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Soluble N-terminal fragment of mutant Huntingtin protein impairs mitochondrial axonal transport in cultured hippocampal neurons

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Neuroscience Bulletin 2014年第1期30卷 74-80页

作者： Jun Tian Ya-Ping Yan Rui Zhou hui-fang lou Ye Rong Bao-Rong Zhang Department of Neurology Second Affiliated Hospital College of Medicine Zhejiang University Department of Neurobiology Key Laboratory of Medical Neurobiology of Ministry of Health of China Zhejiang University School of Medicine

Huntington＇s disease （HD） is an autosomal dominant, progressive, neurodegenerative disorder caused by an unstable expansion of CAG repeats （〉35 repeats） within exon 1 of the interesting transcript 15 （IT15） gene. This gene encodes a protein called Huntingtin （Htt）, and mutation of the gene results in a polyglutamine （polyQ） near the N-terminus of Htt. The N-terminal fragments of mutant Htt （mHtt）, which tend to aggregate, are sufficient to cause HD. Whether these aggregates are causal or protective for HD remains hotly debated. Dysfunctional mitochondrial axonal transport is associated with HD. It remains unknown whether the soluble or aggregated form of mHtt is the primary cause of the impaired mitochondrial axonal transport in HD pathology. Here, we investigated the impact of soluble and aggregated N-terminal fragments of mHtt on mitochondrial axonal transport in cultured hippocampal neurons. We found that the N-terminal fragment of mHtt formed aggregates in almost half of the transfected neurons. Overexpression of the N-terminal fragment of mHtt decreased the velocity of mitochondrial axonal transport and mitochondrial mobility in neurons regardless of whether aggregates were formed. However, the impairment of mitochondrial axonal transport in neurons expressing the soluble and aggregated N-terminal fragments of mHtt did not differ. Our findings indicate that both the soluble and aggregated N-terminal fragments of mHtt impair mitochondrial axonal transport in cultured hippocampal neurons. We predict that dysfunction of mitochondrial axonal transport is an early-stage event in the progression of HD, even before mHtt aggregates are formed.

关键词： Huntington mitochondria axonal transport hippocampal neurons

METHYLATION PATTERN OF LRP15 GENE IN LEUKEMIA

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Chinese Medical Sciences Journal 2007年第3期22卷 187-191页

作者： Li-ping Dou Chang Wang Zhou-min Xu hui-yuan Kang hui Fan fang-ding lou Li Yu Department of Hematology Chinese People＇s Liberation Army General Hospital Beijing 100853

Objective To investigate the methylation status of LRP15 gene in acute leukemia （AL） patients and its role in the tumorigenesis. Methods The methylation of LRP15 promoter and first exon of bone marrow mononuclear cells in 73 patients with AL, 10 with chronic leukemia （CL）, 9 with hematological benign diseases, and 20 healthy transplantation donors was analyzed by using methylation specific polymerase chain reaction. The methylation of LRP15 gene promoter and first exon in COS7, K562, and HL60 cell lines was also assayed. Resuits No LRP15 gene promoter methylation was detected in COS7 cell line. LRP15 gene promoter was methylated in K562 and HL60 cell lines. No deletion of LRP15 gene was detected in all samples. In nearly all French-American-British leukemia subtypes, we found that frequency of LRP15 methylation in adult patients with AL was 71.23% （ 52/73 ）. There was no detectable methylation in any of the 20 healthy donors and 8 chronic myeloid leukemia patients. The difference in frequency of LRP15 methylation between AL patients and healthy donors or CL patients （ 10.00%, 1/10） was significant （P 〈0.01 ）. Hypermethylation of LRP15 gene was found in 57.14% （16/28） of newly diagnosed AL patients, 83.33% of relapsed AL patients respectively, which was significantly different （ P 〈 0.05 ）. We also demonstrated LRP15 methylation in 55.56% （5/9） adults with benign hematological diseases. Conclusions LRP15 methylation changes are common abnormalities in leukemia. LRP15 is postulated to be a tumor suppressor gene.

