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Etomidate protects retinal ganglion cells from hydrogen peroxide-induced injury via Nrf2/hO-1 pathway

International Journal of Ophthalmology(English edition) 2024年第9期17卷 1606-1613页

作者： Xuan Zhao de-Gang Fan Xin-Chao Zhang Si-Wei You Fang Kuang Ming-Mei Wu department of histology and Embryology School of Basic Medical SciencesXi’an Medical UniversityXi’an 710021Shaanxi ProvinceChina department of Neurobiology the Basic Medical Science Academythe Fourth Military Medical UniversityXi’an 710032Shaanxi ProvinceChina department of Spinal Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina College of life Sciences Northwestern UniversityXi’an 710069Shaanxi ProvinceChina

AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(h_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect of ***:Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and *** injury model of h_(2)O_(2)-induced RGCs oxidative stress was established in *** were pretreated with different concentrations of ET(1,5,and 10μmol/l)for 4h,followed by further exposure to h_(2)O_(2)at 1000μmol/*** counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12,24,and 48h after h_(2)O_(2)*** levels of nitric oxide,malondialdehyde,and glutathione in culture media were measured at these time *** reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase(iNOS),nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(hO-1),glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12,24,and 48h after h_(2)O_(2)stimulation and in the retina at 12h after optic nerve transection(ONT).RESUlTS:The applications of 5 and 10μmol/l of ET significantly increased the viability of *** from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and hO-1 in ETpretreated RGCs at 12,24 and 48h after h_(2)O_(2)stimulation,as well as in ET-treated retinas at 12h after *** blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein,along with an increase in the expressions of Nrf2 and hO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in ***:ET is a neuroprotective agent in primary cultured RGCs injured by h_(2)O_(2).The effect of ET is dosedependent with the

关键词： etomidate retinal ganglion cell neuroprotection hydrogen peroxide-induced injury nuclear factor erythroid 2-related factor 2 heme oxygenase 1

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The corpus cavernosum after treatment with dutasteride or finasteride： a histomorphometric study in a benign prostatic hyperplasia rodent model

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Asian Journal of Andrology 2018年第5期20卷 505-510页

作者： Marcello h A Da Silva Waldemar S Costa Francisco J B Sampaio Diogo B de souza Urogenital Research Unit Rio de Janeiro State University Rio de Janeiro RJ 20551-030 Brazil

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia （BPh） rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups： C, untreated control rats; C ＋ D, control rats receiving dutasteride; C ＋ F, control rats receiving finasteride; h, untreated spontaneously hypertensive rats （ShRs）; h ＋ D, ShRs treated with dutasteride; and h ＋ F, ShRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density （Sv） of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni＇s posttest. Groups C ＋ D and C ＋ F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C ＋ D showed less smooth muscle Sv, and Group h showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups h ＋ D and h ＋ F had less smooth muscle Sv than Group h. Group h ＋ D also had more connective tissue and elastic system fiber Sv than Group h. Both dutasteride and finasteride promoted penile modifications in the control rat penis, al.h.ugh this affect was ~reater in Group h animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

关键词： animal models benign prostatic hyperplasia dutasteride erectile dysfunction finasteride penis

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Amyloid-beta and tau protein beyond Al.h.imer's disease

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Neural Regeneration Research 2024年第6期19卷 1262-1276页

作者： Morteza Abyadeh Vivek Gupta Joao A.Paulo Arezoo Gohari Mahmoudabad Sina Shadfar Shahab Mirshahvaladi Veer Gupta Christine T.O.Nguyen David I.Finkelstein Yuyi You Paul A.haynes Ghasem h.Salekdeh Stuart l.Graham Mehdi Mirzaei ProGene Technologies Pty ltd. 2. department of Clinical Medicine Faculty of Medicine Health and Human Sciences Macquarie Medical School Macquarie University department of Cell Biology Harvard Medical School School of Medicine Deakin University department of Optometry and Vision Sciences School of Health Sciences Faculty of Medicine Dentistry and Health Sciences University of Melbourne The Florey Institute of Neuroscience and Mental.h.alth The University of Melbourne School of Natural Sciences Macquarie University

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Al.h.imer’s disease pathogenesis and are considered the main pathological.h.llmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal.h.man body. however, under pathological conditions, abnormal expression, posttranslational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Al.h.imer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

关键词： amyloid-beta cancer cardiovascular diseases diabetes neurodegeneration Tau traumatic brain injury

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high-efficiency Carbonation Modification Methods of Recycled Coarse Aggregates

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Journal of Wuhan University of Technology(Materials Science) 2024年第2期39卷 386-398页

