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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong miao michael S.Wolfe Computational medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-Em structures drug design intramembrane proteolysis molecular dynamics Notch

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Anatomic location of the first dorsal extensor compartment for surgical De-Quervain’s tenosynovitis release:A cadaveric study

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World Journal of Orthopedics 2024年第4期15卷 379-385页

作者： Aditya Thandoni William Nicholas Yetter Steven michael Regal Department of Orthopaedic Surgery Allegheny Health NetworkPittsburghPA 15212United States

BACKGROUND De-Quervain’s tenosynovitis is a disorder arising from the compression and irritation of the first dorsal extensor compartment of the *** who fail conservative treatment modalities are candidates for surgical ***,risks with surgery include damage to the superficial radial nerve and an incomplete release due to inadequate ***,there is a paucity of literature demonstrating the exact anatomic location of the first dorsal extensor compartment in reference to surface ***,this cadaveric study was performed to determine the exact location of the first extensor compartment and to devise a reliable surgical incision to prevent *** To describe the location of the first dorsal compartment in relation to bony surface landmarks to create replicable surgical *** Six cadaveric forearms,including four left and two right forearm specimens were *** were performed by a single fellowship trained upper extremity orthopaedic *** of the first dorsal compartment from landmarks such as Lister’s tubercle,the wrist crease,and the radial styloid were *** variables studied included the presence of the superficial radial nerve overlying the first dorsal compartment,additional compartment subsheaths,number of abductor pollicis longus(APL)tendon slips,and the presence of a *** Distance from the radial most aspect of the wrist crease to the extensor retinaculum was 5.14 mm±0.80 *** distance from Lister’s tubercle to the distal aspect of the extensor retinaculum was 13.37 mm±2.94 ***’s tubercle to the start of the first dorsal compartment was 18.43 mm±2.01 *** radial styloid to the initial aspect of the extensor retinaculum measured 2.98 mm±0.99 *** retinaculum length longitudinally on average was 26.82 mm±3.34 *** cadaveric forearms had separate extensor pollicis brevis *** average number of APL tendon slips was th

关键词： De-Quervain’s tenosynovitis First extensor compartment Cadaveric study Superficial radial nerve Radial styloid Lister’s tubercle

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Insights and reviews on battery lifetime prediction from research to practice

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Journal of Energy Chemistry 2024年第7期94卷 716-739页

作者： Xudong Qu Dapai Shi Jingyuan Zhao manh-Kien Tran Zhenghong Wang michael Fowler Yubo Lian Andrew FBurke Hubei Longzhong Laboratory Hubei University of Arts and ScienceXiangyang 441000HubeiChina Institute of Transportation Studies University of California DavisDavisCA 95616USA Department of Chemical Engineering University of WaterlooWaterlooOntario N2L 3G1Canada BYD Automotive Engineering Research Institute Shenzhen 518118GuangdongChina

The rising demand for energy storage solutions,especially in the electric vehicle and renewable energy sectors,highlights the importance of accurately predicting battery health to enhance their longevity and *** article comprehensively examines various methods used to forecast battery health,including physics-based models,empirical models,and equivalent circuit models,among *** delves into the promise of data-driven prognostics,utilizing both conventional machine learning and cuttingedge deep neural network *** advantages and limitations of hybrid models are thoroughly analyzed,with a focus on the benefits of integrating diverse data sources to improve prognostic *** practical case studies,the article showcases the effectiveness and flexibility of these *** also critically addresses the challenges encountered in applying battery health prognostics in realworld scenarios,such as issues of scalability,complexity,and data *** these challenges,the article underscores the emerging opportunities brought about by recent technological,academic,and research *** include the development of digital twin models for batteries,the use of data-centric AI and standardized benchmarking,the potential integration of blockchain technology for enhanced data security and transparency,and the synergy between edge and cloud computing to boost data analysis and *** primary goal of this article is to enrich the understanding of current battery health prognostic techniques and to inspire further research aimed at overcoming existing hurdles and tapping into new *** concludes with a visionary perspective on future research directions and potential developments in this evolving field,encouraging both researchers and practitioners to explore innovative solutions.

关键词： Batteries Lifetime Health machine learning Deep learning Field Real world

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NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Schafer Sudena Wang michael J.Schmeisser Axel methner Institute for molecular medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

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Estimating the subsolar magnetopause position from soft X-ray images using a low-pass image filter

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Earth and Planetary Physics 2024年第1期8卷 173-183页

作者： Hyangpyo Kim Hyunju K.Connor Jaewoong Jung Brian m.Walsh David Sibeck Kip D.Kuntz Frederick S.Porter Catriana K.Paw U Rousseau A.Nutter Ramiz Qudsi Rumi Nakamura michael Collier Space Research Institute Austrian Academy of Sciences8042 GrazAustria Geophysical Institute University of Alaska FairbanksFairbanksAlaska 99775USA National Aeronautics and Space Administration(NASA)Goddard Space Flight Center GreenbeltMaryland 20771USA Astronomy Department University of Maryland College ParkCollege ParkMaryland 20742USA Center for Space Physics Boston UniversityBostonMassachusetts 02215USA Department of Physics and Astronomy Johns Hopkins UniversityBaltimoreMaryland 21218USA Howard University WashingtonDC 20059USA

