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Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration Research 2025年第11期20卷 3259-3272页

作者： Huidong Li faqin Li Zhaoyi Chen Erwen Wu Xiaoxi Dai Danni Li Haojie An Shiyi zeng Chunyan Wang Li Yang Cheng Long School of Life Sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of Life Sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission

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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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Physarum polycephalum-inspired adaptive optimization design of artificial microtubular networks

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Science China Chemistry 2025年

作者： Si-Min zeng Di-Wei Zheng Ting Pan Xing-Lan Ding Yun Zhang Chi-Hui Yang Si-Xue Cheng Xian-Zheng Zhang Key Laboratory of Biomedical Polymers of Ministry of Education&Department of Chemistry Wuhan University

Natural biological microtubular networks have undergone adaptive evolutionary selection and may offer viable solutions to design challenges in artificial microtubular networks. The plasmodium of the slime mold Physarum polycephalum(P. polycephalum) extends continuously to form a protoplasmic microtubular network structure, directly connecting food *** simulations revealed that the formation of this adaptive P. polycephalum microtubular network could be captured by a mathematical algorithm. Inspired by the P. polycephalum microtubular networks, we propose an adaptive optimization design method for artificial microtubular networks. Specifically, we utilized hydrogels with biodegradable and tissue-adhesive properties to replicate the P. polycephalum microtubular networks via photomask. In Rhodamine B diffusion and glucosecatalyzed reaction experiments, we found that the P. polycephalum microtubular networks exhibited significantly enhanced efficiency compared to vascular and artificial networks. furthermore, we demonstrated the potential for uric acid(UA) degradation of the hydrogels with a real P. polycephalum microtubular network loaded with urate oxidase(UOx) in a rodent model of hyperuricemia. And this network achieved more than double the effect of the artificial network. This underscores the potential of natural microtubular networks to replace artificial microtubular networks.

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Activatable chemiluminescence probe based on four-arm PEGconjugated-pyropheophorbide-a for in vivo autofluorescence-free imaging of peroxynitrite

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Science China Chemistry 2025年

作者： Jianmei Ke Lei Ding Ronggui Lian Cheng Zheng Wenjun Li Aixian Zheng Yupeng Sun Ming Wu Yongyi zeng Xiaolong Liu Maochun Hong Xiaolong Zhang The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Ganjiang Innovation Academy Chinese Academy of Sciences School of Rare Earths University of Science and Technology of China College of Chemistry Fuzhou University State Key Laboratory of Structure Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences

Peroxynitrite（ONOO-） is a highly reactive nitrogen species that plays pivotal roles in cell signal transduction and physiological or pathological progresses. However, commonly used ONOO-optical imaging probes are still hampered by high background/autofluorescence（fluorescence probe）, short emission wavelength, or poor selectivity in the case of chemiluminescence. Herein,we report a facile method to prepare an activatable chemiluminescence probe（PPA-PEG） with good biocompatibility and functionality for in vivo autofluorescence-free imaging of ONOO-. The PPA-PEG consists of pyropheophorbide-a（PPA）, a typical deep red photosensitizer that acts as both the recognition and signaling element, and 4-arm poly（ethylene glycol）(4-arm PEG), which improves the biosafety and water solubility of probe. These components can self-assemble into nanoparticles（namely PPA-PEG nanoprobe） in aqueous solution. The PPA-PEG nanoprobe showed an ultra-low chemiluminescence signal before interacting with ONOO-, but exhibited good selectivity, high sensitivity and a fast response toward ONOO-. The PPAPEG was successfully applied to image cellular ONOO-changes, as well as the endogenous ONOO-changes in inflammation models and subcutaneous or orthotopic hepatocellular carcinoma（HCC） tumors models in living mice. In vitro and in vivo studies verified the good detection and imaging capabilities of PPA-PEG for peroxynitrite, demonstrating suitable tissue penetration and a high signal-to-background ratio（SBR）. Thus, our nanoprobe can serve as a valuable activatable chemiluminescence imaging tool for studying important peroxynitrite-related chemical and biological applications.

