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Adeno-associated virus as a delivery vector for gene therapy of human diseases

Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： jiang-Hui Wang Dominic j.Gessler Wei Zhan Thomas l.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different *** AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various ***,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing *** rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and *** this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing *** discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as *** outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these *** hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

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Creep-induced redistribution of alloying elements in CZ1 zirconium alloys

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journal of Materials Science & Technology 2024年第6期173卷 31-44页

作者： W.T.lin Q.Y.lv D.jiao l.B.Zhang j.Tan G.Sha j.Hu China Nuclear Power Technology Research Institute Shenzhen 518026China School of Material Science and Engineering Nanjing University of Science and TechnologyNanjing 210094China

Introducing minor alloying elements is an effective strategy to improve the corrosion and mechanical properties of zirconium alloys for nuclear *** in-reactor service,external environment and stress can affect the distribution of alloying elements,substantially changing the degradation process of zirconium *** date,there is a lack of in-depth understanding of the interaction between creep and microchemistry ***,we conducted systematic transmission electron microscopy(TEM)and atom probe tomography(APT)investigations to address creep-induced redistribution of alloying elements in CZ1(Zr-Sn-Nb-Fe-Cr-Cu)zirconium alloy with different initial ***,Fe,Sn,and Cu are found to co-segregate at grain *** higher the intermediate annealing temperature,the larger the Gibbsian interfacial excesses of solute elements *** further demonstrate that creep can reduce the excess value of Fe at grain boundaries due to the coarsening of Zr-Fe-Cr second phase particles via grain boundary and dislocation pipe *** the same time,the excess value of Sn is increased by diffusing from the matrix to grain ***,Cu as a minor element in the concentration range of 0.05-0.3 wt.%is found to segregate at dislocations to form the Cottrell atmosphere and develop Cu-rich nanoclusters for suppressing dislocation *** new understanding of the segregation and clustering of minor alloying elements provides guidance for developing zirconium alloys with enhanced creep resistance.

关键词： Zirconium alloy Thermal creep Grain boundary segregation Dislocation segregation Cu-rich nanoclusters

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Greatly enhanced corrosion/wear resistances of epoxy coating for Mg alloy through a synergistic effect between functionalized graphene and insulated blocking layer

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journal of Magnesium and Alloys 2024年第1期12卷 332-344页

作者： Z.Y.Xue X.j.li j.H.Chu M.M.li D.N.Zou l.B.Tong School of Metallurgical Engineering Xi’an University of Architecture and TechnologyXi’an 710055China State key laboratory of Advanced Design and Manufacturing for Vehicle Body Hunan UniversityChangsha 410082China

The poor corrosion and wear resistances of Mg alloys seriously limit their potential applications in various *** conventional epoxy coating easily forms many intrinsic defects during the solidification process,which cannot provide sufficient *** the current study,we design a double-layer epoxy composite coating on Mg alloy with enhanced anti-corrosion/wear properties,via the spin-assisted assembly *** outer layer is functionalized graphene(FG)in waterborne epoxy resin(WEP)and the inner layer is Ce-based conversion(Ce)*** FG sheets can be homogeneously dispersed within the epoxy matrix to fill the intrinsic defects and improve the barrier *** Ce film connects the outer layer with the substrate,showing the transition *** corrosion rate of Ce/WEP/FG composite coating is 2131 times lower than that of bare Mg alloy,and the wear rate is decreased by~90%.The improved corrosion resistance is attributed to the labyrinth effect(hindering the penetration of corrosive medium)and the obstruction of galvanic coupling *** synergistic effect derived from the FG sheet and blocking layer exhibits great potential in realizing the improvement of multi-functional integration,which will open up a new avenue for the development of novel composite protection coatings of Mg alloys.

