基于酶循环放大的DNA生物传感器用于检测食管鳞状细胞癌生物标志物蛋白PDGF-BB

食管鳞状细胞癌(ESCC)患者发病早期由于体内的肿瘤标志物种类少且含量低,难以在患病早期发现疾病从而快速反应并有效治疗.因此,找到一种合适的标志物对其进行快速高效检测是研究者亟待解决的问题.血小板衍生生长因子(PDGF-BB)在恶性肿瘤的早期诊断中具有极其重要的地位.该文基于酶循环放大荧光光谱设计了一种用于PDGF-B...     

The circular chemistry conceptual framework: A way forward to sustainability in industry 4.0

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Design,Synthesis and Anticancer Activity of a New Series of N-aryl-N′-[4-(pyridin-2-ylmethoxy)benzyl]urea Derivatives

The development of cancer treatments requires continuous exploration and improvement, in which the discovery of new drugs for the treatment of cancer is still an important pathway. In this study, based on the molecular hybridization strategy, a new structural framework with an N-aryl-N’-arylmethylurea scaffold was designed, and 16 new target compounds were synthesized and evaluated for their antiproliferative activities against four different cancer cell lines A549, MCF7, HCT116, PC3, and human liver normal cell line HL7702. The results have shown seven compounds with 1-methylpiperidin-4-yl groups having excellent activities against all four cancer cell lines, and they exhibited scarcely any activities against HL7702. Among them, compound 9b and 9d showed greatly excellent activity against the four kinds of cells, and the IC₅₀ for MCF7 and PC3 cell lines were even less than 3 μM.     

In Silico Approach Using Free Software to Optimize the Antiproliferative Activity and Predict the Potential Mechanism of Action of Pyrrolizine-Based Schiff Bases

In the current study, a simple in silico approach using free software was used with the experimental studies to optimize the antiproliferative activity and predict the potential mechanism of action of pyrrolizine-based Schiff bases. A compound library of 288 Schiff bases was designed based on compound 10, and a pharmacophore search was performed. Structural analysis of the top scoring hits and a docking study were used to select the best derivatives for the synthesis. Chemical synthesis and structural elucidation of compounds 16a–h were discussed. The antiproliferative activity of 16a–h was evaluated against three cancer (MCF7, A2780 and HT29, IC₅₀ = 0.01–40.50 μM) and one normal MRC5 (IC₅₀ = 1.27–24.06 μM) cell lines using the MTT assay. The results revealed the highest antiproliferative activity against MCF7 cells for 16g (IC₅₀ = 0.01 μM) with an exceptionally high selectivity index of (SI = 578). Cell cycle analysis of MCF7 cells treated with compound 16g revealed a cell cycle arrest at the G₂/M phase. In addition, compound 16g induced a dose-dependent increase in apoptotic events in MCF7 cells compared to the control. In silico target prediction of compound 16g showed six potential targets that could mediate these activities. Molecular docking analysis of compound 16g revealed high binding affinities toward COX-2, MAP P38α, EGFR, and CDK2. The results of the MD simulation revealed low RMSD values and high negative binding free energies for the two complexes formed between compound 16g with EGFR, and CDK2, while COX-2 was in the third order. These results highlighted a great potentiality for 16g to inhibit both CDK2 and EGFR. Taken together, the results mentioned above highlighted compound 16g as a potential anticancer agent.     

Cyclin-Dependent Kinase 4 and 6 Inhibitors in Cell Cycle Dysregulation for Breast Cancer Treatment

In cell development, the cell cycle is crucial, and the cycle progression’s main controllers are endogenous CDK inhibitors, cyclin-dependent kinases (CDKs), and cyclins. In response to the mitogenic signal, cyclin D is produced and retinoblastoma protein (Rb) is phosphorylated due to activated CDK4/CDK6. This causes various proteins required in the cell cycle progression to be generated. In addition, complexes of CDK1-cyclin A/B, CDK2-cyclin E/A, and CDK4/CDK6-cyclin D are required in each phase of this progression. Cell cycle dysregulation has the ability to lead to cancer. Based on its role in the cell cycle, CDK has become a natural target of anticancer therapy. Therefore, understanding the CDK structures and the complex formed with the drug, helps to foster the development of CDK inhibitors. This development starts from non-selective CDK inhibitors to selective CDK4/CDK6 inhibitors, and these have been applied in clinical cancer treatment. However, these inhibitors currently require further development for various hematologic malignancies and solid tumors, based on the results demonstrated. In drug development, the main strategy is primarily to prevent and asphyxiate drug resistance, thus a determination of specific biomarkers is required to increase the therapy’s effectiveness as well as patient selection suitability in order to avoid therapy failure. This review is expected to serve as a reference for early and advanced-stage researchers in designing new molecules or repurposing existing molecules as CDK4/CDK6 inhibitors to treat breast cancer.     

