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喹啉类HDAC8选择性抑制剂的设计、合成及抗肿瘤活性研究

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药学学报 2024年第4期59卷 979-986页

作者：周易邵文晴杨新颖侯旭奔方浩山东第一医科大学附属省立医院药学部山东济南250021 山东大学药学院天然产物化学生物学教育部重点实验室山东济南250012

作为I亚族组蛋白去乙酰化酶(histone deacetylase,HDAC)成员,HDAC8是重要的抗肿瘤靶点。本研究基于课题组前期构建的HDAC8药效团模型,以喹啉作为母核,设计并合成了13个目标化合物,其中SDFZ-E2和SDFZ-E3具有较好的HDAC8抑制活性和亚型选... 详细信息

作为I亚族组蛋白去乙酰化酶(histone deacetylase,HDAC)成员,HDAC8是重要的抗肿瘤靶点。本研究基于课题组前期构建的HDAC8药效团模型,以喹啉作为母核,设计并合成了13个目标化合物,其中SDFZ-E2和SDFZ-E3具有较好的HDAC8抑制活性和亚型选择性;在细胞实验中,SDFZ-E2和SDFZ-E3表现出优于HDAC8选择性抑制剂PCI-34051的抗肿瘤细胞增殖活性;还通过分子对接和分子动力学模拟研究了SDFZ-E2与HDAC8的结合模式。该项工作是以喹啉为母核发展HDAC8选择性抑制剂的一次探索,相关活性化合物可以作为先导化合物进行进一步的结构改造。

关键词：喹啉衍生物组蛋白去乙酰化酶8抑制剂抗肿瘤活性药效团

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Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

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Oncology Research 2024年第5期32卷 899-910页

作者： YIWEN ZHU LIU yang ying YU ying XIONG PING XIAO XIAO FU xin LUO Department of Rehabilitation Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330006China Department of General Practice The Second Affiliated Hospital of Nanchang UniversityNanchang330006China

Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal *** there is no permanent therapy for this condition,it is necessary to develop a ***,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were *** experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were *** MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity *** reduced the Warburg effect and induced ferroptosis(FPT)in MG63 *** ferroptosis diminished HYSA’s anti-cancer activities in MG63 *** stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 ***-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°*** significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand ***,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 *** is a possible therapeutic option for OC or other cancers.

关键词： Hydroxysafflor yellow A Osteosarcoma HIF-1α FPT

Quantitative prediction model for the depth limit of oil accumulation in the deep carbonate rocks:A case study of Lower Ordovician in Tazhong area of Tarim Basin

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Petroleum Science 2024年第1期21卷 115-124页

作者： Wen-yang Wang Xiong-Qi Pang Ya-Ping Wang Zhang-xin Chen Fu-Jie Jiang ying Chen State Key Laboratory of Lithospheric Evolution Institute of Geology and GeophysicsChinese Academy of SciencesBeijing100029China State Key Laboratory of Petroleum Resources and Prospecting China University of Petroleum(Beijing)Beijing102249China College of Geosciences China University of Petroleum(Beijing)Beijing102249China Research Institute of Exploration and Development PetroChina Southwest Oil&Gas Field CompanyChengdu610041SichuanChina Chemical and Petroleum Engineering Schulich School of EngineeringUniversity of CalgaryCalgaryT2N 1N4Canada

