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Physiological Roles of β-amyloid in Regulating Synaptic Function:Implications for AD Pathophysiology

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Neuroscience Bulletin 2023年第8期39卷 1289-1308页

作者： Wenwen Cai Linxi Li Shaoming Sang xiaoli pan Chunjiu Zhong Department of Neurology Zhongshan HospitalFudan UniversityShanghai 200032China Basic Medical College Nanchang UniversityNanchang 330031China State Key Laboratory of Medical Neurobiology Institutes of Brain Science&Collaborative Innovation Center for Brain ScienceFudan UniversityShanghai 200032China

The physiological functions of endogenous amyloid-β(Aβ),which plays important role in the pathology of Alzheimer's disease(AD),have not been paid enough ***,we review the multiple physiological effects of Aβ,particularly in regulating synaptic transmission,and the possible mechanisms,in order to decipher the real characters of Aβunder both physiological and pathological *** worthy studies have shown that the deprivation of endogenous Aβgives rise to synaptic dysfunction and cognitive deficiency,while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal *** this review,we provide a new view for understanding the role of Aβin AD pathophysiology from the perspective of physiological meaning.

关键词： Aβ Physiological role Synapse LTP Synaptic vesicle cycle Cognition AD

Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer＇s Disease

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Neuroscience Bulletin 2016年第6期32卷 591-596页

作者： xiaoli pan Zhichun Chen Guoqiang Fei Shumei pan Weiqi Bao Shuhua Ren Yihui Guan Chunjiu Zhong Department of Neurology Zhongshan Hospital State Key Laboratory of Medical Neurobiology Institutes of Brain Science and Collaborative Innovation Center for Brain Science Fudan University Shanghai 200032 China PET Center Huashan Hospital Fudan UniversityShanghai 200443 China

Abstract To date, we still lack disease-modifying thera- pies for Alzheimer＇s disease （AD）. Here, we report that long-term administration of benfotiamine improved the cognitive ability of patients with AD. Five patients with mild to moderate AD received oral benfotiamine （300 mg daily） over 18 months. All patients were examined by positron emission tomography with Pittsburgh compound B （PiB-PET） and exhibited positive imaging with β- amyloid deposition, and three received PiB-PET imaging at follow-up. The five patients exhibited cognitive improve- ment as assayed by the Mini-Mental Status Examination （MMSE） with an average increase of 3.2 points at month 18 of benfotiamine administration. The three patients who received follow-up PiB-PET had a 36.7% increase in the average standardized uptake value ratio in the brain com- pared with that in the first scan. Importantly, the MMSE scores of these three had an average increase of 3 points during the same period. Benfotiamine significantly improved the cognitive abilities of mild to moderate AD patients independently of brain amyloid accumulation. Ourstudy provides new insight to the development of disease- modifying therapy.

关键词： Alzheimer's disease. Therapy. Benfotiamine PiB-PET Amyloid deposition

Construction of bifunctional single-atom catalysts on the optimized β-Mo_(2)C surface for highly selective hydrogenation of CO_(2) into ethanol

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Journal of Energy Chemistry 2022年第4期31卷 184-192页

作者： Xue Ye Junguo Ma Wenguang Yu xiaoli pan Chongya Yang Chang Wang Qinggang Liu Yanqiang Huang CAS Key Laboratory of Science and Technology on Applied Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China China University of Chinese Academy of Science Beijing 100049China Dalian Institute of Chemical Physics Chinese Academy of SciencesDalian 116023China

Green and economical CO_(2)utilization is significant for CO_(2)emission reduction and energy ***,the 1D Mo_(2)C nanowires with dominant(101)crystal surfaces were modified by the deposition of atomic functional components Rh and *** unmodifiedβMo_(2)C could only convert CO_(2)to methanol,the designed catalyst of K_(0.2)Rh_(0.2)/β-Mo_(2)C exhibited up to 72.1%of ethanol selectivity at 150℃.It was observed that the atomically dispersed Rh could form the bifunctional active centres with the active carrierβMo_(2)C with the synergistic effects to achieve highly specific controlled C–C *** promoting the CO_(2)adsorption and activation,the introduction of an alkali metal(K)mainly regulated the balanced performance of the two active centres,which in turn improved the hydrogenation ***,the controlled modification ofβMo_(2)C provides a new design strategy for the highly efficient,lowtemperature hydrogenation of CO_(2)to ethanol with single-atom catalysts,which provides an excellent example for the rational design of the complex catalysts.

