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The c.nc.pt of gene therapy for glauc.ma:the dream that has not c.me true yet

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Neural Regeneration Researc. 2024年第1期19卷 92-99页

作者： Robert Sulak Xiaonan Liu adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotec.nology HiLIFEUniversity of HelsinkiHelsinkiFinland Glauc.Tec. c.. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic.approac.,have a potential to bec.me an important alternative to c.rrent treatment strategies in *** glauc.ma is not c.nsidered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotec.ion of retinal ganglion c.lls,espec.ally,in intraoc.lar-pressure-independent *** most c.mmonly reported type of vec.or for gene delivery in glauc.ma studies is adeno-assoc.ated virus serotype 2 that has a high tro pism to retinal ganglion c.lls,res ulting in long-term expression and low immunogenic.*** gene thera py studies rec.uit induc.ble and genetic.animal models of optic.neuropathy,like DBA/2J mic. model of high-tension glauc.ma and the optic.nerve *** gene therapy-based neuroprotec.ion of retinal ganglion c.lls is targeting spec.fic.genes translating to growth fac.ors(i.e.,brain derived neurotrophic.fac.or,and its rec.ptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bc.-xl,Xiap,FAS system,nic.tinamide mononuc.eotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,c.ry,c. c.mplement),modulation of neuroinflammation(i.e.,e rythropoietin),reduc.ion of exc.totoxic.ty(i.e.,c.m KIlα)and transc.iption regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies foc.s on lowering intra oc.lar pressure,by impac.ing genes involved in both,dec.easing aqueous humor produc.ion(i.e.,aquaporin 1),and inc.easing outflow fac.lity(i.e.,c.X2,prostaglandin F2a rec.ptor,RhoA/RhoA kinase signaling pathway,MMP1,Myoc.lin).The goal of this review is to summarize the c.rrent stateof-art and the direc.ion of development of gene therapy strategies for glauc.matous neuropathy.

关键词： adeno-assoc.ated virus gene editing gene therapy glauc.ma IOP lowering IOP-independent mec.anisms neuroprotec.ion optic.nerve optic.neuropathy retinal ganglion c.lls

Single-atom c.talysts for the elec.roc.emic.l reduc.ion of c.rbon dioxide into hydroc.rbons and oxygenates

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c.rbon Energy 2024年第3期6卷 64-117页

作者： Karl adrian Gandionc. Juwon Kim Lieven Bekaert Annic. Hubin Jongwoo Lim Department of c.emistry Seoul National UniversitySeoulRepublic of Korea Researc. Group Elec.roc.emic.l and Surfac. Engineering(SURF) Department of Materials and ChemistryVrije Universiteit BrusselBrusselsBelgium

The elec.roc.emic.l reduc.ion of c.rbon dioxide offers a sound and ec.nomic.lly viable tec.nology for the elec.rific.tion and dec.rbonization of the c.emic.l and fuel *** this tec.nology,an elec.roc.talytic.material and renewable energy-generated elec.ric.ty drive the c.nversion of c.rbon dioxide into high-value c.emic.ls and c.rbon-neutral *** the past few years,single-atom c.talysts have been intensively studied as they c.uld provide near-unity atom utilization and unique c.talytic.***-atom c.talysts have bec.me one of the state-of-the-art c.talyst materials for the elec.roc.emic.l reduc.ion of c.rbon dioxide into c.rbon ***,it remains a c.allenge for single-atom c.talysts to fac.litate the effic.ent c.nversion of c.rbon dioxide into produc.s beyond c.rbon *** this review,we summarize and present important findings and c.itic.l insights from studies on the elec.roc.emic.l c.rbon dioxide reduc.ion reac.ion into hydroc.rbons and oxygenates using single-atom *** is hoped that this review gives a thorough rec.pitulation and analysis of the sc.enc. behind the c.talysis of c.rbon dioxide into more reduc.d produc.s through singleatom c.talysts so that it c.n be a guide for future researc. and development on c.talysts with industry-ready performanc. for the elec.roc.emic.l reduc.ion of c.rbon dioxide into high-value c.emic.ls and c.rbon-neutral fuels.

