Topical delivery of small interfering RNA (siRNA) can be an attractive method for the treatment of skin diseases and improving the quality of life of patients. However, it is difficult for siRNA to pass through the two major barriers of the skin the stratum corneum (SC) and tight junctions. We have previously reported that atopic dermatitis of skin without the SC can be efficiently treated by the intradermal administration of trans-activator of transcription (Tat) peptide and AT1002 (tight junction opening peptide). However, novel drug delivery systems are needed for effective SC penetration. Therefore, in the present study, we aimed to develop a lyotropic liquid crystalline (LC) system containing Tat and AT1002 for effective siRNA penetration through the SC. An LC formulation was prepared using selachyl alcohol and purified water, and its skin penetration ability was evaluated. No fluorescence was observed in mouse skin treated with a siRNA solution, as there was no intradermal localization of siRNA from naked siRNA. However, intradermal delivery of siRNA was remarkable and extensive with the LC formulation containing both Tat and AT1002. Semiquantitative analysis by brightness measurement revealed that the LC formulation containing both Tat and AT1002 had significantly enhanced intact skin permeability than other formulations. These results show that the functional peptides in the LC formulation increased SC penetration and intradermal delivery in the healthy skin. Therefore, this novel LC system may be useful in the treatment of various skin diseases.A method for amide-directed Ni-catalyzed diastereoselective arylboration of cyclopentenes is disclosed. The reaction allows for the synthesis of sterically congested cyclopentane scaffolds that contain an easily derivatized boronic ester and amide functional handles. The nature of the amide directing group and its influence on the reaction outcome are investigated and ultimately reflect a predictably selective reaction based on the solvent and base counterion.The cross-coupling of C-N bond directly from inert C-H bonds is an ideal approach to synthesize saturated azacycles due to its high efficiency and atom economy. In this article, a copper-catalyzed intramolecular amination via the cross coupling of C(sp3)-H and N-H bonds of secondary amine has been reported, which exhibit excellent chemo- and regioselectivity, extensive substrate scope, and functional group tolerance in good to excellent yield, offering an efficient pathway to build nitrogen-containing heterocycle skeletons.This paper describes reversible "on-off" switching of the photoluminescence (PL) intensity of CdSe quantum dots (QDs), mediated by photochromic furylfulgide carboxylate (FFC) molecules chemisorbed to the surfaces of the QDs. Repeated cycles of UV and visible illumination switch the FFC between "closed" and "open" isomers. Reversible switching of the QDs' PL intensity by >80% is enabled by different rates and yields of PL-quenching photoinduced electron transfer (PET) from the QDs to the respective isomers. This difference is consistent with cyclic voltammetry measurements and density functional calculations of the isomers' frontier orbital energies. This work demonstrates fatigue-resistant modulation of the PL of a QD-molecule complex through remote control of PET. https://www.selleckchem.com/products/sd49-7.html Such control potentially enables applications, such as all-optical memory, sensing, and imaging, that benefit from a fast, tunable, and reversible response to light stimuli.Transplantation of neural stem cells (NSCs) is a promising treatment paradigm to replace lost neurons and reconstruct the damaged neural circuit after ischemic stroke. However, most transplanted NSCs often differentiate into astrocytes rather than functional neurons, and the poor neuronal differentiation adversely affects the therapeutic outcome of NSCs and limits their clinical translation for stroke therapy. Herein, a theranostic nanomedicine is developed to codeliver superparamagnetic iron oxide nanoparticles (SPIO) and small interfering RNA/antisense oligonucleotides (siRNA/ASO) against Pnky long noncoding RNA (lncRNA) into NSCs. This nanomedicine not only directs neuronal differentiation of NSCs through silencing the Pnky lncRNA but also allows an in vivo tracking of NSCs with magnetic resonance imaging. The enhanced neuronal differentiation of NSCs significantly improved the structural and functional recovery of the damaged brain after a stroke. The results demonstrate the great potential of the multifunctional nanomedicine targeting lncRNA to enhance stem cell-based therapies for a stroke.The luminescence of CuInS2 quantum dots (QDs) is slower and spectrally broader than that of many other types of QDs. The origin of this anomalous behavior is still under debate. Single-QD experiments could help settle this debate, but studies by different groups have yielded conflicting results. Here, we study the photophysics of single core-only CuInS2 and core/shell CuInS2/CdS QDs. Both types of single QDs exhibit broad PL spectra with fluctuating peak position and single-exponential photoluminescence decay with a slow but fluctuating lifetime. Spectral diffusion of CuInS2-based QDs is qualitatively and quantitatively different from CdSe-based QDs. The differences reflect the dipole moment of the CuInS2 excited state and hole localization on a preferred site in the QD. Our results unravel the highly dynamic photophysics of CuInS2 QDs and highlight the power of the analysis of single-QD property fluctuations.A coronavirus disease (COVID-19) outbreak associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading widely through person-to-person transmission. Various detection approaches have been developed involving quantitative polymerase chain reaction (qPCR) methods, CRISPR-based systems, and direct targeting of specific coronavirus proteins. However, there have only been a few reports on the detection of RNA-dependent RNA polymerase (RdRP), the primer-independent RNA-replicable protein produced by the RNA genes of coronavirus. Here, we introduce a novel diagnostic methodology for COVID-19 using the RNA-directed and de novo RNA replicable function of RdRP. We devised an RNA platform for RdRP-induced transcription (RPRIT) that includes an RNA template that can be directly transcribed by RdRP. By utilizing RPRIT, the presence of RdRP can be readily confirmed within 30 min using isothermal incubation without PCR. This RdRP detection method can provide a new route for rapid diagnosis of RNA virus-infected patients.