作者：张美香 YANG Xiaolin 丁亚红 SUN Bo ZhANG Xianggang lÜXiuwen department of Civil Engineering Henan Polytechnic UniversityJiaozuo 454150China College of Architectural Engineering Xinyu UniversityXinyu 336500China

To solve the problem of only surface carbonation and realize high-efficiency carbonation of recycled coarse aggregate,the method of carbonated recycled coarse aggregate with nano materials pre-soaking was first put *** carbonation effect of modified recycled coarse aggregate with three different carbonation methods was evaluated,and water absorption,apparent density and crush index of modified recycled coarse aggregate were *** with XRD,SEM,and MIP microscopic analysis,the high-efficiency carbonation strengthening mechanism of modified recycled coarse aggregate was *** experimental results show that,compared with the non-carbonated recycled coarse aggregate,the physical and microscopic properties of carbonated recycled coarse aggregate are *** method of carbonation with nano-SiO_(2) pre-soaking can realize the high-efficiency carbonation of recycled coarse aggregate,for modified recycled coarse aggregate with the method,water absorption is reduced by 23.03%,porosity is reduced by 44.06%,and the average pore diameter is 21.82 *** high-efficiency carbonation strengthening mechanism show that the pre-socked nano-SiO_(2) is bound to the hydration product Ca(Oh)_(2) of the old mortar with nano-scale C-S-h,which can improve the CO_(2) absorption rate,accelerate the carbonation reaction,generate more stable CaCO_(3) and nano-scale silica gel,and bond to the dense three-dimensional network structure to realize the bidirectional enhancement of nano-materials and pressurized *** is concluded that the method of carbonation with nano-SiO_(2) pre-soaking is a novel.h.gh-efficiency carbonation modification of recycled coarse aggregate.

关键词： recycled coarse aggregate pressurized carbonation high-efficiency carbonation nano-SiO2 strengthening mechanism

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Microstructural evolution of aluminum alloy during friction stir welding under different tool rotation rates and cooling conditions

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Journal of Materials Science & Technology 2019年第6期35卷 972-981页

作者： X.h. Zeng P. Xue l.h. Wu D.R. Ni B.l. Xiao K.S. Wang Z.Y. Ma Shenyang National laboratory for Materials Science Institute of Metal Research Chinese Academy of Sciences Shenyang 110016 China University of Chinese Academy of Sciences Beijing 100049 China School of Metallurgical Engineering Xi'an University of Architecture and Technology Xi'an 710055 China

The microstructural evolution during friction stir welding(FSW) has long been studied only using one single welding parameter. Conclusions were usually made based on the final microstructure observation and hence were one-sided. In this study, we used the "take-action" technique to freeze the microstructure of an Al-Mg-Si alloy during FSW, and then systematically investigated the microstructures along the material flow path under different tool rotation rates and cooling conditions. A universal characteristic of the microstructural evolution including four stages was identified, i.e. dynamic recovery(DRV), dislocation multiplication, new grain formation and grain growth. however, the dynamic recrystallization(DRX)mechanisms in FSW depended on the welding condition. For the air cooling condition, the DRX mechanisms were related to continuous DRX associated with subgrain rotation and geometric DRX at high and low rotation rates, respectively. Under the water cooling condition, we found a new DRX mechanism associated with the progressive lattice rotation resulting from the pinning of the second-phase *** on the analyses of the influencing factors of grain refinement, it was clearly demonstrated that the delay of DRV and DRX was the efficient method to refine the grains during FSW. Besides, ultra-high strain rate and a short duration at high temperatures were the key factors to produce an ultrafine-grained material.

关键词： Aluminum alloys Grain refinement Dynamic recrystallization Severe plastic deformation Friction stir welding

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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina hromada Patrick heimel Markus Kerbl lászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.heinzel Antal Nógrádi Andreas h.Teuschl-Woller David hercher department life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of dentistry Medical University of ViennaViennaAustria department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria department of hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). however, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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design and optimization of piperidinesubstituted thiophene[3,2-d]pyrimidine-based hIV-1 NNRTIs with improved drug resistance and pharmacokinetic profiles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3110-3124页