With continuous hydrocarbon exploration extending to deeper basins,the deepest industrial oil accumulation was discovered below 8,200 m,revealing a new exploration ***,the extent to which oil exploration can be extended,and the prediction of the depth limit of oil accumulation(DLOA),are issues that have attracted significant attention in petroleum *** it is difficult to characterize the evolution of the physical properties of the marine carbonate reservoir with burial depth,and the deepest drilling still cannot reach the ***,the DLOA cannot be predicted by directly establishing the relationship between the ratio of drilling to the dry layer and the *** this study,by establishing the relationships between the porosity and the depth and dry layer ratio of the carbonate reservoir,the relationships between the depth and dry layer ratio were obtained *** depth corresponding to a dry layer ratio of 100%is the *** on this,a quantitative prediction model for the DLOA was finally *** results indicate that the porosity of the carbonate reservoir,Lower Ordovician in Tazhong area of Tarim Basin,tends to decrease with burial depth,and manifests as an overall low porosity reservoir in deep *** critical porosity of the DLOA was 1.8%,which is the critical geological condition corresponding to a 100%dry layer ratio encountered in the *** depth of the DLOA was 9,000 *** study provides a new method for DLOA prediction that is beneficial for a deeper understanding of oil accumulation,and is of great importance for scientific guidance on deep oil drilling.

关键词： Deep layer Tarim Basin Hydrocarbon accumulation Depth limit of oil accumulation Prediction model

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高分辨质谱技术分析两地缢蛏的脂质差异性

食品安全质量检测学报 2024年第1期15卷 216-224页

作者：张煜炯孙崇鲁杨颖欣岳军治周静峰浙江药科职业大学食品学院宁波315100

目的基于高分辨质谱技术对浙江象山和福建云霄两大主产地缢蛏的脂质差异性进行比较。方法样品经培养后,去壳、去胃进行冷冻干燥,采用脂类提取法提取,以Hypersile Gold C18(100 mm×2.1 mm,1.9μm)色谱柱为分析柱,甲醇/水(A)、甲醇/异丙... 详细信息

目的基于高分辨质谱技术对浙江象山和福建云霄两大主产地缢蛏的脂质差异性进行比较。方法样品经培养后,去壳、去胃进行冷冻干燥,采用脂类提取法提取,以Hypersile Gold C18(100 mm×2.1 mm,1.9μm)色谱柱为分析柱,甲醇/水(A)、甲醇/异丙醇(B)为流动相进行梯度洗脱分离,采用四极杆静电场轨道阱高分辨质谱法对缢蛏脂质进行定性和半定量分析。结果两大主产地缢蛏均检测到脂质78种,潜在生物标记物由磷脂酰乙醇胺(phosphatidyl ethanolamine,PE)、磷脂酰肌醇(phosphatidylinositol,PI)、磷脂酰丝氨酸(phosphatidylserine,PS)、神经酰胺氨乙基亚磷酸(ceramide aminoethyl phosphite,CAEP)、甘油三酯(triglyceride,TAG)和甘油二酯(diglyceride,DAG)组成。浙江象山产地的缢蛏PE(17:1-22:6,15:1-22:6,16:1-22:6,17:1-18:4)、PI(20:3-20:5)和DAG(18:4-18:4)含量为福建云霄产地的2.55~9.11倍;福建云霄产地的缢蛏DAG(16:0-16:0)、CAEP(d18:2-n16:0)和PI(16:0-20:5)含量是浙江象山产地的2.79~2.90倍。结论浙江象山和福建云霄产地的缢蛏存在脂质差异性,为其产地鉴定提供重要依据。

关键词：缢蛏脂类代谢物差异性超高效液相色谱-四极杆静电场轨道阱高分辨质谱法浙江象山福建云霄

Microstructure evolution and strengthening mechanism of high -performance powder metallurgy TA15 titanium alloy by hot rolling

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1426-1436页

作者： ying Gao Ce Zhang Jiazhen Zhang xin Lu Beijing Advanced Innovation Center for Materials Genome Engineering State Key Laboratory for Advanced Metals and MaterialsInstitute for Advanced Ma-terials and TechnologyUniversity of Science and Technology BeijingBeijing 100083China National Engineering Research Center for Advanced Rolling Technology National Engineering Research Center for Flat Rolling EquipmentInstitute of Engin-eering TechnologyUniversity of Science and Technology BeijingBeijing 100083China