Topical delivery of small interfering RNA (siRNA) can be an attractive method for the treatment of skin diseases and improving the quality of life of patients. However, it is difficult for siRNA to pass through the two major barriers of the skin the stratum corneum (SC) and tight junctions. We have previously reported that atopic dermatitis of skin without the SC can be efficiently treated by the intradermal administration of trans-activator of transcription (Tat) peptide and AT1002 (tight junction opening peptide). However, novel drug delivery systems are needed for effective SC penetration. Therefore, in the present study, we aimed to develop a lyotropic liquid crystalline (LC) system containing Tat and AT1002 for effective siRNA penetration through the SC. An LC formulation was prepared using selachyl alcohol and purified water, and its skin penetration ability was evaluated. No fluorescence was observed in mouse skin treated with a siRNA solution, as there was no intradermal localization of siRNA from naked siRNA. However, intradermal delivery of siRNA was remarkable and extensive with the LC formulation containing both Tat and AT1002. Semiquantitative analysis by brightness measurement revealed that the LC formulation containing both Tat and AT1002 had significantly enhanced intact skin permeability than other formulations. These results show that the functional peptides in the LC formulation increased SC penetration and intradermal delivery in the healthy skin. Therefore, this novel LC system may be useful in the treatment of various skin diseases.A method for amide-directed Ni-catalyzed diastereoselective arylboration of cyclopentenes is disclosed. The reaction allows for the synthesis of sterically congested cyclopentane scaffolds that contain an easily derivatized boronic ester and amide functional handles. The nature of the amide directing group and its influence on the reaction outcome are investigated and ultimately reflect a predictably selective reaction based on the solvent and base counterion.The cross-coupling of C-N bond directly from inert C-H bonds is an ideal approach to synthesize saturated azacycles due to its high efficiency and atom economy. In this article, a copper-catalyzed intramolecular amination via the cross coupling of C(sp3)-H and N-H bonds of secondary amine has been reported, which exhibit excellent chemo- and regioselectivity, extensive substrate scope, and functional group tolerance in good to excellent yield, offering an efficient pathway to build nitrogen-containing heterocycle skeletons.This paper describes reversible "on-off" switching of the photoluminescence (PL) intensity of CdSe quantum dots (QDs), mediated by photochromic furylfulgide carboxylate (FFC) molecules chemisorbed to the surfaces of the QDs. Repeated cycles of UV and visible illumination switch the FFC between "closed" and "open" isomers. Reversible switching of the QDs' PL intensity by >80% is enabled by different rates and yields of PL-quenching photoinduced electron transfer (PET) from the QDs to the respective isomers. This difference is consistent with cyclic voltammetry measurements and density functional calculations of the isomers' frontier orbital energies. This work demonstrates fatigue-resistant modulation of the PL of a QD-molecule complex through remote control of PET. https://www.selleckchem.com/products/sd49-7.html Such control potentially enables applications, such as all-optical memory, sensing, and imaging, that benefit from a fast, tunable, and reversible response to light stimuli.Transplantation of neural stem cells (NSCs) is a promising treatment paradigm to replace lost neurons and reconstruct the damaged neural circuit after ischemic stroke. However, most transplanted NSCs often differentiate into astrocytes rather than functional neurons, and the poor neuronal differentiation adversely affects the therapeutic outcome of NSCs and limits their clinical translation for stroke therapy. Herein, a theranostic nanomedicine is developed to codeliver superparamagnetic iron oxide nanoparticles (SPIO) and small interfering RNA/antisense oligonucleotides (siRNA/ASO) against Pnky long noncoding RNA (lncRNA) into NSCs. This nanomedicine not only directs neuronal differentiation of NSCs through silencing the Pnky lncRNA but also allows an in vivo tracking of NSCs with magnetic resonance imaging. The enhanced neuronal differentiation of NSCs significantly improved the structural and functional recovery of the damaged brain after a stroke. The results demonstrate the great potential of the multifunctional nanomedicine targeting lncRNA to enhance stem cell-based therapies for a stroke.The luminescence of CuInS2 quantum dots (QDs) is slower and spectrally broader than that of many other types of QDs. The origin of this anomalous behavior is still under debate. Single-QD experiments could help settle this debate, but studies by different groups have yielded conflicting results. Here, we study the photophysics of single core-only CuInS2 and core/shell CuInS2/CdS QDs. Both types of single QDs exhibit broad PL spectra with fluctuating peak position and single-exponential photoluminescence decay with a slow but fluctuating lifetime. Spectral diffusion of CuInS2-based QDs is qualitatively and quantitatively different from CdSe-based QDs. The differences reflect the dipole moment of the CuInS2 excited state and hole localization on a preferred site in the QD. Our results unravel the highly dynamic photophysics of CuInS2 QDs and highlight the power of the analysis of single-QD property fluctuations.A coronavirus disease (COVID-19) outbreak associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading widely through person-to-person transmission. Various detection approaches have been developed involving quantitative polymerase chain reaction (qPCR) methods, CRISPR-based systems, and direct targeting of specific coronavirus proteins. However, there have only been a few reports on the detection of RNA-dependent RNA polymerase (RdRP), the primer-independent RNA-replicable protein produced by the RNA genes of coronavirus. Here, we introduce a novel diagnostic methodology for COVID-19 using the RNA-directed and de novo RNA replicable function of RdRP. We devised an RNA platform for RdRP-induced transcription (RPRIT) that includes an RNA template that can be directly transcribed by RdRP. By utilizing RPRIT, the presence of RdRP can be readily confirmed within 30 min using isothermal incubation without PCR. This RdRP detection method can provide a new route for rapid diagnosis of RNA virus-infected patients.
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