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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen robert j.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Characterization of a new monoclonal anti-glypican-3 antibody specific to the hepatocellular carcinoma cell line, HepG2

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World j.urnal of Hepatology 2017年第7期9卷 368-384页

作者： Preeyanat Vongchan robert j.linhardt Department of Medical Technology Faculty of Associated Medical SciencesChiang Mai University Rensselaer Polytechnic Institute Departments of ChemistryBiologyChemical and Biomedical Engineering

AIM To characterize the antigen on HepG2 cell that is specifically recognized by a new monoclonal antibody raised against human liver heparan sulfate proteoglycan(HSPG), clone *** The antigen recognized by m Ab 1E4-1D9 was immunoprecipitated and its amino acid sequence was analyzed LC/MS. The transmembrane domain, number of cysteine residues, and glycosylation sites were predicted from these entire sequences. Data from amino acid analysis was aligned with glypican-3(https://***/Tools/msa/clustalo/). The competitive reaction of mA b 1E4-1D9 and anti-glypican-3 on HepG2 cells was demonstrated by indirect immunofluorescence and analyzed by flow cytometry. Moreover, co-immunoprecipitation of mA b 1E4-1D9 and anti-glypican-3 was performed in HepG2 cells by Western immunoblotting. The recognition by mA b 1E4-1D9 of a specific epitope on solid tumor and hematopoietic cell lines was studied using indirect immunofluorescence and analyzed by flow *** Monoclonal antibody 1E4-1D9 reacted with an HSPG isolated from human liver and a band of 67 kD was detected under both reducing and non-reducing conditions. The specific antigen pulled down by m Ab 1E4-1D9, having a MW of 135 kD, was analyzed. The results showed two sequences of interest, gi30722350(1478 amino acid) and gi60219551(1378 amino acid). In both sequences no transmembrane regions were observed. Sequence number gi30722350 was 99.7% showed a match to FYCO1, a molecule involved in induction of autophagy. Sequence number gi60219551 contained 15 cysteines and 11 putative glycosylation sites with 6 predicted N-glycosylation sites. It was also matched with all PDZ domain proteins. Moreover, it showed an 85.7% match to glypican-3. Glypican-3 on HepG2 cells competitively reacted with both phycoerythrin-conj.gated anti-glypican-3 and mA b 1E4-1C2 and resulted in an increase of double-stained cell population when higher concentration of m Ab 1E4-1D9 was used. Moreover, antigens precipitated fro

关键词： Monoclonal anti-glypican-3 Hepatocellular carcinoma HepG2 Heparan sulfate proteoglycan Coimmunoprecipitation

Characterization of squash polysaccharide and the anti-diabetic effect on type 2 diabetic rat revealed by urine metabolomics analysis

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Food Science and Human Wellness 2024年第5期13卷 2937-2946页

作者： Li Liang Fuming Zhang Quanhong Li Baoguo Sun Yuyu Zhang robert j.linhardt Beij.ng Advanced Innovation Center for Food Nutrition and Human Health Beijing Key Laboratory of Flavor ChemistryBeijing Technology and Business University(BTBU)Beijing 100048China Departments of Chemical and Biological Engineering Chemistry and Chemical BiologyBiomedical Engineering and Biological ScienceCenter for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroy 12180USA College of Food Science and Nutritional Engineering China Agricultural UniversityBeijing 100083China China National Engineering Research Center for Fruit and Vegetable Processing Beijing 100083China

