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MFG-E8 Alleviates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Phagocytosing Myelin Debris and Promoting Remyelination

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Neuroscience Bulletin 2024年第4期40卷 483-499页

作者： Xiaohong Dong Zhi Zhang xin Shu zi Zhuang Pinyi Liu Renyuan Liu Shengnan Xia xinyu Bao Yun Xu Yan chen Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210008China Department of Neurology Drum Tower Hospital of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of Neurology Nanjing210008China

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter injury.Microglia phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white matter.However,milk fat globule-epidermal growth factor-factor 8(MFG-E8),a microglial phagocytosis-related protein,has not been well studied in hypoperfusion-related cognitive dysfunction.We found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis(BCAS).MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral tests.In addition,we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron microscopy.Meanwhile,MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after BCAS.Moreover,in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via theαVβ3/αVβ5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes.Interestingly,we found that MFG-E8 was mainly derived from astrocytes,not microglia.Our findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.

关键词： White matter injury Cognitive dysfunction MFG-E8 Remyelination Microglial phagocytosis

Observation of accurately designed bound states in the continuum in momentum space

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Photonics Research 2024年第4期12卷 638-647页

作者： JIAJU WU JINGGUANG chen xin QI ZHIWEI GUO JIAJUN WANG FENG WU YONG SUN YUNHUI LI HAITAO JIANG LEI SHI JIAN zi HONG chen MOE Key Laboratory of Advanced Micro-Structured Materials School of Physics Science and EngineeringTongji UniversityShanghai 200092China State Key Laboratory of Surface Physics Key Laboratory of Micro-and Nano-Photonic Structures(Ministry of Education)and Department of PhysicsFudan UniversityShanghai 200433China School of Optoelectronic Engineering Guangdong Polytechnic Normal UniversityGuangzhou 510665China

Bound states in the continuum(BICs)in artificial photonic structures have received considerable attention since they offer unique methods for the extreme field localization and enhancement of light-matter interactions.Usually,the symmetry-protected BICs are located at high symmetric points,while the positions of accidental BICs achieved by tuning the parameters will appear at some points in momentum space.Up to now,to accurately design the position of the accidental BIC in momentum space is still a challenge.Here,we theoretically and experimentally demonstrate an accurately designed accidental BIC in a two-coupled-oscillator system consisting of bilayer gratings,where the optical response of each grating can be described by a single resonator model.By changing the interlayer distance between the gratings to tune the propagation phase shift related to wave vectors,the position of the accidental BIC can be arbitrarily controlled in momentum space.Moreover,we present a general method and rigorous numerical analyses for extracting the polarization vector fields to observe the topological properties of BICs from the polarization-resolved transmission spectra.Finally,an application of the highly efficient second harmonic generation assisted by quasi-BIC is demonstrated.Our work provides a straightforward strategy for manipulating BICs and studying their topological properties in momentum space.

关键词： polarization tuning resonator

Chain Dynamics Heterogeneity in Plasticized Poly(vinyl butyral)(PVB) as Elucidated by Solid-State NMR

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Chinese Journal of Polymer Science 2024年第1期42卷 113-124,I0010页

作者： Jing Lv Xu chen zi-Shuo Wu Ya-Hui Li Wei chen National Synchrotron Radiation Laboratory Anhui Provincial Engineering Laboratory of Advanced Functional Polymer FilmCAS Key Laboratory of Soft Matter ChemistryUniversity of Scienceand Technology of ChinaHefei 230026China

The chain dynamics heterogeneity of the poly(vinyl butyral)(PVB) plasticized by triethylene glycol bis(2-ethylhexa noate)(TEG-EH) was investigated by various solid-state NMR techniques.The plasticized PVB shows two domains in distinct molecular dynamics differences,namely,rigid and soft domains,where the latter is the plasticizer-rich domain.The time domain low field NMR was first used to investigate the dynamics heterogeneity of the plasticized PVB,and the results show the decreasing activated energy of components in the soft domain of plasticized PVB(E_a=20.2 kJ/mol) as compared with that of the pristine one(E_a=24.3 kJ/mol).Detailed dynamics heterogeneity was obtained by high-field NMR with site-specific features.The quadrupole-echo ~2H-NMR was adopted to elucidate the dynamics heterogeneity of the vinyl alcohol(VA) units,where only the hydroxyl group of VA is deuterated.The ~1H-^(13)C WISE NMR spectra show that there is not much difference in the mobility of the VB unit in PVB with and without plasticizer,whereas the glass transition temperature differed by approximately 53℃.This is further supported by Torchia's T_1 relaxation measurements.The origin of such an unusual phenomenon is attributed to the critical role of the remaining VA(~22%) in the soft domain,where the VA units locally aggregate through hydrogen bonding.Also,the existence of a mobility gradient in the VB unit has been demonstrated.Moreover,the mobility difference for VB with different stereo-geometry(meso or racemic conformation) is observed for the first time.This indicates the importance of modulating the ratio of meso over racemic VB for controlling the macroscopic perfo rmance of PVB.

关键词： Poly(vinyl butyral) Dynamics heterogeneity Plasticizer Solid state NMR

Knocking down AR promotes osteoblasts to recruit prostate cancer cells by altering exosomal circ-DHPS/miR-214-3p/CCL5 pathway

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Asian Journal of Andrology 2024年第2期26卷 195-204页

作者： Zhao Yang Jia-Qi chen Tian-Jie Liu Yu-Le chen Zhen-Kun Ma Yi-Zeng Fan zi-Xi Wang Shan Xu Ke Wang xin-Yang Wang Lei Li Hong-Jun Xie Department of Urology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061China

Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis,and the androgen receptor regulates prostate cancer(PCa)progression.It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment,even bone metastases,through exosomes.Here,we found that exosomes isolated from PCa cells after knocking down androgen receptor(AR)or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts.In addition,AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase(circ-DHPS)in PCa cells,which can be transported to osteoblasts by exosomes.Circ-DHPS acts as a competitive endogenous RNA(ceRNA)against endogenous miR-214-3p to promote C-C chemokine ligand 5(CCL5)levels in osteoblasts.Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment.Thus,blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.

