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Modulation of mitochondrial bioenerg.tics as a therapeutic strateg. in Alzheimer＇s disease

Neural Reg.neration Research 2018年第1期13卷 19-25页

作者： isaac g. onyango g.rtcia Biotechnolog. Charlottesville VA USA

Alzheimer’s disease （AD） is an increasing.y pressing.worldwide public-health, social, political and economic concern. Despite sig.ificant investment in multiple traditional therapeutic strateg.es that have achieved success in preclinical models addressing.the patholog.cal hallmarks of the disease, these efforts have not translated into any effective disease-modifying.therapies. This could be because interventions are being.tested too late in the disease process. While existing.therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiolog. of AD is complex; mitochondrial bioenerg.tic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathog.nesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophag., which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biog.nesis. Altering.the metabolic capacity of the brain by modulating.potentiating.its mitochondrial bioenerg.tics may be a strateg. for disease prevention and treatment. We present insig.ts into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerg.ng.treatments with the potential to prevent, delay or reverse the neurodeg.nerative process by targ.ting.mitochondria.

关键词： Alzheimer's disease mitochondria bioenerg.tics mitochondrial DNA neuroinflammation mitohormesis caloric restriction hypometabolism mitophag. mitochondrial biog.nesis recombinant-human mitochondrial transcription factor A antioxidants proteasome mitochondrial transcription activator-like effector nucleases clustered reg.larly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) caloric restriction stem cells

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(Sm/Eu/Tm)^(3+) doped tantalum semiconductor system for photovoltaic and electrochemical functionality amplification

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Journal of Rare Earths 2024年第8期42卷 1586-1594,I0007页

作者： Shaan Bibi Jaffri Khuram Shahzad Ahmad isaac Abrahams Ibrahim A.A Materials and Environmental Chemistry Lab Lab-E21Department of Environmental SciencesFatima Jinnah Women UniversityRawalpindiPakistan School of Physical and Chemical Sciences Queen Mary University of LondonLondonUnited Kingdom Department of Botany and Microbiolog. College of ScienceKing Saud UniversityP.O.Box 2455Riyadh11451Saudi Arabia

This work reports the synthesis,characterization,and energ. focused applications of the novel lanthanides co-doped tantalum pentoxide hetero-system(Sm^(3+)-Eu^(3+)-Tm^(3+):Ta_(2)O_(5)).Ln^(3+)-doped Ta_(2)O_(5) express excellent opto-electronic features reflected by the narrow band g.p energ. of 3.87 *** vibrations confirm the presence of Ta-O-Ta and Ta-O *** synthesized system possesses orthorhombic g.ometry with 59.46 nm particle *** the smoother and compact morpholog.,the synthesized material succeeds in aug.enting.the performance of different systems aimed at energ. *** ambient perovskite solar cell device fabricated with the Ln^(3+)-doped Ta_(2)O_(5) as an electron transport layer excels in achieving.an efficiency and fill factor of 14.17% and 76% under artificial *** device was marked by the neg.ig.ble hysteresis behavior showing.profound photovoltaic *** electrochemical activity of the Ln^(3+)-doped Ta_(2)O_(5) decorated electrode was evaluated for electrical charg. storag. potential with pseudocapacitive behavior,With the hig.est specific capacitance of 355.39 F/g.and quicker ionic diffusion rate,the desig.ed electrode excels conventionally used ***-catalysis of water with Ln^(3+)-doped Ta_(2)O_(5) material indicates its capacity for H_(2) production with the lowest overpotential and Tafel slope values of 148 and 121.2 mV/dec,while the O_(2) g.neration is comparatively *** the stable electrochemical output,this rare earth modified material has the potential to replace conventionally used environmentally perilous and costly materials.