The present study reports the structural characteristics of 3 polysaccharide fractions(SPS-F1,SPS-F2 and SPS-F3)isolated and purified from ***-F1(molecular weight(Mw)=12.30 kDa)and SPS-F2(Mw=19.40 kDa)were likely to contain HG and RG-I domain of pectic polysaccharide,***-F2(Mw=270.4 kDa)was mainly composed of rhamnose,galactose and *** treatment with SPS decreased body weight gain,glucose and TG levels in type 2 diabetes ***,25 differential metabolites were identified based on urinary metabolomics analysis,which are crucial to the anti-diabetic effect of *** regulation of nicotinamide N-oxide,histamine,cis-aconitate,citrate,L-malic acid,3-(3-hydroxyphenyl)propanoic acid and N-acetyl-L-aspartic acid were mainly associated with energy metabolism,gut microbiota and *** of surface plasmon resonance revealed the binding kinetics with galectin-3(Gal-3)and fibroblast growth factor 2(FGF2).The K_(D)values of SPS-F2 and SPS-F3 to Gal-3 were 4.97×10^(-3)and 1.48×10^(-3)mol/L,indicating a weak binding *** 3 fractions showed moderate binding to FGF2 and the affinity was SPS-F3>SPS-F2>***,the metabolomics and SPR approach were proved to be a promising tool in exploring the anti-diabetes effects of SPS and provided a deep understanding of the mechanisms.

关键词： Polysaccharide Metabolomics Type 2 diabetes Surface plasmon resonance

Bioengineered production of glycosaminoglycans and their analogues

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Systems Microbiology and Biomanufacturing 2021年第2期1卷 123-130页

作者： Weihua j.n Fuming Zhang robert j.linhardt College of Biotechnology and Bioengineering Zhejiang University of TechnologyHangzhou 310014China Department of Chemical and Biological Engineering Center for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyNY 12180USA Department of Biological Science Departments of Chemistry and Chemical Biology and Biomedical EngineeringCenter for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyNY 12180USA

Glycosaminoglycans(GAGs)are a class of linear polysaccharides,consisting of alternating disaccharide sequences of uronic acid and hexosamines(or galactose)with and without *** can interact with various proteins,such as growth factors,receptors and cell adhesion molecules,endowing these with various biological and pharmacological *** activities make GAGs useful in health care products and ***,all GAGs,with the exception of hyaluronan,are produced by extraction from animal ***,limited availability,poor control of animal tissues,impurities,viruses,prions,endotoxins,contamination and other problems have increased the interest in new approaches for GAG *** new approaches include GAGs production by chemical synthesis,chemoenzymatic synthesis and metabolic *** chemically synthesized heparin pentasaccharide,fondaparinux sodium,is in clinical ***,hyaluronan today is prepared by microbial fermentation,largely replacing hyaluronan from rooster *** recent gram scale chemoenzymatic synthesis of a heparin dodecasaccharide suggests its potential to replace currently used animal-sourced low molecular weight heparin(LMWH).Despite these considerable successes,such high-tech approaches still cannot meet worldwide demands for *** review gives a brief introduction on the manufacturing of unfractionated and low molecular weight heparins,the chemical synthesis and chemoenzymatic synthesis of GAGs and focuses on the progress in the bioengineered preparation of GAGs,particularly heparin.

关键词： Glycosaminoglycans Metabolic engineering Chemoenzymatic synthesis Heparin

Bioactive compounds in Hericium erinaceus and their biological properties:a review

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Food Science and Human Wellness 2024年第4期13卷 1825-1844页

作者： Yue Qiu Genglan Lin Weiming Liu Fuming Zhang robert j.linhardt Xingli Wang Anqiang Zhang College of Food Science and Engineering Zhejiang University of TechnologyHangzhou 310014China Zhej.ang Biosan Biotech Co. Ltd.Hangzhou 310052China Department of Chemical and Biological Engineering Center for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyNY 12180USA Departments of Chemistry and Chemical Biology and Biomedical Engineering Biological ScienceCenter for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyNY 12180USA

Hericium erinaceus is a nutritious edible and medicinal fungi,rich in a variety of functional active ingredients,with various physiological functions such as antioxidation,anticancer,and enhancing *** is also effective in protecting the digestive system and preventing neurodegenerative *** this review paper,we summarize the sources,structures and efficacies of the main active components in *** fruiting body,mycelium,and culture media,and update the latest research progress on their biological activities and the related molecular *** on this information,we provide detailed challenges in current research,industrialization and information on the active ingredients of *** for future studies and new applications of *** are proposed.

