二氧化锰型钾离子筛的合成及其对钾的离子交换热力学

以硫酸锰和高锰酸钾为原料合成隐钾锰型水合二氧化锰（CRYMO）,酸改型后得晶体结构为α-MnO2的钾离子筛（CRYMO-H）。CRYMO-H对K+的饱和交换容量达到4.6429 mmol (181.54 mg) K+/g离子筛,对钾离子有较高的表观交换容量。测定了15、25、35、45℃下CRYMO-H对H+-K+体系的离子交换等温线,采用Pitzer电解质溶液理论计算出该离子交换体系的活度系数,得到H+-K+交换的平衡常数 、 、 和 等热力学函数。结果表明： 随温度的升高而降低、CRYMO-H对K+的选择性大于原来可交换阳离子H+的选择性、吸附钾的过程是自发过程（ <0）,该离子交换反应是放热反应。     

聚锑酸离子交换剂对锶的吸附行为研究

研究了聚锑酸离子交换剂吸附0.01 mol/L HNO_3溶液中锶的热力学特征,通过吸附动力学实验,初步探讨了温度对吸附过程的影响.结果表明,聚锑酸对0.01mol/L HNO_3溶液中锶的吸附符合Freundlich 经验公式,表现为吸热的化学吸附过程.根据毛细孔扩散模型,由平衡数据和动力学曲线计算了锶在聚锑酸离子交换剂颗粒内液相有效扩散系数为8.18×10~(-9)cm~2/s(20℃)和1.33×10~(-8)cm~2/s(30℃).     

木纤维对Sr~(2+)和Cs~+的吸附性能及机理研究

采用间歇法研究了木纤维对Sr2+、Cs+的吸附作用,探讨了木纤维的粒度、溶液的pH、不同介质、吸附时间、温度及木纤维用量等因素对Sr2+、Cs+吸附效果的影响,并用准2级动力学模型、扫描电镜、红外光谱及能谱图分析了吸附机理。结果表明,在室温、木纤维用量为0.2 g、浓度分别均为0.5 mmol·L-1的Sr2+、Cs+溶液50 mL、pH为5.0、振荡吸附时间分别为120和60 min的条件下,Sr2+的吸附去除率达到82.4%,Cs+则只有25%;木纤维对Sr2+、Cs+的吸附使表面形态发生变化,其吸附动力学行为符合准2级吸附速率模型(R2分别为0.999 9和1.000);与Sr2+、Cs+相互作用的基团主要是羟基、碳氢键、碳碳双键和亚甲基,木纤维吸附Sr2+、Cs+的过程中存在离子交换。因此,木纤维对Sr2+、Cs+的属于物理和化学混合吸附类型。     

羧酸钠型离子交换纤维对Cu~(2+)的吸附性能研究

以腈纶、水合肼、氢氧化钠为原料制得羧酸钠型离子交换纤维,研究了该纤维对Cu2+的吸附性能。结果表明:羧酸钠型离子交换纤维的交换容量可达4．89 mmol／g,25℃下,pH为5．0时,20 min可达到饱和吸附;CuSO4溶液浓度为2．32 mmoL／L,床流速为2．7 BV／min,穿透吸附时的床体积为149．0时,该纤维对Cu2+的动态穿透沉淀和吸附容量为1．66 mmol／L;该纤维经5次再生后其交换容量由再生前的4．89 mmol／g升高到4．97 mmol/g,饱和吸附时再生纤维吸附容量达到再生前的95．6％,其再生性能良好。     

细菌纤维素硫酸酯的制备及吸附Cu~(2+)的研究

以细菌纤维素为原料,合成细菌纤维素硫酸酯,用于吸附去除水中的Cu2+。采用红外光谱仪对细菌纤维素硫酸酯的结构进行了分析,探讨了反应时间、温度、H2SO4浓度等因素对交换容量的影响,在优化条件下交换容量为2.87mmol·g-1,并对其吸附Cu2+的性能进行了研究。结果表明,细菌纤维素硫酸酯对Cu2+有强的吸附能力,且易于再生。     

离子交换纤维吸附辣椒碱的动力学

采用SEM和IR方法表征了吸附辣椒碱前后的ZB-2强碱性阴离子交换纤维,确定了可以吸附;然后测定了离子交换纤维吸附辣椒碱的速率,确定了吸附在3 min时由液膜扩散控制转入离子交换纤维内扩散控制;最后考察了搅拌速度、溶液浓度和吸附温度对速率的影响,得到了离子交换纤维内扩散控制交换过程的表观活化能、反应级数、速率常数和动力学方程式。     