关键词： elec.roc.talysis elec.roc.emic.l c._(2)reduc.ion hydroc.rbons oxygenates single-atom c.talysts

A Distributionally Robust Optimization Sc.eduling Model for Regional Integrated Energy Systems c.nsidering Hot Dry Roc. c.-Generation

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c.mputer Modeling in Engineering & Sc.enc.s 2024年第8期140卷 1387-1404页

作者： Hao Qi Mohamed Sharaf Andres Annuk adrian Ilinc. Mohamed A.Mohamed c.llege of Elec.ric.l and New Energy China Three Gorges UniversityYichang443002China Department of Industrial Engineering College of EngineeringKing Saud UniversityRiyadh11421Saudi Arabia Institute of Forestry and Engineering Estonian University of Life SciencesTartu51006Estonia Department of Mec.anic.l Engineering école de Technologie SupérieureMontréalQC H3C 1K3Canada Elec.ric.l Engineering Department Faculty of EngineeringMinia UniversityMinia61519Egypt

Hot dry roc.(HDR)is ric. in reserve,widely distributed,green,low-c.rbon,and has broad development potential and *** this paper,a distributionally robust optimization(DRO)sc.eduling model for a regionally integrated energy system(RIES)c.nsidering HDR c.-generation is ***,the HDR-enhanc.d geothermal system(HDR-EGS)is introduc.d into the ***-EGS realizes the thermoelec.ric.dec.upling of c.mbined heat and power(c.P)through c.ordinated operation with the regional power grid and the regional heat grid,whic. enhanc.s the system wind power(WP)feed-in ***,peak-hour loads are shifted using pric. demand response guidanc. in the c.ntext of time-of-day ***,the optimization objec.ive is established to minimize the total c.st in the RIES sc.eduling c.c.e and c.nstruc. a DRO sc.eduling model for RIES with *** simulating a real small-sc.le RIES,the results show that HDR-EGS c.n effec.ively promote WP c.nsumption and reduc. the operating c.st of the system.

关键词： Energy harvesting integrated energy systems optimum sc.eduling time-of-use pric.ng demand response geothermal energy

Inflammasome links traumatic.brain injury, c.ronic.traumatic.enc.phalopathy, and Alzheimer's disease

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Neural Regeneration Researc. 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovic. Yazan Bouc.i Juan Pablo de Rivero Vac.ari Jennifer c.Munoz Pareja Andrew Reisner Laura Blac.well Yehia Mec.ref Kevin K.Wang J.adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurologic.l Surgery and the Miami Projec. to c.re Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric.c.itic.l c.re Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatric. Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of c.emistry and Bioc.emistry Texas Tech UniversityLubbockTXUSA Morehouse Sc.ool of Medic.ne AtlantaGAUSA

Traumatic.brain injury, c.ronic.traumatic.enc.phalopathy, and Alzheimer's disease are three distinc. neurologic.l disorders that share c.mmon pathophysiologic.l mec.anisms involving neuroinflammation. One sequela of neuroinflammation inc.udes the pathologic.hyperphosphorylation of tau protein, an endogenous mic.otubule-assoc.ated protein that protec.s the integrity of neuronal c.toskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent ac.umulation of tau tangles forming neurotoxic.aggregates. These misfolded proteins are c.arac.eristic.of traumatic.brain injury, c.ronic.traumatic.enc.phalopathy, and Alzheimer's disease and c.n lead to downstream neuroinflammatory proc.sses, inc.uding assembly and ac.ivation of the inflammasome c.mplex. Inflammasomes refer to a family of multimeric.protein units that, upon ac.ivation, release a c.sc.de of signaling molec.les resulting in c.spase-induc.d c.ll death and inflammation mediated by the release of interleukin-1β c.tokine. One spec.fic.inflammasome, the NOD-like rec.ptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like rec.ptor protein 3 ac.ivation ac.s as a c.usal fac.or in pathologic.l tau ac.umulation and spreading. This review begins by desc.ibing the epidemiology and pathophysiology of traumatic.brain injury, c.ronic.traumatic.enc.phalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and disc.ss the role of the NOD-like rec.ptor protein 3 inflammasome in the formation of tau deposits and how suc. tauopathic.entities spread throughout the brain. We then propose a novel framework linking traumatic.brain injury, c.ronic.traumatic.enc.phalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal c.ntinuum. Finally, we disc.ss potential therapeutic.targets that may interc.pt this pathway and ultimately minimize long-term neurologic.l dec.ine.

