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Determination of Fragmentation Schemes and Metabolites of Fluorinated Histone Deacetylase Inhibitors for Use as Positron Emission Tomography Imaging Agents Using HPLC-MS/MS

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International Journal of Analytical Mass Spectrometry and Chromatography 2018年第1期6卷 1-19页

作者： Wei-Hsi Chen yu-Chieh Hsiao Ming-Hsin Li Mu-Chen Tsai Chun-Fang Feng Han-Chih Chang hung-wen yu Chyng-Yann Shiue Chemistry Division Institute of Nuclear Energy Research Taiwan Isotope Application Division Institute of Nuclear Energy Research Taiwan PET Center Department of Nuclear Medicine National Taiwan University Hospital Taiwan PET Center Department of Nuclear Medicine Tri-Service General Hospital Taiwan

High performance liquid chromatography coupled with tandem mass spectrometry was developed and validated as a method for the analysis of fluorinated histone deacetylase inhibitors (F-HDACi), and then employed to study their metabolism in biosystems. Four HDACi analogs labeled with the positron emission nuclide 18F constitute a group of potential positron emission tomography imaging agents, which were developed by the Institute of Nuclear Energy Research (INER) and coded as INER-1577 #1, #2, #3, and #4 during animal studies for the diagnosis of dementia. The performance of the method was found to be suitable for the determination of analog #3, and it was employed to determine the structures and fragmentation mechanisms of all four analogs and to study the biotransformations of analogs #3 and #4. The results indicated that the method used for the determination of analog #3 was suitable for determining the abundance of the analogs in chemical and biochemical tests with high precision, accuracy, reproducibility, and recovery. Weaknesses in the chemical bonding of the analogs were found to involve the fluoro, dimethylamino, and benzamide groups in a fragmentation mechanism deduced via tandem mass spectrometry. The metabolites of analogs #3 and #4 in rat liver microsomes and rat plasma were also identified to clarify their characteristic behaviors in biosystems. The major product of analogs #3 in liver microsomes was produced by hydroxylation of the benzylic carbon atom, but in rat plasma the metabolites of analog #3 were produced by hydrolysis of the benzamide group to give a diaminobiphenyl compound with the simultaneous replacement of a fluorine atom by a hydroxyl group. The metabolites of analog #4 in liver microsomes were produced by hydroxylation of the benzylic carbon atom and hydrolysis of the benzamide bond. The results of the studies characterized the chemical and biochemical behaviors of the series F-HADCi analogs.

关键词： Histone Deacetylase Inhibitors Positron Emission Tomography Imaging Agent Dementia LC-Tandem MS Fragmentation Mechanism Metabolism Pathways Epigenetics

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang yu-wen Alvin Huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Cohort study on the treatment of BRAF V600E mutant metastatic colorectal cancer with integrated Chinese and western medicine

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World Journal of Clinical Oncology 2025年第1期16卷 25-33页

作者： Jiang-yu Bian yu-Fang Feng wen-Ting He Tong Zhang Department of Oncology Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China Department of Oncology The Fourth Clinical Medical College of Xinjiang Medical UniversityUrumqi 830001China Department of Oncology Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical UniversityUrumqi 830001China

BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor *** the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal ***,we further explored the survival benefits in the population with BRAF V600E mutant *** To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal *** A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December *** patients were divided into two *** A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,*** analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.

关键词： Metastatic colorectal cancer BRAF V600E mutation Integrated Chinese and Western medicine Cohort study

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Broadband and perfect terahertz absorber based on multilayer metamaterial with cross-ring patterned structures

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Optoelectronics Letters 2025年第1期21卷 1-6页

作者： wen Jin LIU Zhanzhi WU Zhengwei PAN yu ZHANG Ying School of Science Xi'an Shiyou University Shaanxi Key Laboratory of Measurement and Control Technology for Oil and Gas Wells

Broadband and perfect terahertz absorber based on multilayer metamaterial using cross-ring patterned structures is proposed and investigated. The structure of the absorber is double absorption layers consisting of a chromium cross ring and eight isosceles right triangles. The unique structure of the double absorbing layers excites the electric dipole multimode resonance, giving rise to high absorption performance. Meanwhile, the influence of construal parameters on absorber behavior is also discussed. The numerical results show that the absorption achieves over 90% ranging from 2.45 THz to 6.25 THz and 99% absorption in the range of 3.7—5.3 THz. The realization of broadband and perfect absorber is described using the impedance matching principle. It is obviously found that the absorber is insensitive to the high angle of incidence for both transverse electric(TE) and transverse magnetic(TM) polarizations. Compared with the former reports, this absorber has remarkable improved absorption efficiency and smaller period. The terahertz absorber may be found applications in the fields of energy capture and thermal detection.