关键词： Mg alloy Functionalized graphene Epoxy coating Corrosion/wear resistance Blocking layer

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A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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Bio-Design and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.O.Beeren G.Dos Santos P.j.Dijkstra C.Mota j.Bauer H.Ferreira Rui l.Reis N.Neves S.Camarero-Espinosa M.B.Baker l.Moroni Department of Complex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s Research Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate laboratory 4806-909 Braga/GuimarãesPortugal POlYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IkERBASQUE Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering ***,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell *** of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface ***,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCl5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCl75k at different *** porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCl *** a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was *** two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated *** addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface *** together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material ***,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(m

关键词： Additive manufacturing Blending Surface functionalization Surface density Click chemistry Human

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STCF conceptual design report (Volume 1): Physics & detector

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Frontiers of physics 2024年第1期19卷 1-154页

作者： M.Achasov X.C.Ai l.P.An R.Aliberti Q.An X.Z.Bai Y.Bai O.Bakina A.Barnyakov V.Blinov V.Bobrovnikov D.Bodrov A.Bogomyagkov A.Bondar I.Boyko Z.H.Bu F.M.Cai H.Cai j.j.Cao Q.H.Cao X.Cao Z.Cao Q.Chang k.T.Chao D.Y.Chen H.Chen H.X.Chen j.F.Chen k.Chen l.l.Chen P.Chen S.l.Chen S.M.Chen S.Chen S.P.Chen W.Chen X.Chen X.F.Chen X.R.Chen Y.Chen Y.Q.Chen H.Y.Cheng j.Cheng S.Cheng T.G.Cheng j.P.Dai l.Y.Dai X.C.Dai D.Dedovich A.Denig I.Denisenko j.M.Dias D.Z.Ding l.Y.Dong W.H.Dong V.Druzhinin D.S.Du Y.j.Du Z.G.Du l.M.Duan D.Epifanov Y.l.Fan S.S.Fang Z.j.Fang G.Fedotovich C.Q.Feng X.Feng Y.T.Feng j.l.Fu j.Gao Y.N.Gao P.S.Ge C.Q.Geng l.S.Geng A.Gilman l.Gong T.Gong B.Gou W.Gradl j.l.Gu A.Guevara l.C.Gui A.Q.Guo F.k.Guo j.C.Guo j.Guo Y.P.Guo Z.H.Guo A.Guskov k.l.Han l.Han M.Han X.Q.Hao j.B.He S.Q.He X.G.He Y.l.He Z.B.He Z.X.Heng B.l.Hou T.j.Hou Y.R.Hou C.Y.Hu H.M.Hu k.Hu R.j.Hu W.H.Hu X.H.Hu Y.C.Hu j.Hua G.S.Huang j.S.Huang M.Huang Q.Y.Huang W.Q.Huang X.T.Huang X.j.Huang Y.B.Huang Y.S.Huang N.Hüsken V.Ivanov Q.P.ji j.j.jia S.jia Z.k.jia H.B.jiang j.jiang S.Z.jiang j.B.jiao Z.jiao H.j.jing X.l.kang X.S.kang B.C.ke M.kenzie A.khoukaz I.koop E.kravchenko A.kuzmin Y.lei E.levichev C.H.li C.li D.Y.li F.li G.li G.li H.B.li H.li H.N.li H.j.li H.l.li j.M.li j.li l.li l.li l.Y.li N.li P.R.li R.H.li S.li T.li W.j.li X.li X.H.li X.Q.li X.H.li Y.li Y.Y.li Z.j.li H.liang j.H.liang Y.T.liang G.R.liao l.Z.liao Y.liao C.X.lin D.X.lin X.S.lin B.j.liu C.W.liu D.liu F.liu G.M.liu H.B.liu j.liu j.j.liu j.B.liu k.liu k.Y.liu k.liu l.liu Q.liu S.B.liu T.liu X.liu Y.W.liu Y.liu Y.l.liu Z.Q.liu Z.Y.liu Z.W.liu I.logashenko Y.long C.G.lu j.X.lu N.lu Q.F.lü Y.lu Y.lu Z.lu P.lukin F.j.luo T.luo X.F.luo Y.H.luo H.j.lyu X.R.lyu j.P.Ma P.Ma Y.Ma Y.M.Ma F.Maas S.Malde D.Matvienko Z.X.Meng R.Mitchell A.Nefediev Y.Nefedov S.l.Olsen Q.Ouyang P.Pakhlov G.Pakhlova X.Pan Y.Pan E.Passemar Y.P.Pei H.P.Peng l.Peng X.Y.Peng X.j.Peng k.Peters S.Pivovarov E.Pyata B.B.Qi Y.Q.Qi W.B.Qian Y.Qian C.F.Qiao j.j.Qin j.j.Qin l.Q.Qin X.S.Qin T.l.Qiu j.Rademacker C.F.Redmer H.Y.Sang Anhui University Hefei 230039China Beihang University Beijing 100191China Budker Institute of Nuclear Physics Novosibirsk 630090Russia CAS key laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China Cavendish laboratory University of CambridgeJJ Thomson AveCambridge CB30HEUnited Kingdom Central China Normal University Wuhan 430079China Central South University Changsha 410083China China University of Geosciences Wuhan 430074China China University of Mining and Technology Xuzhou 221116China École Polytechnique Fédérale de lausanne(EPFl) LausanneSwitzerland Fudan University Shanghai 200433China Goethe University Frankfurt D-60325 Frankfurt am MainGermany Guangxi Normal University Guilin 541004China Guangxi Uninversity Nanning 530004China Hangzhou Institute for Advanced Study UCASHangzhou 310024China Hebei Normal University Shijiazhuang 050024China Hebei University Baoding 071002China Hefei University of Technology Hefei 230601China Helmholtz Institute Mainz Staudinger Weg 18D-55099 MainzGermany Henan Normal University Xinxiang 453007China Henan University Kaifeng 475004China High Energy Physics Center Chung-Ang UniversitySeoul 06974Korea Higher School of Economy 11 Pokrovsky Bulvar Moscow 109028Russia Huangshan University Huangshan 245000China Hubei University of Automotive Technology Shiyan 442002China Hunan Normal University Changsha 410081China Hunan University of Science and Technology Xiangtan 411201China Hunan University Changsha 410082China Indiana University BloomingtonIndiana 47405USA Inner Mongolia University Hohhot 010021China Institute of Advanced Science Facilities Shenzhen 518107China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China Institute of Physics Academia SinicaTaipeiTaiwan 11529China Institute of Theoretical Physics Chinese Academy of SciencesBeijing 100190China jilin University Changch