The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind magnetosphere Ionosphere Link Explorer(SmILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind *** suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray *** this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is *** assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause *** create synthetic soft X-ray images by using the Open Geospace General Circulation model(OpenGGCm)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson *** then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea *** the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCm subsolar magnetopause location as ground *** method estimates RS with an accuracy of10 *** accuracy improves for greater solar wind densities and during southward interplanetary magnetic *** method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field ***,the technique will enable quantitative analysis of the magnetopause motion and help reveal the daysi

关键词： soft X-ray magnetopause reconnection low-pass filter LEXI SmILE

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Effect of TiB_(2)Addition on microstructure and mechanical Properties of AA8009 Alloy Fabricated by Laser Additive manufacturing

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Acta metallurgica Sinica(English Letters) 2024年第1期37卷 67-77页

作者： Xinxing Xiong Sijie Yu Pei Wang Junfang Qi Haichao Li Xulei Wang michael Ryan Debajyoti Bhaduri Rossitza Setchi Additive manufacturing Institute Shenzhen UniversityShenzhen518060China Henan Key Laboratory of High Performance Carbon Fiber Reinforced Composites Institute of Carbon Matrix CompositesHenan Academy of SciencesZhengzhou450046China School of materials Science and Engineering Shanghai University of Engineering ScienceShanghai201620China School of materials Science and Engineering Zhengzhou University of AeronauticsZhengzhou450046China High-Value manufacturing Research Group School of EngineeringCardiff UniversityCardiffCF243AAUK

The research involves the addition of 5 vol.%TiB_(2)particles into AA8009 alloy powder to synthesize TiB_(2)/AA8009 composite parts produced via laser powder bed fusion(LPBF).The addition of the TiB_(2)particles causes the TiB_(2)/AA8009 composites with and without annealing have lower compressive strength than AA8009 alloy due to the change of the strengthening *** results further indicated that solid solution strengthening was the main strengthening mechanism of the LPBF AA8009 alloy at room temperature whereas Orowan strengthening became the primary strengthening factor after annealing at 673 *** contrast,Orowan strengthening always remained the main strengthening mechanism for the TiB_(2)/AA8009 composite,irrespective of the annealing *** addition,after annealing of the LPBF parts at 673 K,the compressive yield strength(CYS)of the unblended AA8009 alloy specimens had a~2.5 times greater reduction(from 705±16 to 459±30 mPa)compared to that of the composite TiB_(2)/AA8009 samples(from 466±23 to 368±3 mPa).Therefore,TiB_(2)particles can suppress the drop in yield strength of LPBF AA8009 alloy below 673 K,providing a theoretical and experimental basis for the applications of both LPBF AA8009 and TiB_(2)/AA8009 alloys at low and medium temperatures.

关键词： Laser powder bed fusion AA8009 alloy microstructure mechanical properties

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Effect of various aromatic compounds with different functional groups on enzymatic hydrolysis of microcrystalline cellulose and alkaline pretreated wheat straw

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Journal of Bioresources and Bioproducts 2024年第2期9卷 211-221页

作者： Yufeng Yuan Xinyu Guo Bo Jiang Wenjuan Wu Tingwei Zhang michael Sweeney mehraj Ahmad Yongcan Jin Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources International Innovation Center for Forest Chemicals and MaterialsJiangsu Provincial Key Lab of Pulp and Paper Science and TechnologyNanjing Forestry UniversityNanjing 210037China School of Chemistry and Chemical Engineering Queen’s University BelfastBelfast BT71NNNorthern Ireland United Kingdom Department of Food Science and Engineering College of Light Industry and Food EngineeringNanjing Forestry UniversityNanjing 210037China

Low molecular aromatic compounds are detrimental to the enzymatic hydrolysis of ***,the specific role of their functional groups remains ***,a series of nine aromatic compounds as additives were tested to understand their effect on the hydrolysis yield of microcrystalline cellulose(mCC)and alkaline pretreated wheat *** on the results,the inhibition of aldehyde groups on mCC was greater than that of carboxyl groups,whereas for the alkaline pretreated wheat straw case,the inhibitory effect of aldehyde groups was lower than that of carboxyl *** methoxyl groups of aromatic compounds reduced the inhibitory ef-fect on enzymatic hydrolysis of both *** inhibition of aromatic compounds on mCC hydrolysis was detected in comparison with the alkaline pretreated wheat straw,indicating that the substrate lignin can offset the inhibition to a certain *** all aromatic com-pounds,syringaldehyde with one aldehyde group and two methoxyl groups improved the glucan conversion of the alkaline pretreated wheat straw.