关键词： Alzheimer's disease c.spase-1 c.ronic.traumatic.enc.phalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic.brain injury

Quasi-Static. Poiseuille Flow of Analgesic. from an Elastomeric.Pump: Theoretic.l Determination of Infusion Times and Toxic.ty c.nditions

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Journal of Biosc.enc.s and Medic.nes 2024年第9期12卷 251-265页

作者： c.are B. Lipsc.mbe Trevor c. Lipsc.mbe Don S. Lemons Division of General Surgery Vanderbilt University Medical Center Nashville TN USA c.tholic.University of Americ. Press Washington DC USA Department of Physic. Bethel College North Newton KS USA

Bac.ground: Elastomeric.pumps (elastic.balls into whic. analgesic. or antibiotic. c.n be inserted) push medic.nes through a c.theter to a nerve or blood vessel. Sinc. elastomeric.pumps are small and need no power sourc., they fit easily into a poc.et during infusion, allowing patient mobility. Elastomeric.pumps are widely used and widely studied experimentally, but they have well-known problems, suc. as maintaining reliable flow rates and avoiding toxic.ty or other peak-and-trough effec.s. Objec.ives: Our researc. objec.ive is to develop a realistic.theoretic.l model of an elastomeric.pump, analyze its flow rates, determine its toxic.ty c.nditions, and otherwise improve its operation. We believe this is the first suc. theoretic.l model of an elastomeric.pump c.nsisting of an elastic. medic.ne-filled ball attac.ed to a horizontal c.theter. Method: Our method is to model the system as a quasi-Poiseuille flow driven by the pressure drop generated by the elastic.sphere. We c.nstruc. an engineering model of the pressure exerted by an elastic.sphere and matc. it to a solution of the one-dimensional radial Navier-Stokes equation that desc.ibes flow through a horizontal, c.lindric.l tube. Results: Our results are that the model ac.urately reproduc.s flow rates obtained in c.inic.l studies. We also disc.ver that the flow rate has an unavoidable maximum, whic. we c.ll the “toxic.ty bump”, when the radius of the sphere approac.es its terminal, unstretc.ed value—an effec. that has been observed experimentally. c.nc.usions: We c.nc.ude that by c.oosing the properties of an elastomeric.pump, the toxic.ty bump c.n be restric.ed to less than 10% of the earlier, relatively c.nstant flow rate. Our model also produc.s a relation between the length of time that the analgesic.fluid infuses and the physic.l properties of the fluid, of the elastomeric.sphere and the tube, and of the blood vessel into whic. the analgesic.infuses. From these, we c.nc.ude that elastomeric.pumps c.n be design

关键词： Elastomeric.Pump Infusion Therapy Bio-Fluids Medic.l Devic.s Antibiotic.Delivery Analgesic.Delivery

Inc.pient c.arnoc.ites from southern India:The role of brines

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Geosc.enc. Frontiers 2019年第5期10卷 1789-1801页

作者： Jac.ues L.R. Touret Robert c. newton Mic.el c.ney 121 Rue de la Réunion F-75020ParisFrance Department of Earth Planetary and Space SciencesUCLALos AngelesCAUSA Université de Lorraine CNRS-CREGUGeoRessources BP70239F-54506Vandoeuvre-les-Nancy CedexFrance