Hot deformation of sintered billets by powder metallurgy(PM)is an effective preparation technique for titanium alloys,which is more significant for high-alloying *** this study,Ti–6.5Al–2Zr–Mo–V(TA15)titanium alloy plates were prepared by cold press-ing sintering combined with high-temperature hot *** microstructure and mechanical properties under different process paramet-ers were *** microscope,electron backscatter diffraction,and others were applied to characterize the microstructure evolution and mechanical properties strengthening *** results showed that the chemical compositions were uniformly dif-fused without segregation during sintering,and the closing of the matrix craters was accelerated by increasing the sintering *** block was hot rolled at 1200℃ with an 80%reduction under only two passes without *** strength and elongation of the plate at 20–25℃ after solution and aging were 1247 MPa and 14.0%,respectively,which were increased by 24.5%and 40.0%,respect-ively,compared with the as-sintered alloy at 1300℃.The microstructure was significantly refined by continuous dynamic recrystalliza-tion,which was completed by the rotation and dislocation absorption of the substructure surrounded by low-angle grain *** hot rolling combined with heat treatment,the strength and plasticity of PM-TA15 were significantly improved,which resulted from the dense,uniform,and fine recrystallization structure and the synergistic effect of multiple slip systems.

关键词： elemental powder powder metallurgy titanium alloy hot rolling strength and plasticity

Effect of endoscopic sphincterotomy and endoscopic papillary balloon dilation endoscopic retrograde cholangiopancreatographies on the sphincter of Oddi

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1726-1733页

作者： Kai Fu ying-ying yang Hui Chen Guang-xin Zhang Yan Wang Zhi Yin Department of Gastroentero Endoscopy Center Yixing Hospital of Traditional Chinese MedicineWuxi 214200Jiangsu ProvinceChina

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP),with its clinical ad-vantages of less trauma and faster recovery,has become the primary treatment for *** To investigate the effects of different ERCP procedures on the sphincter of *** The clinical data of 91 patients who underwent ERCP at Yixing Hospital of Traditional Chinese Medicine between February 2018 and February 2021 were analyzed *** patients were divided into endoscopic sphinc-terotomy(EST,n=24)and endoscopic papillary balloon dilation(EPBD,n=67)*** duration of operation,pancreatic development,pancreatic sphinc-terotomy,intubation difficulties,stone recurrence,and incidence of reflux cho-langitis and cholecystitis were statistically analyzed in patients with a history of choledocholithiasis,pancreatitis,and Oddi sphincter dysfunction in the EST and EPBD *** Differences in hypertension,diabetes,increased bilirubin,small diameter of the common bile duct,or ampullary diverticulum between the two groups were not *** significant differences were observed between the two groups concerning sex and age(<60 years).Patients with a history of choledocholithiasis,pancreatitis,and Oddi sphincter dysfunction were higher in the EST group than in the EPBD *** number of cases of pancreatic development,pancreatic duct sphincterotomy,and difficult intubation were higher in the EST group than in the EPBD *** number of Oddi’s sphincter manometries,ERCP surgical outcomes,and guidewires entering the pancreatic duct several times in EST group were lower than those in the EPBD *** numbers of stone recurrences,reflux cholangitis,and cholecystitis were higher in the EST group than in the EPBD *** In summary,common bile duct stones,pancreatitis history,and multiple guided wire introductions into the pancreatic duct are independent risk factors for EST and *** on this evidence,this study can provide

关键词： Oddi Cholangiopancreatography Endoscopic retrograde Risk factors Endoscopic sphincterotomy Endoscopic papillary balloon dilation

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

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Neural Regeneration Research 2024年第11期19卷 2522-2531页

作者： Shaojun Wang Siti Tong xin Jin Na Li Pingxiu Dang yang Sui ying Liu Dajiang Wang Division of Ophthalmology The Third Medical Center of PLA General HospitalBeijingChina Department of Ophthalmology Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain *** models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular *** results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and *** single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular *** extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct *** found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of *** study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular *** data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

关键词： apoptosis axon degeneration high intraocular pressure microglia ocular hypertension photoreceptor cells retina retinal degeneration retinal ganglion cells single-cell RNA sequencing

