基于绿视率的城市公园空间满意度调查研究

以城市公园动态图像采集和空间满意度评价为基础，探讨绿视率对空间满意度的影响与相互关系，为科学评价基于心理感知的城市绿色空间质量，促进城市绿色空间结构优化提供理论依据。     

Prey for the Proteasome: Targeted Protein Degradation—A Medicinal Chemist's Perspective

Targeted protein degradation (TPD), the ability to control a proteins fate by triggering its degradation in a highly selective and effective manner, has created tremendous excitement in chemical biology and drug discovery within the past decades. The TPD field is spearheaded by small molecule induced protein degradation with molecular glues and proteolysis targeting chimeras (PROTACs) paving the way to expand the druggable space and to create a new paradigm in drug discovery. However, besides the therapeutic angle of TPD a plethora of novel techniques to modulate and control protein levels have been developed. This enables chemical biologists to better understand protein function and to discover and verify new therapeutic targets. This Review gives a comprehensive overview of chemical biology techniques inducing TPD. It explains the strengths and weaknesses of these methods in the context of drug discovery and discusses their future potential from a medicinal chemist's perspective.     

Conservation of ultrafast photoprotective mechanisms with increasing molecular complexity in sinapoyl malate derivatives

Sinapoyl malate is a natural plant sunscreen molecule which protects leaves from harmful ultraviolet radiation. Here, the ultrafast dynamics of three sinapoyl malate derivatives, sinapoyl L-dimethyl malate, sinapoyl L-diethyl malate and sinapoyl L-di-t-butyl malate, have been studied using transient electronic absorption spectroscopy, in a dioxane and methanol solvent environment to investigate how well preserved these dynamics remain with increasing molecular complexity. In all cases it was found that, upon photoexcitation, deactivation occurs via a trans-cis isomerisation pathway within ∼20–30 ps. This cis-photoproduct, formed during photodeactivation, is stable and longed-lived for all molecules in both solvents. The incredible levels of conservation of the isomerisation pathway with increased molecular complexity demonstrate the efficacy of these molecules as ultraviolet photoprotectors, even in strongly perturbing solvents. As such, we suggest these molecules might be well-suited for augmentations to further improve their photoprotective efficacy or chemical compatibility with other components of sunscreen mixtures, whilst conserving their underlying photodynamic properties.     

Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis**

Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene-containing (Fc-CH₂-OXA), ruthenocene-containing (Rc-CH₂-OXA) and benzene-containing (Ph-CH₂-OXA) OXA derivatives. These derivatives showed excellent in vitro activity against both Schistosoma mansoni larvae and adult worms and S. haematobium adult worms, and were also active in vivo against adult S. mansoni. Encouraged by these promising results, we conducted additional in-depth preclinical studies and report in this investigation on metabolic stability studies, in vivo studies on S. haematobium and juvenile S. mansoni, computational simulations, and formulation development. Molecular dynamics simulations supported the in vitro results on the target protein. Though all three compounds were poorly stable within an acidic environment, they were only slightly cleared in the in vitro liver model. This is likely the reason why the promising in vitro activity did not translate into in vivo activity on S. haematobium. This limitation could not be overcome by the formulation of lipid nanocapsules as a way to improve the in vivo activity. Further studies should focus on increasing the compound's bioavailability, to reach an active concentration in the microenvironment of the parasite.     

运用植物降温机制的围护结构防热设计

通过对植物降温机制进行分类梳理,阐述植物降温机制与建筑围护结构传热方式的联系;同时,对现有的相关研究及应用进行归纳总结,提出基于植物降温机制的围护结构防热设计方法.研究结果表明:运用植物降温机制的围护结构防热设计具有独特的适应性.     

植物线粒体巯基亚硝基化修饰蛋白质组学研究进展

蛋白质S-亚硝基化是一氧化氮(NO)与蛋白质半胱氨酸残基(Cys)共价连接形成S-亚硝基硫醇(-SNO)的过程,被认为是植物中体现NO生物活性的最重要途径.线粒体在依赖S-亚硝基化的NO信号转导中起关键作用.综述了应用蛋白质组学技术鉴定的植物线粒体S-亚硝基化蛋白质的特征,为认识线粒体NO调控网络体系中重要的信号与代谢通路(如光呼吸、三羧酸循环、氧化磷酸化、活性氧分子(ROS)稳态,以及蛋白质加工与周转)提供了线索.     

天坑植物资源研究进展

天坑植物多指一类生长于喀斯特岩溶地貌(天坑)中的特殊植物群。随着天坑中更多植物新物种的发现、坑底坑外生境对比研究的增加以及天坑作为植物"避难所"研究的深入,天坑植物资源方面的研究报道也越来越多。因此,本文对天坑植物群落形成、天坑植物特征、天坑植物资源等进行概述,以期为天坑植物资源的开发、药用植物的发掘与研究、地区经济的发展等奠定基础,同时为当前我国西部岩溶地区开发中的生态治理和生态恢复提供帮助。     

Pathogenesis of Keratinocyte Carcinomas and the Therapeutic Potential of Medicinal Plants and Phytochemicals

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.     

Quinolactacin Biosynthesis Involves Non-Ribosomal-Peptide-Synthetase-Catalyzed Dieckmann Condensation to Form the Quinolone-γ-lactam Hybrid

Quinolactacins are novel fungal alkaloids that feature a quinolone-γ-lactam hybrid, which is a potential pharmacophore for the treatment of cancer and Alzheimer's disease. Herein, we report the identification of the quinolactacin A2 biosynthetic gene cluster and elucidate the enzymatic basis for the formation of the quinolone-γ-lactam structure. We reveal an unusual β-keto acid (N-methyl-2-aminobenzoylacetate) precursor that is derived from the primary metabolite l -kynurenine via methylation, oxidative decarboxylation, and amide hydrolysis reactions. In vitro assays reveal two single-module non-ribosomal peptide synthetases (NRPs) that incorporate the β-keto acid and l -isoleucine, followed by Dieckmann condensation, to form the quinolone-γ-lactam. Notably, the bioconversion from l -kynurenine to the β-keto acid is a unique strategy employed by nature to decouple R*-domain-containing NRPS from the polyketide synthase (PKS) machinery, expanding the paradigm for the biosynthesis of quinolone-γ-lactam natural products via Dieckmann condensation.