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Telomeric DnA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair

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Journal of Molecular Cell Biology 2024年第3期16卷 46-60页

作者： Katrina n.Estep John W.Tobias Rafael J.Fernandez Brinley M.Beveridge F.Brad Johnson Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPA 19104USA Quantiative Biosciences Merck&Co.Inc.West PointPA 19486USA Penn Genomic Analysis Core University of PennsylvaniaPhiladelphiaPA 19104USA

Although mechanisms of telomere protection are well-defined in differentiated cells,how stem cells sense and respond to telomere dysfunction,in particular telomeric double-strand breaks(DSBs),is poorly ***,we report the DnA damage signaling,cell cycle,and transcriptome changes in human induced pluripotent stem cells(iPSCs)in response to telomere-internal *** engineer human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at *** this model,we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DnA damage response,which leads to p53-independent cell cycle arrest in *** CRISPR–Cas9 to cripple the catalytic domain of telomerase reverse transcriptase,we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres,which instead are effectively repaired by robust homologous recombination(HR).In contrast to HR-based telomere maintenance in mouse embryonic stem cells,where HR causes ZSCAn4-dependent extension of telomeres beyond their initial lengths,HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length,which is compatible with sustained survival of the cells over several days of TRF1-FokI *** findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DnA damage.

关键词： telomeres telomerase alternative lengthening of telomeres pluripotent stem cells DnA damage double-strand breaks

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Single atom Cu-n-C catalysts for the electro-reduction of CO_(2) to CO assessed by rotating ring-disc electrode

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Journal of Energy Chemistry 2024年第1期88卷 169-182,I0004页

作者： S.Pérez-Rodríguez M.Gutiérrez-Roa C.Giménez-Rubio D.Ríos-Ruiz P.Arévalo-Cid M.V.Martínez-Huerta A.Zitolo M.J.Lázaro D.Sebastián Instituto de Carboquímica(CSIC) Miguel Luesma Castán 450018 ZaragozaSpain Instituto de Catálisis y Petroleoquímica(CSIC) Marie Curie 228049 MadridSpain Synchrotron SOLEIL L’Orme des MerisiersDépartementale 12891190France

The electrochemical CO_(2) reduction reaction(CO_(2)RR) to controllable chemicals is considered as a promising pathway to store intermittent renewable energy. Herein, a set of catalysts based on copper-nitrogendoped carbon xerogel(Cu-n-C) are successfully developed varying the copper amount and the nature of the copper precursor, for the efficient CO_(2)RR. The electrocatalytic performance of Cu-n-C materials is assessed by a rotating ring-disc electrode(RRDE), technique still rarely explored for CO_(2)RR. For comparison, products are also characterized by online gas chromatography in a H-cell. The as-synthesized Cu-nC catalysts are found to be active and highly CO selective at low overpotentials(from -0.6 to -0.8 V ***) in 0.1 M KHCO_(3), while H_(2) from the competitive water reduction appears at larger overpotentials(-0.9 V vs. RHE). The optimum copper acetate-derived catalyst containing Cu-n_(4) moieties exhibits a CO_(2)-to-CO turnover frequency of 997 h^(-1) at -0.9 V vs. RHE with a H_(2)/CO ratio of 1.8. These results demonstrate that RRDE configuration can be used as a feasible approach for identifying electrolysis products from CO_(2)RR.

