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ATP6AP2,a regulator of LRP6/β-catenin protein trafficking,promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner

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Bone Research 2024年第2期12卷 453-468页

作者： Lei Xiong Hao-Han Guo Jin-Xiu Pan Xiao Ren Daehoon Lee Li Chen Lin Mei Wen-Cheng Xiong Department of Neurosciences School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Louis Stoke VA Medical Center ClevelandOH 44106USA

Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and *** how Wnt/β-catenin signaling is regulated in OBs remain ***6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling ***,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone *** we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone *** knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone *** and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not *** in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not *** cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their *** of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO *** together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

关键词： LRP6 impaired organs

Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead Department of Anatomy and Cell Biology Western UniversityLondonONCanada Schulich School of Medicine and Dentistry Western UniversityLondonONCanada Deparment of Clinical Neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

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高分子多层共挤技术的研究进展

橡胶工业 2024年第3期71卷 232-239页

作者：印可桢 case western Reserve university ClevelandOHUSA 44106

高分子多层共挤技术是一项利用特制的挤出模具将两种高分子材料制成成百上千层薄膜的技术,可突破传统高分子复合材料相分离的限制,实现不同高分子材料的有效结合。高分子多层共挤技术产生的纳米效应、界面效应和结构效应具有广泛的应用... 详细信息

高分子多层共挤技术是一项利用特制的挤出模具将两种高分子材料制成成百上千层薄膜的技术,可突破传统高分子复合材料相分离的限制,实现不同高分子材料的有效结合。高分子多层共挤技术产生的纳米效应、界面效应和结构效应具有广泛的应用性:纳米效应可对高分子晶体晶型和取向进行有效调控;界面效应是研究高分子材料相互作用的有效手段,可用于制造全界面材料等新型材料;结构效应具有独特的光学意义,利用一维有序层状结构产生一维光子晶体并结合高分子材料取向的特点,可对光反射和折射产生独特的影响。高分子多层膜在众多领域拥有良好的科研和应用价值。

关键词：高分子多层共挤技术多层膜纳米效应界面效应结构效应受限结晶

Zircon Zr isotope fractionation during crustal anatexis

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Science China Earth Sciences 2024年第8期67卷 2495-2506页

作者： Erlin ZHU Qiongxia XIA Zhaoya LI Renxu CHEN James VAN ORMAN School of Earth and Space Sciences University of Science and Technology of ChinaHefei 230026China State Key Laboratory of Lithospheric and Environmental Coevolution Hefei 230026China Frontiers Science Center for Planetary Exploration and Emerging Technologies University of Science and Technology of ChinaHefei 230026China Department of Earth Environmental and Planetary SciencesCase Western Reserve UniversityCleveland OH 44106USA

Zirconium is one of high field strength elements but its isotope behavior during geochemical processes is still uncertain because of the limited *** Zr isotopes in magmatic rocks are often used to trace the evolution of magmas through fractional crystallization,it is intriguing how highly heterogeneous Zr isotopes were produced by the growth of zircon during crustal *** address this issue by in-situ zircon Zr isotope analyses of migmatites from two high-temperature metamorphic terranes in the South Lhasa zone and the North Dabie zone,respectively,in *** results show highly variable δ^(94)Zr values from-0.30‰ to +0.81‰ and from-0.58‰ to +0.49‰,*** addition to the relict zircon of magmatic origin,two types of newly-grown zircons were identified in terms of their occurrences,trace elements and δ^(94)Zr *** peritectic zircon,mainly occurring in the in-situ leucosomes,exhibits the highest Nb-Ta-Hf-U contents and variably higher δ^(94)Zr values than those of the relict *** anatectic zircon,mainly occurring in the leucocratic veins,shows higher Nb-Ta-Hf-U contents than and similar δ^(94)Zr values to those of the relict *** calculations demonstrate that the variable Zr isotope compositions of newly-grown zircons would result from decoupled release of Zr from zircon and non-zircon *** Zr supply of the peritectic zircon is mainly derived from the decomposition of Zr-bearing minerals in the in-situ anatectic melt(the non-zircon effect),whereas the Zr supply of the anatectic zircon is mainly from the dissolution of pre-existing zircons in the evolved melt(the zircon effect).The significant Zr isotope variations in the migmatites well illustrate the generation,migration and accumulation of the anatectic melts during the partial ***,Zr isotopes can be used as a powerful means for distinguishing between the peritectic and anatectic zircons during crustal anatexis.

