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Extended survival with metastatic pancreatic cancer under fruquintinib treatment after failed chemotherapy:Two case reports

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World Journal of Clinical Cases 2024年第7期12卷 1296-1304页

作者： dan Wu Qiong Wang Shuai Yan Xia Sun Ya Qin Ming Yuan Nan-Yao Wang Xian-Ting Huang Department of Oncology Jiangyin People's HospitalWuxi 214400Jiangsu ProvinceChina

BACKGROUND Pancreatic cancer is a highly malignant *** decades of treatment progress,the current five-year survival rate for patients is still less than 10%.For later-line treatment,the treatment options are even more ***-angiogenic drugs can improve progression-free survival in patients with advanced pancreatic *** data show that fruquintinib might improve the prognosis of advanced pancreatic cancer by targeting angiogenesis and lymphopoiesis,improving the abnormal vascular structure,and modulating the tumour immune *** SUMMARY We present two cases of third-line fruquintinib monotherapy that brought an extraprolonged progress-free survival(PFS)of 10 *** 1 took adjuvant gemcitabine-based and first-line nab-paclitaxel-based chemotherapy and then used local radiotherapy combined with programmed cell death 1 receptor(PD-1).Each line lasted approximately 7 ***,the patient took third-line fruquintinib,which was followed by stable disease for 10 months,during which no additional adverse effect was *** patient later refused to take fruquintinib due to difficulty urinating and lower abdominal pain after the coronavirus disease 2019(COVID-19)*** patient died in February *** 2 also took two prior lines of chemotherapy and then local radiotherapy combined with *** confirmed disease progression,the patient experienced a continuous partial response after using fruquintinib monotherapy in the third *** the patient had COVID-19 in December 2022,fruquintinib was *** patient died in January 2023 due to disease *** Both cases achieved a PFS benefit from later-line single-agent fruquintinib *** its better safety profile,fruquintinib may be worth exploring and studying in more depth as a later-line treatment for pancreatic cancer patients.

关键词： Pancreatic cancer Anti-vascular endothelial growth factor receptor Fruquintinib Case report

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Wide-color-gamut, high-purity, and high-brightness thin film structural colors based on modified Fano resonant structure

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CHINESE OPTICS LETTERS 2024年第8期22卷 082601-082601页

作者： Chen, Weijie He, Zexiang Duan, Zhenzhen Yang, Jian Wang, Ning Wang, dan Hu, Zexiong Chen, Nan Luo, Zhengqian Bu, Yikun Xiamen Univ Sch Elect Sci & Engn Natl Model Microelect Coll Xiamen 361005 Peoples R China Xiamen Univ Fujian Key Lab Ultrafast Laser Technol & Applicat Xiamen 361005 Peoples R China

Recently, the Fano resonance has played an increasingly important role in improving the color performance of structural colors. In this study, we further elucidate the asymmetric spectral shape generated by Fano resonance from a phase perspective and explore four distinct continuum state structures. By integrating the proposed cavity-like structure with a metal-dielectric-metal discrete state, multilayered thin-film structural colors with minimal background reflection, as low as 8%, were successfully achieved. The reflection peak of this structure exhibits a bandwidth of approximately 50 nm and reaches up to 80%, indicating heightened saturation and color brightness. Moreover, by adjusting the thickness, we effortlessly obtained a broader color gamut compared to Adobe ROB (45.2%), covering 56.7% of the CIE color space. Even adjusting a single layer can achieve a color gamut of 47.1%. In experiments, by deliberately choosing low oxygen- dependent materials, excellent ROB colors with high brightness and in high consistency with simulation results were successfully achieved. Therefore, the scheme's simple process for structural color creation, along with its excellent color performance and the ability to effectively replicate simulation characteristics makes it highly valuable in fields like anti- counterfeiting, decoration, display devices, and solar cell panels.

关键词： Fano resonance structural colors full color thin films high saturation

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Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2581-2597页

作者： Hongliang Qiu Sihui Huang Yuting Liu Libo Liu Fengming Guo Yingying Guo dan Li Xianfeng Cen Yajie Chen Meng Zhang Yan Che Man Xu Qizhu Tang Department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan 430060China

Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively *** was recently identified as a major mechanism of DOX-induced ***,a novel ferroptosis inhibitor,is a well-described clinical drug widely ***,its role and pathological mechanism in DOX-induced cardiotoxicity are still *** this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced *** results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in *** and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by ***,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of *** could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with *** results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination *** conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.