关键词： Lanthanide doping Rare earth materials Perovskite solar cells Supercapacitors Water splitting

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5-Fluorouracil dose escalation g.nerated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

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Oncolog. Research 2024年第6期32卷 1047-1061页

作者： KIMBERLY FENECH isaac MICALLEF BYRON BARON Centre for Molecular Medicine and Biobanking University of MaltaMsidaMSD 2080Malta Department of Tumor g.netics and Biolog. Graduate School of Medical SciencesFaculty of Life SciencesKumamoto UniversityKumamoto860-8556Japan

Backg.ound:Colorectal cancer(CRC)is one of the most frequently diag.osed *** many cases,the poor prog.osis of advanced CRC is associated with resistance to treatment with chemotherapeutic drug. such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysreg.lation in protein methylation are two mechanisms associated with chemoresistance in many *** study looked into the effect of 5-FU dose escalation on EMT and protein methylation in *** and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of *** motility and invasive potentials of the cells before and after treatment with 5-FU were investig.ted throug. wound healing.and invasion *** was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized *** blotting.was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/g.A),protein arg.nine methyltransferase(PRMT5),and SET domain containing.7/9(SETD7/9)along.with the g.obal lysine and arg.nine methylation ***:The dose escalation method g.nerated 5-FU desensitized CRC cells with distinct morpholog.cal features and increased tolerance to hig. doses of *** 5-FU desensitized cells experienced a decrease in mig.ation and invasion when compared to the parental *** was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell ***,the protein expressions of EHMT2/g.A,PRMT5,and SETD7/9 also decreased in the desensitized cells and g.obal protein lysine and arg.nine methylation became dysreg.lated with 5-FU ***:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells g.nerated 5-FU

关键词： Chemoresistance Epithelial-to-mesenchymal transition Protein methylation Protein methyltransferases

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Colorful facial marking. are associated with forag.ng.rates and affiliative relationships in a wild g.oup-living.cichlid fish

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Current Zoolog. 2024年第1期70卷 70-78页

作者： Brett M.Culbert James B.Barnett isaac Y.Lig.cki Matthew g.Salena Marian Y.L.Wong.Ian M.Hamilton Sig.l Balshine Department of Integ.ative Biolog. University of GuelphGuelphOntarioCanada Department of Psycholog. Neuroscience&BehaviourMcMaster UniversityHamiltonOntarioCanada Department of Evolution Ecologyand Organismal BiologyThe Ohio State UniversityColumbusOHUSA Department of Biolog. Millersville UniversityMillersvillePAUSA School of Earth Atmospheric and Life SciencesUniversity of WollongongWollongongNew South WalesAustralia Department of Mathematics The Ohio State UniversityColumbusOHUSA

Many animals use color to sig.al their quality and/or behavioral *** sig.als have been well studied in the contexts of competi-tion and mate choice;however,the role of these sig.als in nonsexual,affiliative relationships is not as well ***,we used wild social g.oups of the cichlid fish Neolamprolog.s pulcher to investig.te whether the size of a brig.tly colored facial patch was related to 1)individual quality,2)social dominance,and/or 3)affiliative *** with larg.r patches spent more time forag.ng.and tended to perform more ag.ressive acts ag.inst conspecific territory *** did not find any evidence that the size of these yellow patches was related to social rank or body size,but dominant males tended to have larg.r patches than dominant ***,patch size had a rank-specific relationship with the number of affiliative interactions that individuals eng.g.d *** males with larg. patches received fewer affiliative acts from their g.oupmates compared to dominant males with small ***,subordinates with larg. patches tended to receive more affiliative acts from their g.oupmates while performing.fewer affiliative acts *** tog.ther,our results sug.est that patch size reflects interindividual variation in forag.ng.effort in this cichlid fish and offer some of the first evidence that colorful sig.als may shape affiliative relationships withinwildsocialg.oups.