关键词： Zr isotopes Zircon effect Non-zircon effect Migmatite Crustal anatexis

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小鼠中通过链转移反应增强脂质过氧化用于磁共振成像指导的癌症治疗

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Science Bulletin 2024年第5期69卷 636-647页

作者：胥俊涛关国强叶知非张成郭义博马原陆畅雷玲玲张晓兵宋国胜 State Key Laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China Department of Chemistry Case Western Reserve UniversityCleveland OH 44106USA

Lipid peroxidation(LPO),the process of membrane lipid oxidation,is a potential new form of cell death for cancer ***,the radical chain reaction involved in LPO is comprised of the initiation,propagation(the slowest step),and termination stages,limiting its effectiveness in *** address this limitation,we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation,thereby promoting endogenous lipid peroxidation and enhancing therapeutic ***,radical chain transfer agent(CTA-1)/Fe nanoparticles(CTA-Fe NPs-1)was ***,CTA-1 convert low activity peroxyl radicals(ROO·)into high activity alkoxyl radicals(RO·),creating the cycle of free radical oxidation and increasing the propagation of lipid ***,CTA-1/Fe ions enhance reactive oxygen species(ROS)generation,consume glutathione(GSH),and thereby inactivate GPX-4,promoting the initiation stage and reducing termination of free radical ***-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes,leading to highly effective treatment in cancer *** addition,CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging(MRI).In summary,CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation,propagation,and inhibiting termination step,promoting the cycle of free radical reaction,resulting in effective anticancer outcomes in tumor-bearing mice.

关键词： Lipid peroxidation Chain transfer reaction Cancer therapy Biocatalysis

Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

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World Journal of Gastroenterology 2024年第24期30卷 3086-3105页

作者： Miao-Miao Lin Shan-Shan Yang Qiu-Yue Huang Guang-Hui Cui Xiao-Fen Jia Yao Yang Zong-Ming Shi Hui Ye Xue-Zhi Zhang Department of Integrated Traditional Chinese and western Medicine Peking University First HospitalBeijing 100034China Institute of Integrated Traditional Chinese and western Medicine Peking UniversityBeijing 100034China

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric *** infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to *** has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in *** In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected *** vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,*** most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm *** assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm *** violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP *** effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain ***-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD *** HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the *** had str

关键词： Qingre Huashi decoction Helicobacter pylori Drug resistance Biofilm Metabolomics

Ferroptosis in chronic obstructive pulmonary disease:From cellular mechanisms to therapeutic applications

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Chinese Medical Journal 2024年第10期137卷 1237-1239页

作者： Mengli Yan Shiyu Xu Han Wang Shoujin Dong Chunheng Mo The Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Nephrology Henan Provincial Clinical Research Center for Kidney DiseaseHenan Provincial Key Laboratory of Kidney Disease and ImmunologyHenan Provincial People’s Hospital and People’s Hospital of Zhengzhou UniversityZhengzhouHenan 450000China Department of Biochemistry School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Center for RNA Science and Therapeutics School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Department of Pulmonary and Critical Care Medicine Chengdu First People’s HospitalChengduSichuan 610095China

To the Editor:Chronic obstructive pulmonary disease(COPD)is a global public health challenge without effective treatment currently available,affecting>300 million individuals *** understanding the pathogenesis of this disease is ***,ferroptosis,a form of cell death driven by iron-dependent lipid peroxidation,has been associated with the pathogenesis of COPD.[1]Multiple signaling pathways,such as glutathione peroxidase 4(GPX4),ferroptosis suppressor protein 1(FSP1),and tetrahydrobiopterin-dependent pathways,as well as iron metabolism,are involved in regulating ferroptosis[2,3][Figure 1A].Here,we provide a comprehensive overview of recent advances in understanding the role of ferroptosis in COPD,highlighting potential therapeutic strategies targeting ferroptosis for treating the disease.

关键词： therapeutic metabolism peroxidation

Transfer learning framework for multi-scale crack type classification with sparse microseismic networks

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International Journal of Mining Science and Technology 2024年第2期34卷 167-178页

作者： Arnold Yuxuan Xie Bing QLi Department of Civil and Environmental Engineering Western UniversityLondon N6A 3K7Canada

Rock fracture mechanisms can be inferred from moment tensors(MT)inverted from microseismic ***,MT can only be inverted for events whose waveforms are acquired across a network of *** is limiting for underground mines where the microseismic stations often lack azimuthal ***,there is a need for a method to invert fracture mechanisms using waveforms acquired by a sparse microseismic ***,we present a novel,multi-scale framework to classify whether a rock crack contracts or dilates based on a single *** framework consists of a deep learning model that is initially trained on 2400000+manually labelled field-scale seismic and microseismic waveforms acquired across 692 *** learning is then applied to fine-tune the model on 300000+MT-labelled labscale acoustic emission waveforms from 39 individual experiments instrumented with different sensor layouts,loading,and rock types in *** optimal model achieves over 86%F-score on unseen waveforms at both the lab-and *** model outperforms existing empirical methods in classification of rock fracture mechanisms monitored by a sparse microseismic *** facilitates rapid assessment of,and early warning against,various rock engineering hazard such as induced earthquakes and rock bursts.

关键词： Multi-scale Fracture processes Microseismic Acoustic emission Source mechanism Deep learning

Growth of Ag/g-C_(3)N_(4) nanocomposites on nickel foam to enhance photocatalytic degradation of formaldehyde under visible light

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Journal of Environmental Sciences 2024年第3期137卷 432-442页

作者： Ze Wang Zhi Huang Jiang Yu Xiao Shao Weidong Peng Jie Yu Yinying Jiang Department of Environmental Science and Engineering College of Architecture and EnvironmentSichuan UniversityChengdu 610065China Institute of New Energy and Low Carbon Technology Sichuan UniversityChengdu 610065China School of Agriculture and Environment University of Western AustraliaPerth 6907Western AustraliaAustralia Yibin Institute of Industrial Technology Sichuan UniversityYibin 644000China

Formaldehyde is a pollutant that significantly affects the indoor air ***,conventional remediation approaches can be challenging to deal with low-concentration formaldehyde in an indoor *** this study,Photocatalysts of Ag/graphitic carbon nitride(g-C_(3)N_(4))/Ni with 3D reticulated coral structure were prepared by thermal polymerization and liquid phase photo-deposition,using nickel foam(NF)as the *** demonstrated that when the Ag concentration was 3%,and the relative humidity was 60%,the Ni/Ag/g-C_(3)N_(4)showed the maximum degradation rate of formaldehyde at 90.19%under visible light irradiation,and the formaldehyde concentration after degradation was lower than the Hygienic standard stated by the Chinese *** porous structure of Ni/Ag/g-C_(3)N_(4)and the formation of Schottky junctions promoted the Adsorption efficiency and degradation of formaldehyde,while the nickel foam carrier effectively promoted the desorption of degradation ***,the degradation rate was only reduced by3.4%after 16 recycles,the three-dimensional porous structure extended the lifetime of the *** study provides a new strategy for the degradation of indoor formaldehyde at low concentrations.

关键词： Graphitic carbon nitride(g-C_(3)N_(4)) Nickel foam(NF) Ag Formaldehyde Photocatalysis