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Sequence-activated chemiluminescence probes: programmable illumination for high-contrast in vivo sensing and imaging

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Science China Chemistry 2025年第1期68卷 26-34页

作者： Yutao Zhang Juan Li Wei-Hong Zhu Zhiqian Guo shanghai Key Laboratory of Functional Materials Chemistry Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Institute of Fine Chemicals School of Chemistry and Molecular Engineering East China University of Science and Technology State Key Laboratory of Bioreactor Engineering Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell MetabolismEast China University of Science & Technology

Sequence-activated chemiluminescence(CL) technique offers a unique approach to detecting specific biomolecules or cellular events with high sensitivity and spatial resolution. The fundamental principle behind sequence-activated CL probes involves tailoring highly-controllable CL signals in response to specific sequences or events of interest, thus enabling high-contrast signals under complex physiological conditions. This sequential activation could be triggered by enzymes, reactive oxygen species(ROS), biothiols or changes in the microenvironment. These unique sequence-activated CL probes bestow several advantages, including minimal background, deep-tissue penetration, and the ability of non-invasive or minimally invasive detection. The sequence-activated CL techniques represent a significant advancement in molecular imaging and diagnostics. In this mini-review, we focus on the latest developments in sequential CL probes, addressing the technical challenges and discussing the future trajectory by harnessing CL signaling and molecular recognition.

关键词： chemiluminescnece sequence-activation in-vivo bioimaging cyclic peroxide

In vivo direct neuronal conversion as a therapeutic strategy for ischemic stroke

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Neural Regeneration Research 2025年第8期20卷 2309-2310页

作者： Takashi Irie Taito Matsuda Department of Stem cell biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan Department of Neurology Neurological InstituteGraduate School of Medical SciencesKyushu UniversityFukuokaJapan

Stroke causes neuronal loss,which ultimately results in persistent neurological ***,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart *** that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.

关键词： neonatal death therapeutic

Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

High Fe‑Loading Single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

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Nano-Micro Letters 2025年第2期17卷 187-203页

作者： Si Chen Fang Huang Lijie Mao Zhimin Zhang Han Lin Qixin Yan Xiangyu Lu Jianlin Shi Department of Cardiology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200092People’s Republic of China shanghai institute of Ceramics Chinese Academy of SciencesShanghai 200050People’s Republic of China shanghai Frontiers Science Center of Nanocatalytic Medicine School of MedicineTongji UniversityShanghai 200092People’s Republic of China

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site ***,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with *** constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial ***,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading ***,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/*** addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)*** in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound *** work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

关键词： Nanocatalytic medicine Single-atom catalysts Reactive oxygen species(ROS) High metal loading Oxidase catalysis

Isobaric enzymatic assays reveal depth-dependent variation in microbial ectoenzyme activities in the deepest ocean on Earth

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Science China Earth Sciences 2025年第1期68卷 185-194页

作者： Junwei CAO Jiahua WANG Hongge ZHANG Junhao DENG Binbin PAN Jiawang CHEN Li ZHANG Jiasong FANG College of Oceanography and Ecological Science Shanghai Ocean University Ocean College Zhejiang University Laboratory for Marine biology and Biotechnology Qingdao National Laboratory for Marine Science and Technology

Microbial ectoenzymes play essential roles in the transformation and mineralization of organic matter in the ***, conventional methods for measuring microbial ectoenzyme activities(MEAs) in the deep ocean under atmospheric conditions can misrepresent the metabolic activities of indigenous microbial communities. To overcome this limitation, we measured the activities of three microbial ectoenzymes(aminopeptidase, α-glucosidase, and β-glucosidase) under both atmospheric and in situ pressure conditions in seawater collected using pressure-retaining and non-pressure-retaining samplers in the Challenger Deep, Mariana Trench. In the case of aminopeptidase and α-glucosidase, the highest isobaric MEAs were observed in the surface layer(50 m), followed by those at abyssopelagic depths(4,000–6,000 m) for aminopeptidase, hadal realm(10,903 m)for α-glucosidase, while β-glucosidase activity exhibited the highest value at 10,903 m. Furthermore, the isobaric MEAs in hadal waters were commonly found to be higher than the decompressed counterparts, highlighting the importance of pressure-retaining sampling and isobaric enzymatic assays. The half-saturation constant(Km) showed a general decreasing trend with depth,suggesting that the deep ocean microbes might have adapted to the high-pressure and oligotrophic environment by increasing their ectoenzyme's affinity to substrate. Furthermore, particle-free MEAs contribute more to the total MEAs in the deep ocean than particle-associated MEAs, suggesting the significance of cell-associated and dissolved ectoenzymes in ocean *** study provides a foundation for future investigations of MEAs in the ocean and has important implications for understanding the dynamics of microbially mediated biogeochemical cycling in marine ecosystems.

