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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

Acoustic streaming and Sun's meridional circulation

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Research in Astronomy and Astrophysics 2016年第9期16卷 101-106页

作者： jose manuel valverde Faculty of Physics University of Seville

A vast number of physical processes involving oscillations of a bounded viscous fluid are relevantly influenced by acoustic streaming. When this happens a steady circulation of fluid develops in a thin boundary adjacent to the interface. Some examples are refracted sound waves, a fluid inside a spherical cavity undergoing torsional oscillations or a pulsating liquid droplet. Steady streaming around circular interfaces consists of a hemispherically symmetric recirculation of fluid from the equatorial plane to the polar axes closely resembling the meridional circulation pattern observed in the Sun＇s convection zone that determines the solar cycle. In this paper, it is argued that the acoustic pulsations exhibited by the Sun would lead to acoustic streaming in the boundary of the convection zone. A simple estimation using a typical dominant frequency of 3 mHz and the observed surface oscillation amplitude yields a steady streaming velocity Us - 10 m s^-1, which is on the order of the meridional circulation velocity observed in the Sun＇s convection zone.

关键词： Sun general -- Sun helioseismology -- Sun granulation -- Sun oscillations -- Sun fun-damental parameters -- Sun activity

magnetic field assisted fluidization:A modified Richardson-Zaki equation

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China Particuology 2007年第1期5卷 61-70页

作者： jose manuel valverde Antonio Castellanos Faculty of Physics Universidad de Sevilla Avenida Reina Mercedes s/n 41012 Sevilla Spain

magnetic particles can be uniformly fluidized by coupling the gas flow with an externally imposed magnetic field. Interparticle forces generated by the magnetic field cause aggregation of the particles in chain-like structures preferentially oriented along the magnetic field lines. In the present paper, we study the implications of the formation of these special types of aggregates on the empirical Richardson-Zaki （RZ） equation, originally proposed to describe the expansion of fluidized beds of non-aggregated particles. We have addressed two important issues, namely the flow regime, which is a function of the size of the aggregates, and the effect of shape and orientation of the chain-like aggregates with respect to gas flow on fluid drag. We propose a modified RZ equation （mRZE） in which the velocity scale, given by the terminal settling velocity of the individual aggregates, and the RZ exponent are predetermined as a function of the chain length. The chain length depends on the ratio of the magnetic energy to gravitational energy, and is estimated from the magnetic field intensity, and particle magnetization, size and density. Predictions of the mRZE are successfully compared with published results in the literature on the expansion of magnetic particles in the presence of externally applied magnetic fields.

关键词： Fluidization Geldart B magnetic particles Aggregation Richardson-Zaki equation

Condition-dependence and sexual ornamentation： Effects of immune challenges on a highly sexually dimorphic grasshopper

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Insect Science 2018年第4期25卷 617-630页

作者： j. Pablo valverde Hendrik Eggert joachim Kurtz Holger Schielzeth Department of Evolutionary Biology Bielefeld University Bielefeld Germany Institute for Evolution and Biodiversity Westfalische Wilhelms-Universitat Munster Munster Germany and 3 Department of Population Ecology Institute of Ecology Friedrich Schiller University Jena Germany Department of Population Ecology Institute of Ecology Friedrich Schiller University Jena Germany

Sexual ornaments contribute substantially to phenotypic diversity and it is particularly relevant to understand their evolution. Ornaments can assume the function of signals-of-quality that the choosy sex uses to evaluate potential mating partners. Often there are no obvious direct benefits and investment into mate choice is primarily rewarded by beneficial alleles that are inherited to the offspring. Inter-sexual communication via sexual ornaments requires honesty of the sexual signal, yet the question of what maintains honesty remains only partially solved. One solution is that honesty is maintained by trait expression being dependent on individual condition, since condition-dependent trait expression offers an effectively inexhaustible source of genetic variability. Here we test in the highly sexually dimorphic club-legged grasshopper Gomphocerus sibiricus if putative sexual ornaments, in particular the striking front-leg clubs, are more strongly affected by a lipopolysaccharide （LPS） immune challenge than putatively not sexually selected traits. Our results show overall little condition-dependent expression of morphological and song traits, with sexually selected traits exhibiting effects comparable to nonsexually selected traits （with the possible exception of stridulatory file length and syllable-to-pause ratio in advertisement songs）. Interestingly, field observations of individuals of lethally parasitized individuals suggest that a very strong environmental challenge can specifically affect the expression of the front-leg clubs. The presence of 1% of males in natural populations with missing or heavily deformed clubs plus 5% with minor club deformations furthermore indicate that there are risks associated with club development during final ecdysis and this might act as a filter against deleterious alleles.

关键词： Acrididae honest signaling Orthoptera phenotypic plasticity sexualselection

Effect of dietary fibre on the gastrointestinal microbiota during critical illness:A scoping review

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World journal of Critical Care medicine 2025年第1期14卷 49-59页

作者： Angajendra N Ghosh Calum j Walsh matthew j maiden Tim P Stinear Adam m Deane Department of Intensive Care The Northern HospitalEpping 3076VictoriaAustralia Department of microbiology and Immunology The Peter Doherty Institute for Infection and ImmunityMelbourne 3052VictoriaAustralia Department of Intensive Care The Royal Melbourne HospitalThe University of MelbourneParkville 3050VictoriaAustralia Department of Intensive Care medicine The Royal Melbourne HospitalParkville 3050VictoriaAustralia

The systemic effects of gastrointestinal(GI)microbiota in health and during chronic diseases is increasingly *** strategies to modulate the GI microbiota during chronic diseases have demonstrated *** changes in dietary intake can rapidly change the GI microbiota,the impact of dietary changes during acute critical illness on the microbiota remain *** fibre is metabolised by carbohydrate-active enzymes and,in health,can alter GI *** aim of this scoping review was to describe the effects of dietary fibre supplementation in health and disease states,specifically during critical *** controlled trials and prospective cohort studies that include adults(>18 years age)and reported changes to GI microbiota as one of the study outcomes using non-culture methods,were *** show dietary fibres have an impact on faecal microbiota in health and *** fibre,inulin,has a marked and specific effect on increasing the abundance of faecal *** chain fatty acids produced by Bifidobacteria have been shown to be beneficial in other patient *** few trials have evaluated the effect of dietary fibre on the GI microbiota during critical *** research is necessary to establish optimal fibre type,doses,duration of intervention in critical illness.