内蒙高庙子膨润土对放射性核素锶和铯的吸附性能研究

采用静态吸附实验方法,研究了吸附时间、溶液p H值、吸附剂投加量和溶液初始浓度等因素对内蒙高庙子膨润土吸附Sr2+和Cs+的性能,结果表明:高庙子膨润土对含Cs+放射性废水的处理效果要优于对含Sr2+的处理效果,其原因在于Cs+离子水合半径比Sr2+的离子水合离子小,当Sr2+和Cs+与蒙脱石矿物层间Na+、K+、Ca2+和Mg2+等发生离子交换时,Cs+离比Sr2+离子更易于进入蒙脱石层间而被固定。     

新疆沸石对放射性核素锶和铯的吸附性能研究

采用静态吸附实验方法,研究了吸附时间、溶液p H值、吸附剂投加量和溶液初始浓度等因素对新疆沸石吸附Sr2+和Cs+的性能的影响。结果表明:新疆沸石对含Cs+放射性废水的处理效果要优于对含Sr2+的处理效果,其原因在于Cs+离子水合半径比Sr2+的离子水合离子小,当Sr2+和Cs+与沸石层间Na+、K+、Ca2+和Mg2+等发生离子交换时,Cs+离比Sr2+离子更易于进入蒙脱石层间而被固定。     

树脂离子交换提取拜耳法流程中钒的动力学

采用201′7树脂对拜耳法生产Al2O3流程中种分母液沉钒后再浸出,对制得的Na2VO4溶液进行了静态吸附动力学研究,分析了吸附机理. 采用批式离子交换法,考察了树脂粒径、温度、搅拌速率、溶液浓度对离子交换过程的影响,并用动边界模型对树脂吸附钒的离子交换过程进行了描述. 结果表明,离子交换过程由颗粒内扩散控制,搅拌速率和反应温度对交换速率影响较小,吸附速率随Na2VO4溶液中钒初始浓度的增加而升高;交换过程的反应速率常数为10.052 cm4/(mol×s),反应级数n为0.5507,表观活化能为39.67 kJ/mol. 吸附机理分析结果表明,在动力学实验过程中201′7树脂主要吸附的钒阴离子为V10O286-.     

低湿条件下离子交换纤维吸附性能的研究

以超高交联聚丙烯-苯乙烯-二乙烯基苯(PP-ST-DVB)纤维为母体,分别经磺化、氯甲基化和胺化反应制得强酸或强碱离子交换纤维;研究了在低湿条件下对酸碱有害气体的动态吸附性能。结果表明:强酸离子交换纤维(交换容量为2.92 mmol/g)对NH_3气体的穿透吸附量约为40.95 mg/g,高于Fiban K-1磺酸型离子交换纤维的穿透吸附量;强碱离子交换纤维对SO_2气体的穿透吸附量约为77.50 mg/g,是Fiban A-1强碱离子交换纤维的1.55倍,自制的强酸、强碱离子交换纤维可多次再生使用。     

Separation of Carrier-Free 90Y from 90Sr by SLM Technique Using D2EHPA in N-Dodecane as Carrier

Solvent extraction studies on Sr²⁺ and Y³⁺ are carried out from varying concentrations (0.01–6.0 M) of nitric acid using di-(2-ethylhexyl)phosphoric acid (D2EHPA) as extractant. Extraction of yttrium is observed to be higher than that of strontium at all the acidities and is found to increase substantially with decreasing concentration of nitric acid. Practically negligible extraction (D < 10^?3) of Sr²⁺ is observed from feed solutions containing nitric acid in the range of 1.0 to 4.0 M. These solvent extraction data are used to optimize the transport of ⁹⁰Sr and ⁹⁰Y across the supported liquid membrane (SLM) individually as well as from their mixture (due to insitue growth) under different experimental conditions. Selective separation of ⁹⁰Y (>90%) from ⁹⁰Sr is obtained in 6 h, when the concentration of nitric acid in feed is kept at 1.0 M and that of receiving phase is maintained at 4.0 M. 20% D2EHPA in n-dodecane is found to be the optimum carrier concentration for the efficient transport of ⁹⁰Y in SLM mode. Under these conditions transport of strontium is found to be negligible. Radiochemical purity of the product ⁹⁰Y is checked by following its decay as well as by extraction paper chromatography. The contamination of ⁹⁰Sr in ⁹⁰Y product is found to be < 0.001%. Based on the experimental results, a single stage SLM system for the generation of carrier-free ⁹⁰Y from ⁹⁰Sr source is described. The system is amenable for automation and scale up.     