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Optimized Bi-level Control for Day-ahead and Real-time Active Power Balancing of an Off-grid Wind Power-to-hydrogen System With ESS Considering Wind Power Uncertainty

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Dianwang Jishu/Power System Technology 2025年第1期49卷 52-62页

作者： Qiu, Yiwei Sun, Qingjie Wu, Chenxu Zhu, Jie zeng, Yangjun Chen, Shi Zhou, Buxiang College of Electrical Engineering Sichuan University Sichuan Province Chengdu 610065 China State Grid Ningbo Power Supply Company Zhejiang Province Ningbo 315012 China

Since off-grid wind power-to-hydrogen (Wp2H) systems are not connected to the utility grid, the hydrogen production load and the energy storage system (ESS) must be coordinated to absorb wind power fluctuations and maintain system stability. Such coordination must consider the flexibility constraints of hydrogen production units, the overall hydrogen yield, and the degradation of batteries in the ESS to meet the economic goals of green hydrogen production. Therefore, an optimized bi-level control method for the active power balance is proposed. firstly, using the Itô process to characterize wind power fluctuations and considering the real-time flexibility reserve of multiple electrolyzers, the upper level is formulated as an intra-day scheduling problem with a 15-minute resolution. Secondly, the lower level optimizes the real-time power of the electrolyzers and the ESS based on their on-off states and baseline power commanded by the upper level, considering the degradation cost of the ESS. This helps to absorb second-level wind power fluctuations. finally, based on a project plan in Inner Mongolia, China, a case study verifies the effectiveness of the proposed method. © 2025 Power System Technology Press. All rights reserved.

关键词： Hydrogen storage

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浅圆仓地震侧压力计算公式推导与分析

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地震工程学报 2025年第1期47卷 33-40页

作者：张国祥曾荣中南大学土木工程学院湖南长沙410075

仓壁侧压力是浅圆仓抗震设计的重要参数,在规范中没有给出确切的浅圆仓仓壁地震侧压力的理论计算公式。对此,基于极限平衡法,将浅圆仓看作特殊的曲线挡墙,取单位弧长的滑动楔体为研究对象,采用拟静力法与旋转地震角法简化地震力以进行... 详细信息

仓壁侧压力是浅圆仓抗震设计的重要参数,在规范中没有给出确切的浅圆仓仓壁地震侧压力的理论计算公式。对此,基于极限平衡法,将浅圆仓看作特殊的曲线挡墙,取单位弧长的滑动楔体为研究对象,采用拟静力法与旋转地震角法简化地震力以进行极限平衡分析,并推导出浅圆仓锥堆与平堆工况下的地震侧压力计算公式。通过算例分析,比较满仓状态下地震侧压力的实测数据值及理论计算值,初步验证公式的正确性。对地震侧压力进行数值模拟与参数分析,结果表明模型拟合效果良好,仓壁摩擦力影响较大,在计算中不可忽视;在平堆工况下半径取值对大直径浅圆仓地震侧压力的影响较小,可将其简化为直线挡墙计算。研究成果可为完善筒仓规范中地震侧压力的计算推导提供一定的参考依据。

关键词：浅圆仓极限平衡法滑动楔体地震侧压力拟静力法旋转地震角法

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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1期68卷 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.

关键词： metabolon Diels-Alder reaction semipinacol rearrangement biosynthesis notoamides spiro polycyclic alkaloids

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Dynamical complexity of Anosov systems driven by a quasi-periodic force

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Science China Mathematics 2025年第1期 89-136页

作者： Wen Huang zeng Lian Kening Lu Department of Mathematics University of Science and Technology of China School of Mathematics Sichuan University

Consider C2Anosov systems on a compact manifold driven by a quasi-periodic *** study their dynamical complexity on various levels from the perspectives of both path-wise dynamics and stochastic *** that these systems are non-wandering（i.e.,every point in the phase space is nonwandering）,we prove a set of results:（1） the existence of abundance of random periodic points;（2） a random Liv?ic theorem;（3） a random Ma?é-Bousch-Conze-Guivarc'h lemma;（4） the existence of strong random ***,a concrete example constructed on a 2-dimensional torus is also given to uncover some interesting phenomena of the systems.

