MDM2‐Associated Clusterization‐Triggered Emission and Apoptosis Induction Effectuated by a Theranostic Spiropolymer

Heteroatom‐containing spiropolymers were constructed in a facile manner by a catalyst‐free multicomponent spiropolymerization route. P1a2b as the most potent of these spiropolymers, demonstrates cluster‐triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti‐apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating a good biocompatibility and non‐toxicity in non‐cancerous cells. The combined results from solution and cell‐based cluster‐triggered emission studies, docking, protein expression experiments and cytotoxicity data strongly support the MDM2‐binding hypothesis and indicate a potential application as a fluorescent cancer marker as well as therapeutic for this spiropolymer.     

Genotyping of single nucleotide polymorphism in MDM2 genes by universal fluorescence primer PCR and capillary electrophoresis

Single nucleotide polymorphism (SNP) 309 in the promoter region of the murine double minute 2 (MDM2) gene plays an important role in human tumorigenesis. We established a simple and effective CE method for SNP detection in the MDM2 gene. We designed one universal fluorescence-based nonhuman-sequence primer and one fragment-oriented primer, which were combined in one tube, and proceeded with the polymerase chain reaction (PCR). The amplicons were analyzed by capillary electrophoresis using single-strand conformation polymorphism method. PCR fragments generated from this two-in-one PCR displayed either T/T or G/G homozygosity or T/G heterozygosity. A total of 304 samples were blindly genotyped using this developed method, which included the DNA from 138 healthy volunteers, 43 chronic myeloid leukemia (CML) patients, and 123 colorectal cancer (CRC) patients. The results were confirmed by DNA sequencing and showed good agreement. The SSCP-CE method was feasible for SNP screening of MDM2 in large populations.     

Nondenaturing polyacrylamide gel electrophoresis to study the dissociation of the p53·MDM2/X complex by potentially anticancer compounds

A new analytical method to study the dissociation of the complexes between the oncosuppressor p53 and its negative modulators murine double‐minute protein 2 (MDM2) or MDMX, is proposed. This technique is reliable to determine the dissociative power exerted by small molecules on the complex taking advantage of the appearance of migrating MDM2 or MDMX in a native polyacrylamide gel, when inhibitors are added to the complex mixture. Therefore, we propose this new approach to easily screen library of compounds, with potential pharmacological anticancer activity.     

Dual Targeting of MDM4 and FTH1 by MMRi71 for Induced Protein Degradation and p53-Independent Apoptosis in Leukemia Cells

MDM2 and MDM4 are cancer drug targets validated in multiple models for p53-based cancer therapies. The RING domains of MDM2 and non-p53-binder MDM2 splice isoforms form RING domain heterodimer polyubiquitin E3 ligases with MDM4, which regulate p53 stability in vivo and promote tumorigenesis independent of p53. Despite the importance of the MDM2 RING domain in p53 regulation and cancer development, small molecule inhibitors targeting the E3 ligase activity of MDM2-MDM4 are poorly explored. Here, we describe the synthesis and characterization of quinolinol derivatives for the identification of analogs that are capable of targeting the MDM2-MDM4 heterodimer E3 ligase and inducing apoptosis in cells. The structure-activity-relationship (SAR) study identified structural moieties critical for the inhibitory effects toward MDM2-MDM4 E3 ligase, the targeted degradation of MDM4 and FTH1 in cells, and anti-proliferation activity. Lead optimization led to the development of compound MMRi71 with improved activity. In addition to accumulating p53 proteins in wt-p53 bearing cancer cells as expected of any MDM2 inhibitors, MMRi71 effectively kills p53-null leukemia cells, an activity that conventional MDM2-p53 disrupting inhibitors lack. This study provides a prototype structure for developing MDM4/FTH1 dual-targeting inhibitors as potential cancer therapeutics.     