关键词： Idebenone DOX-induced cardiotoxicity Ferroptosis FSP1 Ubiquitination Lipid peroxidation Iron overload Clinical translation

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x86处理器向量条件访存指令安全脆弱性分析

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计算机学报 2024年第3期47卷 525-543页

作者：李丹萍朱子元史岗孟丹中国科学院信息工程研究所北京100085 中国科学院大学网络空间安全学院北京100049

单指令多数据流(single Instruction stream,Multiple Data streams,SIMD)是一种利用数据级并行提高处理器性能的技术,旨在利用多个处理器并行执行同一条指令增加数据处理的吞吐量.随着大数据、人工智能等技术的兴起,人们对数据并行化... 详细信息

单指令多数据流(single Instruction stream,Multiple Data streams,SIMD)是一种利用数据级并行提高处理器性能的技术,旨在利用多个处理器并行执行同一条指令增加数据处理的吞吐量.随着大数据、人工智能等技术的兴起,人们对数据并行化处理的需求不断提高,这使得SIMD技术愈发重要.为了支持SIMD技术,Intel和AMD等x86处理器厂商从1996年开始在其处理器中陆续引入了MMX(MultiMedia Extensions)、SSE(Streaming SIMD Extensions)、AVX(Advanced Vector eXtensions)等SIMD指令集扩展.通过调用SIMD指令,程序员能够无需理解SIMD技术的硬件层实现细节就方便地使用它的功能.然而,随着熔断、幽灵等处理器硬件漏洞的发现,人们逐渐认识到并行优化技术是一柄双刃剑,它在提高性能的同时也能带来安全风险.本文聚焦于x86 SIMD指令集扩展中的VMASKMOV指令,对它的安全脆弱性进行了分析.本文的主要贡献如下:(1)利用时间戳计数器等技术对VMASKMOV指令进行了微架构逆向工程,首次发现VMASKMOV指令与内存页管理和CPU Fill Buffer等安全风险的相关性;(2)披露了一个新的处理器漏洞EvilMask,它广泛存在于Intel和AMD处理器上,并提出了3个EvilMask攻击原语:VMASKMOVL+Time(MAP)、VMASKMOVS+Time(XD)和VMASKMOVL+MDS,可用于实施去地址空间布局随机化攻击和进程数据窃取攻击;(3)给出了2个EvilMask概念验证示例(Proof-of-Concept,PoC)验证了EvilMask对真实世界的信息安全危害;(4)讨论了针对EvilMask的防御方案,指出最根本的解决方法是在硬件层面上重新实现VMASKMOV指令,并给出了初步的实现方案.

关键词：处理器安全单指令多数据流(SIMD) 微体系结构侧信道攻击 VMASKMOV指令地址空间布局随机化(ASLR)

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Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants

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Chronic Diseases and Translational Medicine 2024年第2期10卷 118-129页

作者： Huan Zhang Yuxi Chen Peng Xu dan Liu Naqiong Wu Laiyuan Wang Xingbo Mo Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Department of EpidemiologySchool of Public HealthMedical College of Soochow UniversitySuzhouJiangsuChina Cardiometabolic Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Cardiovascular Epidemiology&Department of Epidemiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina MOE Key Laboratory of Geriatric Diseases and Immunology School of Public HealthCenter for Genetic Epidemiology and GenomicsMedical College of Soochow UniversitySuzhouJiangsuChina

Background Genome-wide association studies(GWAS)have identified more than a thousand loci for blood pressure(BP).Functional genes in these loci are cell-type *** aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms(RNAm-SNPs).Methods Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium,we identified associations between RNAm-SNPs and *** association between RNAm-SNPs,gene expression,and BP were *** A total of 355 RNAm-SNPs related to m6A,m1A,m5C,m7G,and A-to-I modification were associated with *** related genes were enriched in the pancreatic secretion pathway and renin secretion *** BP GWAS signals were significantly enriched with m6A-SNPs,highlighting the potential functional relevance of m6A in physiological processes influencing ***,m6A-SNPs in CYP11B1,PDE3B,HDAC7,ACE,SLC4A7,PDE1A,FRK,MTHFR,NPPA,CACNA1D,and HDAC9 were *** methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were ***-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection(AD)cases and *** scRNA-seq study,we identified ARID5A,HLA-DPB1,HLA-DRA,IRF1,LINC01091,MCL1,MLF1,MLXIPL,NAA16,NADK,RERG,SRM,and USP53 as differential expression genes for AD in aortic *** The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs,gene expression,and *** identified BP-associated genes in aortic cells were associated with AD.