关键词： CO_(2)hydrogenation C–C coupling Single-atom catalyst Ethanol synthesis

Scission of C–O and C–C linkages in lignin over RuRe alloy catalyst

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Journal of Energy Chemistry 2022年第4期31卷 492-499页

作者： Xinxin Li Yangming Ding xiaoli pan Yanan Xing Bo Zhang Xiaoyan Liu Yuanlong Tan Hua Wang Changzhi Li CAS Key Laboratory of Science and Technology on Applied Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023LiaoningChina University of Chinese Academy of Science Beijing 100049China

The performance of lignin depolymerization is basically determined by the interunit C–O and C–C *** C–O bond cleavage strategies have been developed, while the cleavage of C–C bond between the primary aromatic units remains a challenging task due to the high dissociation energy of C–C ***, a multifunctional Ru Re alloy catalyst was designed, which exhibited exceptional catalytic activity for the cleavage of both C–O and C–C linkages in a broad range of lignin model compounds(β-1, a-5, 5–5,β-O-4, 4-O-5) and two stubborn lignins(kraft lignin and alkaline lignin), affording 97.5% overall yield of monocyclic compounds from model compounds and up to 129% of the maximum theoretical yield of monocyclic products based on C–O bonds cleavage from realistic lignin. Scanning transmission electron microscopy(STEM) characterization showed that Ru Re(1:1) alloy particles with hexagonal close-packed structure were homogeneously dispersed on the support. Quasi-in situ X-ray photoelectron spectroscopy(XPS), and X-ray absorption spectroscopy(XAS) indicate that Ru species were predominantly metallic state, whereas Re species were partially oxidized;meanwhile, there was a strong interaction between Ru and Re, where the electron transfer from Re to Ru was occurred, resulting in great improvement on the capability of C–O and C–C bonds cleavage in lignin conversion.

关键词： C–C bonds Ru Re alloy catalyst Lignin depolymerization

Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease

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Chinese Medical Journal 2022年第10期135卷 1172-1181页

作者： xiaoli pan Yanqiao Zhang Department of Integrative Medical Sciences Northeast Ohio Medical UniversityRootstownOH 44272USA.

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.

关键词： Nonalcoholic fatty liver disease Hepatocyte nuclear factor 4α Lipogenesis Inflammation Fibrosis Liver Lipotoxicity Apoptosis

Enhanced stability of Pt/Al_(2)O_(3) modified by Zn promoter for catalytic dehydrogenation of ethane

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Journal of Energy Chemistry 2020年第12期29卷 14-20页

作者： Xiaoyu Li Yanliang Zhou Botao Qiao xiaoli pan Chaojie Wang Liru Cao Lin Li Jian Lin Xiaodong Wang CAS Key Laboratory of Science and Technology on Applied Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023LiaoningChina University of Chinese Academy of Sciences Beijing 100049China

Catalytic ethane dehydrogenation(EDH) to ethylene over Pt-based catalysts has received increasing interests in recent years as it is a potential alternative route to conventional steam cracking. However, the catalysts used in this reaction often suffer from rapid deactivation due to serious coke deposition and metal sintering. Herein, we reported the effects of Zn modification on the stability of Pt/Al2 O3 for *** Zn-modified sample(PtZn2/Al2 O3) exhibits stable ethane conversion(20%) with over 95% ethylene selectivity. More importantly, it exhibits a significantly low deactivation rate of only 0.003 h-1 at 600 °C for70 h, which surpasses most of previously reported catalysts. Detailed characterizations including in situ FT-IR, ethylene adsorption microcalorimetry, and HAADF-STEM etc. reveal that Zn modifier reduces the number of Lewis acid sites on the catalyst surface. Moreover, it could modify Pt sites and preferentially cover the step sites, which decrease surface energy and retard the sintering of Pt particle, then prohibiting the further dehydrogenation of ethylene to ethylidyne. Consequently, the good stability is realized due to anti-sintering and the decrease of coke formation on the Pt Zn2/Al2 O3 catalyst.

