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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei Huang Jiayi Wen Xin Xiong Ting xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

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Neural Regeneration Research 2025年第6期20卷 1582-1598页

作者： Yanxi Li Jing xue Yuejia Ma Ke Ye xue Zhao Fangliang Ge Feifei Zheng Lulu Liu xu Gao Dayong Wang Qing Xia Department of Biochemistry and Molecular Biology College of Basic Medical SciencesHarbin Medical UniversityHarbinHeilongjiang ProvinceChina College of Basic Medical Sciences Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Basic Medical Institute Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Key Laboratory of Heilongjiang Province for Genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be a

关键词： Alzheimer's disease cell self-renewal central nervous system memory microglia nerve regeneration neurodegenerative diseases neurogenesis RNA methylation

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20世纪三四十年代马克思主义史家的新经世致用论——以马克思主义史学四大家为中心

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河北学刊 2025年第1期45卷 111-121页

作者：徐国利上海财经大学人文学院

20世纪三四十年代,中国马克思主义史学形成了一种新经世致用论。这种新经世致用论以马克思主义“科学性与革命性相统一”的原则为指导,是对传统经世致用论批判与继承的产物,具体表现为史学求真与致用的统一,体现了马克思主义的实践理性... 详细信息

20世纪三四十年代,中国马克思主义史学形成了一种新经世致用论。这种新经世致用论以马克思主义“科学性与革命性相统一”的原则为指导,是对传统经世致用论批判与继承的产物,具体表现为史学求真与致用的统一,体现了马克思主义的实践理性精神。马克思主义与中国传统文化都有实践理性精神,而传统经世致用思想则为马克思主义史家新经世致用论提供了历史解释的视域。马克思主义史家虽然认为革命性是以科学性为基础的,但往往为了革命性而忽视科学性。故史学要真正做到经世致用,必须以尊重史学科学性为前提。

关键词：马克思主义史家新经世致用论科学性革命性实践理性

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Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第01期 288-296页

作者： Shuai Liu Wen-Qiang xu Ying-Tong Di Man-Cheng Tang Ding-Kang Chen Ming-Ming Cao Yao-Wen Chang Hong-Yu Tang Chun-Mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo Zi-Fei xu Ying Zeng Yun-Dong Wu Xiao-Jiang Hao Key Laboratory of Phytochemistry and Natural Medicines (Chinese Academy of Sciences) Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay Laboratory State Key Laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental Center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan Key Laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of Natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

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Profile of Dr. Tao xu

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Science China(Life Sciences) 2018年第11期61卷 1310-1311页

作者： xu Tao

*** xu is an outstanding biophysicist on membrane trafficking and super-resolution *** has mainly focused on two aspects:one is to identify key proteins and molecular regulatory mechanisms involved in the docking,priming and fusion of different secretory vesicles such as DCVs and GSVs dense core vesicles (DCVs)and GLUT4 storage vesicles(GSVs).

关键词： vesicles DCVs outstanding biophysicist membrane

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Bullous pemphigoid associated with acquired hemophilia A: A case report

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World Journal of Clinical Cases 2025年第4期13卷 28-33页

作者： Su-Ye Hu Meng-Can Li Zi-Jia Hao xu-Ya Chai Pei-Sai Li Yang Liu Li-Xia Liu Ying xu Pan-Pan Yang Ling-E Li Department of Dermatology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina Graduate School Hebei University of Traditional Chinese MedicineShijiazhuang 050051Hebei ProvinceChina Department of Pathology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must *** SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (< 1.0%). Furthermore, the FⅧ inhibitor titer had greatlyincreased (59.2 Bethesda units). Therefore, the patient was diagnosed as having BP associated with AHA, prescribed 0.05% topical halometasone cream, and transferred to a higher-level hospitalfor effective treatment;however, he died after 2 *** AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.

关键词： Bullous pemphigoid Acquired hemophilia A Acquired hemophilia A FactorⅧ Case report

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Visualization of the protective role of estrogen against female liver fibrosis via an ER viscosity NIR fluorescent probe

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Science China Chemistry 2025年第1期 360-368页

作者： Zheng Liu Changyu Zhang Zipeng Li Wanying Ma Jia Liu Xiang Xia Ning xu Wen Sun Jianjun Du Jiangli Fan Xiaojun Peng State Key Laboratory of Fine Chemicals Dalian University of Technology Ningbo Institute of Dalian University of Technology

Endoplasmic reticulum(ER) viscosity has emerged as a new potential biomarker for hepatic fibrosis(HF). Herein, we report the first ER-targeting viscosity-responsive near-infrared(NIR) fluorescent probe HBT-PP for investigations of HF *** twisted intramolecular charge transfer(TICT) and the excited state intramolecular proton transfer(ESIPT) are combined to endow HBT-PP with the selective response towards viscosity(～62-fold) and a super large stokes shift(～320 nm). HBT-PP mainly targets organelle ER and is able to image the drug-or alcohol-induced viscosity elevation in living cells. Significantly,HBT-PP was successfully applied to visualize the gender difference in HF and the protective role of estrogen in restraining HF progression. Of note, after 10 min of stain with HBT-PP, HF lesions showed a stage-based response, indicating the potential of this probe in fast and early diagnosis of HF. These results clearly demonstrated the promising application of HBT-PP as a new tool for exploring ER viscosity-involved physiological and pathological processes.