关键词： Metamaterials

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Metal-organic frameworks with dinuclear metal centers for synergistically boosting CO2 photoreduction

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Science China Chemistry 2025年第01期 201-208页

作者： Hui-Feng Wang wen-Jie Shi yu-Xin Yang Bao-Xia Dong Tong-Bu Lu Di-Chang Zhong School of Chemistry and Chemical Engineering Yangzhou University Institute for New Energy Materials and Low Carbon Technologies School of Materials Science and Engineering Tianjin University of Technology

Dinuclear metal synergistic catalysis （DMSC） has been proved powerful in boosting CO2reduction,while this has not been achieved in heterogeneous catalysts with long-range order *** this study,we,by introduction of metal catalytic centers into an indium-based metal-organic framework （MOF）,obtained a series of isostructural In-MOFs,including three MOFs with mononuclear metal catalytic center （M-In）,three MOFs with dinuclear homometallic catalytic centers （MM-In）,and three MOFs with dinuclear heterometallic catalytic centers (MM’-In,M/M’=Co（II）,Ni（II）,Zn（II）).It was found that all these MOFs can serve as catalysts for photochemical CO2reduction to *** with M-In,the catalytic activities of MM-In were obviously enhanced,and that of MM’-In was further significantly *** example,the CO yield of Co Zn-In reaches a record value of 12,700μmol g-1h-1,which is 4.0,8.1,9.4,and 18.6-fold higher than that of Co Co-In,Zn Zn-In,Co-In,and Zn-In,***,the catalytic activities of Co Ni-In and Ni Zn-In also show different fold increase than those of corresponding dinuclear homometallic and mononuclear metallic *** results of control experiments and theoretical calculation reveal that the higher catalytic activities of MM-In over M-In can be ascribed to the DMSC effect,and the higher catalytic activity of MM’-In over MM-In can be ascribed to the strengthened DMSC *** work reveals the relationship between DMSC effect and bimetal centers in CO2reduction,which provides new insights into the DMSC and paves a new way to design highly active catalysts for photochemical CO2reduction.

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Comparative analysis of empirical and deep learning models for ionospheric sporadic E layer prediction

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Earth and Planetary Physics 2025年第1期9卷 10-19页

作者： BingKun yu PengHao Tian XiangHui Xue Christopher JScott HaiLun Ye JianFei Wu wen Yi TingDi Chen XianKang Dou Institute of Deep Space Sciences Deep Space Exploration LaboratoryHefei 230088China CAS Key Laboratory of Geospace Environment School of Earth and Space SciencesUniversity of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230088China Department of Meteorology University of ReadingReading RG66BBUK

Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 *** they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite *** this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde *** deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular.

关键词： ionospheric sporadic E layer radio occultation ionosondes numerical model deep learning model artificial intelligence

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Cerebral fat embolism following autologous fat injection in facial reconstruction:A case report

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World Journal of Clinical Cases 2025年第2期13卷 50-58页

作者： Xiu-Ying Chen Fa Shen Chang Cheng yu-Han Wang wen-Chao Cheng De-Zhi yuan wen Huang Department of Neurology Chongqing Emergency Medical CenterChongqing University Central HospitalChongqing 400000China Department of Neurology Xinqiao HospitalThe Army Medical University(Third Military Medical University)Chongqing 400000China