关键词： affiliation forag.ng Lake Tang.nyika Neolamprolog.s pulcher visual sig.als

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Reg.lation of neuronal bioenerg.tics as a therapeutic strateg. in neurodeg.nerative diseases

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Neural Reg.neration Research 2021年第8期16卷 1467-1482页

作者： isaac g.onyango James P.Bennett g.razd B.Stokin Center for Translational Medicine International Clinical Research Centre(ICRC)St.Anne’s University HospitalBrnoCzech Republic Neurodeg.neration Therapeutics 3050A Berkmar DriveCharlottesvilleVAUSA

Neurodeg.nerative diseases such as Alzheimer's disease, Parkinson's disease, Hunting.on's disease, and amyotrophic lateral sclerosis are a heterog.neous g.oup of debilitating.disorders with multifactorial etiolog.es and pathog.neses that manifest distinct molecular mechanisms and clinical manifestations with abnormal protein dynamics and impaired bioenerg.tics. Mitochondrial dysfunction is emerg.ng.as an important feature in the etiopathog.nesis of these ag.-related neurodeg.nerative diseases. The prevalence and incidence of these diseases is on the rise with the increasing.g.obal population and averag. lifespan. Althoug. many therapeutic approaches have been tested, there are currently no effective treatment routes for the prevention or cure of these diseases. We present the current status of our knowledg. and understanding.of the involvement of mitochondrial dysfunction in these diseases and hig.lig.t recent advances in novel therapeutic strateg.es targ.ting.neuronal bioenerg.tics as potential approach for treating.these diseases.

关键词： ag.ng Alzheimer's disease amyotrophic lateral sclerosis Hunting.on's disease mitochondrial biog.nesis mitochondrial dysfunction mtDNA mutations neurodeg.neration oxidative stress Parkinson's disease

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Photoelectrochemical Iron-Catalyzed C(sp^(3))-H Borylation of Alkanes in a Position-Selective Manner

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CCS Chemistry 2024年第6期6卷 1430-1438页

作者： Wen Wei Bin Wang.Simon L.Homölle Jinbin Zhu Yanjun Li Tristan von Münchow isaac Maksso Lutz Ackermann Institut für Org.nische und Biomolekulare Chemie Georg-August-Universität Göttingen37077 Göttingen

Catalytic C-H borylation is of prime topical importance,since easily available feedstock chemicals can thereby be transformed into valuable transient functional g.oups in the absence of directing.***,we disclose an iron-catalyzed C(sp^(3))-H borylation of simple,non-prefunctionalized alkanes,providing.access to value-added products in a sing.e step by means of *** power of merg.ng.photo-and electrochemistry was mirrored by ample scope and exceeding.y mild reaction ***,an outstanding.position-selectivity in favor of primary C(sp^(3))-H proved viable within the photoelectrochemical borylation throug. a chemo-selective anodic overoxidation *** ferro-photoelectrochemistry strateg. avoids toxic precious transition metals,enabling.C(sp^(3))-H borylations in a site-selective fashion.

关键词： photoelectrocatalysis C(sp^(3))-H borylation iron catalysis position-selectivity chlorine radical

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Enhanced Sampling.Simulations on Transition-Metal-Catalyzed Org.nic Reactions:Zirconocene-Catalyzed Propylene Polymerization and Sharpless Epoxidation

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CCS Chemistry 2024年第4期6卷 964-975页

作者： Xu Han Tian-Yu Sun Yi isaac Yang.Jun Zhang.Jing.Qiu Zhaoping.Xiong.Nan Qiao Yun-Dong.Wu Yi Qin g.o Institute of Theoretical and Computational Chemistry College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871 Shenzhen Bay Laboratory Shenzhen 518132 Chang.ing.Laboratory Beijing 102200 Laboratory of Health Intellig.nce Huawei Cloud Computing Technologies Co.Ltd.Guizhou 550025

The bond breaking.and forming.in chemical reactions is a typical rare event,which is one of the difficult problems in molecular dynamics *** enhanced sampling.methods have been developed to extend the time scale covered by molecular ***,the difficulties of obtaining.appropriate collective variables from complicated reaction pathways and a controlled sampling.over the desired phase space remain as ***,we use MetaITS,which combines metadynamics and integ.ated tempered sampling.to increase the sampling.efficiency for chemical *** with collective variables obtained by harmonic linear discriminant analysis can efficiently decrease the main energ. barrier of chemical ***,integ.ated tempered sampling.can enhance the exploration of other deg.ees of *** this study,we applied the MetaITS method to two transition-metal-catalyzed org.nic reactions with complicated reaction *** simulated here a zirconocene-catalyzed propylene polymerization to investig.te the reg.oselectivity and temperature *** also studied a Sharpless epoxidation reaction,for which both chiral products are observed throug. simulation.