关键词： Aromatic compound Functional group Enzymatic hydrolysis Alkaline pretreated wheat straw microcrystalline cellulose

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A randomized,controlled,open label non-inferiority trial of intravenous ferric carboxymaltose versus iron sucrose in patients with iron deficiency anemia in China

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Frontiers of medicine 2024年第1期18卷 98-108页

作者： Jie Jin Zhihua Ran Emanuele Noseda Bernard Roubert matthieu marty Anna mezzacasa Udo michael Göring The First Affiliated Hospital Zhejiang University College of MedicineHangzhou310058China Renji Hospital Shanghai Jiao Tong University School of MedicineShanghai200025China Vifor Pharma Glattbrugg8152Switzerland

Iron deficiency(ID)and ID anemia(IDA)pose significant public health concerns in *** iron sucrose(IS)treatment is well-established in the country,ferric carboxymaltose(FCm)offers the advantage of higher doses and fewer *** open label,randomized,controlled,non-inferiority trial was conducted at multiple sites in China to compare the outcomes of FCm(maximum of 2 doses,500 or 1000 mg iron)and IS(up to 11 infusions,200 mg iron)treatments in subjects with *** primary endpoint was the achievement of hemoglobin(Hb)response(an increase of⩾2 g/dL from baseline)within 8 weeks,whereas secondary endpoints included changes in Hb,transferrin saturation,and serum ferritin *** the 371 randomized subjects,a similar percentage of subjects treated with FCm and IS achieved Hb-response(FCm 99.4%,IS 98.3%),thereby confirming the non-inferiority of FCm compared with IS(difference 1.12(−2.15,4.71;95%confidence interval(CI))).Furthermore,a significantly higher proportion of FCm-treated subjects achieved early Hb-response at Week 2(FCm 85.2%,IS 73.2%;difference 12.1(3.31,20.65;95%CI)).Additionally,the increase in TSAT and serum ferritin levels from baseline was significantly greater at all time points for FCm-treated *** safety profiles of FCm and IS were comparable,with the exception of transient hypophosphatemia and pyrexia,which are consistent with FCm’s known safety *** conclusion,FCm proves to be an efficacious treatment for IDA,providing faster Hb-response and correction of ID with fewer administrations than IS.

关键词： iron deficiency anemia intravenous iron ferric carboxymaltose iron sucrose Hb response early response

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Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

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General Psychiatry 2024年第1期37卷 103-111页

作者： Viktor H Ahlqvist Christina Dardani Paul madley-Dowd Harriet Forbes Jessica Rast Caichen Zhong Renee m Gardner Christina Dalman Kristen Lyal cRAIG Newschaffer Torbjorn Tomson michael Lundberg Daniel Berglind Neil m Davies Brian K Lee Cecilia magnusson Dheeraj Rai Department of Global Public Health Karolinska InstitutetStockholmSweden medical Research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK Centre for Academic mental Health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical MedicineLondonUK A.J.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of Health and Human Development Pennsylvania State UniversityState CollegePAUSA Department of Clinical Neuroscience Karolinska InstitutetStockholmSweden Centre for Epidemiology and Community medicine Region StockholmStockholmSweden K.G Jebsen Center for Genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK NIHR Biomedical Research Centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

Background Psychiatric comorbidities are common in patients with *** for the co-occurrence of psychiatric conditions and epilepsy remain poorly *** We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these *** Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with *** then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score ***,we assessed the potential bidirectional relationships using two-sample mendelian *** In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric *** example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,pmore pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,pm mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric *** Psychiatric comorbidities are common in patients with *** correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric *** findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psy

关键词： epilepsy Psychiat lifetime

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Convergent Data-Driven Regularizations for CT Reconstruction

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Communications on Applied mathematics and Computation 2024年第2期6卷 1342-1368页

作者： Samira Kabri Alexander Auras Danilo Riccio Hartmut Bauermeister martin Benning michael moeller martin Burger Helmholtz Imaging Deutsches Elektronen-Synchrotron DESYNotkestr.8522607 HamburgGermany Institute for Vision and Graphics University of SiegenAdolf-Reichwein-Straße 2a57076 SiegenGermany School of mathematical Sciences Queen Mary University of LondonMile End RoadLondon E14NSUK The Alan Turing Institute British Library96 Euston RdLondon NW12DBUK Fachbereich mathematik Universitat HamburgBundesstrasse 5520146 HamburgGermany

The reconstruction of images from their corresponding noisy Radon transform is a typical example of an ill-posed linear inverse problem as arising in the application of computerized tomography(CT).As the(naive)solution does not depend on the measured data continuously,regularization is needed to reestablish a continuous *** this work,we investigate simple,but yet still provably convergent approaches to learning linear regularization methods from *** specifically,we analyze two approaches:one generic linear regularization that learns how to manipulate the singular values of the linear operator in an extension of our previous work,and one tailored approach in the Fourier domain that is specific to *** prove that such approaches become convergent regularization methods as well as the fact that the reconstructions they provide are typically much smoother than the training data they were trained ***,we compare the spectral as well as the Fourier-based approaches for CT-reconstruction numerically,discuss their advantages and disadvantages and investigate the effect of discretization errors at differentresolutions.

关键词： Inverse problems Regularization Computerized tomography(CT) machine learning

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