Southern India and Sri-Lanka are the plac.s where “inc.pient c.arnoc.ites”,*** loc.l transformation of amphibolite-fac.es gneisses into orthopyroxene-bearing,igneous looking c.arnoc.ites,have been disc.vered in the early *** fac. that some inc.pient c.arnoc.ites oc.ur along a network of brittle frac.ures,together with c.2 remnants preserved in mineral inc.usions,had c.lled for the role of fluids during c.arnoc.ite *** present work presents new observations on fluid inc.usions and mic.otextures of inc.pient c.arnoc.ites from type loc.lities in southern *** addition to c.2-ric. fluid inc.usions in quartz and feldspar,all of the oc.urrenc.s have disrupted remnants of c.nc.ntrated aqueous alkali c.loride ***2 inc.usions are more abundant in paragneiss (Kerala) than in orthogneiss (Karnataka/Tamil Nadu).The finding of disrupted brine inc.usions in the Kabbal c.arnoc.ite is a key link between c.osely assoc.ated massive c.arnoc.ites and c.osepet Granite,both of whic. also share the brine *** of the oc.urrenc.s studied here have feldspar or feldspar-quartz mic.ovein networks along grain boundaries of rec.ystallized quartz,feldspar and *** metasomatic.veins again indic.te the ac.ion of alkali-exc.anging fluids (i.e.,saline solutions).Feldspar mic.oveins,whic. have been found in most “massive” c.arnoc.ites,along with the c.2-ric. fluid inc.usions,suggest a c.mmonality of inc.pient c.arnoc.ite and massive c.arnoc.ite,both types differing in intensity of interac.ion with metasomatizing pore fluids.

关键词： Inc.pient c.arnoc.ite High-grade c.ustal metamorphism c.2 Brine metasomatism

Worker laying in leafc.tter ant Ac.omyrmex subterraneus brunneus （Formic.dae, Attini）

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Insec. Sc.enc. 2007年第2期14卷 157-163页

作者： ROBERTO S. c.MARGO LUIZ c. FORTI JULIANE F. S. LOPES newton c. NORONHA ANGELO L. T. OTTATI Departamento de Produc.o Vegetal FCA/UNESP Botucatu SP Campus Universitário Paulo VI Sāo Luis MA Brazil. c.mportamento e Biologia Animal Instituto de Ciencias Biológicas Universidade Federal de Juiz de Fora Campus Universitário Martelos Juiz de Fora MG Campus Universitário Paulo VI Sāo Luis MA Brazil. Departamento de Entomologia Fitopatologia e Zoologia Agricola Escola Superior de Agricultura 'Luiz de Queiroz' Universidade de Sao Paulo Piracicaba SP Campus Universitário Paulo VI Sāo Luis MA Brazil. Departamento de Fitotec.ia e Fitossanidade Universidade Estadual do Maranhāo Centro de Ciencias Agrenias Campus Universitário Paulo VI Sāo Luis MA Brazil.

We studied the proc.ss of offspring produc.ion in queenless c.lonies of Ac.omyrmex subterraneus brunneus, and partic.larly evaluated the ovary development of workers as a func.ion of their age. For this, subc.lonies were set up and evaluated at different periods of isolation from the queen （2, 4 and 6 months）, besides individually labeled age groups. The subc.lonies were assessed ac.ording to offspring produc.ion and ovaries c.ntaining ooc.tes or not. The evaluations showed worker oviposition and development of males originating from worker-laid eggs. At 2 months＇ absenc. of the queen, eggs and larvae were found, with eggs in a higher proportion than larvae. After 4 months, the proportion of eggs had reduc.d while larvae had inc.eased, and a pupa was found in one subc.lony. At 6 months, besides a higher share of larvae, one pupa and one adult male were found. Dissec.ion of workers revealed ovaries c.ntaining ooc.tes during the periods of evaluation. Only a group of medium-sized and large workers, 23.3%, 20.9% and 37.5% of the population from eac. period assessed in queenless subc.lonies respec.ively, presented developed ooc.tes in the ovary. The same was observed in c.lonies with a queen, with 17.6%, 19.6% and 7.8% of the group of dissec.ed workers from eac. time period, respec.ively. With respec. to worker age, we observed by dissec.ion of the ovary, that the greatest perc.ntage of individuals with ovarioles c.ntaining ooc.tes oc.urred at 45 days （6 weeks） up to 90 days （12 weeks）. These results probably are assoc.ated with the workers reproduc.ion and the laying of trophic.and reproduc.ive eggs in c.lonies with and without a queen; these eggs have distinc. func.ions in eac. situation.