The superτ-charm facility(STCF)is an electron–positron collider proposed by the Chinese particle physics *** is designed to operate in a center-of-mass energy range from 2 to 7 GeV with a peak luminosity of 0.5×10^(35) cm^(–2)·s^(–1) or *** STCF will produce a data sample about a factor of 100 larger than that of the presentτ-charm factory—the BEPCII,providing a unique platform for exploring the asymmetry of matter-antimatter(charge-parity violation),in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions,as well as searching for exotic hadrons and physics beyond the Standard *** STCF project in China is under development with an extensive R&D *** document presents the physics opportunities at the STCF,describes conceptual designs of the STCF detector system,and discusses future plans for detector R&D and physics case studies.

关键词： electron–positron collider tau-charm region high luminosity STCF detector conceptual design

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Full-spectrum Bi@SrTiO_(3) for bi-directional promotion effects on photocatalytic redox reaction:Insight into intermediates and mechanism

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journal of Rare Earths 2024年第5期42卷 917-929,I0004页

作者： Bin liu Nanhao Zhou jun liu Xinglei Wang Peter k.j.Robertson Xiaoyuan Chen Chao Chen jianmin luo Chuanyi Wang School of Chemistry and Civil Engineering Shaoguan UniversityShaoguan512005China Chengdu Customs Technology Center Chengdu610041China key laboratory of Pollutant Chemistry and Environmental Treatment College of Chemistry and Environmental ScienceYili Normal UniversityYining835000China School of Chemistry and Chemical Engineering Queen's University BelfastStranmillis RoadBelfastBT95AGUnited Kingdom Guangzhou Institute of Industrial Intelligence(GIII) Guangzhou511400China

