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LRRK2 regulates actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis

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Journal of Molecular Cell Biology 2022年第1期14卷 21-31页

作者： Zhen-Nan Pan Jing-Cai Liu jia-qian ju Yue Wang Shao-Chen Sun College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China

Leucine-rich-repeat kinase 2 (LRRK2) belongs to the Roco GTPase family and is a large multidomain protein harboring both GTPase and kinase activities. LRRK2 plays indispensable roles in many processes, such as autophagy and vesicle trafficking in mitosis. In this study, we showed the critical roles of LRRK2 in mammalian oocyte meiosis. LRRK2 is mainly accumulated at the meiotic spindle periphery during oocyte maturation. Depleting LRRK2 led to the polar body extrusion defects and also induced large polar bodies in mouse oocytes. Mass spectrometry analysis and co-immunoprecipitation results showed that LRRK2 was associated with several actin-regulating factors, such as Fascin and Rho-kinase (ROCK), and depletion of LRRK2 affected the expression of ROCK, phosphorylated cofilin, and Fascin. Further analysis showed that LRRK2 depletion did not affect spindle organization but caused the failure of spindle migration, which was largely due to the decrease of cytoplasmic actin filaments. Moreover, LRRK2 showed a similar localization pattern to mitochondria, and LRRK2 was associated with several mitochondria-related proteins. Indeed, mitochondrial distribution and function were both disrupted in LRRK2-depleted oocytes. In summary, our results indicated the critical roles of LRRK2 in actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis.

关键词： actin spindle LRRK2 oocyte meiosis

Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3095-3112页

作者： Fengcheng Deng Dan Yang Lingxi Qing Yifei Chen Jilian Zou Meiling jia qian Wang Runda jiang Lihua Huang College of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain *** gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine ***,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host *** reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological *** coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological *** study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological *** pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional *** can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage *** findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

关键词： cyclic adenosine monophosphate emotional disorders gut microbiota neurodegenerative diseases neurological diseases protein kinase A reciprocal regulation signaling pathway strategy therapies

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu Xiao-jia Yang qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of jiangsu and Ministry of Education and Coinnovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

Synthesis of chiral phosphine derivatives through a copper（I）-catalyzed desymmetric SNAr reaction

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Science China Chemistry 2025年

作者： Shuai Zhang Pei-Zhi Liu Yan-Bo Li Qi Zhang jun-Zhao Xiao Yi-Fan Wang Tian-Yu Wei jia-Wei jiang Ye Wang qian Peng Liang Yin Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials Shanghai Institute of Organic Chemistry University of Chinese Academy of Sciences Chinese Academy of Sciences State Key Laboratory of Elemento-Organic Chemistry and Tianjin Key Laboratory of Biosensing and Molecular Recognition College of Chemistry Frontiers Science Center for New Organic Matter Nankai University Haihe Laboratory of Sustainable Chemical Transformations

Axially chiral phosphines are a class of extremely important ligands in asymmetric catalysis. Herein, an unprecedented copper（I）-catalyzed asymmetric SNAr reaction with HP（S）R2is uncovered, which delivers a series of axially chiral phosphine derivatives in high yields with excellent enantioselectivity. Furthermore, the diastereoselective reaction with the kinetic resolution of racemic HP（S）ArR proceeds smoothly, providing the products with moderate diastereoselectivity and excellent enantioselectivity. Control experiments indicate that HP（S）Ph2is much more active than HPPh2and HP（O）Ph2as the pronucleophile in the present reaction. It is found that the SNAr reaction （the first SNAr） proceeds in a desymmetric manner, providing the desired chiral products while a continued SNAr reaction （the second SNAr） slightly occurs in a kinetic resolution manner in the present catalytic system, which enhances the ee of the desired chiral products. DFTcalculations support a concerted reaction pathway rather than a step-wise mechanism. Finally, axially chiral olefin-phosphines produced by the present method work as suitable ligands in Pdcatalyzed asymmetric allylic substitution with C-, N-, and O-nucleophiles and Rh-catalyzed asymmetric addition of arylboronic acid to benzil.

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Mechanism of action of Linggui Zhugan Decoction in treating non-alcoholic fatty liver disease using untargeted metabolomics approach

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Traditional Medicine Research 2025年第2期10卷 65-76页

作者： Huan Pei Ren-Lin Li Xin-Ran Song qian-qian Wan Yu-Ming Wang Han-Zhou Li Wei-Quan Xu jia-Bao Liao Wei-Bo Wen Jing Miao Huan-Tian Cui School of Basic Medicine Yunnan University of Chinese MedicineKunming 650599China School Clinical Medical College Yunnan University of Chinese MedicineKunming 650599China First School of Clinical Medicine Yunnan University of Chinese MedicineKunming 650599China School of Integrative Chinese and Western Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pharmacy Tianjin Second People's HospitalTianjin 300192China

Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver *** studies showed that metabolic dysfunction can promote NAFLD *** Zhugan Decoction(LGZGD)has therapeutic effects on *** mechanism of LGZGD still remains *** study was to examine the impact of LGZGD on the metabolic processes involved in the development of ***:A mice model of NAFLD was treated with *** therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of ***,this study also evaluated the influence of LGZGD on liver inflammation and oxidative ***:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD *** improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the *** metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate *** RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.

