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Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

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Neural Regeneration Research 2024年第1期19卷 29-34页

作者： Marta Zagrebelsky Martin Korte Division of Cellular Neurobiology Zoological InstituteTU BraunschweigBraunschweigGermany Helmholtz Centre for infection Research AG NINDBraunschweigGermany

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin rec

关键词： Alzheimer's disease brain-derived neurotrophic factor depression Parkinson's disease tropomyosin receptor kinase B receptor

Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex David J.Calkins vanderbilt Eye institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts institute of Technology.We take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this purpose.The National Eye institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in 2021.Therefore,we focus on this timespan.Data sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

Oncostatin M:a love-hate relationship in neuroinflammation

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Neural Regeneration Research 2024年第12期19卷 2571-2572页

作者： Doryssa Hermans Niels Hellings Bieke Broux University MS Center Campus DiepenbeekDiepenbeekBelgium Neuro-Immune Connections and Repair Lab Department of Immunology and InfectionBiomedical Research InstituteHasselt UniversityDiepenbeekBelgium

Oncostatin M and multiple sclerosis:Every 5minutes,someone in the world is diagnosed with multiple sclerosis(MS),a chronic inflammatory and degenerative disease of the central nervous system(CNS).MS appears in unpredictable episodes of symptoms,which are highly patient-dependent,but often include visual impairment,muscle weakness/spasms,fatigue,cognitive difficulties,and bladder.***.or sexual dysfunction.

关键词： visual bladder someone

Implications for brainstem recovery from studies in primates after sensory loss from arm

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Neural Regeneration Research 2024年第3期19卷 479-480页

作者： Jamie L.Reed Hui-Xin Qi Jon H.Kaas Department of Psychology Vanderbilt UniversityNashvilleTNUSA

For decades,researchers have known that when neurons lose their activating inputs,they can atrophy and even die.For example,removing sensory nerve inputs from the arm to the spinal cord after amputation or cutting the spinal nerves can shrink the post-synaptic target zones(e.g.,Woods et al.,2000).From touch receptors for the hand and arm,primary nerve afferents enter the spinal cord,and axons travel in the dorsal columns to target the cuneate nucleus(Cu)of the brainstem on the same side of the body(Figure 1).When sensory loss is unilateral,the overwhelming result is for the associated primary target zone to shrink in total size(cross-sectional area),as compared to the size of the opposite side.

关键词： brainstem shrink removing

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary.Fractional dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is unknown.This study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.Methods Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days later.Humoral and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,respectively.Results Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4+,SNM-specific IL-2+CD8+,S-specific IL-2+CD8+,N-specific IL-2+CD4+,N-specific IL-2+CD8+and M-specific IL-2+CD4+responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was inferior.For ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2+CD4+,interferon-γ+CD8+and IL-2+CD8+responses were superior and non-inferior to IM-CCC.The estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,respectively.The ID groups reported more local,mild adverse reactions.Conclusion This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

A complete genome for a commercial duck

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Frontiers of Agricultural Science and Engineering 2024年第2期11卷 344-346页

作者： Jim KAUFMAN institute for Immunology and infection Research University of Edinburgh Department of Veterinary Medicine University of Cambridge

Biology has been revolutionized by the availability of whole genome sequences, along with all the associated approaches including genome-wide association studies, various-omics methodologies and now precise genome editing[1–6]. The study of domesticated animal food species has already benefitted from these basic technologies(for a few examples out of many[7–14]), and it is anticipated that there will be enormous advances arising from deep understanding and precise intervention. However, these improvements depend on the availability of a complete high-quality genomes.

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Two hits are better than one:rational dual strategy efficiently fights neuroblastoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1802-1804页

作者： Jacques Zimmer Camille Rolin Markus Ollert Department of infection and Immunity Luxembourg Institute of HealthEsch-sur-AlzetteLuxembourg University of Luxembourg Esch-sur-AlzetteLuxembourg Department of Dermatology and Allergy Center Odense Research Center for Anaphylaxis(ORCA)University of Southern DenmarkOdenseDenmark

The recently published landmark paper by Bergaggio et al.from Roberto Chiarle’s group in Cancer Cell1 investigates an elegant double-hit strategy to improve anti-cancer immunotherapy.This important approach demonstrates in a preclinical model that chimeric antigen receptor(CAR)-T cell treatment can be rendered more efficient by increasing the cell surface expression of the CAR target structure via a small molecule.

关键词： neuroblastoma al. Cancer

Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

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Protein & Cell 2024年第6期15卷 403-418页

作者： Song Xue Yuru Han Fan Wu Qiao Wang Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecurityShanghai Frontiers Science Center of Pathogenic Microorganisms and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles.Point mutations,particularly those within the receptor binding domain(RBD)of SARS-CoV-2 spike(S)protein,lead to the functional alteration in both receptor engagement and monoclonal antibody(mAb)recognition.Here,we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune evasion.Many single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding affinity.However,this weakened effect could be largely compensated by specific epistatic mutations,such as N501Y,thus maintaining the overall ACE2 affinity for the spike protein of all major variants.The predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two dimensions.Together,this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained,emphasizing the significance of comprehensive assessment of spike mutations.

关键词： ACE2 affinity maintained

Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key Laboratory of Molecular Virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen institute of Microbes and infections College of Life Sciences Nanjing Normal University State Key Laboratory of Virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan University The institute of infection and Health Research Fudan University Key Laboratory of Medical Molecular Virology(MOE/MOH) Shanghai Medical CollegeFudan University Laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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