Induction of DR5-Dependent Apoptosis by PGA2 through ATF4-CHOP Pathway

Prostaglandin (PG) A₂, a cyclopentenone PG, induced apoptosis in both HCT116 and HCT116 p53 −/− cells. Although PGA₂-induced apoptosis in HCT116 cells was dependent on the p53-DR5 pathway, the mechanism underlying PGA₂-induced apoptosis in HCT116 p53 −/− cells remains unknown. In this study, we observed that PGA₂ caused an increase of mRNA expression of DR5 and protein expression even in HCT116 p53 −/− cells, accompanied by caspase-dependent apoptosis. Knockdown of DR5 expression by RNA interference inhibited PGA₂-induced apoptosis in HCT116 p53 −/− cells. Parallel to the induction of apoptosis, PGA₂ treatment upregulated expression of genes upstream of DR5 such as ATF4 and CHOP. Knockdown of CHOP prevented DR5-dependent cell death as well as the expression of DR5 protein. Furthermore, knockdown of ATF4 by RNA interference decreased both mRNA and protein levels of CHOP and DR5, thereby suppressing PGA₂-induced cell death. Consistently, the DR5 promoter activity increased by PGA₂ was not stimulated when the CHOP binding site in the DR5 promoter was mutated. These results collectively suggest that PGA₂ may induce DR5-dependent apoptosis via the ATF4-CHOP pathway in HCT116 p53 null cells.     

发射光谱法测定金属钴中的16个元素

金属钴经化学预处理后,其其体和杂质元素均转化为氧化物,用发射光谱法测定其中１６个杂质元素,该方法的测定范围可基本满足国际ＧＢ６５１７－８６中对一号钴与三号钴的分析要求,方法的相对标准偏差为６．８９％－１８．２４％。     

Infrared Emission of Air Pollutants Induced by a CO2 Laser

Abstract

A possible method for the measurement of air pollutants is described. It is based on infrared emission from gases at specific wavelengths induced by a CO₂ laser. The emission level can be increased by adding a sensitizing gas (e.g. SF.) to the sample gas. Although the mechanism of the emission is not fully understood experimental data indicate that the emission is of thermal origin. Spectra of some air polluting gases are included in this paper.     

Reevaluating Protein Photoluminescence: Remarkable Visible Luminescence upon Concentration and Insight into the Emission Mechanism

It is a textbook knowledge that protein photoluminescence stems from the three aromatic amino acid residues of tryptophan(Trp), tyrosine (Tyr), and phenylalanine (Phe), with predominant contributions from Trp. Recently, inspired by the intrinsic emission of nonaromatic amino acids and poly(amino acids) in concentrated solutions and solids, we revisited protein light emission using bovine serum albumin (BSA) as a model. BSA is virtually nonemissive in dilute solutions (≤0.1 mg mL^?1), but highly luminescent upon concentration or aggregation, showing unique concentration‐enhanced emission and aggregation‐induced emission (AIE) characteristics. Notably, apart from well‐documented UV luminescence, bright blue emission is clearly observed. Furthermore, persistent room‐temperature phosphorescence (p‐RTP) is achieved even in the amorphous solids under ambient conditions. This visible emission can be rationalized by the clustering‐triggered emission (CTE) mechanism. These findings not only provide an in‐depth understanding of the emissive properties of proteins, but also hold strong implications for further elucidating the basis of tissue autofluorescence.     

Porous and Water Stable 2D Hybrid Metal Halide with Broad Light Emission and Selective H2O Vapor Sorption

In this work we report a strategy for generating porosity in hybrid metal halide materials using molecular cages that serve as both structure-directing agents and counter-cations. Reaction of the [2.2.2] cryptand (DHS) linker with Pb^II in acidic media gave rise to the first porous and water-stable 2D metal halide semiconductor (DHS)₂Pb₅Br₁₄. The corresponding material is stable in water for a year, while gas and vapor-sorption studies revealed that it can selectively and reversibly adsorb H₂O and D₂O at room temperature (RT). Solid-state NMR measurements and DFT calculations verified the incorporation of H₂O and D₂O in the organic linker cavities and shed light on their molecular configuration. In addition to porosity, the material exhibits broad light emission centered at 617 nm with a full width at half-maximum (FWHM) of 284 nm (0.96 eV). The recorded water stability is unparalleled for hybrid metal halide and perovskite materials, while the generation of porosity opens new pathways towards unexplored applications (e.g. solid-state batteries) for this class of hybrid semiconductors.     

Pressure-Tuned Multicolor Emission of 2D Lead Halide Perovskites with Ultrahigh Color Purity

The chemical diversity and structural flexibility of lead halide perovskites (LHPs) offer tremendous opportunities to tune their optical properties through internal molecular engineering and external stimuli. Herein, we report the wide-range and ultrapure photoluminescence emissions in a family of homologous 2D LHPs, [MeOPEA]₂PbBr_4−4xI_4x (MeOPEA=4-methoxyphenethylammonium; x=0, 0.2, 0.425, 0.575, 1) enabled through internal chemical pressure and external hydrostatic pressure. The chemical pressure, induced by the C−H⋅⋅⋅π interactions and halogen doping/substitution strengthens the structural rigidity to give sustained narrow emissions, and regulates the emission energy, respectively. Further manipulation of physical pressure leads to wide-range emission tuning from 412 to 647 nm in a continuous and reversible manner. This work could open up new pathways for developing 2D LHP emitters with ultra-wide color gamut and high color purity which are highly useful for pressure sensing.     