关键词： Hericium erinaceus Bioactive compounds Biological activities Antioxidation Neuroprotection Immunoregulation

N-glycans released from glycoproteins using a commercial kit and comprehensively analyzed with a hypothetical database

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j.urnal of Pharmaceutical Analysis 2017年第2期7卷 87-94页

作者： Xue Sun Lei Tao Lin Yi Yilan Ouyang Naiyu Xu Duxin Li robert j.linhardt Zhenqing Zhang j.angsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences Soochow University Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute

The glycosylation of proteins is responsible for their structural and functional roles in many cellular *** work describes a strategy that combines an efficient release, labeling and liquid chromatography–mass spectral analysis with the use of a comprehensive database to analyze N-glycans. The analytical method described relies on a recently commercialized kit in which quick deglycosylation is followed by rapid labeling and cleanup of labeled glycans. This greatly improves the separation, mass spectrometry（MS） analysis and fluorescence detection of N-glycans. A hypothetical database, constructed using Glyc Resoft, provides all compositional possibilities of N-glycans based on the common sugar residues found in N-glycans. In the initial version this database contains ＆gt; 8,700 N-glycans, and is compatible with MS instrument software and expandable. N-glycans from four different well-studied glycoproteins were analyzed by this strategy. The results provided much more accurate and comprehensive data than that had been previously reported. This strategy was then used to analyze the N-glycans present on the membrane glycoproteins of gastric carcinoma cells with different degrees of differentiation. Accurate and comprehensive N-glycan data from those cells was obtained efficiently and their differences were compared corresponding to their differentiation states. Thus, the novel strategy developed greatly improves accuracy, efficiency and comprehensiveness of N-glycan analysis.

关键词： N-glycan Hypothetical database Glycoproteins Gastric carcinoma cells Glycomics

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA j.mes L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain inj.ry(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

Fluorescence Enhancement Ratio Dropdown at Low Fluences during Femtosecond Double Pulse Laser Ablation

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Chinese Physics Letters 2008年第7期25卷 2653-2656页

作者： Sima SINGHA robert j. GORDON 胡湛 Institute of Atomic and Molecular Physics Jilin University Changchun 130021 Department of Chemistry University of Illinois at Chicago Chicago Illinois 60607-7061 USA

In the study of double pulse ablation of materials （silicon and copper）, a dropdown of double pulse to single pulse fluorescence signal enhancement at low fluences is observed. The dropdown is analysed with a simple theoretical one-dimensional heat diffusion model and verified by fluorescence time constants change as a function of fluence. The dropdown is explained as a result of liquid-solid mixture layer at the liquid and solid boundary. The effect of the layer becomes important at low fluences.

关键词： the power-law exponents precipitation durative abrupt precipitation change

The impact of macroalgae on mean and turbulent flow fields

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j.urnal of Hydrodynamics 2015年第3期27卷 427-435页

作者： THOMAS robert E. MCLELLAND Stuart j. Department of Geography Environment and Earth Sciences University of Hull

In this paper, we attempt to quantify the mean and turbulent flow fields around live macroalgae within a tidal inlet in Norway. Two Laminaria digitata specimens - 0.50 m apart were selected for detailed study and a profiling ADV was used to collect 45 velocity profiles, each composed of up to seven 0.035 m-high profiles collected for 240 s at 100 Hz, at a streamwise spacing of 0.25 m and cross-stream spacing of 0.20 m. To quantify the impact of the macroalgae, measurements were repeated over a sparser grid after the region had been completely cleared of algae and maj.r roughness elements.

关键词： dealiasing laminaria digitata turbulence vectrino profiler velocity profile