Pyridine-regulated Sb@InSbS_(3)ultrafine nanoplates as high-capacity and long-cycle anodes for sodium-ion batteries

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Rare Metals 2024年第5期43卷 2080-2092页

作者： Jia-ying Ren Xiang-Lin Yu Chang-Miao Chen xin-Yu Hu Ting yang Ming Zhang College of Materials Science and Engineering and College of Science Central South University of Forestry and TechnologyChangsha 410004China College of Semiconductors(College of Integrated Circuits) Changsha Semiconductor Technology and Application Innovation Research InstituteHunan UniversityChangsha 410082China

Sb-based materials exhibit considerable potential for sodium-ion storage owing to their high theoretica ***,the bulk properties of Sb-based materials always result in poor cycling and rate *** overcome these issues,pyridine-regulated Sb@InSbS_(3)ultrafine nanoplates loaded on reduced graphene oxides(Sb@InSbS_(3)@rGO)were designed and *** the synthesis process,pyridine was initially adopted to coordinate with In^(3+),and uniformly dispersed In_(2)S_(3)ultrafine nanoplates on reduced graphene oxide were generated after ***,partial In^(3+)was exchanged with Sb^(3+),and Sb@InSbS_(3)@rGO was obtained by using the subsequent annealing *** unique structure of Sb@InSbS_(3)@rGO effectively shortened the transfer path of sodium ions and electrons and provided a high *** the anode in sodium-ion batteries,the Sb@InSbS_(3)@rGO electrode demonstrated a significantly higher reversible capacity better stability(445 m Ah·g^(-1)at 0.1 A·g^(-1)after 200 cycles and 212 mAh·g^(-1)at 2 A·g^(-1)after 1200 cycles),and superior rate(210 mAh·g^(-1)at 6.4 A·g^(-1))than the electrode without pyridine(355 mAh·g-1at 0.1 A·g-1after 55 cycles and 109 mAh·g^(-1)at 2 A·g^(-1)after 770 cycles)Furthermore,full cells were assembled by using the Sb@InSbS_(3)@rGO as anode and Na_(3)V_(2)(PO_(4))_(3)as cathode which demonstrated good cycling and rate performances and exhibited promising application *** results indicate that adjusting the microstructure of electrode materials through coordination balance is A·good strategy for obtaining high-capacity,high-rate,and longcycle sodium storage performances.

关键词： Sodium-ion battery Sb-based anode material Pyridine coordination Reduced size nanostructure Half/full cell

Love wave propagation in one-dimensional piezoelectric quasicrystal multilayered nanoplates with surface effects

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Applied Mathematics and Mechanics(English Edition) 2024年第4期45卷 619-632页

作者： xin FENG Liaoliang KE yang GAO College of Science China Agricultural UniversityBeijing 100083China School of Mechanical Engineering Tianjin UniversityTianjin 300350China

The exact solutions for the propagation of Love waves in one-dimensional(1D)hexagonal piezoelectric quasicrystal(PQC)nanoplates with surface effects are *** electro-elastic model is developed to investigate the anti-plane strain problem of Love wave *** introducing three shape functions,the wave equations and electric balance equations are decoupled into three uncorrelated *** the boundary conditions of the top surface on the covering layer,the interlayer interface,and the matrix,a dispersive equation with the influence of multi-physical field coupling is provided.A surface PQC model is developed to investigate the surface effects on the propagation behaviors of Love waves in quasicrystal(QC)multilayered structures with nanoscale thicknesses.A novel dispersion relation for the PQC structure is derived in an explicit closed form according to the non-classical mechanical and electric boundary *** examples are given to reveal the effects of the boundary conditions,stacking sequence,characteristic scale,and phason fluctuation characteristics on the dispersion curves of Love waves propagating in PQC nanoplates with surface effects.

关键词： piezoelectric quasicrystal(PQC)material multilayered plate dispersion characteristic surface effect