亚稳态能量转移发射光谱法测定锌的研究

本文提出了一种测定锌的亚稳态能量转移发射光谱法。以氮气为工作气体,利用微波放电产生活化氮余辉,采用电热蒸发微量进样装置进样。考察了各实验参数对测定锌的影响,在472.2nm处测定锌,检出限为2.3ng。对实际样品中锌的测定取得了令人满意的结果。并讨论了氧对活化氮余辉的影响。     

Analysis of Caffeine Deutero Isotopomers by Gas Chromatography and Atomic Emission Detection

Abstract

This paper describes the behaviour of various caffeine deutero isotopo-mers analyzed using gas chromatography coupled wiih atomic emission detection. Results are given concerning the linearity of the response and the detection limits for carbon, nitrogen, hydrogen and deuterium. It is demonstrated that neither the number of deuterium atoms per isotopomer nor the location of deuterium labeling modify the analytical response.     

Unveiling the “Three‐Finger Pharmacophore” Required for p53–MDM2 Inhibition by Saturation‐Transfer Difference (STD) NMR Initial Growth‐Rates Approach

Inhibitors of the p53‐MDM2 protein–protein interaction are emerging as a new and validated approach to treating cancer. Herein, we describe the synthesis and inhibitory evaluation of a series of isoquinolin‐1‐one analogues, and highlight the utility of an initial growth‐rates saturation‐transfer difference (STD) NMR approach supported by protein–ligand docking to investigate p53‐MDM2 inhibition. The approach is illustrated by the study of compound 1 , providing key insights into the binding mode of this kind of MDM2 ligands and, more importantly, readily unveiling the previously proposed three‐finger pharmacophore requirement for p53‐MDM2 inhibition.     

两基准试样法及其在激光显微光谱分析中的应用

本文提出了采用两基准试样法进行激光显微光谱定量分析的座标系统和计算公式,并对其可行性和适用性进行了初步探讨。     

Cascade Energy Transfer and White-Light Emission in Chirality-Controlled Crystallization-Driven Two-Dimensional Co-assemblies from Donor and Acceptor Dye-Conjugated Polylactides

Achieving predictable and programmable two-dimensional (2D) structures with specific functions from exclusively organic soft materials remains a scientific challenge. This article unravels stereocomplex crystallization-driven self-assembly as a facile method for producing thermally robust discrete 2D-platelets of diamond shape from biodegradable semicrystalline polylactide (PLA) scaffolds. The method involves co-assembling two PLA stereoisomers, namely, PY-PDLA and NMI-PLLA , which form stereocomplex (SC)-crystals in isopropanol. By conjugating a well-known Förster resonance energy transfer (FRET) donor and acceptor dye, namely, pyrene ( PY ) and naphthalene monoimide ( NMI ), respectively, to the chain termini of these two interacting stereoisomers, a thermally robust FRET process can be stimulated from the 2D array of the co-assembled dyes on the thermally resilient SC-PLA crystal surfaces. Uniquely, by decorating the surface of the SC-PLA crystals with an externally immobilized guest dye, Rhodamine-B, similar diamond-shaped structures could be produced that exhibit pure white-light emission through a surface-induced two-step cascade energy transfer process. The FRET response in these systems displays remarkable dependence on the intrinsic crystalline packing, which could be modulated by the chirality of the co-assembling PLA chains. This is supported by comparing the properties of similar 2D platelets generated from two homochiral PLLAs ( PY-PLLA and NMI-PLLA ) labeled with the same FRET pair.     