关键词： NAFLD LGZGD untargeted metabolomics glycerophospholipid metabolism citrate cycle

Prioritizing Test Cases for Memory Leaks in Android Applications

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Journal of Computer Science & Technology 2016年第5期31卷 869-882页

作者： ju qian College of Computer Science and Technology Nanjing University of Aeronautics and Astronautics Nanjing 210016 China State Key Laboratory of Software Engineering Wuhan University Wuhan 430072 China Collaborative Innovation Center of Novel Software Technology and Industrialization Nanjing 210023 China

Mobile applications usually can only access limited amount of memory. Improper use of the memory can cause memory leaks, which may lead to performance slowdowns or even cause applications to be unexpectedly killed. Although a large body of research has been devoted into the memory leak diagnosing techniques after leaks have been discovered, it is still challenging to find out the memory leak phenomena at first. Testing is the most widely used technique for failure discovery. However, traditional testing techniques are not directed for the discovery of memory leaks. They may spend lots of time on testing unlikely leaking executions and therefore can be inefficient. To address the problem, we propose a novel approach to prioritize test cases according to their likelihood to cause memory leaks in a given test suite. It firstly builds a prediction model to determine whether each test can potentially lead to memory leaks based on machine learning on selected code features. Then, for each input test case, we partly run it to get its code features and predict its likelihood to cause leaks. The most suspicious test cases will be suggested to run at first in order to reveal memory leak faults as soon as possible. Experimental evaluation on several Android applications shows that our approach is effective.

关键词： Android memory leak test case prioritization test execution

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian jia jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming qian jiashu Lian Xin Hua jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

数字赋能乡村教育现代化的实然困境与优化路径

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教学与管理 2025年第1期 6-11页

作者：王倩吴家华胡恒钊安徽大学马克思主义学院合肥230601 江西农业大学马克思主义学院南昌330045

以数字赋能为发展契机,推进乡村教育现代化是中国式教育现代化的必然要求,也是乡村全面振兴的重要依托。在教育领域,数字技术蕴含着驱动乡村教育现代化发展的重要价值,能够有效扩大优质教育资源的覆盖范围、变革乡村教育形态、推动乡土... 详细信息

以数字赋能为发展契机,推进乡村教育现代化是中国式教育现代化的必然要求,也是乡村全面振兴的重要依托。在教育领域,数字技术蕴含着驱动乡村教育现代化发展的重要价值,能够有效扩大优质教育资源的覆盖范围、变革乡村教育形态、推动乡土文化的交流传播。但在推动数字赋能乡村教育现代化的实践中,面临着数字教育观念淡薄、数字基础条件不足、师生数字素养薄弱等现实阻碍,迫切需要从重塑价值观念、完善数字设施、培养师生数字素养、加强体制建设入手,为数字赋能乡村教育现代化发展注入新动力,以适应中国式教育现代化发展的新生态。

关键词：数字赋能乡村教育中国式教育现代化乡土文化

A Photometric Study of the W UMa-Type Contact Binary RZ Com

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Chinese Journal of Astronomy and Astrophysics 2008年第4期8卷 465-471页

作者： jia-jia He Sheng-Bang qian National Astronomical Observatories / Yunnan Observatory Chinese Academy of Sciences Kunming 650011 China United Laboratory of Optical Astronomy Chinese Academy of Sciences （ULOAC） Beijing 100012 China Graduate School of Chinese Academy of Sciences Beijing 100049 China

We present results of CCD photometric observations of the short-period W UMatype contact binary system, RZ Com. The light curve of the binary has changed from Wsubtype to A-subtype from 1998 to 2003, then back to W-subtype in 2004. An analysis was carried out using the 2003 version of the Wilson-Devinney code. It is confirmed that RZ Com is a low-degree, overcontact f = 20.1% （±7.4%） binary system with a high inclination of i = 81.°40 （＋0.°40）, and a mass ratio q = 2.351 （＋0.031）. Combining four newly determined times of light minimum with others in the literature, the variations in orbital period is examined. A small-amplitude oscillation （A=0.0065d）, with a period of 41.5 year, is discovered superimposed on a long-term increase at rate dP/dt = ＋3.97 × 10^-8d yr^-1. The period oscillation can be explained either by the light-time effect due to the presence of an unseen third body, or by cycles of magnetic activity on the components. Combining our photometric solution with the spectroscopic elements obtained by Mclean ＆ Hilditch, the absolute dimensions ofRZ Com are： M1 = 1.14 （±0.19）M⊙, M2 = 0.50 （±0.09）M⊙, R1 = 1.12 （±0.01）R⊙, R2 = 0.78 （＋0.01）R⊙ and A = 2.41 （±0.02）R⊙.

关键词： stars binaries close - stars binaries eclipsing - stars individual RZ Com