The development of full-spectrum photocatalysts active in the near-infrared(NIR)region has gained increasing attention for deleterious pollutant *** integration of plasmonic metals with semico nductors is an effective way to widen the light re sponse range of photocatalysts due to the strong light absorption and fast plasmonic energy transfer of the localized surface plasmon resonance(lSPR).In this work,the full-spectrum responsive Bi@SrTiO_(3) was prepared via facile solvothermal chemical *** optimal Bi@SrTiO_(3) achieves exceptional photocatalytic Cr(VI)reduction efficiency and tetracycline degradation,realizing bi-directional promotion effects on redox *** to density functional theory(DFT)simulations,the extraordinary photocatalytic performance is attributed to the tunable builtin electric field(IEF)of the Ohmic *** favorable adaptability in real water and high stability of BSTO-25 were proved by experime ntal *** the po ssible photocatalytic mechanism was proposed based on theoretical calculation and experimental ***,the non-toxicity of the BSTO-25 was evaluated by *** cultivation,which further proves the feasibility of treating wastewater with *** work provides a new perspective on constructing full-spectrum-driven photocatalysts for applications dealing with environmental remediation.

关键词： Full-spectrum photocatalysts localized surface plasmon resonance Ohmic contact Cr(Ⅵ)reduction Antibiotic degradation Rare earths

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Highly sensitive ratiometric fluorescent fiber matrices for oxygen sensing with micrometer spatial resolution

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Bio-Design and Manufacturing 2024年第3期7卷 292-306页

作者： Giuliana Grasso Valentina Onesto Stefania Forciniti Eliana D’Amone Francesco Colella lara Pierantoni Valeria Famà Giuseppe Gigli Rui l.Reis j.Miguel Oliveira loretta l.del Mercato nstitute of Nanotechnology National Research Council(CNR-NANOTEC)c/o Campus Ecoteknevia Monteroni73100 LecceItaly Department of Mathematics and Physics“Ennio De Giorgi” University of Salentoc/o Campus Ecoteknevia Monteroni73100 LecceItaly 3B’s Research Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate laboratory 4806-909 Braga/GuimarãesPortugal Department of Experimental Medicine University of Salentoc/o Campus Ecoteknevia Monteroni73100 LecceItaly

Oxygen(O_(2))-sensing matrices are promising tools for the live monitoring of extracellular O_(2) consumption levels in long-term cell *** this study,ratiometric O_(2)-sensing membranes were prepared by electrospinning,an easy,low-cost,scalable,and robust method for fabricating ***(ε-caprolactone)and poly(dimethyl)siloxane polymers were blended with tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)dichloride,which was used as the O_(2)-sensing probe,and rhodamine B isothiocyanate,which was used as the reference *** functionalized scaffolds were morphologically characterized by scanning electron microscopy,and their physicochemical profiles were obtained by Fourier transform infrared spectroscopy,thermogravimetric analysis,and water contact angle *** sensing capabilities were investigated by confocal laser scanning microscopy,performing photobleaching,reversibility,and calibration curve studies toward different dissolved O_(2)(DO)*** sensing nanofibers showed a high response to changes in DO concentrations in the physiological-pathological range from 0.5%to 20%and good stability under ratiometric *** addition,the sensing systems were highly biocompatible for cell growth promoting adhesiveness and growth of three cancer cell lines,namely metastatic melanoma cell line Sk-MEl2,breast cancer cell line MCF-7,and pancreatic ductal adenocarcinoma cell line Panc-1,thus recreating a suitable biological environment in *** O_(2)-sensing biomaterials can potentially measure alterations in cell metabolism caused by changes in ambient O_(2)content during drug testing/validation and tissue regeneration processes.

关键词： Electrospinning Ruthenium(II)dichloride Oxygen sensors Ratiometric imaging Fluorescence

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A novel diagnostic gene region for distinguishing between two pest fruit flies:Bactrocera tryoni(Froggatt)and Bactrocera neohumeralis(Hardy)(Diptera:Tephritidae)

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Insect Science 2024年第4期31卷 1285-1295页