关键词： Cu-n-C Carbon xerogel Rotating ring disc electrode Carbon dioxide reduction reaction Carbon monoxide

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Design of a novel Exoskeleton with Passive Magnetic Spring Self-locking and Spine Lateral Balancing

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Journal of Bionic Engineering 2024年第1期21卷 236-255页

作者： Jhon F.Rodríguez-León Betsy D.M.Chaparro-Rico Daniele Cafolla Francesco Lago Eduardo Castillo-Castañeda Giuseppe Carbone Centro de Investigacion en Ciencia Aplicada y Tecnologia Avanzada Unidad Querétaro MecatronicaInstituto Politécnico NacionalCerro Blanco 14176090 Colinas del CimatarioQuerétaroMexico Department of Mechanical Energy and Management EngineeringUniversity of CalabriaVia P.Bucci Cubo 46 C87036 RendeItaly Faculty of Science and Engineering Department of Computer ScienceSwansea UniversitySwanseaUK CESTER University of Cluj-NapocaCluj-NapocaRomania

This paper proposes a new upper-limb exoskeleton to reduce worker physical *** proposed design is based on a novel PRRRP(P-Prismatic;R-Revolute)kinematic chain with 5 passive Degrees of Freedom(DoF).Utilizing a magnetic spring,the proposed mechanism includes a specially designed locking mechanism that maintains any desired task *** proposed exoskeleton incorporates a balancing mechanism to alleviate discomfort and spinal torsional effects also helping in limb weight *** paper reports specific models and simulations to demonstrate the feasibility and effectiveness of the proposed *** experimental characterization is performed to validate the performance of the mechanism in terms of forces and physical strain during a specific application consisting of ceiling-surface drilling *** obtained results preliminarily validate the engineering feasibility and effectiveness of the proposed exoskeleton in the intended operation task thereby requiring the user to exert significantly less force than when not wearing it.

关键词： Assistive mechanism Exoskeleton Locking mechanism Bionic robot

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Temporally Preserving Latent Variable Models:Offline and Online Training for Reconstruction and Interpretation of Fault Data for Gearbox Condition Monitoring

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Journal of Dynamics, Monitoring and Diagnostics 2024年第2期3卷 156-177页

作者： Ryan Balshaw P.Stephan Heyns Daniel n.Wilke Stephan Schmidt Center for Asset Integrity Management Department of Mechanical and Aeronautical EngineeringUniversity of PretoriaPretoriaSouth Africa

Latent variable models can effectively determine the condition of essential rotating machinery without needing labeled *** models analyze vibration data via an unsupervised learning *** preservation is necessary to obtain an informative latent manifold for the fault diagnosis *** a temporalpreserving context,two approaches exist to develop a condition-monitoring methodology:offline and *** latent variable models,the available training modes are not *** many traditional methods use offline training,online training can dynamically adjust the latent manifold,possibly leading to better fault signature extraction from the vibration *** study explores online training using temporal-preserving latent variable *** online training,there are two main methods:one focuses on reconstructing data and the other on interpreting the data *** are considered to evaluate how they diagnose faults over *** two experimental datasets,the study confirms that models from both training modes can detect changes in machinery health and identify faults even under varying ***,the complementarity of offline and online models is emphasized,reassuring their versatility in fault *** the implications of the training approach and the available model formulations is crucial for further research in latent variable modelbased fault diagnostics.

关键词： Condition monitoring unsupervised learning latent variable models temporal preservation training approaches

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Mechanocatalysis of CO to CO_(2)on TiO_(2)surface controlled at atomic scale

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nano Research 2024年第7期17卷 5826-5834页

作者： Yuuki Adachi Robert Turanský Ján Brndiar Kamil Tokár Qiang Zhu Huan Fei Wen Yasuhiro Sugawara IvanŠtich Yan Jun Li Department of Applied Physics Osaka University2-1 YamadaokaSuitaOsaka 565-0871Japan Institute of Physics Slovak Academy of SciencesBratislava 84511Slovakia Institute of Informatics Slovak Academy of SciencesBratislava 84507Slovakia Faculty of natural Sciences University of Ss.Cyril and MethodiusTrnava 91701Slovakia Key Laboratory of Instrumentation Science and Dynamic Measurement School of Instrument and ElectronicsNorth University of ChinaTaiyuan 030051China

