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Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer’s pathophysiology:unveiling therapeutic potential

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Neural Regeneration Research 2025年第1期20卷 54-66页

作者： Jennie Z.li Nagendran Ramalingam Shaomin li Ann Romney Center for Neurologic Diseases Brigham and Women’s Hospital and Harvard Medical SchoolBostonMAUSA

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to *** evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental *** memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic *** life,environmental factors can lead to enduring changes in gene expression and the emergence of brain *** changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal *** this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic ***,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic ***,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s *** suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

关键词： Alzheimer’s disease DNA methylation enriched environments histone modification microRNAs non-invasive brain stimulation synaptic plasticity

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拜氏梭菌发酵玉米秸秆水解液生产燃料丁醇

可再生能源 2015年第4期33卷 618-624页

作者：田磊刘自勇张培玉张全刘振乔凯李福利青岛大学环境科学与工程学院山东青岛266071 中国科学院青岛生物能源与过程研究所山东青岛266101 中国石化抚顺石油化工研究院辽宁抚顺113001

以柠檬酸-柠檬酸钠缓冲液代替传统的乙酸-乙酸钠缓冲液作为玉米秸秆预处理物酶解的缓冲液,经过72~96 h水解,水解液中还原糖浓度较之前高出14%。在50℃,110 r/min条件下,以Ca（OH）2对水解液进行脱毒处理,Clostridium beijerinckii 8052... 详细信息

以柠檬酸-柠檬酸钠缓冲液代替传统的乙酸-乙酸钠缓冲液作为玉米秸秆预处理物酶解的缓冲液,经过72~96 h水解,水解液中还原糖浓度较之前高出14%。在50℃,110 r/min条件下,以Ca（OH）2对水解液进行脱毒处理,Clostridium beijerinckii 8052发酵脱毒后的水解液获得丁醇的量为8.7 g/L,比脱毒前高出52.6%。通过紫外诱变提高*** 8052的糖摄取量,以此来提高丁醇产量,经过20轮的连续诱变,获得一株突变株CM20,利用其发酵脱毒后的水解液,糖利用率提高了14%,ABE（丙酮、丁醇和乙醇）产量可达19 g/L,其中丁醇产量为10.8 g/L。

关键词：丁醇抑制剂 Ca(OH)2 C.beijerinckii 8052 紫外诱变

联合肝脏分割和门静脉结扎二步肝切除术大鼠模型的建立

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中国普通外科杂志 2017年第1期26卷 50-56页

作者：刘伟伟刘洪余锋柏杨李福利罗昆仑安徽医科大学无锡临床学院肝胆外科江苏无锡214044 中国人民解放军第一0一医院肝胆外科江苏无锡214044

目的:建立联合肝脏分割和门静脉结扎(PVL)二步肝切除术(ALPPS)大鼠模型。方法:将健康60只SD雄性大鼠随机均分为PVL组、ALPPS组、假手术组。PVL组行肝左外叶、左中叶、右叶门静脉分支结扎及尾状叶切除,保留肝右中叶分支;ALPPS组在PVL组... 详细信息

目的:建立联合肝脏分割和门静脉结扎(PVL)二步肝切除术(ALPPS)大鼠模型。方法:将健康60只SD雄性大鼠随机均分为PVL组、ALPPS组、假手术组。PVL组行肝左外叶、左中叶、右叶门静脉分支结扎及尾状叶切除,保留肝右中叶分支;ALPPS组在PVL组手术的基础上,将肝左中叶与右中叶在缺血带处离断;假手术组仅游离出门静脉各分支,不结扎。检测大鼠术后肝再生率(HRR)、肝功能情况,以及肝左中叶病理损伤程度与肝右中叶Ki-67的表达。结果:与假手术组比较,ALPPS组、PVL组术后各时间点肝右中叶HRR均明显升高(均P0.05)。组织病理学检查显示,ALPPS组术后第1天肝左中叶坏死明显多于PVL组;ALPPS组肝右中叶Ki-67表达第2、4天明显高于PVL组(85.36%vs.61.84%;43.40%vs.29.06%,均P<0.05)。结论:ALPPS与PVL均能促进肝再生,并且ALPPS比PVL能更快的促进肝再生;成功建立大鼠ALPPS模型,为研究ALPPS肝再生机制及相关并发症奠定了基础。

关键词：肝切除术肝再生模型,动物大鼠

丙酮丁醇梭菌硫氧还蛋白系统在溶剂生产过程中的功能

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微生物学报 2022年第3期62卷 993-1003页

作者：杨汇照范奕萱蒋丹丹 Armin Ehrenreich 刘晓环李福利刘自勇中国海洋大学环境科学与工程学院山东青岛266100 中国科学院生物燃料重点实验室中国科学院青岛生物能源与过程研究所山东青岛266101 大连工业大学生物工程学院辽宁大连116034

