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The concept of gene therapy for glaucoma:the dream that has not come true yet

Neural Regeneration Research 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 Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,crry,c3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,cOX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

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Single-atom catalysts for the electrochemical reduction of carbon dioxide into hydrocarbons and oxygenates

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carbon Energy 2024年第3期6卷 64-117页

作者： Karl adrian Gandionco Juwon Kim Lieven Bekaert Annick Hubin Jongwoo Lim Department of chemistry Seoul National UniversitySeoulRepublic of Korea Research Group Electrochemical and Surface Engineering(SURF) Department of Materials and ChemistryVrije Universiteit BrusselBrusselsBelgium

The electrochemical reduction of carbon dioxide offers a sound and economically viable technology for the electrification and decarbonization of the chemical and fuel *** this technology,an electrocatalytic material and renewable energy-generated electricity drive the conversion of carbon dioxide into high-value chemicals and carbon-neutral *** the past few years,single-atom catalysts have been intensively studied as they could provide near-unity atom utilization and unique catalytic ***-atom catalysts have become one of the state-of-the-art catalyst materials for the electrochemical reduction of carbon dioxide into carbon ***,it remains a challenge for single-atom catalysts to facilitate the efficient conversion of carbon dioxide into products beyond carbon *** this review,we summarize and present important findings and critical insights from studies on the electrochemical carbon dioxide reduction reaction into hydrocarbons and oxygenates using single-atom *** is hoped that this review gives a thorough recapitulation and analysis of the science behind the catalysis of carbon dioxide into more reduced products through singleatom catalysts so that it can be a guide for future research and development on catalysts with industry-ready performance for the electrochemical reduction of carbon dioxide into high-value chemicals and carbon-neutral fuels.

关键词： electrocatalysis electrochemical cO_(2)reduction hydrocarbons oxygenates single-atom catalysts

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A Distributionally Robust Optimization Scheduling Model for Regional Integrated Energy Systems considering Hot Dry Rock co-Generation

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computer Modeling in Engineering & Sciences 2024年第8期140卷 1387-1404页

作者： Hao Qi Mohamed Sharaf Andres Annuk adrian Ilinca Mohamed A.Mohamed college of Electrical 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 Mechanical Engineering école de Technologie SupérieureMontréalQC H3C 1K3Canada Electrical Engineering Department Faculty of EngineeringMinia UniversityMinia61519Egypt

Hot dry rock(HDR)is rich in reserve,widely distributed,green,low-carbon,and has broad development potential and *** this paper,a distributionally robust optimization(DRO)scheduling model for a regionally integrated energy system(RIES)considering HDR co-generation is ***,the HDR-enhanced geothermal system(HDR-EGS)is introduced into the ***-EGS realizes the thermoelectric decoupling of combined heat and power(cHP)through coordinated operation with the regional power grid and the regional heat grid,which enhances the system wind power(WP)feed-in ***,peak-hour loads are shifted using price demand response guidance in the context of time-of-day ***,the optimization objective is established to minimize the total cost in the RIES scheduling cycle and construct a DRO scheduling model for RIES with *** simulating a real small-scale RIES,the results show that HDR-EGS can effectively promote WP consumption and reduce the operating cost of the system.

关键词： Energy harvesting integrated energy systems optimum scheduling time-of-use pricing demand response geothermal energy

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Principles for managing marine ecosystems prone to tipping points

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Ecosystem Health and Sustainability 2015年第5期1卷 15-32页

作者： Kimberly A.Selkoe Thorsten Blenckner Margaret R.caldwell Larry B.crowder Ashley L.Erickson Timothy E.Essington James A.Estes Rod M.Fujita Benjamin S.Halpern Mary E.Hunsicker carrie V.Kappel Ryan P.Kelly John N.Kittinger Phillip S.Levin John M.Lynham Megan E.Mach Rebecca G.Martone Lindley A.Mease Anne KSalomon Jameal F.Samhouri courtney Scarborough adrian c.stier crow White Joy Zedler National center for Ecological Analysis and Synthesis 735 State StreetSuite 300Santa BarbaraCalifornia 93101 USA Hawaii Institute of Marine Biology University of HawaiiKaneoheHawaii 96744 USA Stockholm Resilience centre Stockholm UniversityKra¨ftriket 2B10691 StockholmSweden center for Ocean Solutions Stanford Woods Institute for the EnvironmentStanford University473 Via Ortega Room 193StanfordCalifornia 94305 USA School of Aquatic and Fishery Sciences University of WashingtonSeattleWashington 98195 USA Department of Ecology and Evolutionary Biology 100 Shaffer RoadUniversity of CaliforniaSanta CruzCalifornia 95060 USA Environmental Defense Fund 123 Mission Street28th FloorSan FranciscoCalifornia 94105 USA Bren School of Environmental Science and Management University of CaliforniaSanta BarbaraCalifornia 93106 USA Imperial college London Silwood Park CampusBuckhurst RoadAscot SL57PY United Kingdom School of Marine and Environmental Affairs University of Washington3707 Brooklyn Avenue NESeattleWashington 98105-6715 USA conservation International Betty and Gordon Moore Center for Science and Oceans7192 Kalaniana‘ole HighwaySuite G230HonoluluHawaii 96825 USA conservation Biology Division Northwest Fisheries Science CenterNational Marine Fisheries ServiceNational Oceanic and Atmospheric Administration2725 Montlake Boulevard EastSeattleWashington 98112 USA Department of Economics University of Hawaii at ManoaHonoluluHawaii 96822 USA School of Resource and Environmental Management Simon Fraser UniversityBurnabyBritish Columbia V5A1S6 Canada Department of Biological Sciences California Polytechnic State UniversitySan Luis ObispoCalifornia 93407 USA Botany Department University of WisconsinMadisonWisconsin 53706 USA

As climatic changes and human uses intensify,resource managers and other decision makers are taking actions to either avoid or respond to ecosystem tipping points,or dramatic shifts in structure and function that are often costly and hard to *** indicates that explicitly addressing tipping points leads to improved management *** on theory and examples from marine systems,we distill a set of seven principles to guide effective management in ecosystems with tipping points,derived from the best available *** principles are based on observations that tipping points(1)are possible everywhere,(2)are associated with intense and/or multifaceted human use,(3)may be preceded by changes in earlywarning indicators,(4)may redistribute benefits among stakeholders,(5)affect the relative costs of action and inaction,(6)suggest biologically informed management targets,and(7)often require an adaptive response to *** suggest that early action to preserve system resilience is likely more practical,affordable,and effective than late action to halt or reverse a tipping *** articulate a conceptual approach to management focused on linking management targets to thresholds,tracking early-warning signals of ecosystem instability,and stepping up investment in monitoring and mitigation as the likelihood of dramatic ecosystem change *** approach can simplify and economize management by allowing decision makers to capitalize on the increasing value of precise information about threshold relationships when a system is closer to tipping or by ensuring that restoration effort is sufficient to tip a system into the desired regime.

关键词： critical transition ecosystem-based management marine spatial planning nonlinear relationships restoration ecology stakeholder engagement

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer c.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref 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 Neurological Surgery and the Miami Project to cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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