Among the d 10 coinage metal complexes, cyclic trinuclear complexes (CTCs) or trinuclear metallocycles with intratrimer metal−metal interactions are fascinating and important metal−organic or organometallic π-acids/bases. Each CTC of characteristic planar or near-planar trimetal nine-membered rings consists of Au(I)/Ag(I)/Cu(I) cations that linearly coordinate with N and/or C atoms in ditopic anionic bridging ligands. Since the first discovery of Au(I) CTC in the 1970s, research of CTCs has involved several fundamental areas, including noncovalent and metallophilic interaction, excimer/exciplex, acid−base chemistry, metalloaromaticity, supramolecular assemblies, and host/guest chemistry. These allow CTCs to be embraced in a wide range of innovative potential applications that include chemical sensing, semiconducting, gas and liquid adsorption/separation, catalysis, full-color display, and solid-state lighting. This review aims to provide a historic and comprehensive summary on CTCs and their extension to higher nuclearity complexes and coordination polymers from the perspectives of synthesis, structure, theoretical insight, and potential applications.
Purpose: Inherited retinal dystrophy (IRD) is a leading cause of blindness worldwide. Because of extreme genetic heterogeneity, the etiology and genotypic spectrum of IRD have not been clearly defined, and there is limited information on genotype-phenotype correlations. The purpose of this study was to elucidate the mutational spectrum and genotype-phenotype correlations of IRD. Methods:We developed a targeted panel of 164 known retinal disease genes, 88 candidate genes, and 32 retina-abundant microRNAs, used for exome sequencing. A total of 179 Chinese families with IRD were recruited. Results:In 99 unrelated patients, a total of 124 mutations in known retinal disease genes were identified, including 79 novel mutations (detection rate, 55.3%). Moreover, novel genotype-phenotype correlations were discovered, and phenotypic trends noted. Three cases are reported, including the identification of AHI1 as a novel candidate gene for nonsyndromic retinitis pigmentosa. Conclusion:This study revealed novel genotype-phenotype correlations, including a novel candidate gene, and identified 124 genetic defects within a cohort with IRD . The identification of novel genotype-phenotype correlations and the spectrum of mutations greatly enhance the current knowledge of IRD phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments of IRD patients.
Targeting genes to specific neuronal or glial cell types is valuable both for understanding and for repairing brain circuits. Adeno-associated viral vectors (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is a challenge. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that ~11% of these AAVs specifically target expression to neuronal and glial cell types in the mouse retina, mouse brain, non-human primate retina in vivo, and in the human retina in vitro. We demonstrate applications for recording, stimulation, and molecular characterization, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast, and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.Despite the central importance for both basic and translational research, most current technologies available for cell-type-targeting rely on transgenic animals, which limits their applicability. Either the genetic tool that senses or modulates brain function, or the enzyme, such as Cre recombinase, that allows the genetic tool to be conditionally expressed, is expressed from the animal's genome. The inclusion of a transgenic component in the cell-type-targeting strategy excludes its use in therapy for humans, limits its range of application in pre-clinical, non-human primate research, and complicates its use in model organisms such as mice. The development of transgenic non-human primates and mice is costly and slow, especially since cell-type targeting is often applied in the context of other genetic manipulations, such as double or triple gene knockouts, or when targeting different cell types with different tools.Viral vectors for cell-type-targeting may overcome such limitations. AAVs are the most frequently used vectors in both basic research and gene therapy, as they are safe for use in all tested species, including humans and non-human primates, and their production is simple, cheap, and fast (Planul and Dalkara, 2017). They have three important components: the capsid for cell entry, the promoter that drives transgene expression, and the gene of interest to be expressed in the transduced cells, and they drive expression episomally (Duan et al., 1998; Penaud-Budloo et al., 2008). Futhermore, many genetic tools are small enough to fit into AAVs, different AAVs can be injected together, and synthetic AAV capsids allow brain-wide delivery (Deverman et al., 2016).Cell-type-targeting by AAVs could be achieved by engineering the capsid and/or by using specific promoters. Capsid protein mutations can be used to tune the efficacy of
Multifunctional theranostic nanoplatforms (NPs) in response to environment stimulations for ondemand drug release are highly desirable. Herein, the nearinfrared (NIR)-absorbing dye, indocyanine green (ICG), and the antitumor drug, doxorubicin (DOX), were efficiently coencapsulated into the thermosensitive liposomes based on natural phase-change material. Folate and conjugated gadolinium (Gd) chelate-modified liposome shells enhance active targeting and magnetic resonance performance of the NPs while maintaining the size of the NPs. The ICG/DOXloaded and gadolinium chelate conjugated temperaturesensitive liposome nanoplatforms (ID@TSL-Gd NPs) exhibited NIR-triggered drug release and prominent chemo-, photothermal, and photodynamic therapy properties. With the coencapsulated ICG, DOX, and the conjugated gadolinium chelates, the ID@TSL-Gd NPs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging)-guided combination tumor therapy (chemotherapy, photothermotherapy, and photodynamic therapy). After tail vein injection, the ID@TSL-Gd NPs accumulated effectively in subcutaneous HeLa tumor of mice. The tumor was effectively suppressed by accurate imaging-guided NIR-triggered phototherapy and chemotherapy, and no tumor regression and side effects were observed. In summary, the prepared ID@TSL-Gd NPs achieved multimodal imaging-guided cancer combination therapy, providing a promising platform for improving diagnosis and treatment of cancer.
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