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

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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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FHL2 deficiency aggravates Candida albicans infection through decreased myelopoiesis

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Science China Life Sciences 2025年

作者： Rongmei Gao Kanchao Chen Yimin Wang Rongxia Guo Xiaoyu Zhang Peng Wu Weili Wang Qingxiang huang Xuemei Xie Shangda Yang Yanling Lü Qian Ren fei liu Song Chen Fengxia Ma Tao Cheng Hui Cheng State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College CAMS Center for Stem Cell Medicine PUMC Department of Stem Cell and Regenerative Medicine

Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation, which is crucial for maintaining homeostasis. Acute infections can prompt a hematopoietic response known as emergency myelopoiesis. In this study, using a Candida albicans (C. albicans) infection model, we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates. Impaired myeloid hematopoiesis and immune cell production were evident, as proved by the decreased numbers of hematopoietic stem and progenitor cells (HSPCs) and granulocytes in the bone marrow of Fhl2-deficient mice. In conclusion, FHL2 regulated emergency myelopoiesis in response to C. albicans, affecting the host’s defense against pathogens.

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Engineering high-performance chemiluminescent probes via enzymatic pocket targeting: high-throughput screening for ultralong afterglow imaging of orthotopic hepatocellular carcinoma

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Science China Chemistry 2025年

作者： Shuai huang Shuaige Bai Ting Luo Bin Feng Min liu Fan Zheng Shuang huang Yanpeng Fang Dan Ding Wenbin Zeng Xiangya School of Pharmaceutical Sciences Central South University College of Life Sciences Nankai University

Hepatocellular carcinoma （HCC） is a highly aggressive liver malignancy and the main form of liver cancer. Early diagnosis and treatment of HCC can effectively reduce mortality. Carboxylesterase （CE）-specific detection and imaging can be used for early diagnosis and image-guided surgical of HCC. However, traditional optical probes suffer from poor selectivity and low imaging signal-to-noise ratio. Here, we have constructed a series of chemiluminescent probes for carboxylesterase detection based on the strategy of enzymatic pocket-oriented steric tailoring techniques. The probes with different unique and excellent properties have been obtained through the structure-based steric hindrance adjustment on the recognition site. Here, CE-2 has been successfully used for high-throughput screening of rapid carboxylesterase inhibitors due to its extremely low detection limit (2.5×10-4U mL-1) and fast recognition ability. CE-3 has been successfully used for image-guided surgery of orthotopic hepatocellular carcinoma due to its ultra-long chemiluminescence imaging （over 12 h） of hepatocellular carcinoma. This study may promote advances in the rapid detection and screening of inhibitory drugs for CE and the field of surgical navigation in HCC.

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Design and characterization study of dual D-shaped no-core fiber based SPR sensor for refractive index and temperature measurement

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Optoelectronics Letters 2025年

作者： liu Yinggang Li Rui Li fei Xu Xinyi Zhou Rui Shaanxi Engineering Research Center of Oil and Gas Resource Optical Fiber Detection & Shaanxi Key Laboratory of Measurement and Control Technology for Oil and Gas wells， Xi'an Shiyou University

To address the issue of temperature cross-sensitivity in refractive index （RI） measurement， a fiber-optic Surface Plasmon Resonance （SPR） sensor based on dual D-shaped no-core fiber （NCF） is proposed and designed. The sensor mainly consists of D-shaped NCF， Ag/Fe2O3composite film， and polydimethylsiloxane （PDMS）， where the silver and Fe2O3are successively coated on both D-shaped surfaces of NCF to generate SPR and enhance the oxidation resistance. The layer of PDMS coated on one D-shaped surface acts as a tunable ambient medium sensing the temperature variation and affecting the transmission spectrum of the sensor. Since the surface plasmon waves are excited in the two D-shaped surfaces with different films， the two RI and temperature-dependent spectral resonance peaks with different wavelengths will be produced. Research results demonstrate that the two peaks’ wavelengths have different responses to the variations of ambient RI and temperature. In the refractive index range of 1.36-1.376 and temperature range of 10-100 °C， the RI and temperature sensitivities reach to 5000 nm/RIU and -0.546 nm/°C， respectively. With the sensitivity coefficient matrix， simultaneous measurement of refractive index and temperature can be realized， and the corresponding accuracy is superior to 0.4×10-5RIU and 0.037°C.

