 and PI3KCD kinases,as evidenced by molecular docking scores and molecular dynamics *** interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target ***-jP-0004 displayed an half-maximal inhibitory concentration(IC_(50))value of 118.9 nm against jAK2 kinase and 200.9 nm against PI3KCD ***-jP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells,with half-maximal growth inhibitory concentration(GI50)values of 250.8 and 516.3 nm,respectively.A significant elevation in the early phase apoptosis(28.53%in KATOIII cells and 26.85%in SNU-5 cells)and late phase apoptosis(17.37%in KATOIII cells and 10.05%in SNU-5 cells)were observed with SBL-jP-0004 treatment compared to 2.1%and 2.83%in their respective ***:The results highlight SBL-jP-0004 as a promising dual inhibitor targeting jAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： Gastric cancer(GC) Dual inhibition jAK2 PI3KCD SBL-jP-0004 molecular docking molecular dynamics simulation

mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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维普期刊数据库

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： josém.Izquierdo Centro de Biología molecular Severo Ochoa(CBm) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： josep Tomàs víctor Cilleros-mañé Laia just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal marta Tomàs Carolina Silvera-Simón manel m.Santafé maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

Consistent individual differences in fathering in threespined stickleback Gasterosteus aculeatus

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Current Zoology 2012年第1期58卷 45-52页

作者： Laura R Stein Alison m bell Department of Animal Biology University of Illinois Urbana-Champaign Urbana IL 61801 USA.

There is growing evidence that individual animals show consistent differences in behavior. For example, individual threespined stickleback fish differ in how they react to predators and how aggressive they are during social interactions with con- specifics. A relatively unexplored but potentially important axis of variation is parental behavior. In sticklebacks, fathers provide all of the parental care that is necessary for offspring survival; therefore paternal care is directly tied to fitness. In this study, we assessed whether individual male sticklebacks differ consistently from each other in parental behavior. We recorded visits to nest, total time fanning, and activity levels of 11 individual males every day throughout one clutch, and then allowed the males to breed again. Half of the males were exposed to predation risk while parenting during the first clutch, and the other half of the males ex- perienced predation risk during the second clutch. We detected dranlatic temporal changes in parental behaviors over the course of the clutch： for example, total time fanning increased six-fold prior to eggs hatching, then decreased to approximately zero. De- spite these temporal changes, males retained their individually-distinctive parenting styles within a clutch that could not be ex- plained by differences in body size or egg mass. moreover, individual differences in parenting were maintained when males re- produced for a second time. males that were exposed to simulated predation risk briefly decreased fanning and increased activity levels. Altogether, these results show that individual sticklebacks consistently differ from each other in how they behave as parents [Current Zoology 58 （1）： 45-52, 2012].

关键词： Paternal care Personality Behavioral syndrome Fathers Temperament Antipredator behavior