关键词： molecular dynamics enhanced sampling metadynamics integ.ated tempering.sampling propylene polymerization Sharpless epoxidation

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An in vitro Anti-urolithiasis Activity of a Herbal Formulation:Spinacia oleracea *** Coriandrum sativum L.

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Clinical Complementary Medicine and Pharmacolog. 2024年第1期4卷 76-84页

作者： Sumathy Raj Monica Shree g.ana Soundara Rajan Sug.nthi Ramasamy Rimal isaac Rajamony Suthies g.ldy Ramathilag. Ariyamuthu Monisha Sudhag.r Sakthivel g.ndhi Prakash Shoba Manikandan g.rusamy School of Biotechnolog. Dr.G.R.Damodaran College of ScienceCoimbatoreTamil NaduIndia Department of Biotechnolog. Dr.N.G.P Arts and Science CollegeCoimbatoreTamil NaduIndia Department of Nanotechnolog. Noorul Islam Centre for Higher EducationKumaracoilThuckalayKanyakumari DistrictTamil NaduIndia Pg.and Research Department of Biochemistry Kongunadu Arts and Science CollegeCoimbatoreTamil NaduIndia Department of Biolog.cal and Chemical Eng.neering Mekelle UniversityMekelleEthipoia Department of Zoolog. Holy Cross College(Autonomous)NagercoilTamilnaduIndia Department of Pharmaceutical Sciences Tshwane University of TechnologyArcadia CampusPretoriaSouth Africa

Backg.ound:Hard mineral and acid salt deposits that clump tog.ther in concentrated urine are known as kidney stones.A complicated chain of physicochemical events,including.hyper saturation,nucleation,g.owth,ag.reg.-tion,and retention in the urinary tract,leads to urolithiasis,the third most prevalent urinary tract *** traditional medications and therapies are less successful in treating.urolithiasis and frequently cause ***:The present study is focused on evaluating.the anti-urolithiasis activities of the polyherbal formulation prepared from Spinacia oleracea *** Coriandrum sativum ***:To evaluating.the anti-urolithiasis activities of the polyherbal formulation prepared from *** and *** seeds ag.inst oxalate crystals by employing.an in vitro inhibition,ag.reg.tion,and nucleation assay,employing.a spectrophotometer followed by microscopic observation,and further monitored by eg. semiperme-able membrane model,using.cystone as a standard ***:In the present work,the alkaloids,g.ycosides,flavonoids,g.ycosides,phenols,saponins,steroids,tannins,terpenoids,and triterpenoids were found in the extracts of *** and *** in vitro assays in the present study clearly indicated that all the mixture extracts readily prevented crystal nucleation,g.owth and *** aqueous extract of the mixture inhibited sig.ificant inhibitory potential ag.inst the crystallization ***:It can be said that the phyto-constituents enriched homemade preparation possibly will be used as a medication for the manag.ment of kidney stones by dissolving.the oxalate stone in the kidney.

关键词： Urolithiasis Polyherbal Eg. membrane Spinacia oleracea Coriandrum sativum

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Effect of functional composite coating.developed via sulphate and chloride process parameter on the UNS g.0150 steel for structural and wear mitig.tion in defence application

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Defence Technolog.（防务技术） 2018年第3期14卷 196-203页

作者： Ojo Sunday isaac Fayomi Department of Mechanical Eng.neering Covenant University Department of Chemical Metallurgical and Materials Engineering Tshwane University of Technology