关键词： leukemia LRP15 gene methylation

Effect of catalyst diesel particulate filter aging and catalyst loadings on particulate emission characteristics from a diesel vehicle

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Journal of Environmental Sciences 2024年第2期136卷 35-44页

作者： Yunhua Zhang Diming lou Piqiang Tan Zhiyuan Hu Liang fang School of Automotive Studies Tongji UniversityShanghai 201804China

In this study,the effect of new and used catalyzed diesel particulate filter(CDPF)with different catalyst loadings on the particulate emissions including the particle mass(PM),particle number(PN),particle size distribution(PSD)and geometric mean diameter(GMD)from a diesel vehicle were investigated based on a heavy chassis *** showed that more than 97.9%of the PN and 95.4%of the PM were reduced by the CDPF,and the reduction efficiency was enhanced by the catalyst *** using the CDPF,the PSD transformed from bimodal to trimodal with the peak shifting towards smaller particle size,more nucleation mode particles were reduced compared with accumulation mode ones,but the reduction effect on the accumulation mode particles was more significantly influenced by the catalyst ***,the CDPF increased the accumulation mode particles proportion,producing a larger *** the used CDPF,its reduction effect on the particulate emissions enhanced,especially for the PM in accumulation *** PSD returned to bimodal,but the peak at accumulation mode began to be higher than that at nucleation mode,illustrating that more nucleation mode particles was *** aging of the CDPF resulted in greater effect on the PN-based PSD than that of PM-based PSD,but the effect of catalyst loading on the PN and PM emission factors was *** used CDPF further increased the GMD,and the effect of catalyst loading on the GMD was strengthened,a higher catalyst loading led to a reduction in the GMD.

关键词： Catalyzed diesel particulate filter (CDPF) Catalyst loading Aging Particle Particle size distribution Geometric mean diameter

Advancing cell-based therapy in sepsis:An anesthesia outlook

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Chinese Medical Journal 2024年第13期137卷 1522-1534页

作者： hui Ye Xiaoyu Zou Xiangming fang Department of Anesthesiology and Intensive Care The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310003China The Children’s Hospital National Clinical Research Center for Child HealthSchool of MedicineZhejiang UniversityHangzhouZhejiang 312000China

Sepsis poses a health challenge globally owing to markedly high rates of morbidity and *** employing bundle therapy over two decades,approaches including transient organ supportive therapy and clinical trials focusing on signaling pathways have failed in effectively reversing multiple organ failure in patients with *** and appropriate perioperative management for surgical patients with concurrent sepsis is ***,innovative therapies focusing on remedying organ injuries are *** therapy has emerged as a promising therapeutic avenue for repairing local damage to vital organs and restoring homeostasis during perioperative treatment for *** the pivotal role of immune cell responses in the pathogenesis of sepsis,stem cell-based interventions that primarily modulate immune responses by interacting with multiple immune cells have progressed into clinical *** strides made in single-cell sequencing and gene-editing technologies have advanced the understanding of disease-specific immune responses in *** antigen receptor(CAR)-immune cell therapy offers an intriguing option for the treatment of *** review provides a concise overview of immune cell therapy,its current status,and the strides made in the context of sepsis research,discussing potential strategies for the management of patients with sepsis during perioperative stages.

关键词： Sepsis Perioperative Receptors,chimeric antigen Immunotherapy,adoptive Perfusion Tissue repair Multiple organ failure Shock,septic

Uniqueness on Difference Operators of Meromorphic Functions of Infinite Order

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Acta Mathematica Sinica,English Series 2024年第2期40卷 511-527页

作者： hui LI Ming Liang fang Xiao YAO School of Science China University of Mining and TechnologyBeijing 100083P.R.China Institute of Mathematics Academy of Mathematics and System SciencesChinese Academy of SciencesBeijing 100190P.R.China School of Sciences Hangzhou Dianzi UniversityHangzhou 310012P.R.China School of Mathematical sciences and LPMC Nankai UniversityTianjin 300071P.R.China

We investigate the uniqueness problems of meromorphic functions and their difference operators by using a new *** is proved that if a non-constant meromorphic function f shares a non-zero constant and ∞ counting multiplicities with its difference operators Δcf(z) and Δ_(c)^(2)f(z), thenΔcf(z)≡Δ_(c)^(2)f(z).In particular,we give a difference analogue of a result of *** method has two distinct features:(ⅰ) It converts the relations between functions into the corresponding *** makes it possible to deal with the uniqueness problem by linear algebra and combinatorics.(ⅱ) It circumvents the obstacle of the difference logarithmic derivative lemma for meromorphic functions of infinite order,since this method does not depend on the growth of the ***,the idea in this paper can also be applied to the case for several variables.

