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Journal of Pharmaceutical Analysis 2016年第2期6卷 103-111页

作者： milagros montemurro maría m.de zan juan c.robles Laboratorio de Control de Calidad de medicamentos Facultad de Bioqufmica y Ciendas Biologicas Universidad Nacional del Litoral Santa Fe Argentina

methotrexate （mTX） is an antineoplastic drug, and due to its high toxicity, the therapeutic drug mon- itoring is strictly conducted in the clinical practice. The chemometric optimization and validation of a high performance liquid chromatography （HPLC） method using core-shell particles is presented for the determination of mTX in plasma during therapeutic monitoring. Experimental design and response surface methodology （RSm） were applied for the optimization of the chromatographic system and the analyte extraction step. A Poroshel1120 EC-C18 （3.0 mm × 75 mm, 2.7 μm） column was used to obtain a fast and efficient separation in a complete run time of 4 min. The optimum conditions for the chroma- tographic system resulted in a mobile phase consisting of acetic acid/sodium acetate buffer solution （85.0 mm, pH =4.00） and 11.2% of acetonitrile at a flow rate of 0.4 mL/min. Selectivity, linearity, accuracy and precision were demonstrated in a range of 0.10-6.0 μm of mTX. The application of the optimized method required only 150μL of patient plasma and a low consumption of solvent to provide rapid re- sults.

关键词： HPLC Core-shell particles methotrexate Drug monitoring

multiple responses optimization in the development of a headspace gas chromatography method for the determination of residual solvents in pharmaceuticals

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Journal of Pharmaceutical Analysis 2015年第5期5卷 296-306页

作者： Carla m.Teglia milagros montemurro maría m.de zan maría S.Cmara Laboratorio de Control de Calidad de medicamentos Facultad de Bioquimica y Ciencias BiologicasUniversidad Nacional del Litoral

An efficient generic static headspace gas chromatography （HSGC） method was developed, optimized and validated for the routine determination of several residual solvents （RS） in drug substance, using a strategy with two sets of calibration. Dimethylsulfoxide （DmSO） was selected as the sample diluent and internal standards were used to minimize signal variations due to the preparative step. A gas chroma- tograph from Agilent m.del 6890 equipped with flame ionization detector （FID） and a DB-624 （30 m × 0.53 mm i.d., 3.00 μm film thickness） column was used. The inlet split ratio was 5：1. The influ- encing factors in the chromatographic separation of the analytes were determined through a fractional factorial experimental design. Significant variables： the initial temperature （IT）, the final temperature （FT） of the oven and the carrier gas flow rate （F） were optimized using a central composite design. Response transformation and desirability function were applied to find out the optimal combination of the chromatographic variables to achieve an adequate resolution of the analytes and short analysis time. These conditions were 30 ℃ for IT, 158 ℃ for FT and 1.90 mL/min for F. The method was proven to be accurate, linear in a wide range and very sensitive for the analyzed solvents through a comprehensive validation according to the ICH guidelines.

关键词： Headspace gas chromatographyResidual solventsPharmaceuticalsSurface response methodologydesirabiliW function

New Amphiphilic Amino Acid derivatives for Efficient DNA Transfection in Vitro

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Advances in Chemical Engineering and Science 2017年第2期7卷 191-205页

作者： Lucía C.Pena maría F.Argaraná maría m.de zan Antonella Giorello Sebastián Antuna Claudio C.Prieto Carolina m.I.Veaute Diana m.müller LAQUImAP Dto.Química OrgánicaUniversidad Nacional del LitoralSanta FeArgentina Cát.microbiología General Universidad Nacional del LitoralSanta FeArgentina Laoratorio de Control de medicamentos Universidad Nacional del LitoralSanta FeArgentina Instituto de Investigaciones en Catálisis y Petroquímica Universidad Nacional del LitoralSanta FeArgentina Laboratorio de Cultivos Celulares Universidad Nacional del LitoralSanta FeArgentina Laboratorio de Inmunología Básica Universidad Nacional del LitoralSanta FeArgentina