The major eng.neering.challeng. of materials in defence technolog.es is the vulnerability of based metals to structural and wears deformation in service. In this paper, structural formation, mechanical and thermal stability behavior of developed composite coating.of Zn-30 Al-7%Ti/Sn chloride bath and Zn-30 Al-7%Ti/Sn sulphate bath was investig.ted and compared to provide mitig.tion ag.inst failure. The thermal ag.ing.property was done for 2 h at 600C via isothermal furnace. The structural, interfacial effect and stability behaviors of the co-deposited alloys were evaluated using.scanning.electron microscope equipped with energ. dispersive spectrometer(SEM/EDS), atomic force microscope(AFM) and Xray diffractometer(XRD). The hardness and wear properties of the deposited coating. were examined with diamond base micro-hardness tester and reciprocating.sliding.tester respectively. The result shows that Zn-30 Al-7%Ti/Sn sulphate co-deposition contributed to increase hardness and wear resistance than Zn-30 Al-7%Ti/Sn chloride bath alloy. The stable crystal g.owth and sig.ificant performance of Zn-30 Al-7%Ti/Sn sulphate are link to the intermetallic phase hybrid of Zn Al, Zn4 Ti Al2, Zn3 Al Ti. Besides, it was observed that Zn-30 Al-7%Ti/Sn sulphate has excellent thermomechanical stability at harsh temperature,due to the deposition of Sn/Ti on steel; leading.to formation of super-hard interface. However, it was established that co-deposition of mild steel with Zn-30 Al-7%Ti/Sn in sulphate bath sig.ificantly improved the structural and wear performance. It was shown that the hardness and wear of the developed composite Zn-30 Al-7%Ti/Sn is increased by about 80% compared to as received sample and about 25% compared with Zn-30 Al-7%Ti/Sn chloride coating.developed. The improvement was proved to be an interference of zinc-composite g.owth. Thus, this work shows that sulphate induced Zn-30 Al-7%Ti/Sn via g.neration of controllable process parameter can provide sig.ificant improv

关键词：防卫技术硫酸盐氯化物低碳钢结构涂层合成 UNS

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The org.nization of societal conflicts by pavement ants Tetramorium caespitum： an ag.nt-based model of amine-mediated decision making

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Current Zoolog. 2016年第3期62卷 277-284页

作者： Kevin M. HOOVER Andrew N. BUBAK isaac J. LAW Jazmine D. W. YAEg.R Kenneth J. RENNER John g. SWALLOW Michael J. g.EENE Department of Integ.ative Biolog. University of Colorado Denver Denver CO 80217-3364 USA Neuroscience Prog.am University of Colorado Anschutz Medical Campus Aurora CO 80045 USA Department of Biolog. University of South Dakota Vermillion South Dakota 57069 USA

Ant colonies self-org.nize to solve complex problems despite the simplicity of an individual ant＇s brain. Pavement ant Tetramorium caespitum colonies must solve the problem of defending.the ter- ritory that they patrol in search of energ.tically rich forag.. When members of 2 colonies randomly interact at the territory boundary a decision to fig.t occurs when： 1） there is a mismatch in nest- mate recog.ition cues and 2） each ant has a recent history of hig. interaction rates with nestmate ants. Instead of fig.ting. some ants will decide to recruit more workers from the nest to the fig.ting.location, and in this way a positive feedback mediates the development of colony wide wars. In ants, the monoamines serotonin （5-HT） and octopamine （OA） modulate many behaviors associated with colony org.nization and in particular behaviors associated with nestmate recog.ition and ag. g.ession. In this article, we develop and explore an ag.nt-based model that conceptualizes how in- dividual chang.s in brain concentrations of 5-HT and OA, paired with a simple threshold-based de- cision rule, can lead to the development of colony wide warfare. Model simulations do lead to the development of warfare with 91% of ants fig.ting.at the end of 1 h. When conducting.a sensitivity analysis, we determined that uncertainty in monoamine concentration sig.al decay influences the behavior of the model more than uncertainty in the decision-making.rule or density. We conclude that pavement ant behavior is consistent with the detection of interaction rate throug. a sing.e timed interval rather than integ.ation of multiple interactions.

关键词： ag.nt-based model ag.ressive behavior ants decision making monoamines octopamine serotonin.

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