Distinct epigenetic modifiers ensure coordinated control over genes that govern a myriad of cellular processes. Growing evidence shows that dynamic regulation of histone methylation is critical for almost all stages of development. Notably, the KDM5 subfamily of histone lysine-specific demethylases plays essential roles in the proper development and differentiation of tissues, and aberrant regulation of KDM5 proteins during development can lead to chronic developmental defects and even cancer. In this review, we adopt a unique perspective regarding the context-dependent roles of KDM5A and KDM5B in development and tumorigenesis. It is well known that these two proteins show a high degree of sequence homology, with overlapping functions. However, we provide deeper insights into their substrate specificity and distinctive function in gene regulation that at times divert from each other. We also highlight both the possibility of targeting KDM5A and KDM5B to improve cancer treatment and the limitations that must be overcome to increase the efficacy of current drugs.Subject terms: Methylation, Tumour biomarkers相似文献
Investigation of fluid behavior in a cavity enclosure has been a significant issue from the past in the field of fluid mechanics. In the present study, hydrothermal evaluation of hybrid nanofluid with a water–ethylene glycol (50–50%) as the base fluid which contains MoS2–TiO2 hybrid nanoparticles, in an octagon with an elliptical cavity in the middle of it, has been performed. In this problem, the effects of the radiation parameter, porosity, and the magnetic parameter have been analyzed on temperature distribution and fluid flow streamlines and also, on the local and average Nusselt numbers. The governing equations have been solved by the finite element method (FEM). As a novelty, the Taguchi method has been utilized for test design. Further, the response surface method (RSM) has been applied to achieving the optimum value of the involved parameters. The obtained results illustrate that with an augment in the Rayleigh number from 10 to 100, the average Nusselt number will improve by about 61.82%. Additionally, regarding the correlation, it is indeed transparent that the Rayleigh number has the most colossal contribution comparing other factors on the achieved equation, by about 61.88%.
Electron-deficient acridones and in situ generated acridinium salts are reported as potent, closed-shell photooxidants that undergo surprising mechanisms. When bridging acyclic triarylamine catalysts with a carbonyl group (acridones), this completely diverts their behavior away from open-shell, radical cationic, ‘beyond diffusion’ photocatalysis to closed-shell, neutral, diffusion-controlled photocatalysis. Brønsted acid activation of acridones dramatically increases excited state oxidation power (by +0.8 V). Upon reduction of protonated acridones, they transform to electron-deficient acridinium salts as even more potent photooxidants (*E1/2=+2.56–3.05 V vs SCE). These oxidize even electron-deficient arenes where conventional acridinium salt photooxidants have thusfar been limited to electron-rich arenes. Surprisingly, upon photoexcitation these electron-deficient acridinium salts appear to undergo two electron reductive quenching to form acridinide anions, spectroscopically-detected as their protonated forms. This new behaviour is partly enabled by a catalyst preassembly with the arene, and contrasts to conventional SET reductive quenching of acridinium salts. Critically, this study illustrates how redox active chromophoric molecules initially considered photocatalysts can transform during the reaction to catalytically active species with completely different redox and spectroscopic properties. 相似文献
Oxidative coupling reaction of 1‐hexyl–3,4‐dimethylpyrrole affords a conjugated conducting poly(1‐hexyl‐3,4‐dimethyl‐2,5‐pyrrolylene) (PHDP), which is completely soluble in common organic solvents. The luminescence of PHDP is comparable to that of poly(N‐vinylcarbazole) (PVK), which has been widely used in electroluminescence devices. The quantum efficiency of PHDP is 2.5 times higher than that of PVK. A rationalization is presented relating the conductivity of PHDP to its polymer structure. 相似文献
This paper mainly discusses the applicability of using soft x-ray tomography technology to examine the multidimensional structure of metal–organic frameworks, such as their core-shell and hollow framework, by visually observing their corresponding images in different energy bands by different excitation energies for different elements. The results show that the use of soft x-ray tomography (SXT) can effectively observe the distribution of metals in the structure, as well as observe the type of hollow pores the metal – organic framework (MOF) possesses. This pioneering evaluation of MOFs via SXT shows excellent performance in the structure identification of multidimensional metal–organic frameworks. 相似文献
A widely applicable, practical, and scalable synthetic method for efficient ene-type double oxidation of alkenes is reported via a two-step alkenyl thianthrenium umpolung/Kornblum-Ganem oxidation strategy. This chemo- and stereoselective procedure allows easy access to various α,β-unsaturated carbonyls that may be otherwise difficult or cumbersome to synthesize by conventional methods. For α-olefins, this metal-free transformation can be tuned according to synthetic needs to produce either the elusive (Z)-unsaturated aldehydes or their (E) counterparts. Moreover, this strategy has enabled streamlined synthesis of distinct butadienyl pheromones and kairomones. 相似文献
Mitragynine pseudoindoxyl, a kratom metabolite, has attracted increasing attention due to its favorable side effect profile as compared to conventional opioids. Herein, we describe the first enantioselective and scalable total synthesis of this natural product and its epimeric congener, speciogynine pseudoindoxyl. The characteristic spiro-5-5-6-tricyclic system of these alkaloids was formed through a protecting-group-free cascade relay process in which oxidized tryptamine and secologanin analogues were used. Furthermore, we discovered that mitragynine pseudoindoxyl acts not as a single molecular entity but as a dynamic ensemble of stereoisomers in protic environments; thus, it exhibits structural plasticity in biological systems. Accordingly, these synthetic, structural, and biological studies provide a basis for the planned design of mitragynine pseudoindoxyl analogues, which can guide the development of next-generation analgesics. 相似文献
Prenylation is a ubiquitous late-stage modification in nature that often confers significantly improved bioactivity for secondary metabolites. While this lipophilic modification renders enhanced potency, the lipophilic tag(s) can diminish bioavailability and adversely alter drug transportation and metabolism. Thus, a functional-group-tolerant, mild, and selective late-stage C−H functionalization of prenyl tags would present a great potential in drug discovery programs but could also impact other fields, such as agrochemistry and chemical biology. Herein we report an exocyclic-strain-driven cross-metathesis reaction of prenyl tags, a formal double C−H oxidation protocol, that can be used for the selective late-stage derivatization of prenylated compounds and natural products. This methodology avoids the need for prefunctionalization of target molecules and affords ready access to an unprecedented library of oxo- and aza-prenylated complex molecules. Thus, in a broader context, this methodology extends late-stage functionalization beyond that available to nature. 相似文献