【目的】探究丙酮丁醇梭菌硫氧还蛋白系统在生长和代谢过程中的功能。【方法】使用ClosTron系统对硫氧还蛋白系统中的硫氧还蛋白还原酶基因(trxB)进行插入失活,得到突变株,通过Southern杂交方法验证插入内含子的拷贝数;在基本培养基中... 详细信息

【目的】探究丙酮丁醇梭菌硫氧还蛋白系统在生长和代谢过程中的功能。【方法】使用ClosTron系统对硫氧还蛋白系统中的硫氧还蛋白还原酶基因(trxB)进行插入失活,得到突变株,通过Southern杂交方法验证插入内含子的拷贝数;在基本培养基中进行分批发酵,比较并分析突变株的生长特点;通过pH控制,利用限磷的连续发酵方法使丙酮丁醇梭菌稳定地在产酸期和产溶剂期生长,分析野生型菌株和突变株在稳定的产酸期和产醇期的生长和产物合成情况;通过添加不同浓度的过氧化氢检测野生型和突变株的抗氧化压力。【结果】抗性筛选和基因测序结果表明,成功构建了硫氧还蛋白还原酶失活的突变株,命名为Clostridiumacetobutylicum trxB::int(29)。在分批发酵中,突变株和野生型菌株的最大生长量相近,细胞在600 nm处的光吸收值(OD_(600))达到6.5,但是突变株在36 h的OD_(600)达到最大,较野生型推迟12 h;在连续发酵的产酸期,野生型菌株与突变株生长变化不大,OD_(600)分别稳定在4.6和4.4,且葡萄糖的消耗和酸产量相差不大;在产溶剂期,突变株的OD_(600)稳定在3.5,低于野生型的4.0,同时,丙酮产量达到25.5 mmol/L,高于野生型(18 mmol/L),丁醇产量达到36.1 mmol/L,低于野生型(48 mmol/L);添加低浓度的过氧化氢对突变株的影响不大,高浓度的过氧化氢对突变株造成的损伤大于野生型。【结论】硫氧还蛋白还原酶基因的失活不是致死突变,突变株在产酸期的生长和产酸能力与野生型相近,表明该基因的失活没有影响产酸期的代谢过程;trxB基因的失活主要影响了产溶剂期的氧化还原平衡,造成丙酮/丁醇的比率升高。

关键词：丙酮丁醇梭菌硫氧还蛋白限磷连续发酵 ClosTron系统

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

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Neural Regeneration Research 2025年第10期20卷 2807-2822页

作者： Xizi Song Ruixin li Xiaolei Chu Qi li Ruihua li Qingwen li Kai-Yu Tong Xiaosong Gu Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Haihe Laboratory of Brain-Machine Interface and Human-Machine Fusion TianjinChina Department of Rehabilitation Tianjin University Tianjin HospitalTianjinChina Department of Hand Microsurgery Tianjin University Tianjin HospitalTianjinChina School of Exercise and Health Tianjin University of SportTianjinChina Department of Biomedical Engineering the Chinese University of Hong KongHong Kong Special Administrative RegionChina

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and *** on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target *** has led to restrictions on current therapeutic *** this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target *** peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal *** nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury *** damage to target organs can occur,including skeletal muscle atrophy and sensory receptor *** then provide a brief review of the research advances in therapeutic approaches to peripheral nerve *** main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical ***,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ ***,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

关键词： central nervous system central peripheral target organ multilevel pathological analysis nerve regeneration peripheral nerve injury peripheral nervous system target organs therapeutic approach

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细菌微室及其在合成生物学中的应用进展

南京工业大学学报（自然科学版） 2022年第5期44卷 490-499页

作者：张俊哲张全刘自勇马小清刘立成李福利中国科学院青岛生物能源与过程研究所山东青岛266101 中国石化大连(抚顺)石油化工研究院辽宁大连116045 山东能源研究院山东青岛266101

细菌微室(BMCs)是一种原核生物细胞器,由半渗透性的蛋白质外壳和被封装的酶构成,其结构保守而功能非常多样化。蛋白质外壳可以将特定的代谢过程与细胞质环境分隔开来,酶和代谢中间体的区室化可以增加代谢反应的通量并保护细胞免受有毒... 详细信息

细菌微室(BMCs)是一种原核生物细胞器,由半渗透性的蛋白质外壳和被封装的酶构成,其结构保守而功能非常多样化。蛋白质外壳可以将特定的代谢过程与细胞质环境分隔开来,酶和代谢中间体的区室化可以增加代谢反应的通量并保护细胞免受有毒中间体的影响。因此,细菌微室提高了细菌的代谢多样性与环境适应力。同时,在以细菌微室为代谢元件、外壳蛋白改造、人工构建新型细菌微室等多个方面都取得了一定的研究进展。细菌微室的上述特性表明其在合成生物学中具有巨大的应用潜力,以细菌微室为基础的合成生物学改造,有望推动绿色生物制造快速发展。