Separation of Carrier Free 90Y from 90Sr by Hollow Fiber Supported Liquid Membrane Containing Bis(2-ethylhexyl) Phosphonic Acid

The present article gives a comparative account of the efficiency of carrier-free ⁹⁰Y separation from ⁹⁰Sr by solvent extraction, flat sheet-supported liquid membrane (FSSLM) and hollow fiber-supported liquid membrane (HFSLM) methods using bis(2-ethylhexyl) phosphonic acid (PC88A) as the carrier extractant. The major focus of this work has been to develop the HFSLM method for the separation of Y(III) on a relatively large scale. The feed and receiver phase conditions were optimized by carrying out batch solvent-extraction studies. The extraction of Sr(II) by PC88A was negligible in the acidity range of 0.01–3 M HNO₃, whereas the extraction of Y(III) was significantly large at lower acidity (≤0.1 M HNO₃) with a separation factor (SF = D_Y/D_Sr) of 8.5 × 10⁴. HFSLM studies suggested selective and efficient transport of Y(III) into 3 M HNO₃ from a feed solution containing a mixture of Y(III) and Sr(II) at 0.1 M HNO₃. On the other hand, transport of Sr(II) was negligible in the receiver phase. The purity of the separated ⁹⁰Y was ascertained by paper chromatography and by half-life measurement. The radiation stability of the carrier was excellent as studied up to 1000 KGy dose.     

Structure‐Based and in silico Design of Hsp90 Inhibitors

The molecular chaperone Hsp90 is responsible for activation and stabilization of several oncoproteins in cancer cells, and has emerged as an important target in cancer treatment because of this pivotal role. In recent years, interests have arisen around structure‐based design of small molecules aimed at inhibiting the chaperone activity of Hsp90. In this review, we illustrate the recent advances in structure‐based and in silico strategies aimed at discovering and optimizing Hsp90 inhibitors.     

Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer

Early detection and discovery of new therapeutic targets are urgently needed to improve the breast cancer treatment outcome. Here we conducted an official clinical trial with cross-validation to corroborate human plasma Hsp90α as a novel breast cancer biomarker. Importantly, similar results were noticed in detecting early-stage breast cancer patients. Additionally, levels of plasma Hsp90α in breast cancer patients were gradually elevated as their clinical stages of regional lymph nodes advanced. In orthotopic breast cancer mouse models, administrating with recombinant Hsp90α protein increased both the primary tumor lymphatic vessel density and sentinel lymph node metastasis by 2 and 10 times, respectively. What is more, Hsp90α neutralizing antibody treatment approximately reduced 70% of lymphatic vessel density and 90% of sentinel lymph node metastasis. In the in vitro study, we demonstrated the role of extracellular Hsp90α (eHsp90α) as a pro-lymphangiogenic factor, which significantly enhanced migration and tube formation abilities of lymphatic endothelial cells (LECs). Mechanistically, eHsp90α signaled to the AKT pathway through low-density lipoprotein receptor-related protein 1 (LRP1) to upregulate the expression and secretion of CXCL8 in the lymphangiogenic process. Collectively, this study proves that plasma Hsp90α serves as an auxiliary diagnosis biomarker and eHsp90α as a molecular mediator promoting lymphangiogenesis in breast cancer.     

Studies on the Development of a Two Stage SLM System for the Separation of Carrier‐free 90Y using KSM‐17 and CMPO as Carriers

Abstract

Solvent extraction studies of Y³⁺ and Sr²⁺ with 2‐ethylhexyl 2‐ethylhexyl phosphonic acid (KSM‐17) and octyl(phenyl)‐N,N‐diisobutylcarbamoylmethylphosphine oxide (CMPO) are carried out from aqueous media containing a wide range of nitric acid and other potential reagents to arrive at the operating conditions for the selective transport of ⁹⁰Y using supported liquid membrane (SLM) containing these reagents as carriers. Since the transport data of ⁹⁰Y using single cell SLM with KSM‐17 was available from our earlier experiments, single cell transport studies with CMPO carrier are only carried out to optimize the strippant phase. Transport studies with pure ⁹⁰Y is carried out using a transport cell with two SLMs one with KSM‐17 and the other CMPO carriers to optimize the transport parameters. Based on these data the development of a two stage SLM system for the generation of carrier free ⁹⁰Y from ⁹⁰Sr source is described. The procedure described is amenable for automation and scale up.     