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响应面法优化酱牛肉超声-脉动滚揉腌制工艺

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南京农业大学学报 2025年第1期48卷 206-219页

作者：曾晓庆冯美琴孙健南京农业大学食品科学技术学院/肉品质量控制与新资源创制全国重点实验室江苏南京210095 金陵科技学院动物科学与食品工程学院江苏南京210038

[目的]本文旨在明确超声和脉动滚揉腌制联用对酱牛肉品质的具体工艺参数。[方法]以牛腿肉为原料,分别以超声时间、超声功率、脉动滚揉时间为单因素,通过质构、剪切力、模糊感官评分、色差筛选出较优的单因素范围,并在单因素试验基础上... 详细信息

[目的]本文旨在明确超声和脉动滚揉腌制联用对酱牛肉品质的具体工艺参数。[方法]以牛腿肉为原料,分别以超声时间、超声功率、脉动滚揉时间为单因素,通过质构、剪切力、模糊感官评分、色差筛选出较优的单因素范围,并在单因素试验基础上以剪切力、模糊感官评分为响应值进行响应面优化试验。[结果]试验得到最佳工艺参数:超声时间108 min、超声功率255 W、脉动滚揉时间3 h。此时得到酱牛肉剪切力为37.94 N,模糊感官评分为89.70分,与模型理论值相近。与传统静态腌制相比,用最佳超声-脉动滚揉腌制工艺制作的酱牛肉剪切力显著降低、模糊感官评分提高,色泽得到改善。两因素交互作用结果表明,超声功率和超声时间对酱牛肉剪切力影响显著,超声时间和脉动滚揉时间对酱牛肉模糊感官评分影响显著,因此在实际生产中需根据需求选择合适的腌制参数。[结论]超声-脉动滚揉腌制工艺提高了酱牛肉的嫩度,同时改善了酱牛肉的质构和色泽,提高了酱牛肉品质;超声-脉动技术联用是促进超声技术应用与肉制品腌制的有效策略。

关键词：超声腌制脉动滚揉酱牛肉响应面法优化

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代谢工程改造大肠杆菌合成甲萘醌-7

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食品与发酵工业 2025年第1期51卷 1-10页

作者：何雨锴曾伟主徐沙江南大学生物工程学院江苏无锡214122 江南大学粮食发酵工艺与技术国家工程实验室江苏无锡214122 江南大学未来食品科学中心江苏无锡214122

甲萘醌-7(menaquinone-7,MK-7),作为维生素K2亚型之一,具有治疗骨质疏松,保护心血管健康等作用。常见MK-7生产主要由纳豆等食品发酵而来,但存在产量低,提取复杂等问题,而枯草芽孢杆菌作为MK-7常见生产菌株,也面临发酵周期长,发酵产量低... 详细信息

甲萘醌-7(menaquinone-7,MK-7),作为维生素K2亚型之一,具有治疗骨质疏松,保护心血管健康等作用。常见MK-7生产主要由纳豆等食品发酵而来,但存在产量低,提取复杂等问题,而枯草芽孢杆菌作为MK-7常见生产菌株,也面临发酵周期长,发酵产量低的问题。该研究对一株引入甲羟戊酸途径的大肠杆菌进行改造,首先利用DLKcat模型比较筛选出4个关键酶,包括七聚异戊二烯焦磷酸合酶BtHepS\BtHepT、1,4-二羟基-2-萘甲酸七烯基转移酶MnMenA、甲萘醌生物合成C-甲基转移酶NtMenG,将其进行表达优化,构建了大肠杆菌内源合成MK-7途径。随后,整合表达异戊烯基焦磷酸异构酶EcIdi提升前体供应,再对得到的菌株进行补料分批发酵条件优化,包括延迟诱导时间,提升溶氧量至60,MK-7产量达到929.58 mg/L,但出现1217.58 mg/L的去甲基甲萘醌-7(DMK-7)大量堆积的现象。进一步筛选了不同来源的MenG降低DMK-7的堆积,发现Bacillus subtilis 168来源的MenG可以较好地降低DMK-7堆积。最终,在5 L发酵罐上MK-7的产量达到1090.45 mg/L,DMK-7降低至231.14 mg/L。该研究结果对应用大肠杆菌生产MK-7具有一定的指导意义。

关键词：甲萘醌-7 大肠杆菌 DLKcat 去甲基甲萘醌-7 发酵优化

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