关键词：细菌微室合成生物学代谢工程原核生物细胞器

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Calcium sulfate whisker prepared by flue gas desulfurization gypsum:A physical–chemical coupling production process

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Chinese Journal of Chemical Engineering 2020年第8期28卷 2221-2226页

作者： Jing Gao Qiang li fuli liu College of Mining Liaoning Technical UniversityFuxin 123000China CAS Key Laboratory of Green Process and Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China College of Chemical and Environmental Engineering China University of Mining and TechnologyBeijing 100083China

In this paper,the solid waste desulfurization gypsum produced by coal-fired power plants was used as a raw material to prepare calcium sulfate whiskers with high application *** sulfate whiskers with uniform morphology and high aspect ratio can be prepared by hydrothermal method in sulfuric acid solution.A new process of desulfurization gypsum activated by high-energy grinding to reduce the reaction temperature and sulfuric acid concentration was *** the comparison of product morphology,the best grinding time was determined to be 3.5 *** mechanism of desulfurization gypsum through physical–chemical coupling to reduce energy consumption was *** activation of desulfurization gypsum by grinding and the acidic environment provided by the sulfuric acid solution made the calcium sulfate solution reached rapid saturation and accelerated the nucleation *** calculating the conversion and crystallization rate of calcium sulfate whiskers,it was found that there were obvious"autocatalytic"kinetic characteristics during the crystallization process.

关键词： Flue gas desulfurization gypsum Calcium sulfate whiskers Crystallization kinetic Physical–chemical coupling

多功能蛋白聚糖Versican与TNF-α在胆囊癌组织的表达及意义

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中国普通外科杂志 2016年第2期25卷 225-230页

作者：李福利方征夏咸军刘洪赵海滨罗昆仑江苏大学医学院江苏镇江212013 中国人民解放军第一0一医院肝胆外科江苏无锡214044 中国人民解放军第一0一医院病理科江苏无锡214044

目的:探讨多功能蛋白聚糖Versican与TNF-α在胆囊癌组织中的表达及意义。方法:应用免疫组化方法检测并比较Versican与TNF-α在62例胆囊癌组织(肿瘤组)、30例胆囊结石伴慢性炎症的胆囊组织(炎症组)、20例正常胆囊组织(正常组)中的表达,... 详细信息

目的:探讨多功能蛋白聚糖Versican与TNF-α在胆囊癌组织中的表达及意义。方法:应用免疫组化方法检测并比较Versican与TNF-α在62例胆囊癌组织(肿瘤组)、30例胆囊结石伴慢性炎症的胆囊组织(炎症组)、20例正常胆囊组织(正常组)中的表达,分析两者与胆囊癌患者临床病理特征及预后的关系。结果:Versican与TNF-α在正常组、炎症组、肿瘤组中阳性表达率均呈依次逐渐增高,差异均有统计学意义(均P0.05)。结论:Versican与TNF-α可能在胆囊癌的发生发展过程中起重要作用,且Versican与TNF-α的阳性表达为胆囊癌的不良预后因素。

关键词：胆囊肿瘤多功能蛋白聚糖类肿瘤坏死因子α 预后

Control of Corner Separation for a linear Compressor Cascade via Bionic Slanting Riblets at the Endwall

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Journal of Thermal Science 2025年第1期34卷 129-144页

作者： ZHANG Peng li Yonghong CHENG Rixin Key Laboratory of Civil Aircraft Airworthiness Technology Civil Aviation University of China College of Aeronautical Engineering Civil Aviation University of China

A new passive control approach,utilizing bionic slanting riblets,is employed to mitigate the flow close to the blade endwall in a linear cascade,and its effectiveness and mechanism in controlling corner separation are investigated through numerical *** slanting riblets are positioned at the endwall upstream of the cascade channel,and the influence of riblet height,yaw angle and relative position on the control of corner separation is *** findings indicate that the application of slanting riblets can efficiently counteract corner separation across the stable operational ***,the introduction of riblets with a height of merely 0.1 times the boundary layer thickness results in a significant reduction in total pressure loss by up to 14.53%,while simultaneously enhancing the static pressure coefficient by 21.74%.Flow analysis reveals that minute vortices produced within the riblet channels tend to coalesce,forming a potent large-scale vortex near the boundary layer's base *** phenomenon results in reduced additional losses compared to conventional vortex ***,the induced vortex promotes enhanced mixing between the mainstream flow and boundary layer,inhibiting the lateral displacement of low-energy fluids within the endwall boundary ***,this delays the onset of separation vortex formation and eliminates vortex rings in the corner region,ultimately enhancing the aerodynamic efficiency of the cascade.

关键词： additional losses compressor cascade corner separation slanting riblets vortex generator