作者： Yanying Sun Zhenzhen Zhou Zhongling Shi Fabao Zhao Minghui Xie Zongji Zhuo Erik de Clercq Christophe Pannecouqueb Dongwei Kang Peng Zhan Xinyong liu department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Jinan 250012China

hIV-1 reverse transcriptase(RT)has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome(AIDS),but the inevitable drug resistance and side effects have always been major challenges faced by non-nucleoside reverse transcriptase inhibitors(NNRTIs).This work aimed to identify novel chemotypes of anti-hIV-1 agents with improved drugresistance profiles,reduced toxicity,and excellent druggability.A series of diarylpyrimidine(DAPY)derivatives were prepared via structural modifications of the leads K-5a2 and *** them,15a with dimethyl.h.sphine oxide moiety showed the most prominent antiviral potency against all of the tested viral panel,being 1.6-fold(WT,EC_(50) Z 1.75 nmol/l),3.0-fold(l100I,EC_(50) Z 2.84 nmol/l),2.4-fold(K103N,EC_(50) Z 1.27 nmol/l),3.3-fold(Y181C,EC50 Z 5.38 nmol/l),2.9-fold(Y188l,EC_(50) Z 7.96 nmol/l),2.5-fold(E138K,EC_(50) Z 4.28 nmol/l),4.8-fold(F227l/V106A,EC_(50) Z 3.76 nmol/l)and 5.3-fold(RES056,EC_(50) Z 15.8 nmol/l)more effective than that of the marketed drug *** docking results illustrated the detailed interactions formed by compound 15a and WT,F227l/V106A,and RES056 ***,15a-hCl carried outstanding pharmacokinetic(t1/2 Z 1.32 h,F Z 40.8%)and safety profiles(lD_(50)>2000 mg/kg),which demonstrated that 15a hCl is a potential anti-hIV-1 drug candidate.

关键词： hIV-1 NNRTIs NNIBP Structural alert Anti-hIV-1 drug candidate

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The oceanic cycles of the transition metals and their isotopes

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Acta Geochimica 2017年第3期36卷 359-362页

作者： derek Vance Corey Archer Susan h.little Michael Kobberich Gregory F.de souza department of Earth Sciences Institute of Geochemistry and Petrology ETH Zürich Clansiusstrasse 25 8092 Zürich Switzerland department of Earth Science and Engineering Imperial College London South Kensington Campus Exhibition Road London SW7 2AZ UK

The stable isotope systems of the transition metals potentially provide constraints on the current and past operation of the biological pump,and on the state of ocean redox in Earth *** we focus on two exemplar metals,nickel(Ni)and zinc(Zn).The oceanic dissolved pool of both elements is isotopically heavier than the known inputs,implying an output with light isotope *** modern oceanic cycle of both these elements is dominated by biological uptake into photosynthesised organic matter and output to *** is increasingly clear,however,that such uptake is associated with only very minor isotope *** suggest that the isotopic balance is instead closed by the sequestration of light isotopes to sul.h.de in anoxic and organic-rich sediments,so that it is ocean chemistry that controls these isotope systems,and suggesting a different but equally interesting array of questions in Earth history that can be addressed with these systems.

关键词： Ocean biogeochemistry Metal micronutrients Stable isotopes

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Racial and Ethnic Differences in Orthorexia Nervosa Symptomatology and Other Disordered Eating

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Open Journal of Psychiatry 2024年第4期14卷 287-299页

作者： Dilan h. Arreguin Kendria S. Shields-Rhodes Melissa l. harel Crystal D. Oberle department of Psychology Texas State University San Marcos TX USA

While some research has explored racial and ethnic differences in disordered eating, this study may be the first to examine these differences in orthorexia nervosa, involving obsessive-compulsive thoughts and behaviors concerning heal.h. eating, which negatively impact one’s life. Adult participants, recruited from college courses and social media, completed an online survey with the Orthorexia Nervosa Inventory (ONI) and the Eating Attitudes Test-26 (EAT-26). Regarding racial and ethnic background, 743 were White, 249 were hispanic, 87 were Black, 61 were Asian or Pacific Islander, and 110 were biracial/multiracial. A MANCOVA revealed that the racial and ethnic groups did not differ on the ONI subscales assessing orthorexic behaviors, impairments, and emotions, after accounting for gender, BMI, and EAT-26 total scores that were covariates. In contrast, a second MANCOVA did reveal group differences on the EAT-26 subscales, after accounting for gender, BMI, and ONI total scores that were covariates. Black participants scored significantly lower than the other racial and ethnic groups on the subscale assessing dieting behaviors characteristic of anorexia nervosa, and the subscale assessing binge-eating and purging behaviors characteristic of bulimia nervosa. Further, hispanic participants scored significantly lower than White participants on the latter subscale. These findings suggest that while orthorexic symptomatology does not differ based on race and ethnicity, a Black race and hispanic ethnicity may be protective factors against disordered eating, perhaps related either to cultural norms concerning body image or to the resiliency and social support among the Black and hispanic communities.

关键词： Race Ethnicity Orthorexia Disordered Eating

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Carbonates in Continental Settings: Geochemistry, Diagenesis and Applications 1st ed.

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丛书名： developments in sedimentology

2010年

作者： A.M. Alonso-Zarza and l.h. Tanner (Eds.)

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