作者： Melissa l.Starkie Elizabeth V.Fowler Alexander M.Piper Xiaocheng Zhu Pauline Wyatt David Gopurenko Matt N.krosch Francesca Strutt karen F.Armstrong Hamish Patrick Mark k.Schutze Mark j.Blacket Department of Agriculture and Fisheries BiosecurityBrisbaneQueenslandAustralia Agriculture Victoria AgriBioBundooraVictoriaAustralia Department of Primary Industries Wagga Wagga Agricultural InstituteWagga WaggaNew South WalesAustralia Forensic Services Group Queensland Police ServiceBrisbaneQueenslandAustralia Department of Pest-management and Conservation Lincoln UniversityLincolnNew Zealand Better Border Biosecurity(B3 B3nz.org.nz)LincolnNew Zealand

Bactrocera tryoni and Bactrocera neohumeralis are morphologically similar sibling pest fruit fly species that possess different biological attributes,geographic distributions,and host *** need to differentiate between the two species is critical for accurate pest status assessment,management,biosecurity,and maintenance of reference *** morphologically similar,adults may be separated based on subtle characters;however,some characters exhibit intraspecific variability,creating overlap between the two ***,there is currently no single molecular marker or rapid diagnostic assay that can reliably distinguish between *** and ***;therefore,ambiguous samples remain *** we report the first molecular marker that can consistently distinguish between *** and *** diagnostic region consists of two adjacent single nucleotide polymorphisms(SNPs)within the pangolin(pan)gene *** confirmed the genotypes of each species are consistent across their distributional range,then developed a tetra-primer amplification refractory mutation system(ARMS)PCR assay for rapid diagnosis of the *** assay utilizes four primers in multiplex,with two outer universal primers,and two internal primers:one designed to target two adjacent SNPs(AA)present in *** and the other targeting adjacent SNPs present in ***(GG).The assay accurately discriminates between the two species,but their SNP genotypes are shared with other nontarget tephritid fruit fly ***,this assay is most suited to adult diagnostics where species confirmation is necessary in determining ambiguous surveillance trap catches;maintaining pure colony lines;and in Sterile Insect Technique management responses.

关键词： ARMS-PCR colony molecular diagnostics pangolin tetra-primer

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Anneal-free ultra-low loss silicon nitride integrated photonics

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light(Science & Applications) 2024年第8期13卷 1565-1577页

作者： Debapam Bose Mark W.Harrington Andrei Isichenko kaikai liu jiawei Wang Nitesh Chauhan Zachary l.Newman Daniel j.Blumenthal Department of Electrical and Computer Engineering University of California Santa BarbaraSanta BarbaraCA 93106USA Octave Photonics LouisvilleCO 80027USA

Heterogeneous and monolithic integration of the versatile low-loss silicon nitride platform with low-temperature materials such as silicon electronics and photonics,III–V compound semiconductors,lithium niobate,organics,and glasses has been inhibited by the need for high-temperature annealing as well as the need for different process flows for thin and thick *** techniques are needed to maintain the state-of-the-art losses,nonlinear properties,and CMOS-compatible processes while enabling this next generation of 3D silicon nitride *** report a significant advance in silicon nitride integrated photonics,demonstrating the lowest losses to date for an anneal-free process at a maximum temperature 250℃,with the same deuterated silane based fabrication flow,for nitride and oxide,for an order of magnitude range in nitride thickness without requiring stress mitigation or *** report record low anneal-free losses for both nitride core and oxide cladding,enabling 1.77 dBm^(-1) loss and 14.9 million Q for 80 nm nitride core waveguides,more than half an order magnitude lower loss than previously reported sub 300℃ *** 800 nm-thick nitride,we achieve as good as 8.66 dBm^(-1) loss and 4.03 million Q,the highest reported Q for a low temperature processed resonator with equivalent device area,with a median of loss and Q of 13.9 dBm^(-1) and 2.59 million each *** demonstrate laser stabilization with over 4 orders of magnitude frequency noise reduction using a thin nitride reference cavity,and using a thick nitride micro-resonator we demonstrate OPO,over two octave supercontinuum generation,and four-wave mixing and parametric gain with the lowest reported optical parametric oscillation threshold per unit resonator *** results represent a significant step towards a uniform ultra-low loss silicon nitride homogeneous and heterogeneous platform for both thin and thick waveguides capable of linear and nonlinear photonic circuits and

关键词： resonator thick free

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Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael j.lee Ryota l.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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