关键词： Uniqueness meromorphic functions difference operators infinite order

Influence of Mixture Gas Conditions on the Laminar Combustion Characteristics of Natural Gas

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Journal of Thermal Science 2024年第3期33卷 1231-1241页

作者： lou Diming ZHU Kan ZHANG Yunhua REN Yedi TAN Piqiang fang Liang FAN Lanlan School of Automotive Studies Tongji UniversityShanghai201804China Ji’nan Power Co.Ltd Sinotruk GroupJi’nan250200China

Natural gas is a promising alternative fuel for the internal combustion engine,and natural gas engine has become an efficient and feasible measure to deal with the energy shortage and climate *** the laminar flame characteristics are the foundation of the turbulent flame,the laminar flame characteristics of natural gas have a significant impact on the combustion status and efficiency of the engine.A visual constant volume bomb was used to study the influence of the gas components,different excess air coefficient(λ),and initial conditions on the laminar combustion characteristics of natural *** experimental results showed that when the initial pressure and temperature were 0.1 MPa and 300 K respectively,compared to propane,ethane had a remarkable influence on the equivalent-combustion laminar-combustion-speed,with an average increase of approximately 5.1%for every 2.5%increase in the ethane *** laminar combustion velocity of the natural gas under different excess air coefficients had a maximum value at aboutλ=1.0,and the Markstein length of the flame decreased with the increase of theλ.The increase in the initial pressure of the mixture resulted in a decrease in the equivalent-combustion laminar-combustion-speed of the flame,a significant decrease in the Markstein *** increase of the initial temperature of the mixture led to a rapid increase of the equivalent-combustion laminar-combustion-speed,but the effect on the flame Markstein length was not dominant.

关键词： constant volume bomb natural gas engine combustion characteristics laminar combustion velocity Markstein length

Adaptive Algorithms on Maximizing Monotone Nonsubmodular Functions

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Journal of the Operations Research Society of China 2024年第2期12卷 428-445页

作者： Bin Liu hui Su Shu-fang Gong Qi-Zhi fang School of Mathematical Sciences Ocean Universityof ChinaQingdao266100ShandongChina

Submodular optimization is widely used in large *** order to speed up the problems solving,it is essential to design low-adaptive algorithms to achieve acceleration in *** general,the function values are given by a value oracle,but in practice,the oracle queries may consume a lot of ***,how to strike a balance between optimizing them is *** this paper,we focus on maximizing a normalized and strictly monotone set function with the diminishing-return ratio under a cardinality constraint,and propose two algorithms to deal with *** apply the adaptive sequencing technique to devise the first algorithm,whose approximation ratio is arbitrarily close to 1-e^(-γ)in O(logn·log(log k/γ)) adaptive rounds,and requires O(logn^(2)·log(log k/γ)) *** by adding preprocessing and parameter estimation steps to the first algorithm,we get the second *** second algorithm trades a small sacrifice in adaptive complexity for a significant improvement in query *** the same approximation and adaptive complexity,the query complexity is improved *** the best of our knowledge,this is the first paper of designing adaptive algorithms for maximizing a monotone function using the diminishing-return ratio.

关键词： Approximation algorithm Adaptivity Nonsubmodular maximization Cardinality constraint

Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

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Genes & Diseases 2024年第3期11卷 338-350页

作者： Xin Xu Yuan fang Somaira Nowsheen Ye-Xiong Li Zhenkun lou Min Deng State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Department of General Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of Dermatology University of California San DiegoSan DiegoCA 92093USA Department of Oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor *** is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy *** studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic *** this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)*** found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM *** regulation of AMPK requires the Hippo kinases but not LKB1/*** kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM ***,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival *** activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC ***,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

Structure and 2p decay mechanism of^(18)Mg

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Nuclear Science and Techniques 2024年第6期35卷 145-154页

作者： Long Zhou De-Qing fang Si-Min Wang hui Hua Key Laboratory of Nuclear Physics and Ion-beam Application(MOE) Institute of Modern PhysicsFudan UniversityShanghai 200433China Shanghai Research Center for Theoretical Nuclear Physics NSFC and Fudan UniversityShanghai 200438China School of Physics and State Key Laboratory of Nuclear Physics and Technology Peking UniversityBeijing 100871China

The recently discovered,extremely proton-rich nuclide 18 Mg exhibits ground-state decay via two sequential two-proton(2p)emissions through the intermediate nucleus,*** study investigates the structure and the initial 2p decay mechanism of^(18)Mgby examining the density and correlations of the valence protons using a three-body Gamow coupled-channel *** results show that the ground state of^(18)Mgis significantly influenced by the continuum,resulting in a significant s-wave ***,based on the current framework,this does not lead to a significant deviation in mirror symmetry in either the structure or spectroscopy of the 18Mg-18C ***,the time evolution analysis of the^(18)Mgground state suggests a simultaneous 2p emission during the first step of *** observed nucleon-nucleon correlations align with those of the light-mass 2p emitters,indicating a consistent decay behavior within this nuclear region.

关键词： Structure of^(18)Mg Two-proton decay Proton-proton correlation