Nucleic acids-based therapies have recently developed as next-generation agents for treating and preventing viral infection, cancer, and genetic disorders, but their use is still limited due to its relatively poor delivery into targeted cells. We designed and synthesized new amphiphilic amino acid derivatives (cysteine-based) of low molecular weight, formed by the same pentapeptide (AG2: WWCOO) N-acylated, with different hydrophobic chains containing from 12 to 18 carbons, named AG2-Cn (N), which dimerize by oxidation in the presence of pLenti-CmV-GFP Puro plasmid (P) in the respective gemini. We determined transfection efficiency, critical micelle concentration, particle size, ζ-potential and cytotoxicity for the derivatives obtained. We found that all the synthesized compounds were active for DNA delivery and had greater ability to transfect CHO-K1 cells. In particular, AG2-C18 is a promising carrier for gene delivery because it showed no cytotoxicity and its activity was greater than or equal to the commercial actives currently used.

关键词： Amphiphile N-Acylated Cysteine Gemini Ornithine Transfection

Organic Brønsted Acid-Catalyzed Stereoselective Cationic RAFT Polymerization:The Effect of RAFT Agents

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Chinese Journal of Polymer Science 2024年第6期42卷 711-717页

作者： Zheng-Yi Zhang zan Yang Yun Liao Sai-Hu Liao Key Laboratory of molecule Synthesis and Function Discovery(Fujian Province University) College of ChemistryFuzhou UniversityFuzhou350108China State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China Beijing National Laboratory for molecular Sciences Beijing100190China

The tacticity of vinyl polymers is a key factor affecting the properties of ***,organic Brønsted acids have been demonstrated as effective catalysts for the development of highly stereoselective cationic reversible addition-fragmentation chain transfer(RAFT)polymerizations of vinyl ethers,in which the use of RAFT agents could allow the control the molecular weight and tacticity of polymer products ***,the effect of RAFT agents on the tacticity-regulation remains elusive and lacks of *** this study,we synthesized four types of RAFT agents and evaluated their influence in the stereoselective cationic polymerization of isobutyl vinyl ether in the presence of PADI as a Brønsted acid catalyst,which unveils that the Z group of RAFT agents could not only affect the polydispersity of the products,but also exert a profound effect on the *** extensive screening of the RAFT agents,high stereoregularity(isotacticity,90%m)was obtained when using dithiocarbonate ester-type RAFT agents with a benzyloxy Z group.

关键词： Bronsted acid catalysis Stereoselective cationic polymerization RAFT polymerization Chain transfer agents Tacticity

A folic acid-decorated nanoparticles loaded JQ1 for oral squamous cell carcinoma therapy

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Chinese Chemical Letters 2024年第3期35卷 332-336页

作者： dequan Zeng Zhongkai ma Xin zan Ting Luo Xiang Wang Xiang Gao Xianghui Fu School of Health management Xihua UniversityChengdu 610039China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China College of StomatologySichuan UniversityChengdu 610041China department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Breast Disease Center Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality *** poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC *** that,a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these ***,we produced a therapeutic nano drug delivery system(FA-PEG-PLA-JQ1)through encapsulating JQ1[a small-molecule inhibitor of bromodomain containing protein 4(BRD4)]into the folic acid(FA)-modified nanoparticle(PEG-PLA),which could prolong the half-life of JQ1 and target the tumor *** then,JQ1 released from this nanoparticle could prevent OSCC growth inducing tumor cell apoptosis,inhibiting tumor angiogenesis and the polarization of m2 type *** conclusion,our date demonstrated the therapeutic benefits of FA-PEG-PLA-JQ1 against OSCC in vivo or in vitro,which could be a novel treatment strategy for OSCC in coming days.