关键词： Pressure-retaining sampling Microbial ectoenzyme activity Deep-sea microbes High pressure Mariana Trench

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68卷 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.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

Crosstalk among canonical Wnt and Hippo pathway members in skeletal muscle and at the neuromuscular junction

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Neural Regeneration Research 2025年第9期20卷 2464-2479页

作者： Said Hashemolhosseini Lea Gessler institute of biochemistry Medical FacultyFriedrich-Alexander-University of Erlangen-NürnbergErlangenGermany

Skeletal muscles are essential for locomotion,posture,and metabolic *** understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle *** process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle *** contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular *** muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate *** of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction *** development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as *** regulators coordinate the diffe rentiation of myoblasts into mature muscle *** pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient *** ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal *** interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular *** molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling *** recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular *** fact,research in the last few years now suggests that these two signaling pathways are interconnected and

关键词： canonical Wnt"Wingless-related integration site"pathway beta-catenin(CTNNB1) Hippo pathway myogenesis myotube neuromuscular junction satellite cell skeletal muscle fiber transcriptional co-activator with PDZ-binding motif(TAZ) T-cell-specific transcription factor/lymphoid enhancer-binding factor(TCF/LEF) TEA domain family member(TEAD) transducin-like enhancer of split(TLE) yes-associated protein 1(YAP1)

Experimental Study on Diesel Spray and Flame Asymmetry Characteristics of Dual-Orifice Nozzles for a Medium-Speed Engine

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Journal of Thermal Science 2025年第1期34卷 303-322页

作者： JU Dehao LIU Rui ZHENG Liang DENG Jiahui ZHANG Wenzheng HUO Jinlu HUANG Li shanghai Marine Diesel Engine Research institute National Key Laboratory of Marine Engine Science and Technology Key Laboratory for Power Machinery and Engineering Ministry of EducationShanghai Jiao Tong University

The asymmetry of the multi-orifice spray will cause uneven heat load of the marine diesel engine,thereby affecting its working performance and service ***,an in-depth understanding of the spray and flame characteristics of multi-orifice nozzles will guide the optimization of the nozzle structure,needle design and diesel atomization and combustion *** this reason,four groups of dual-orifice nozzles with different hole diameters(0.1-0.55 mm) and mass flow rates covering the typical marine medium-speed diesel injections are designed and customized,and the constant volume chamber(CVC) with high temperature and pressure is used to simulate the actual in-cylinder working conditions of the diesel engine for the spray visualization *** study the asymmetry of the fuel sprays discharged from a diesel injector,the multi-orifice nozzle is simplified as a dual-orifice nozzle in this *** with X-ray Computed Tomography(CT) imaging technology,the influences of the nozzle internal structure on the spray and flame asymmetry are studied in the constructed supercritical *** is found that the asymmetry of the inlet angle and the equivalent length-diameter ratio is positively correlated with the inconsistency of the dual *** an increase in the injection pressure and nozzle diameter,the asymmetry of the dual spray becomes more pronounced,resulting in greater disparities in the ignition delay times and ignition positions of the two ***,the increase in nozzle diameter also leads to combustion instability,resulting in a flame with a serrated *** the increase of ambient temperature,the proportion of liquid phase in the jet decreases and the relative density of spray front decreases.

关键词： atomization dual-orifice nozzle nozzle structure spray flame asymmetry

Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang Li Pengjun Wang Xiaoxu Zhang Song Mao Yini Li Dongzhen Yu Xiaoyan Li Yazhi Xing Haibo Shi Shankai Yin Department of Otolaryngology Head and Neck Surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck Surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron