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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

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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

Bird Species Diversity and Spatio-temporal Variation in the Sihong Hongze Lake Wetland National Nature reserve in Eastern China

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Journal of Resources and Ecology 2024年第4期15卷 826-837页

作者： HU Huali XIAO Lihui ZHANG Manyu WANG Silu CHEN Taiyu LU Changhu College of Life Science Nanjing Forestry UniversityNanjing 210037China Eastern Hongze Lake Wetland Natural reserve HuaianJiangsu 223100China Institute of Wildlife Conservation Jiangxi Academy of ForestryNanchang 330037China

As an important hub on the East Asian-Australian Flyway(EAAF),Hongze Lake is an important migratory stopover and wintering site for hundreds of thousands of ***,research on bird community diversity in this area is still *** conducted a bird survey from July 2020 to June 2021 using the line transect method on the terrestrial habitat,as well as the fixed-point method in the lake wetland at the Sihong Hongze Lake Wetland National Nature reserve located in northwestern Hongze Lake,and analyzed the temporal-spatial variation in the bird *** results showed that a total of 170432 detections of 215 bird species belonging to 18 orders and 55 families were *** terms of species composition,the proportion of terrestrial birds was relatively high,followed by waterfowl richness,with high numbers of Anatidae species and *** bird species abundance,waterfowl had the highest abundance of common coot(Fulica atra),belonging to the Rallidae family,followed by Anatidae and Ardeidae *** abundance of shorebirds was extremely low,and that of non-waterfowl was also *** terms of temporal patterns,the number of bird species and richness index were higher in spring and autumn but lower in winter and *** bird abundance was the highest in winter,and the remaining three seasons were similar in terms of bird *** diversity index and evenness index were higher in spring,summer and autumn,and lowest in *** the spatial pattern,the open water in the western part of the reserve included the most densely distributed areas for birds,and the number of bird species and their abundance were both the highest in that *** were significant differences in the bird community structures among the four *** species number and richness index of birds in the reed habitat were the highest,and the bird abundance was also high,but the diversity index and evenness index were *** the bird abundance in the lake habitat wa

关键词： bird diversity seasonal variation spatial distribution Sihong Hongze Lake Wetland National Nature reserve

Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael J.Lee Ryota L.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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

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

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第6期30卷 515-524页

作者： CAO Liu-jing LIU Li-ya CHEN You-qin HAN Yu-ying WEI Li-hui YAO Meng-ying FANG Yi WU Mei-zhu CHENG Ying Thomas J.Sferra LIU Hui-xin LI Li PENG Jun SHEN A-ling Clinical Research Institute the Second Affiliated Hospital&Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhou350122China Fujian Key Laboratory of Integrative Medicine in Geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Pediatrics Case Western Reserve University School of MedicineUH Rainbow Babies and Children’s HospitalClevelandOH44106USA Innovation and Transformation Center Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Health Management Fujian Provincial HospitalShengli Clinical College of Fujian Medical UniversityFuzhou000000China

ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) *** polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in *** treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

关键词： colorectal cancer Pien Tze Huang Chinese medicine partner of NOB1 proliferation p53/p21 pathway

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

Predicting hepatocellular carcinoma: A new non-invasive model based on shear wave elastography

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World Journal of Gastroenterology 2024年第25期30卷 3166-3178页

作者： Dong Jiang Yi Qian Yi-Jun Gu Ru Wang Hua Yu Hui Dong Dong-Yu Chen Yan Chen Hao-Zheng Jiang Bi-Bo Tan Min Peng Yi-Ran Li Department of Ultrasound Eastern Hepatobiliary Surgery HospitalThe Third Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of Pathology Shanghai Eastern Hepatobiliary Surgery HospitalThird Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of College of Art and Science Case Western Reserve UniversityClevelandOH 44106United States Ultrasound Diagnosis PLA Naval Medical CenterShanghai 200437China

BACKGROUND Integrating conventional ultrasound features with 2D shear wave elastography(2D-SWE)can potentially enhance preoperative hepatocellular carcinoma(HCC)*** To develop a 2D-SWE-based predictive model for preoperative identification of *** A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery *** patients were divided into the modeling group(n=720)and the control group(n=164).The study included conventional ultrasound,2D-SWE,and preoperative laboratory *** logistic regression was used to identify independent predictive factors for RESULTS In the modeling group analysis,maximal elasticity(Emax)of tumors and their peripheries,platelet count,cirrhosis,and blood flow were independent risk indicators for *** factors yielded an area under the curve of 0.77(95%confidence interval:0.73-0.81)with 84%sensitivity and 61%*** model demonstrated good calibration in both the construction and validation cohorts,as shown by the calibration graph and Hosmer-Lemeshow test(P=0.683 and P=0.658,respectively).Additionally,the mean elasticity(Emean)of the tumor periphery was identified as a risk factor for microvascular invasion(MVI)in malignant liver tumors(P=0.003).Patients receiving antiviral treatment differed significantly in platelet count(P=0.002),Emax of tumors(P=0.033),Emean of tumors(P=0.042),Emax at tumor periphery(P<0.001),and Emean at tumor periphery(P=0.003).CONCLUSION 2D-SWE’s hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions,correlating significantly with MVI and antiviral treatment efficacy.

关键词： Shear wave elastography Predicting model Microvascular invasion Antiviral treatment Hepatocellular carcinoma