关键词： aortic dissection blood pressure genome-wide association study RNA modification single-cell

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Wafer-level substrate-free YIG single crystal film for a broadband tunable terahertz isolator

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Photonics Research 2024年第3期12卷 505-513页

作者： XILAI ZHANG dan ZHAO DING ZHANG QIANG XUE FEI FAN YULONG LIAO QINGHUI YANG QIYE WEN School of Electronic Science and Engineering State Key Laboratory of Electronic Thin Film and Integrated DevicesUniversity of Electronic Science and Technology of ChinaChengdu 610054China Tianjin Key Laboratory of Optoelectronic Sensor and Sensing Network Technology Institute of Modern OpticsNankai UniversityTianjin 300350China Shenzhen Institute for Advanced Study University of Electronic Science and Technology of ChinaShenzhen 518110China

Yttrium iron garnet(YIG)is a promising material for various terahertz applications due to its special optical *** present,a high-quality YIG wafer is the desire of terahertz communities and it is still challenging to prepare substrate-free YIG single crystal *** this work,we prepared wafer-level substrate-free La:YIG single crystal films,for the first time,to our *** optical and magneto-optical properties of La:YIG films were characterized by terahertz time domain spectroscopy(THz-TDS).Results show that the as-prepared La:YIG film has an insertion loss of less than 3 dB and a low absorption coefficient of less than10 cm-1below 1.6 *** from the thickness of the substrate-free YIG films and low insertion loss,their terahertz properties could be further manipulated by simply using a wafer-stacking *** four La:YIG films were stacked,there was an insertion loss of less than 10 dB in the range of 0.1-1.2 *** Faraday rotation angle of the four-layer-stacked La:YIG films reached 19°,and the isolation could reach17 *** further increasing the stacking number to eight pieces,a remarkable Faraday rotation angle of45°was achieved with an isolation of 23 dB,which is important for practical application in the THz *** material may provide a milestone opportunity to make various non-reciprocal devices,such as isolators and phase shifters.

关键词： YIG film insertion

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前导肽介导的SprD蛋白体外折叠研究

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中国农业科技导报 2024年第9期26卷 54-61页

作者：李丹四川大学生命科学学院成都610065

为提高以前体形式合成的蛋白质折叠与成熟效率,以枯草杆菌蛋白酶SprD为研究对象,通过蛋白重组表达、氨基酸定点突变、包涵体纯化结合体外复性、酶催化性能测定等方法比较各前体蛋白折叠成熟情况。结果表明,野生型前导肽介导的SprD前体... 详细信息

为提高以前体形式合成的蛋白质折叠与成熟效率,以枯草杆菌蛋白酶SprD为研究对象,通过蛋白重组表达、氨基酸定点突变、包涵体纯化结合体外复性、酶催化性能测定等方法比较各前体蛋白折叠成熟情况。结果表明,野生型前导肽介导的SprD前体蛋白可以在230 min内完成成熟,时间较长;成熟肽序列中E112A、S221A及S221C等突变导致相应前体蛋白成熟时间延长或成熟失败;而前导肽串联表达和切割位点酪氨酸缺失等措施可以将蛋白成熟时间缩短至80~160 min,成熟效率提高0.5~2.0倍,且成熟酶催化能力不受影响。前导肽序列中单个氨基酸位点改变对蛋白成熟影响较小,但对酶催化能力提升有一定帮助。因此,前导肽介导的蛋白成熟与酶催化能力的改变是2个相对独立的过程,前导肽表达方式与切割位点变化是促进蛋白体外成熟的较优方案。研究结果为加速蛋白成熟与蛋白改造提供了可参考方法。

关键词：前导肽 SprD蛋白蛋白复性折叠成熟

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Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS Center for Stem Cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

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响应面法优化碱法提取狐臭柴叶多糖工艺及生物活性研究

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天然产物研究与开发 2024年第1期36卷 94-101,85页

作者：杨丹丹朱玉昌周大寨生物资源保护与利用湖北省重点实验室湖北民族大学林学园艺学院湖北民族大学生物与食品工程学院恩施445000

优化狐臭柴叶碱溶性多糖(PLAP)提取工艺,探讨PLAP的体外抗氧化和抗肿瘤活性。采用狐臭柴叶经酸提取法提取的残渣为原料,在单因素基础上,利用响应面优化PLAP的提取工艺,通过抗氧化实验和抗肿瘤实验对PLAP的体外生物活性进行研究。结果表... 详细信息