Discovery and biological activity of 6BrCaQ as an inhibitor of the Hsp90 protein folding machinery

Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy, due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and viability. Here, a novel series of Hsp90 inhibitors containing a quinolein‐2‐one scaffold was synthesized and evaluated in cell proliferation assays. Results from these structure–activity relationships studies enabled identification of the simplified 3‐aminoquinolein‐2‐one analogue 2 b (6BrCaQ), which manifests micromolar activity against a panel of cancer cell lines. The molecular signature of Hsp90 inhibition was assessed by depletion of standard known Hsp90 client proteins. Finally, processing and activation of caspases 7, 8, and 9, and the subsequent cleavage of PARP by 6BrCaQ, suggest stimulation of apoptosis through both extrinsic and intrinsic pathways.     

Carborane-Based Analogues of 5-Lipoxygenase Inhibitors Co-inhibit Heat Shock Protein 90 in HCT116 Cells

5-Lipoxygenase converts arachidonic acid into leukotrienes, which are involved in inflammation and angiogenesis. The introduction of carboranes can improve the pharmacokinetic behavior of metabolically less stable pharmaceutics. Herein we report the syntheses of several carborane-based inhibitors of the 5-lipoxygenase pathway. The isosteric replacement of phenyl rings by carboranes leads to improved cytotoxicity toward several melanoma and colon cancer cell lines. For the colon cancer cell line HCT116, the co-inhibition of heat shock protein 90 was observed.     

Expression of Cancer Stem Cell Markers EpCAM and CD90 Is Correlated with Anti- and Pro-Oncogenic EphA2 Signaling in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Additionally, the efficacy of targeted molecular therapies with multiple tyrosine kinase inhibitors is limited. In this study, we focused on the cellular signaling pathways common to diverse HCC cells and used quantitative reverse phase protein array (RPPA) and statistical analyses to elucidate the molecular mechanisms determining its malignancy. We examined the heterogeneity of 17 liver cancer cell lines by performing cluster analysis of their expression of CD90 and EpCAM cancer stem cell markers. Gaussian mixture model clustering identified three dominant clusters: CD90-positive and EpCAM-negative (CD90+), EpCAM-positive and CD90-negative (EpCAM+) and EpCAM-negative and CD90-negative (Neutral). A multivariate analysis by partial least squares revealed that the former two cell populations showed distinct patterns of protein expression and phosphorylation in the EGFR and EphA2 signaling pathways. The CD90+ cells exhibited higher abundance of AKT, EphA2 and its phosphorylated form at Ser⁸⁹⁷, whereas the EpCAM+ cells exhibited higher abundance of ERK, RSK and its phosphorylated form. This demonstrates that pro-oncogenic, ligand-independent EphA2 signaling plays a dominant role in CD90+ cells with higher motility and metastatic activity than EpCAM+ cells. We also showed that an AKT inhibitor reduced the proliferation and survival of CD90+ cells but did not affect those of EpCAM+ cells. Taken together, our results suggest that AKT activation may be a key pro-oncogenic regulator in HCC.     

Structural Basis for Design of New Purine-Based Inhibitors Targeting the Hydrophobic Binding Pocket of Hsp90

Inhibition of the molecular chaperone heat shock protein 90 (Hsp90) represents a promising approach for cancer treatment. BIIB021 is a highly potent Hsp90 inhibitor with remarkable anticancer activity; however, its clinical application is limited by lack of potency and response. In this study, we aimed to investigate the impact of replacing the hydrophobic moiety of BIIB021, 4-methoxy-3,5-dimethylpyridine, with various five-membered ring structures on the binding to Hsp90. A focused array of N⁷/N⁹-substituted purines, featuring aromatic and non-aromatic rings, was designed, considering the size of hydrophobic pocket B in Hsp90 to obtain insights into their binding modes within the ATP binding site of Hsp90 in terms of π–π stacking interactions in pocket B as well as outer α-helix 4 configurations. The target molecules were synthesized and evaluated for their Hsp90α inhibitory activity in cell-free assays. Among the tested compounds, the isoxazole derivatives 6b and 6c, and the sole six-membered derivative 14 showed favorable Hsp90α inhibitory activity, with IC₅₀ values of 1.76 µM, 0.203 µM, and 1.00 µM, respectively. Furthermore, compound 14 elicited promising anticancer activity against MCF-7, SK-BR-3, and HCT116 cell lines. The X-ray structures of compounds 4b, 6b, 6c, 8, and 14 bound to the N-terminal domain of Hsp90 were determined in order to understand the obtained results and to acquire additional structural insights, which might enable further optimization of BIIB021.