关键词： Folic acid Nanoparticles JQ1 Oral squamous cell carcinoma macrophages

Effect of Al_(2)O_(3)on the mechanical Properties of(B_(4)C+Al_(2)O_(3))/Al Neutron Absorbing materials

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Acta metallurgica Sinica(English Letters) 2024年第8期37卷 1411-1420页

作者： J.X.Cai B.m.Shi N.Li Y.Liu Z.G.Zhang Y.N.zan Q.Z.Wang B.L.Xiao Z.Y.ma Shi‑Changxu Innovation Center for Advanced materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China Key Laboratory of Nuclear materials and Safety Assessment Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China Nuclear Equipment Division Beijing Institute of Nuclear EngineeringChina Nuclear Power Engineering Co.Ltd.Beijing 100840China department of materials Science School of Mechanical EngineeringShenyang UniversityShenyang 110044China

B_(4)C/Al composites are widely utilized as neutron absorbing materials for the storage and transportation of spent nuclear *** order to improve the high-temperature mechanical properties of B_(4)C/Al composites,in-situ nano-Al_(2)O_(3)was introduced utilizing oxide on Al powder *** this study,the Al_(2)O_(3)content was adjusted by utilizing spheroid Al powder with varying diameters,thereby investigating the impact of Al_(2)O_(3)content on the tensile properties of(B_(4)C+Al_(2)O_(3))/Al *** was found that the pinning effect of Al_(2)O_(3)on the grain boundaries could hinder the recovery of dislocations and lead to dislocation accumulation at high *** the result,with the increase in Al_(2)O_(3)content and the decrease in grain size,the high-temperature strength of the composites increased *** finest Al powder used in this investigation had a diameter of 1.4μm,whereas the resultant composite exhibited a maximum strength of 251 mPa at room temperature and 133 mPa at 350℃,surpassing that of traditional B_(4)C/Al composites.

关键词： Al matrix composites Neutron absorbing materials (B_(4)C+Al_(2)O_(3))/Al composites High-temperature strength

YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling

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Journal of Pharmaceutical Analysis 2024年第4期14卷 525-541页

作者： Hua Sui Wanli deng Qiong Chai Bing Han Yuli Zhang Zhenzhen Wei zan Li Ting Wang Jiling Feng man Yuan Qingfeng Tang Hongxi Xu medical Experiment Center Jiading Branch of Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai201803China Translational medicine Research Center for Cancer Prevention and Treatment Shanghai General Hospital Jiading Branch-School of Pharmacy of Shanghai University of Traditional Chinese Medicine Joint LaboratoryShanghai201803China department of medical Oncology Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai201203China The Second Clinical medical College of Henan University of Traditional Chinese medicine Zhengzhou450000China Shanghai University of Traditional Chinese medicine Shanghai201203China Precision Research Center for Refractory Diseases Institute for Clinical ResearchShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai201620China

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon *** previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling ***,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is *** this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling ***,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TmE),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)m.del with Wnt5a ***,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC m.del to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)***,our findings demon-strate a significant reduction in m2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOm)/dextran sodium sulfate(DSS)***,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with m2 ***,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in ***,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within

关键词： Tumor microenvironment Intestinal epithelial cells Treg/Th17 cells metabolism Wnt5a/JNK signaling Tumorigenesis

mETTL14 downregulation drives S100A4^(+)monocyte-derived macrophages via myD88/NF-κB pathway to promote mAFLD progression

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2176-2192页

作者： Yue-fan Wang Wen-li Zhang Zhi-xuan Li Yue Liu Jian Tan Hao-zan Yin Zhi-chao Zhang Xian-jie Piao min-hao Ruan Zhi-hui Dai Si-jie Wang Chen-yang mu Ji-hang Yuan Shu-han Sun Hui Liu Fu Yang The Third department of Hepatic Surgery Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University200438 ShanghaiChina The department of medical Genetics Naval Medical University200433 ShanghaiChina Translational medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital100048 BeijingChina The department of Pharmaceutical Analysis School of PharmacyNaval Medical University200433 ShanghaiChina Key Laboratory of Biosafety defense Ministry of Education200433 ShanghaiChina Shanghai Key Laboratory of medical Biodefense 200433 ShanghaiChina