优化狐臭柴叶碱溶性多糖(PLAP)提取工艺,探讨PLAP的体外抗氧化和抗肿瘤活性。采用狐臭柴叶经酸提取法提取的残渣为原料,在单因素基础上,利用响应面优化PLAP的提取工艺,通过抗氧化实验和抗肿瘤实验对PLAP的体外生物活性进行研究。结果表明:PLAP最佳提取工艺为:料液比1∶50 g/mL、NaOH浓度为0.25 mmol/L、提取时间110 min、此条件下PLAP提取率为(11.80±0.50)%。PLAP有较强的抗氧化活性,对DPPH自由基、羟基自由基和ABTS自由基清除率IC 50值分别为12.38、3.22和0.18 mg/mL。同时细胞实验表明,PLAP在一定范围内抑制A549细胞和HepG2细胞的增殖与迁移,呈现剂量效应关系。本文为狐臭柴资源的充分开发、临床应用提供理论依据。

关键词：狐臭柴叶多糖提取工艺响应面实验抗氧化活性抗肿瘤活性

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非经典型多梳抑制复合物1.6的电镜结构分析

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上海交通大学学报（医学版） 2024年第9期44卷 1136-1145页

作者：蔡单黄晶上海交通大学医学院附属第九人民医院上海精准医学研究院上海200125

目的·通过负染色及透射电子显微镜(电镜)技术分析非经典型多梳抑制复合物1.6(polycomb repressive complex 1.6,PRC1.6)的蛋白结构,获得人源PRC1.6七元复合物的三维轮廓信息。方法·将PRC1.6复合物中7个组分基因RNF2、PCGF6、RYBP、L3M... 详细信息

目的·通过负染色及透射电子显微镜(电镜)技术分析非经典型多梳抑制复合物1.6(polycomb repressive complex 1.6,PRC1.6)的蛋白结构,获得人源PRC1.6七元复合物的三维轮廓信息。方法·将PRC1.6复合物中7个组分基因RNF2、PCGF6、RYBP、L3MBTL2、CBX3、E2F6和TFDP1分别克隆至N端带有6×His-3×Flag标签的pMLink载体中,利用聚乙烯亚胺瞬时转染的方式在悬浮培养的哺乳动物细胞Expi293F中表达PRC1.6七元复合物,依次使用anti-DYKDDDDK标签亲合树脂、分子筛Superdex 200 Increase 10/300 GL(凝胶过滤层析)和甘油密度梯度离心分离纯化PRC1.6复合物;通过液相色谱-串联质谱法(liquid chromatography-tandem mass spectrometry,LC-MS/MS)确认PRC1.6七元复合物组分;利用泛素化活性实验和电泳迁移率变动分析(electrophoretic mobility shift assay,EMSA)对复合物的体外泛素化活性以及与核小体结合亲和力进行验证;使用乙酸双氧铀进行样品制备并通过透射电镜观察蛋白样品,随后通过单颗粒重构技术对PRC1.6复合物的三维结构信息进行分析;利用UCSF Chimera软件将蛋白质结构数据库(Protein Data Bank,PDB)中的目的蛋白相关原子结构模型与重构获得的PRC1.6电子密度图进行拟合,预测PRC1.6七元复合物中各亚基的定位。结果·通过真核表达、亲和层析、凝胶过滤层析和甘油密度梯度离心,以及LC-MS/MS验证,获得了纯度较高、均一性较好的PRC1.6七元复合物,且泛素化活性实验和EMSA发现该复合物在体外具有泛素化活性和核小体结合亲和力。利用负染色、透射电镜和单颗粒重构技术初步解析了分辨率约为15.2Å(1Å=10-10 m)的PRC1.6七元复合物的三维结构,将已有RNF2、PCGF6、RYBP、L3MBTL2、CBX3和DP1部分氨基酸序列的原子模型以及E2F6的AlphaFold2预测结构与重构获得的电子密度图进行匹配,初步确认了7个亚基在PRC1.6复合物三维结构中的定位情况。结论·使用负染色和透射电镜,以及单颗粒重构技术搭建了人源PRC1.6七元复合物的三维结构模型。

关键词：多梳抑制复合物1 表观遗传调控组蛋白泛素化负染色透射电子显微镜蛋白质三维结构

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