The common ways to activate a chemical reaction are by heat,electric current,or ***,mechanochemistry,where the chemical reaction is activated by applied mechanical force,is less common and only poorly understood at the atomic *** we report a tip-induced activation of chemical reaction of carbon monoxide to dioxide on oxidized rutile TiO_(2)(110)*** activation is studied by atomic force microscopy,Kelvin probe force microscopy under ultrahigh-vacuum and liquid nitrogen temperature conditions,and density functional theory(DFT)*** reaction is inferred from hysteretic behavior of frequency shift signal further supported by vector force mapping of vertical and lateral forces needed to trigger the chemical reaction with torque motion of carbon monoxide towards an oxygen *** reaction is found to proceed stochastically at very small tip-sample ***,the local contact potential difference reveals the atomic-scale charge redistribution in the reactants required to unlock the *** results open up new insights into the mechanochemistry on metal oxide surfaces at the atomic scale.

关键词： atomic resolution mechanochemistry atomic force microscopy Kelvin probe force microscopy density functional theory(DFT)simulation CO oxidation catalysis rutile TiO_(2)surface

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The new era of cardiovascular research:revolutionizing cardiovascular research with 3D models in a dish

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Medical Review 2024年第1期4卷 68-85页

作者： Yuan Yang Hao Yang Fedir n.Kiskin Joe Z.Zhang Institute of neurological and Psychiatric Disorders Shenzhen Bay LaboratoryShenzhenGuangdong ProvinceChina Institute of neurological and Psychiatric Disorders Shenzhen Bay LaboratoryShenzhen 518132Guangdong ProvinceChina

Cardiovascular research has heavily relied on studies using patient samples and animal ***,patient studies often miss the data from the crucial early stage of cardiovascular diseases,as obtaining primary tissues at this stage is *** animal models can offer some insights into disease mechanisms,although they usually do not fully recapitulate the phenotype of cardiovascular diseases and their *** recent years,a promising breakthrough has emerged in the form of in vitro three-dimensional(3D)cardiovascular models utilizing human pluripotent stem *** innovative models recreate the intricate 3D structure of the human heart and vessels within a controlled *** advancement is pivotal as it addresses the existing gaps in cardiovascular research,allowing scientists to study different stages of cardiovascular diseases and specific drug responses using human-origin *** this review,we first outline various approaches employed to generate these *** then comprehensively discuss their applications in studying cardiovascular diseases by providing insights into molecular and cellular changes associated with cardiovascular condi***,we highlight the potential of these 3D models serving as a platform for drug testing to assess drug efficacy and *** their immense potential,challenges persist,particularly in maintaining the complex structure of 3D heart and vessel models and ensuring their function is comparable to real ***,overcoming these challenges could revolutionize cardiovascular *** has the potential to offer comprehensive mechanistic insights into human-specific disease processes,ultimately expediting the development of personalized therapies.

关键词： pluripotent stem cells three-dimensional(3D)models cardiac microtissues cardiac organoids vessel organoids organ-on-a-chip

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Impacts of interactions with low-mineralized water on permeability and pore behavior of carbonate reservoirs

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Energy Geoscience 2024年第4期5卷 278-290页

作者： Dmitriy A.Martyushev Inna n.Ponomareva Vasiliy I.Chernykh Shadfar Davoodi Yousef Kazemzadeh Tianshou Ma Department of Oil and Gas Technologies Perm National Research Polytechnic UniversityPermRussia School of Earth Sciences&Engineering Tomsk Polytechnic UniversityLenin AvenueTomskRussia Enhanced Oil Recovery(EOR)Research Center IOR/EOR Research InstituteShiraz UniversityShirazIran State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Southwest Petroleum UniversityChengduSichuanPR China