电解液对LiCr0.1Mn1.9O4电化学性能的影响

容量;循环特性;自放电;电解液对LiCr0.1Mn1.9O4电化学性能的影响     

Synthesis,cytotoxicity, apoptosis and cell cycle arrest of a monoruthenium(II)-substituted Dawson polyoxotungstate

By 5-h reaction of cis-[Ru^IICl₂(DMSO)₄] (M2) with K₁₀[α₂-P₂W₁₇O₆₁] (M3) in ice-cooled, HCl-acidic aqueous solution, a water-soluble 1:2-type diamagnetic ruthenium(II) complex of formula K₁₈[Ru^II(DMSO)₂(P₂W₁₇O₆₁)₂]·35H₂O (M1) was unexpectedly obtained as an analytically pure, homogeneous tan-colored solid, in which two DMSO ligands are coordinated to the ruthenium(II) atom. The cytotoxic potential of the complex was tested on C33A, DLD-1, and HepG-2 cancer cells and human normal embryonic lung fibroblasts cell MRC-5; the viability of the treated cells was evaluated by MTT assay. The mode of cell death was assessed by morphological study of DNA damage and apoptosis assays. Compound M1 induced cell death in a dose-dependent manner, and the mode of cell death was essentially apoptosis though necrosis was also noticed. Cell cycle analysis by flow cytometry indicated that M1 caused cell cycle arrest and accumulated cells in S phase.     

Biotransformation of 20(R)-panaxatriol by the fungus Aspergillus flavus Link AS 3.3950

Microbial transformation of 20(R)-panaxatriol by the fungus Aspergillus flavus Link AS 3.3950 was performed. Four new (1–4), along with two previously reported metabolites (5 and 6), were obtained. Their chemical structures were elucidated on the basis of extensive spectroscopic analyses. Furthermore, the inhibitory effects of those compounds on K562/ADR, Du-145, Hela, MCF-7 and HepG2 cell lines were evaluated by MTT assay. Among them, compound 15β-hydroxy-20(R)-panaxatriol (4) exhibited selective inhibitory effects on human leukaemic progenitor cells K562/ADR through arresting cell cycle, which was associated with obvious decrease of cyclin B1, cyclin D1 and cyclin-dependent kinase (CDK) 1/2/4/6 protein expression.     

Scale-up and Sustainability Evaluation of Biopolymer Production from Citrus Waste Offering Carbon Capture and Utilisation Pathway

Poly(limonene carbonate) (PLC) has been highlighted as an attractive substitute to petroleum derived plastics, due to its utilisation of CO₂ and bio-based limonene as feedstocks, offering an effective carbon capture and utilisation pathway. Our study investigates the techno-economic viability and environmental sustainability of a novel process to produce PLC from citrus waste derived limonene, coupled with an anaerobic digestion process to enable energy cogeneration and waste recovery maximisation. Computational process design was integrated with a life cycle assessment to identify the sustainability improvement opportunities. PLC production was found to be economically viable, assuming sufficient citrus waste is supplied to the process, and environmentally preferable to polystyrene (PS) in various impact categories including climate change. However, it exhibited greater environmental burdens than PS across other impact categories, although the environmental performance could be improved with a waste recovery system, at the cost of a process design shift towards energy generation. Finally, our study quantified the potential contribution of PLC to mitigating the escape of atmospheric CO₂ concentration from the planetary boundary. We emphasise the importance of a holistic approach to process design and highlight the potential impacts of biopolymers, which is instrumental in solving environmental problems facing the plastic industry and building a sustainable circular economy.     

A Kinetic Evidence for the Nitroxyl Radicals Recycling Mechanism in the Photostabilizing Process of HALS

The photoinduced bulk polymerization of a reactive-hindered amine fight stabilizers(r-HALS), 4-acryloyl-2, 2, 6, 6-tetramethylpiperidinyl (ATMP), was performed at 80℃ by using a DPC technique. An unique periodic exponential attenuation-type oscillating curve was found when the polymerization was carried out in air, but this phenomenon was not found in nitrogen.It is supposed that this unique kinetic performance may be attributed to nitroxyl radicals that are produced in situ from the oxidation of ATMP. ATMP polymer with narrow polydispersity (d =1.03) can be obtained by photoinduced solution polymerization of ATMP. The signal detected in ESR may be assigned to the nitroxyl radicals in the matrix of ATMP polymer. Since this kind of recycling of nitroxyl radicals is well documented for the photostabilizing mechanism of HALS, the present results may serve as a kinetic evidence for this mechanism.