Photophysical Properties of Emissive Pyrido[3,2‐c]carbazole Derivatives and Apoptosis Induction: Development towards Theranostic Agents in Response to Light Stimulus

Pyridocarbazole moieties are present in many natural products, such as olivacine and ellipticine, and their derivatives are well‐known anticancer agents. To develop functional therapeutic and diagnostic compounds, three emissive pyrido[3,2‐c]carbazole derivatives, PC‐X , containing secondary or tertiary amine groups, were synthesized from an aminoquinoline derivative using a palladium complex as the catalyst. X‐ray diffraction analyses revealed that PC‐X showed highly planar structures between the pyridine ring and the carbazole framework, exhibiting high fluorescence intensities along with solvatochromic behavior. Imaging of HeLa cells treated with PC‐X showed no specific accumulation into the organelles; however, a comparative examination showed that the accumulation in mitochondria was the highest as compared to nuclei and lysosomes. Cytotoxicity analysis using HeLa cells showed that PC‐H, containing a secondary amine group showed the highest cytotoxicity (IC₅₀≈20 μm ) as compared to another PC‐X having a tertiary amine group. Colocalization with MitoTracker, a typical mitochondrial staining dye, showed apoptosis‐like behavior with remarkable appearance of blebbing during irradiation with near UV light (403 nm), suggesting that the PC‐H may not only behave as a fluorescence probe for the imaging organelles, but also as a therapeutic agent for inducing apoptosis in HeLa cells, thereby functioning as a theranostic agent.     

Pressure-Induced Free Exciton Emission in a Quasi-Zero-Dimensional Hybrid Lead Halide

Structural dimensionality and electronic dimensionality play a crucial role in determining the type of excitonic emission in hybrid metal halides (HMHs). It is important but challenging to achieve free exciton (FE) emission in zero-dimensional (0D) HMHs based on the control over the electronic dimensionality. In this work, a quasi-0D HMH (C₇H₁₅N₂Br)₂PbBr₄ with localized electronic dimensionality is prepared as a prototype model. With increasing pressure onto (C₇H₁₅N₂Br)₂PbBr₄, the broad and weak self-trapped exciton (STE) emission at ambient conditions is considerably enhanced before 3.6 GPa, which originates from more distorted [PbBr₄]²⁻ seesaw units upon compression. Notably, a narrow FE emission in (C₇H₁₅N₂Br)₂PbBr₄ appears at 3.6 GPa, and then this FE emission is gradually strengthened up to 8.4 GPa. High pressure structural characterizations reveal that anisotropic contraction of (C₇H₁₅N₂Br)₂PbBr₄ results in a noticeable reduction in the distance between adjacent [PbBr₄]²⁻ seesaw units, as well as an obvious enhancement of crystal stiffness. Consequently, the electronic connectivity in (C₇H₁₅N₂Br)₂PbBr₄ is sufficiently promoted above 3.6 GPa, which is also supported with theoretical calculations. The elevation of electronic connectivity and enhanced stiffness together lead to pressure-induced FE emission and subsequent emission enhancement in quasi-0D (C₇H₁₅N₂Br)₂PbBr₄.     

温度及药物诱导肿瘤细胞凋亡的实验观察

将微量热法和透射电镜技术相结合,研究了温度对人卵巢癌细胞代谢的影响,不同温度下癌细胞超微结构的变化和加抗肿瘤药物(嘧福绿)的协同作用.从宏观到微观,深入探讨了热疗与化疗协同作用对肿瘤细胞杀伤作用的机理.实验结果表明,在高温下细胞代谢降低,肿瘤细胞的形态发生一系列恶性变化,且高热可能诱导肿瘤细胞的凋亡;热疗加化疗的协同作用则能加速肿瘤细胞的凋亡,使细胞的能量代谢更低,随着作用时间的延长,最终导致细胞死亡.     

干法灰化-发射光谱法测定植物样品中B和Sn

地球化学样品中的元素硼和锡属于难溶易挥发元素,湿法样品前处理技术相对较难,目前基本以一米光栅发射光谱法测定为主,其固体进样方式避免了复杂的样品前处理,实现了对地球化学样品中元素硼和锡的绿色分析。植物样品经过适宜的高温灰化后,基体成分基本一致,体积质量均发生富集现象,称取的样品灰分成分和基物、缓冲剂(比例1:1:2)经过研磨充分混匀,在优化的实验条件下,以国家一级合成硅酸盐光谱分析标准物质制作校准曲线,构建植物样品中硼和锡的分析方法,该方法硼和锡的检出限分别为0.042μg·g-1、0.019μg·g-1,方法经过国家一级标准物质验证,硼方法精密度:5.6%~13%,正确度(RE)的绝对值均小于10%;锡方法精密度:7.2%~18%,正确度(RE)的绝对值均小于28%。实验结果表明:植物样品经过干法灰化富集后,对植物样品中元素硼基本能够实现精准测定,对元素锡含量接近于检测下限的值测定结果相对较差,对高含量值也能够实现精准测定,方法具有较好的应用价值。