Laboratory filtration experiments are employed to investigate effective well killing while minimizing its impacts on surrounding *** novelty of this experimental study lies in the prolonged exposure of rock samples to the killing fluid for seven days,corresponding to the average duration of well workovers in the oilfields in Perm Krai,*** findings indicate that critical factors influencing the interactions between rocks and the killing fluid include the chemical composition of the killing fluid,the mineralogical composition of the carbonate rocks,reservoir pressure and temperature,and the contact *** analyses using multi-scale X-ray computed tomography,field emission scanning electron microscopy,and X-ray diffraction were conducted on samples both before and after the well killing *** experiments were performed using real samples of cores,crude oil,and the killing *** results from this study indicate that low-mineralized water(practically fresh water)is a carbonate rock *** water causes the dissolution of rock components,the formation of new calcite crystals and amoeba-like secretions,and the migration of small particles(clay,quartz,and carbonates).The formation of deep channels was also *** assessment reveals that the change in the pH of the killing fluid indicates that the observed mineral reactions were caused by carbonate *** combined phenomena led to a decrease in the total number of voids in the core samples,which was 25%on average,predominantly among voids measuring between 45 and 70μm in *** change in the pore distribution in the bulk of the samples resulted in decreases in porosity of 1.8%and permeability of 67.0%in the studied core *** results from this study indicate the unsuitability of low-mineralized water as a well killing fluid in carbonate *** composition of the killing fluid should be optimized,for example,in terms of the ionic composition of water,

关键词： Fine particle Clay mineral Low-mineralized water Geochemical dissolution Carbonate reservoir

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Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

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World Journal of Gastroenterology 2024年第7期30卷 714-726页

作者： Pui-Yin Leung Wenjing Chen Anissa n Sari Poojitha Sitaram Pui-Kei Wu Susan Tsai Jong-In Park Department of Biochemistry Medical College of WisconsinMilwaukeeWI 53226United States Department of Surgery Medical College of WisconsinMilwaukeeWI 53226United States

BACKGROUnD Pancreatic cancer is a leading cause of cancer-related *** activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug ***,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic *** previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell *** has not been tested for this *** To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell ***Δψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell *** viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive *** synergy between erlotinib and MitoQ was then analyzed using SynergyFinder *** preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line *** Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive *** triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of *** suggested that these drugs synergistically induced tumor cell *** with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each *** Our findings suggest tha

关键词： Pancreatic cancer Erlotinib Mitochondria-targeted ubiquinone Mitochondria Combination therapy

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Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

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Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

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Journal of Sport and Health Science 2024年第2期13卷 245-255页

作者： Cecilie Skarstad norevik Aleksi M.Huuha Ragnhild n.RФsbjФrgen Linda Hildegard Bergersen Kamilla Jacobsen Rodrigo Miguel-dos-Santos Liv Ryan Belma Skender Jose Bianco n.Moreira Asgeir Kobro-Flatmoen Menno P.Witter nathan Scrimgeour Atefe R.Tari Cardiac Exercise Research Group(CERG) Department of Circulation and Medical ImagingNorwegian University of Science and Technology7491TrondheimNorway Department of neurology and Clinical neurophysiology St.Olavs University Hospital7030TrondheimNorway Institute of Oral Biology University of Oslo0372OsloNorway Department of Physiology Federal University of SergipeS~ao Cristov~ao49100-000SergipeBrazil Centre of Molecular Inflammation Research Department of Clinical and Molecular MedicineNorwegian University of Science and Technology7491TrondheimNorway Kavli Institute for Systems neuroscience Centre for Neural Computationand Egil and Pauline Braathen and Fred Kavli Centre for Cortical MicrocircuitsNorwegian University of Science and Technology7030TrondheimNorway K.G.Jebsen Centre for Alzheimer’s Disease Norwegian University of Science and Technology7030TrondheimNorway

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne *** we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and ***:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity *** in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)*** function,amyloid plaque pathology,and neurogenesis were *** plasma used for the treatment was analyzed for 23 ***:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(pn amyloid-β-treated *** vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated *** of 7 cytokines were significantly reduced in exercised plasma compared to sedentary ***:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat *** effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

关键词： Cytokines High-intensity interval training Inflammation neurons Plasma transfusion

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