关键词： androgen receptor circRNA exosome prostate cancer

Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance

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Cancer Communications 2024年第2期44卷 205-225页

作者： chen Ming-Kun chen zi-Xian Cai Mao-Ping chen Hong chen Zhuang-Fei Zhao Shan-Chao Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhouGuangdongP.R.China The Third Clinical College Southern Medical UniversityGuangzhouGuangdongP.R.China Luoyang Key Laboratory of Organic Functional Molecules College of Food and DrugLuoyang Normal UniversityLuoyangHenanP.R.China Department of Urology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malig-nant tumor cells remain significant clinical challenges.However,there are only few effective methods to address these issues.Extracellular vesicles(EVs),actively secreted by cells,play a crucial role in intercellular information transmis-sion and cargo transportation.Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects.Nevertheless,there is an urgent need for further improvements in the isolation and purification of EVs,surface modification techniques,drug assem-bly processes,and precise recognition of tumor cells for targeted drug delivery purposes.In this review,we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance,and current challenges asso-ciated with engineered EVs are also discussed.This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

关键词： drug delivery drug resistance extracellular vesicles nanoparticles

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

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Zoological Research 2024年第1期45卷 79-94页

作者： Ya-Ling Zhu Lei-Lei Meng Jin-Hu Ma xin Yuan Shu-Wen chen xin-Rui Yi xin-Yu Li Yi Wang Yun-Shu Tang Min Xue Mei-zi Zhu Jin Peng Xue-Jin Lu Jian-Zhen Huang zi-chen Song Chong Wu Ke-Zhong Zheng Qing-Qing Dai Fan Huang Hao-Shu Fang Department of Pathophysiology Anhui Medical UniversityHefeiAnhui 230032China Laboratory Animal Research Center School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhui 230032China Department of Hepatobiliary Surgery First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China College of Animal Science and Technology Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

关键词： Non-alcoholic fatty liver disease C/EBPβ Lipopolysaccharide-binding protein H3K27ac Integrative analysis Enhancer

Surgical treatment of an old avulsion fracture of the ischial tuberosity and ischial ramus: A case report

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World Journal of Orthopedics 2024年第1期15卷 94-100页

作者： zi-Ru chen Shi-Jie Liao Fu-Chun Yang Department of Orthopedic Trauma and Hand Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Avulsion fracture of the ischial tuberosity is a relatively clinically rare type of trauma that is mainly incurred by adolescents during competitive sports activities.According to previous literature,the most commonly involved sports are soccer,sprinting,and gymnastics,in descending order.Dance-induced avulsion fracture of the ischial tuberosity and ischial ramus is extremely clinically rare.CASE SUMMARY A case of a neglected avulsion fracture of the ischial tuberosity and ischial ramus was diagnosed in a young female dancer who complained of pain and restricted movement of her right hip.She stated that she had suffered the injury while performing a split leap during a dance performance 9 mo prior.Eventually,she underwent surgery and obtained satisfactory treatment results.CONCLUSION Early diagnosis of these fractures is important to ensuring early proper treatment towards a quicker recovery.For old fractures with nonunion and chronic buttock pain,surgery is a preferred therapeutic choice with good treatment outcomes.

关键词： Ischial tuberosity Ischial ramus Avulsion fracture Delayed diagnosis Splitleap injury Case report

Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C.elegans

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Journal of Genetics and Genomics 2024年第5期51卷 507-516页

作者： Xiao Zang Qi Wang Hanxin Zhang Yiyan Zhang zi Wang zixing Wu Di chen Model Animal Research Center of Medical School Nanjing UniversityNanjingJiangsu 210061China Zhejiang University-University of Edinburgh Institute School of MedicineZhejiang UniversityHainingZhejiang 314400China Department of Colorectal Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China

The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关键词： Aging targetof rapamycin DAF-15 DAF-16 C.elegans

Ion-Velocity Imaging Study of Dissociative Charge Exchange Reactions between Ar^(+)and trans-/cis-Dichloroethylene

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化学物理学报(英文) 2023年第5期36卷 509-516,I0001页

作者： zi-xin chen Jie Hu Yaya Zhi Chun-Xiao Wu Shan Xi Tian Hefei National Research Center for Physical Sciences at the Microscale Department of Chemical PhysicsUniversity of Science and Technology of ChinaHefei 230026China

Dissociative charge exchange re-actions between Ar^(+)ion and trans-/cis-dichloroethylene(trans-/cis-C_(2)H_(2)Cl_(2))are investi-gated with the ion-velocity imag-ing technique.The dechlorinated product C_(2)H_(2)Cl^(+)is the predomi-nant,and most of this product show the spatial distribution around the target,implying that the dissociation occurs in the large impact-parameter collision and via the energy resonant charge transfer.Meanwhile,a few C_(2)H_(2)Cl^(+)locate around the center-of-mass,which is at-tributed to the fragmentation of intimate association between C_(2)H_(2)Cl_(2)and Ar^(+)or in the small impact-parameter collision.The product C_(2)HCl_(+)exhibits the velocity distribution fea-tures similar to those of C_(2)H_(2)Cl_(+).The rarest product C_(2)HCl_(2)+shows the distributions around the molecular target,due to the quick dehydrogenation after the energy-resonant charge transfer in the large impact-parameter collision.

关键词： Ion-molecule reaction Dissociative charge exchange Velocity map imaging