关键词： Gastrointestinal microbiota Dietary fibre Health Critical illness Short chain fatty acids

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

Clinical,laboratory,and therapeutic differences between immunoglobulin E-mediated and non-immunoglobulin E-mediated cow’s milk protein allergy in children

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World journal of Clinical Pediatrics 2025年第1期14卷 78-92页

作者： Hasan m Isa marwa j Abdulnabi Nawra S Naser Fatema N Lahmda Noor m AlAnsari Zahra H Isa Afaf m mohamed Department of Pediatrics Salmaniya Medical ComplexManama 26671Bahrain Department of Pediatrics Arabian Gulf UniversityManama 26671Bahrain Faculty of medicine Mansoura UniversityMansoura 35516Egypt Public Health Directorate Ministry of HealthManama 26671Bahrain

BACKGROUND Although breast milk is ideal for newborns,in some cases,it is replaced with cow’s milk,which contains proteins that increase the risk of cow’s milk protein allergy(CmPA).AIm To evaluate CmPA prevalence in Bahrain and compare clinical characteristics of children with immunoglobulin E(IgE)-and non-IgE-mediated *** This retrospective cohort study examined children with CmPA diagnosed at the pediatric gastroenterology outpatient clinic of the Salmaniya medical Complex,Bahrain,between 2014 and 2022,and assessed CmPA *** presentations,laboratory findings,dietary modifications,and outcomes were compared between children with IgE-mediated and non-IgE-mediated *** variables were compared using Fisher’s exact test or Pearson’sχ2 test,whereas continuous variables were compared using Student’s t-test or the mann-Whitney U *** Of 8332 patients,6022(72.3%)adhered to their *** them,618(10.3%)were suggested of having CmPA and 595(96.3%)were included;CmPA prevalence was 2%.most patients were Bahraini(93.8%)and males(55.3%).Non-IgE-mediated type accounted for 77.3%cases and IgE-mediated type,22.7%.IgE-mediated CmPA presented more in boys(P=0.030),and later in life(5.1 months±4.5 months vs 4.2 months±4.2 months,P=0.016,95%CI:0.08-1.73),had more associated diseases(Pmore cutaneous(P=0.024)and respiratory(P=0.003)manifestations,severe symptoms[rash/dry skin(P=0.031),facial swelling/angioedema(P=0.003),failure to thrive(P=0.013),apparent life-threatening event(Pmediated *** patients were exclusively fed cow milk formula(50.3%).The amino acid-based formula(AAF)was most prescribed(60.5%)with no difference between the two types(P=0.173).Although breastfeeding was recommended to 49.6%,only 8.2%were exclusively ***-mediated CmPA was associated with a longer follow-up duration than non-IgE-mediated CmPA(17.3 months±14.0 mo

关键词： Children milk allergy Immunoglobulin E Breastfeeding Infant formula Bahrain

CONSTANS alters the circadian clock in Arabidopsis thaliana

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molecular Plant 2024年第8期17卷 1204-1220页

作者： Pedro de los Reyes Gloria Serrano-Bueno Francisco j.Romero-Campero He Gao jose m.Romero Federico valverde Plant Development Group-Institute for Plant Biochemistry and Photosynthesis Consejo Superior de Investigaciones CientificasUniversidad de SevillaSevilleSpain Department of Computer Science and Artificial Intelligence Universidad de SevillaSevilleSpain Department of Plant Developmental Biology Max Planck Institute for Plant Breeding ResearchCologneGermany Department of Plant Biochemistry and molecular Biology Universidad de SevillaSevilleSpain

Plants are sessile organisms that have acquired highly plastic developmental strategies to adapt to the *** these processes,the floral transition is essential to ensure reproductive success and is finelyregulated by several internal andexternal genetic *** photoperiodic pathway,which controls plant response to day length,is one of the most important pathways controlling *** Arabidopsis photoperiodic flowering,CONSTANS(CO)is the central gene activating the expression of the florigen FLOWERING LOCUS T(FT)in the leaves at the end of a long *** circadian clock strongly regulates Co ***,to date,no evidence has been reported regarding a feedbackloop from the photoperiod pathway back to the circadian *** transcriptional networks,we have identified relevant network motifs regulating the interplay between the circadian clock and the photoperiod *** expression,chromatin immunoprecipitation experiments,and phenotypic analysis allowed us to elucidate the role of Co over the circadian *** with altered cO expression showed a different internal clock period,measured by daily leaf rhythmic *** showed that co upregulates the expression of key genes related to the circadian clock,such as CCA1,LHY,PRR5,and Gl,at the end of a long day by bindingto specific sites on their ***,a high numberof PRR5-repressed target genes are upregulated by CO,and this could explain the phase transition promoted by *** CO-PRR5 complex interacts with the bZiP transcriptionfactor HY5andhelps to localize the complex in the promoters of clock *** together,our results indicate that there may be a feedback loop in which co communicates back to the circadian clock,providing seasonal information to the circadian system.

关键词： CONSTANS circadian clock photoperiod