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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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蛙皮素-蜂毒素杂合肽基因在大肠杆菌中的克隆与诱导表达

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生物工程学报 2001年第2期17卷 207-210页

作者：黄音刘飞鹏周天鸿朱嘉明上海复旦大学遗传所暨南大学生物工程系广州510632

A hybrid peptide gene was designed and synthesized. Its encoding peptide is constructed from residues 3～14 of magainin and residues 1～13 of melittin. The MA E gene was cloned into plasmids pUC18 and pBV220. By DNA sequencing, the whole sequences of this gene is confirmed to be correct. The recombinant plasmid pBMA\|E was expressed in \%***\% DH5α. A gene product band can be seen with Tricine\|SDS\|PAGE. The MA E hybrid peptide was purified by immobilized metal affinity chromatography. Bioactivity assay was carried out in liquid turbidity method. The bactericide value to \%***\% K 12 D 31 is 0.182.

关键词：抗菌肽 MA-E基因大肠杆菌抗菌活性表达克隆蛙皮素-蜂毒素杂合肽基因

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Mitigating methodology of hardware non-ideal characteristics for non-volatile memory based neural networks

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Science China(Information Sciences) 2025年

作者： Lixia HAN Peng huang Yijiao WANG Zheng ZHOU Haozhang YANG Yiyang CHEN Xiaoyan liu Jinfeng KANG School of Integrated Circuits Peking University Beijing Advanced Innovation Center for Integrated Circuits School of Integrated Circuit Science and Engineering Beihang University

Non-volatile memory-based computing-in-memory (nvCIM) paradigm has been extensively studied to boost the energy efficiency of neural network accelerators in edge ***,the degradation of inference accuracy induced by the non-ideal characteristics across circuits,arrays,and devices is becoming a crucial *** this work,we establish a hardware characteristic behavior model to analyze the impact of nvCIM non-ideal characteristics on neural network *** we propose a hardware aware training and weight mapping correction methods to mitigate inference accuracy *** simulation verification,about 95%inference accuracy degradation is recovered by adopting the proposed mitigation method for various non-ideal characteristics and various neural network *** feasibility of the proposed method is further proved in an experimental example with a flash-based LeNet recognition system.

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升降散改善MNNG诱导的胃黏膜损伤及其机制

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中国药理学通报 2025年第1期41卷 178-185页

作者：刘轶璜张思佳刘菲陈苹苹河北中医药大学药学院河北石家庄050091 河北省离子通道功能与创新中药国际联合研究中心河北石家庄050091 河北中医药大学中西医结合学院河北石家庄050091

目的确定升降散对胃黏膜损伤的改善作用并探讨其机制。方法通过文献计量学研究了解升降散的研究现状。采用液质联用技术获取升降散主要药效成分,通过网络药理学分析预测机制。对胃黏膜损伤大鼠灌胃给予阳性药及不同剂量升降散,通过HE染... 详细信息

目的确定升降散对胃黏膜损伤的改善作用并探讨其机制。方法通过文献计量学研究了解升降散的研究现状。采用液质联用技术获取升降散主要药效成分,通过网络药理学分析预测机制。对胃黏膜损伤大鼠灌胃给予阳性药及不同剂量升降散,通过HE染色,观察胃组织形态。ELISA实验检测血清中TNF-α、IL-1β的水平。IHC实验评价胃黏膜MUC5AC、MUC6的表达。结果文献计量学分析表明,升降散在内外伤杂病治疗方面应用广泛。根据升降散主要药效成分中浓度前20位的化合物得到的作用靶点525个,与胃炎相关靶点相交集的129个;GO分析得条目数2127条,KEGG分析得通路140条;说明升降散具有多靶点多通路改善胃黏膜损伤的可能性。HE染色结果显示,升降散确能改善大鼠胃黏膜炎症。ELISA实验结果显示,升降散可有效下调大鼠血清中的TNF-α和IL-1β。IHC实验结果表明,升降散有效下调MUC5AC的表达、上调MUC6的表达。结论升降散能以缓解炎症、调节表面黏液屏障的方式改善胃黏膜损伤。

关键词：升降散慢性胃炎文献计量学网络药理学胃组织结构炎症因子免疫组织化学

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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng huang Zhijun Wu Baitao liu Hongjie huang Haijun Wang Yongjian Wang Dingge liu Zhihua Zhang Kaiping liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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