Without intervention,a considerable proportion of patients with metabolism‐associated fatty liver disease(mAFLD)will progress from simple steatosis to metabolism‐associated steatohepatitis(mASH),liver fibrosis,and even hepatocellular ***,the molecular mechanisms that control progressive mAFLD have yet to be fully ***,we unraveled that the expression of the N6-methyladenosine(m6A)methyltransferase mETTL14 is remarkably downregulated in the livers of both patients and several murine m.dels of mAFLD,whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation,liver injury,and ***,hepatic mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet(HFD).Notably,in vivo and in vitro mechanistic studies indicated that mETTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner,which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1^(+)Ccr2^(+)monocyte-derived macrophages(mo-macs).In detail,Cx3cr1^(+)Ccr2^(+)mo-macs can be categorized into m1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells(HSCs)to promote liver *** experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/myD88/NF-κB signaling pathway in Cx3cr1^(+)Ccr2^(+)*** of mETTL14 or GLS2,or interfering with this signal transduction pathway such as inhibiting myD88 could ameliorate liver injuries and *** together,these findings indicate potential therapies for the treatment of mAFLD progression.

关键词： S100A4 myD88 metabolism

多级离散扩展移相控制双有源桥DC-DC变换器的原理、参数设计与性能

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电工技术学报 2024年第12期39卷 3761-3773页

作者：刘赞沙金邱高峰陈丽蓉西南交通大学电气工程学院成都610031 圣邦微电子(北京)股份有限公司北京100005

该文提出一种双有源桥(DAB)DC-DC变换器的多级离散扩展移相(mD-EPS)控制,旨在提升DAB DC-DC变换器系统的动态响应性能。同时,考虑效率优化,兼顾额定功率范围、输出电压纹波等性能指标,研究mD-EPS控制的离散参数分布方式对控制性能的影... 详细信息

该文提出一种双有源桥(DAB)DC-DC变换器的多级离散扩展移相(mD-EPS)控制,旨在提升DAB DC-DC变换器系统的动态响应性能。同时,考虑效率优化,兼顾额定功率范围、输出电压纹波等性能指标,研究mD-EPS控制的离散参数分布方式对控制性能的影响及参数设计方法。通过搭建160 W小功率实验样机对mD-EPS的控制性能进行了验证。实验结果表明,与传统扩展移相控制相比,DABDC-DC变换器的mD-EPS控制能够大幅提升变换器系统的动态响应速度(响应时间缩短99.95%),最高效率为94.54%。

关键词：双有源桥变换器离散移相动态性能效率

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一例锶配合物的合成、结构及表征

人工晶体学报 2024年第2期53卷 293-299页

作者：保玉婷梁毅农孙赞青海民族大学化学化工学院西宁810007 青藏高原资源化学与生态环境保护国家民委重点实验室西宁810007

在溶剂热条件下,以1,4,5,8-萘四羧酸(H_(4)L1)为配体,六水合氯化锶为金属源合成了一例锶配合物[Sr(L)_(2)(H_(2)O)_(4)]_(n)(1)。通过元素分析(EA)、X射线单晶衍射(SXRD)、X射线粉末衍射(PXRD)、红外光谱(IR)和热重分析(TGA)进行结构表... 详细信息

在溶剂热条件下,以1,4,5,8-萘四羧酸(H_(4)L1)为配体,六水合氯化锶为金属源合成了一例锶配合物[Sr(L)_(2)(H_(2)O)_(4)]_(n)(1)。通过元素分析(EA)、X射线单晶衍射(SXRD)、X射线粉末衍射(PXRD)、红外光谱(IR)和热重分析(TGA)进行结构表征。X射线单晶衍射结果表明,1,4,5,8-萘四羧酸(H_(4)L1)发生原位反应生成1,3-二氧代-1H,3H-苯并[脱]异色烯-6,7-二羧酸(H2L)。在配合物1中,每个锶原子位于四方反棱柱的几何构型中,配体连接金属延伸形成一维链状结构,链与链之间通过氢键与π…π堆积作用形成2D超分子结构。探究了配合物的固态发光行为,发现配合物在211 nm的激发波长下产生宽的发射光谱带(450~690 nm),并在535 nm处出现最大发射波长,因此可知配合物是一种潜在的绿光材料。

关键词：溶剂热合成锶配合物晶体结构荧光性质原位反应

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