BACKGROUND Autologous fat injection in facial reconstruction is a common cosmetic *** cerebral fat embolism(CFE)as a complication is rare,it carries serious health *** SUMMARY We present a case of a 29-year-old female patient who developed acute CFE following facial fat filling *** the surgery,the patient experienced symptoms including headache,nausea,vomiting,and difficulty breathing,which was followed by neurological symptoms such as slurred speech and left-sided *** physical examination and auxiliary investigations,including blood tests,head and neck computed tomography angiography,and cranial magnetic resonance diffusion-weighted imaging,were performed upon *** clinical diagnosis was acute cerebral embolism following facial fat filling *** included measures to improve cerebral circulation,dehydration for intracranial pressure reduction,nutritional support,and rehabilitation therapy for left limb *** patient showed a significant improvement in symptoms after 2 weeks of *** recovered left limb muscle strength to grade 5,had clear speech,and experienced complete relief of *** Our case highlights the potential occurrence of severe complications in patients undergoing fat injection in facial *** prevent these complications,plastic surgeons should enhance their professional knowledge and skills.

关键词： Cerebral fat embolism Mechanical thrombectomy Thrombolysis Steroid therapy Symptomatic treatment Case report

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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao yuan Lingqi yu Xudong Zhuang Dongjing wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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后交叉韧带胫骨附着点撕脱骨折:关节镜治疗中的材料、植入物及内固定技术

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中国组织工程研究 2025年第4期29卷 872-880页

作者：余铭王文贵州医科大学贵州省贵阳市550004 暨南大学附属广州市红十字会医院广东省广州市510220

背景:治疗后交叉韧带胫骨附着点撕脱骨折的最佳手术技术仍值得商榷。随着关节镜手术的应用与成熟,它在后交叉韧带胫骨附着点撕脱骨折的诊疗中有很大前景。目的:综述关节镜技术在后交叉韧带胫骨附着点撕脱骨折治疗中的应用与进展,包括不... 详细信息

背景:治疗后交叉韧带胫骨附着点撕脱骨折的最佳手术技术仍值得商榷。随着关节镜手术的应用与成熟,它在后交叉韧带胫骨附着点撕脱骨折的诊疗中有很大前景。目的:综述关节镜技术在后交叉韧带胫骨附着点撕脱骨折治疗中的应用与进展,包括不同关节镜治疗方法、手术入路、胫骨隧道设计、缝合材料选择以及内固定植入物选择等。方法:通过计算机对中国知网、PubMed、Web of Science及ScienceDirect等数据库中的相关文献进行检索,检索时间为2003年1月至2023年11月,中文检索词为“后交叉韧带,后十字韧带,撕脱骨折,关节镜”;英文检索词为“posterior cruciate ligament,avulsion,fracture,tibia,arthroscopic,operation,fixation,treatment”。共纳入97篇文献进行综述。结果与结论:关节镜技术提供了一种可靠的治疗方式来治疗后交叉韧带胫骨附着点撕脱骨折。根据入路、缝合材料类型以及用于缝合的入路和胫骨隧道数量等不同,关节镜技术可以分为关节镜下缝线固定结合自体移植物增强重建、关节镜下多交叉带缝合桥固定、关节镜下高强度缝线固定以及关节镜下直接前后缝合悬吊固定等几类。在各种研究中,常用的临床结果评估指标包括关节活动度、Lysholm评分、国际膝关节文献委员会评分及KT-2000关节测量仪差等,研究显示关节镜手术后末次随访时上述指标检测结果较术前显著改善,影像学随访结果显示关节镜手术都取得了令人满意的结果。在随访过程中,接受关节镜技术治疗后的各类交叉韧带胫骨附着点撕脱骨折患者都未出现严重并发症,例如创伤性关节炎、神经血管损伤、围手术期伤口感染、血栓形成以及骨折不愈合等。

关键词：后交叉韧带胫骨撕脱骨折关节镜手术缝合材料内固定治疗

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Sine oculis homeobox homolog family function in gastrointestinal cancer:Progression and comprehensive analysis

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World Journal of Clinical Oncology 2025年第1期16卷 10-24页

作者： Yang-Zheng Lan Zheng Wu wen-Jia Chen Xin-Ning yu Hua-Tao Wu Jing Liu Department of The Breast Center Cancer Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of General Surgery First Affiliated Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including *** six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX *** or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular *** to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor *** the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic ***,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular *** conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.

关键词： Sine oculis homeobox homolog Gastrointestinal cancer Transcription factor Development Regulation Diagnosis Therapeutics

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