关键词： Catalytic dehydrogenation of ethane Stability PtZn/Al2O3 Zn promoter Coke

Predictive Model of Ursodeoxycholic Acid Treatment Response in Primary Biliary Cholangitis

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 187-193页

作者： Yanyun Shu Yuhu Song Tao Bai xiaoli pan Haitao Shang Ling Yang Jin Ye Fan Du Division of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina

Background and Aims:Although ursodeoxycholic acid(UDCA)treatment in primary biliary cholangitis is effective in many patients,there are still many people who respond poorly to *** and intervening these patients early is ***,exploring the risk factors and proposing a predictor index to predict the UDCA treatment nonresponse earlier among primary biliary cholangitis patients were the aims of this ***:A total of 135 primary biliary cholangitis patients treated with UDCA(13–15 mg/kg/d)were enrolled in this retrospective *** response to treatment was evaluated based on Paris I *** univariate and logistic multivariate regression analyses were adopted to determine the independent risk factors and propose a predictor *** operating characteristic curve was used to evaluate the predictive ability of the predictor ***:Total bilirubin,albumin,globulin,immunoglobin M,and aspartate aminotransferase-to-platelet ratio index were the five independent risk factors associating with early biochemical nonresponse to UDCA *** on these factors,we established a predictor index with the predictive value being 0.886(sensitivity:82.80%,specificity:84.40%).Conclusions:We developed a predictor index that had an accurate prediction of the early biochemical nonresponse to UDCA treatment,which is expected to provide valuable information for the high-risk group before treatment begins.

关键词： Primary biliary cholangitis Therapy Risk factors Statistical model

Development of small molecule extracellular signal-regulated kinases(ERKs) inhibitors for cancer therapy

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2171-2192页

作者： xiaoli pan Junping Pei Aoxue Wang Wen Shuai Lu Feng Faqian Bu Yumeng Zhu Lan Zhang Guan Wang Liang Ouyang State Key Laboratory of Biotherapy and Cancer Center Innovation Center of Nursing ResearchNursing Key Laboratory of Sichuan ProvinceNational Clinical Research Center for GeriatricsWest China Hospitaland Collaborative Innovation Center of BiotherapySichuan UniversityChengdu 610041China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

The mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase 1/2(ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance.

关键词： Mitogen-activated protein kinases Cancer Extracellular signalregulated kinase 1/2 inhibitors Extracellular signalregulated kinase 5 inhibitors Inhibition Selectivity

Regeneration of copper catalysts mediated by molybdenum-based oxides

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Journal of Energy Chemistry 2024年第8期95卷 618-625,I0013页

作者： Changyu Ding xiaoli pan Isla E.Gow Xia Wu Hongchen Cao Zhounan Yu Xiaoyan Liu Xiaofeng Yang Qinggang Liu Yanqiang Huang CAS Key Laboratory of Science and Technology on Applied Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023LiaoningChina University of Chinese Academy of Sciences Beijing 100049China Cardiff Catalysis Institute School of ChemistryTranslational Research HubCardiff UniversityCardiff CF244HQUnited Kingdom College of Chemistry Chemical Engineering and Resource UtilizationNortheast Forestry UniversityHarbin 150040HeilongjiangChina

Cu catalysts,known for their unparalleled catalytic capabilities due to their unique electronic structure,have faced inherent challenges in maintaining long-term effectiveness under harsh hydrogenation ***,we demonstrate a molybdenum-mediated redispersion behavior of Cu under hightemperature oxidation *** oxidized Cu nanoparticles with rich metal-support interfaces tend to dissolve into the MoO_(3)support upon heating to 600℃,which facilitates the subsequent regeneration in a reducing atmosphere.A similar redispersion phenomenon is observed for Cu nanoparticles supported on Zn O-modified MoO_(3).The modification of ZnO significantly improves the performance of the Cu catalyst for CO_(2)hydrogenation to methanol,with the high activity being well maintained after four repeated oxidation-reduction *** situ spectroscopic and theoretical analyses suggest that the interaction involved in the formation of the copper molybdate-like compound is the driving force for the redispersion of *** method is applicable to various Mo-based oxide supports,offering a practical strategy for the regeneration of sintered Cu particles in hydrogenation applications.

关键词： Cu-based catalysts Aggregation Regeneration Oxidation CO_(2)hydrogenation