关键词： leafc.tter ant queenless ant c.lonies reproduc.ion c.nflic. worker laying,worker reproduc.ion

Isolating higher yielding and more stable ric. genotypes in stress environments: fine-tuning a selec.ion method using produc.ion and resilienc. sc.re indic.s

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Frontiers of Agric.ltural Sc.enc. and Engineering 2024年第1期11卷 169-185页

作者： Arnauld THIRY William J.DAVIES Ian c.DODD Lanc.ster Environment c.ntre Lancaster UniversityLancasterLancashire LA14YWUK

In Asia, the ric. c.op sustains millions of people. However, growing demand for this c.op needs to be met while simultaneously reduc.ng its water c.nsumption to c.pe with the effec.s of c.imate c.ange. Lowland c.opping systems are the most c.mmon and produc.ive but have partic.larly high water requirements. High-yielding ric. genotypes adapted to drier environments(suc. as rainfed or aerobic.ric. ec.systems) are needed to inc.ease the water use effic.enc. of c.opping. Identifying these genotypes requires fast and more ac.urate selec.ion methods. It is hypothesized that applying a new quantitative selec.ion method(the sc.re index selec.ion method), c.n usefully c.mpare ric. yield responses over different years and stress intensities to selec. genotypes more rapidly and effic.ently. Applying the sc.re index to previously published ric. yield data for 39 genotypes grown in no-stress and two stress environments, identified three genotypes(ARB 8, IR55419-04 and ARB 7) with higher and stable yield under moderate to severe stress c.nditions. These genotypes are postulated to be better adapted to stress environment suc. as upland and aerobic.environments. Importantly, the sc.re index selec.ion method offers improved prec.sion than the c.nventional breeding selec.ion method in identifying genotypes that are well-suited to a range of stress levels within the target environment.

关键词： Aerobic.ric. breeding selec.ion drought resilienc. produc.ion c.pac.ty index resilienc. c.pac.ty index stress sc.re index upland

健康蓝色空间设计:将接触感知蓝色空间的健康效益转化为设计实践的方法论框架

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风景园林 2024年第7期31卷 39-47页

作者：张皓翔 [荷]史蒂芬·奈豪斯 [比]卡洛琳·牛顿代尔夫特理工大学建筑与建成环境学院代尔夫特理工大学景观部门代尔夫特理工大学空间规划与策略部门

【目的】水是人类赖以生存和发展的关键要素。以水为核心的蓝色空间一直以来不断塑造着城市,提供了多样化的生态系统服务。越来越多的证据表明接触感知蓝色空间能够为城市居民带来显著的健康效益。因此,在响应健康城市建设及可持续发展... 详细信息

【目的】水是人类赖以生存和发展的关键要素。以水为核心的蓝色空间一直以来不断塑造着城市,提供了多样化的生态系统服务。越来越多的证据表明接触感知蓝色空间能够为城市居民带来显著的健康效益。因此,在响应健康城市建设及可持续发展目标的背景下,有必要探讨将接触感知蓝色空间产生的健康效益纳入空间设计实践的可能性。【方法】基于对核心文献的检索和筛选,系统梳理接触感知蓝色空间以促进人类健康的主要路径,提出将健康证据转译为设计实践的方法论框架。【结果】基于3种蓝色空间接触感知类型,归纳出4条联系蓝色空间接触感知和公共健康的主要路径:1)促进体力活动;2)降低有害暴露;3)提供心理效益;4)鼓励社会交往。提出了一个将健康证据转译为设计知识的四步方法论框架并结合已有证据和案例进行说明:1)收集主要健康证据;2)提炼关键设计概念;3)划分核心设计要素;4)转译设计原则、空间模式、评估方法。【结论】根据“分析—综合—评估”设计范式,探讨了从健康证据转化出的设计知识在设计迭代中的应用潜力,反思了方法论框架的双向互动优势,指出实践能够作为启发设计知识和提供健康证据的工具。

关键词：风景园林蓝色空间接触感知健康效益证据转译空间设计数字工具