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Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer＇s disease

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Neural Regeneration Research 2018年第6期13卷 1066-1080页

作者： Sara H.Mokhtar Min Joung Kim Kylie A.Magee Pei Mun Aui Speros Thomas Maha M.Bakhuraysah Amani A.Alrehaili Jae Young Lee David L.Steer Rachel Kenny Catriona Mc Lean Michael F.Azari Antonis Birpanagos Ewlina Lipiec philip heraud Bayden Wood Steven Petratos Department of Neuroscience Central Clinical School Monash University Prahran Victoria Australia Department of Biochemistry and Molecular Biology Monash Universityl Clayton Victoria Australia Department of Anatomy & Developmental Biology Monash University Clayton Victoria Australia Department of Anatomical Pathology Alfred Hospital Prahran Victoria Australia School of Health and Biomedical Sciences RMIT University Bundoora Victoria Australia Division of Animal and Human Physiology Department of Biology National and Kapodistrian University of Athens Ilisia Athens Greece The Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences Department of Applied Spectroscopy RadzikowskiegoKrakow Poland Centre for Biospectroscopy and Department of Microbiology Monash University Clayton Victoria Australia

Alzheimer’s disease（AD）is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles.Prior to the development of these characteristic pathological hallmarks of AD,anterograde axonal transport is impaired.However,the key proteins that initiate these intracellular impairments remain elusive.The collapsin response mediator protein-2（CRMP-2）plays an integral role in kinesin-1-dependent axonal transport and there is evidence that phosphorylation of CRMP-2releases kinesin-1.Here,we tested the hypothesis that amyloid-beta（Aβ）-dependent phosphorylation of CRMP-2 disrupts its association with the kinesin-1（an anterograde axonal motor transport protein）in AD.We found that brain sections and lysates from AD patients demonstrated elevated phosphorylation of CRMP-2 at the T555 site.Additionally,in the transgenic Tg2576 mouse model of familial AD（FAD）that exhibits Aβaccumulation in the brain with age,we found substantial co-localization of p T555CRMP-2and dystrophic neurites.In SH-SY5Y differentiated neuronal cultures,Aβ-dependent phosphorylation of CRMP-2 at the T555 site was also elevated and this reduced the CRMP-2 association with kinesin-1.The overexpression of an unphosphorylatable form of CRMP-2 in neurons promoted the re-establishment of CRMP-2-kinesin association and axon elongation.These data suggest that Aβ-dependent phosphorylation of CRMP-2 at the T555 site may directly impair anterograde axonal transport protein function,leading to neuronal defects.

关键词： amyloid-beta protein kinases collapsin response mediator protein microtubules kinesin tubulin

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Light-deformable microrobots shape up for the biological obstacle course

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Light(Science & Applications) 2024年第5期13卷 803-805页

作者： philip Wijesinghe Centre of Biophotonics SUPASchool of Physics and AstronomyUniversity of St AndrewsNorth HaughSt AndrewsFife KY169SSUK

Euglena gracilis microalga has been transformed into a soft bio-microrobot with light-controlled motion and deformation that can address diverse bio-challenges,such as drug delivery,diseased cell removal,and photodyna... 详细信息

关键词： Euglena transformed obstacle

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MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

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Neural Regeneration Research 2024年第3期19卷 557-562页

作者： Bridget Martinez philip V.Peplow Department of Pharmacology University of Nevada-RenoRenoUSA Department of Medicine University of Nevada-RenoRenoUSA Department of Anatomy University of OtagoDunedinNew Zealand

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat

关键词： adults attention deficit hyperactivity disorder biomarkers blood plasma blood serum children microRNA total white blood cells whole blood

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MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

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Neural Regeneration Research 2024年第7期19卷 1523-1531页

作者： Bridget Martinez philip V.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

关键词： antipsychotics biomarkers blood exosomes blood plasma brain tissue exosomes brain tissues leukocytes microRNAs neural stem cells olfactory neuroepithelium schizophrenia whole blood

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Empirical Wavelet Transform Based Method for Identification and Analysis of Sub-synchronous Oscillation Modes Using PMU Data

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Journal of Modern Power Systems and Clean Energy 2024年第1期12卷 34-40页

作者： Joice G.philip Jaesung Jung Ahmet Onen the Department of Energy Systems Research Ajou UniversitySuwonSouth Korea the Department of Electrical and Electronic Engineering Abdullah Gul UniversityKayseri38080Turkey the Department of Electrical and Computer Engineering College of EngineeringSultan Qaboos UniversityAl-KhoudMuscatOman

This paper proposes an empirical wavelet transform(EWT)based method for identification and analysis of sub-synchronous oscillation(SSO)modes in the power system using phasor measurement unit(PMU)data.The phasors from PMUs are preprocessed to check for the presence of oscillations.If the presence is established,the signal is decomposed using EWT and the parameters of the mono-components are estimated through Yoshida algorithm.The superiority of the proposed method is tested using test signals with known parameters and simulated using actual SSO signals from the Hami Power Grid in Northwest China.Results show the effectiveness of the proposed EWT-Yoshida method in detecting the SSO and estimating its parameters.