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A Flexible Smart Healthcare Platform Conjugated with Artificial Epidermis Assembled by Three‑Dimensionally Conductive MOF Network for Gas and Pressure Sensing

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Nano-Micro Letters 2025年第2期17卷 601-620页

作者： Qingqing Zhou Qihang Ding Zixun Geng Chencheng Hu Long Yang Zitong Kan Biao Dong Miae Won Hongwei Song Lin xu Jong Seung Kim State Key Laboratory of Integrated Optoelectronics College of Electronic Science and EngineeringJilin UniversityChangchun 130012People’s Republic of China Department of Chemistry Korea UniversitySeoul 02841Republic of Korea TheranoChem Incorporation Seoul 02856Republic of Korea

The rising flexible and intelligent electronics greatly facilitate the noninvasive and timely tracking of physiological information in telemedicine *** building bionic-sensitive moieties is vital for designing efficient electronic skin with advanced cognitive functionalities to pluralistically capture external ***,realistic mimesis,both in the skin’s three-dimensional interlocked hierarchical structures and synchronous encoding multistimuli information capacities,remains a challenging yet vital need for simplifying the design of flexible logic ***,we construct an artificial epidermal device by in situ growing Cu_(3)(HHTP)_(2) particles onto the hollow spherical Ti_(3)C_(2)T_(x) surface,aiming to concurrently emulate the spinous and granular layers of the skin’s *** bionic Ti_(3)C_(2)T_(x)@Cu_(3)(HHTP)_(2) exhibits independent NO_(2) and pressure response,as well as novel functionalities such as acoustic signature perception and Morse code-encrypted message ***,a wearable alarming system with a mobile application terminal is self-developed by integrating the bimodular senor into flexible printed *** system can assess risk factors related with asthmatic,such as stimulation of external NO_(2) gas,abnormal expiratory behavior and exertion degrees of fingers,achieving a recognition accuracy of 97.6%as assisted by a machine learning *** work provides a feasible routine to develop intelligent multifunctional healthcare equipment for burgeoning transformative telemedicine diagnosis.

关键词： Ti_(3)C_(2)T_(x)@Cu_(3)(HHTP)_(2)composites NO_(2)/pressure flexible sensors Health-monitoring Machine learning

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基于RUSLE和地理探测器的皖南地区土壤侵蚀时空分异及定量归因

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水土保持研究 2025年第1期32卷 21-29页

作者：许长安王乃举合肥大学生物食品与环境学院合肥大学旅游与会展学院

[目的]揭示皖南地区土壤侵蚀时空分异特征及成因可为该区域的土壤侵蚀防治提供科学依据。[方法]基于RUSLE模型和地理探测器，结合多源遥感数据，探查皖南地区土壤侵蚀时空分布及其影响因素。[结果](1) 2002—2022年该地区土壤侵蚀空间... 详细信息

[目的]揭示皖南地区土壤侵蚀时空分异特征及成因可为该区域的土壤侵蚀防治提供科学依据。[方法]基于RUSLE模型和地理探测器，结合多源遥感数据，探查皖南地区土壤侵蚀时空分布及其影响因素。[结果](1) 2002—2022年该地区土壤侵蚀空间分布差异显著。安庆市北部大别山区、安庆市东南部大别山余脉大龙山片、铜陵市东部与芜湖市中西部狮子山片、池州市与宣城市南部、黄山市内黄山山区和周边齐云山及白际山等地区系主要侵蚀区；而皖江诸市沿江平原及其他诸河河谷平原土壤侵蚀较小。(2) 2002—2022年该地区的土壤侵蚀总体呈“下降—上升—下降”趋势。其中，2002年总侵蚀量为2 231.41万t/a, 2007年降至2 118.05万t/a,而2012年增至2 452.36万t/a,之后持续下降至2022年的2 060.67万t/a。(3)因子探测器的各因子解释力结果显示：土地覆盖类型、坡度、海拔、降雨是该地区的主要影响因素。(4) 2002年、2017年、2022年土地覆盖类型与其他因子共同作用对土壤侵蚀的解释力大于其他因子，而2007年、2012年为植被覆盖度与其他因子共同作用对土壤侵蚀的解释力较为突出。(5)基于2022年的土壤侵蚀数据及因子数据所识别的高风险区域为植被覆盖度63.96°、海拔1 056～1 819 m、年均温度10.46～11.3℃的灌丛。[结论]皖南地区在过去20年中土壤侵蚀状况有所改善，但坡度大、植被覆盖度低、降雨强度高及不合理土地利用的山地丘陵区仍然是高侵蚀风险区域，未来的防治工作应针对这些重点区域。

关键词：土壤侵蚀 RUSLE模型地理探测器皖南地区

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng xue Xiaokun xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

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