关键词： Empirical wavelet transform(EWT) sub-synchronous oscillation Prony-based method Yoshida algorithm variational mode decomposition phasor measurement unit(PMU)

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Distinct vibrational signatures and complex phase behavior in metallic oxygen

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Matter and Radiation at Extremes 2024年第2期9卷 4-11页

作者： philip Dalladay-Simpson Bartomeu Monserrat Li Zhang Federico Gorelli Center for High Pressure Science Technology Advanced Research 1690 Cailun RoadShanghai 201203China Department of Materials Science and Metallurgy University of Cambridge27 Charles Babbage RoadCambridge CB3 OFSUnited Kingdom Cavendish Laboratory University of CambridgeJ.J.Thomson AvenueCambridge CB3 OHEUnited Kingdom Istituto Nazionale di Ottica Consiglio Nazionale delle Ricerche(CNR-INO)50125 FlorenceItaly Shanghai Advanced Research in Physical Sciences(SHARPS) ShanghaiChina

Evidence for metallization in dense oxygen has been reported for over 30 years[Desgreniers et al.,J.Phys.Chem.94,1117(1990)]at a now routinely accessible 95 GPa[Shimizu et al.,Nature 393,767(1998)].However,despite the longevity of this result and the technological advances since,the nature of the metallic phase remains poorly constrained[Akahama et al.,Phys.Rev.Lett.74,4690(1995);Goncharov et al.,Phys.Rev.B 68,224108(2003);Ma,Phys.Rev.B 76,064101(2007);and Weck et al.,Phys.Rev.Lett.102,255503(2009)].In this work,through Raman spectroscopy,we report the distinct vibrational characteristics of metallicζ-O_(2) from 85 to 225 GPa.In comparison with numerical simulations,weﬁnd reasonable agreement with the candidate structure up to about 150 GPa.At higher pressures,the C2/mstructure is found to be unstable and incompatible with experimental observations.Alternative candidate structures,and Ci,with C2/m C2/conly two molecules in the primitive unit cell,are found to be stable and more compatible with measurements above 175 GPa,indicative of the dissociation of(O_(2))4 units.Further,we report and discuss a strong hysteresis and metastability with the precursory phaseϵ-O_(2).Theseﬁndings will reinvigorate experimental and theoretical work into the dense oxygen system,which will have importance for oxygen-bearing chemistry,prevalent in the deep Earth,as well as fundamental physics.

关键词： metallic phase vibrational

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Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 146-153页

作者： philip C.Muller Matthias Pfister Dilmurodjon Eshmuminov Kuno Lehmann Department of Surgery and Transplantation University Hospital ZurichRämistrasse 100Zurich CH-8091Switzerland

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.

关键词： Liver transplantation Neuroendocrine liver metastases Liver resection Selection criteria Tumor biology

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Dynamic Event-Triggered Consensus Control for Input Constrained Multi-Agent Systems With a Designable Minimum Inter-Event Time

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IEEE/CAA Journal of Automatica Sinica 2024年第3期11卷 649-660页

作者： Meilin Li Yue Long Tieshan Li Hongjing Liang C.L.philip Chen the School of Automation Engineering University of Electronic Science and Technology of ChinaChengdu 611731China IEEE the Yangtze Delta Region Institute University of Electronic Science and Technology of ChinaHuzhou 313000 the Laboratory of Electromagnetic Space Cognition and Intelligent Control Beijing 100089China the School of Computer Science and Engineering South China University of TechnologyGuangzhou 510006

This paper investigates the consensus control of multi-agent systems(MASs) with constrained input using the dynamic event-triggered mechanism(ETM).Consider the MASs with small-scale networks where a centralized dynamic ETM with global information of the MASs is first designed.Then,a distributed dynamic ETM which only uses local information is developed for the MASs with large-scale networks.It is shown that the semi-global consensus of the MASs can be achieved by the designed bounded control protocol where the Zeno phenomenon is eliminated by a designable minimum inter-event time.In addition,it is easier to find a trade-off between the convergence rate and the minimum inter-event time by an adjustable parameter.Furthermore,the results are extended to regional consensus of the MASs with the bounded control protocol.Numerical simulations show the effectiveness of the proposed approach.

关键词： Constrained input designable minimum inter-event time directed communication topology dynamic event-triggered mechanism MASs consensus control

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Adaptive neural network control of a 2-DOF helicopter system considering input constraints and global prescribed performance

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Science China(Information Sciences) 2024年第7期67卷 224-239页

作者： Zhijia ZHAO Jiale WU Zhijie LIU We HE C.L.philip CHEN School of Mechanical and Electrical Engineering Guangzhou University School of Intelligence Science and Technology and Key Laboratory of Intelligent Bionic Unmanned Systems of Ministry of Education University of Science and Technology Beijing School of Computer Science and Engineering South China University of Technology Pazhou Lab

In this study, an adaptive neural network(NN) control is proposed for nonlinear two-degree-offreedom(2-DOF) helicopter systems considering the input constraints and global prescribed performance.First, radial basis function NN(RBFNN) is employed to estimate the unknown dynamics of the helicopter system. Second, a smooth nonaffine function is exploited to approximate and address nonlinear constraint functions. Subsequently, a new prescribed function is proposed, and an original constrained error is transformed into an equivalent unconstrained error using the error transformation and barrier function transformation methods. The analysis of the established Lyapunov function proves that the controlled system is globally uniformly bounded. Finally, the simulation and experimental results on a constructed Quanser's test platform verify the rationality and feasibility of the proposed control.

关键词： adaptive NN control 2-DOF helicopter global prescribed performance input constraints

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MicroRNAs as potential diagnostic biomarkers for bipolar disorder

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Neural Regeneration Research 2025年第6期20卷 1681-1695页

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysre

关键词： biomarker bipolar disorder blood leukocytes blood plasma blood plasma extracellular vesicles/exosomes blood serum brain tissue brain tissue extracellular vesicles/exosomes lymphoblastoid cell lines microRNA neural progenitor cells whole blood

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