Animal development depends on not only the linear genome sequence that embeds millions of
cis
-regulatory elements, but also the three-dimensional (3D) chromatin architecture that orchestrates the ...interplay between
cis
-regulatory elements and their target genes. Compared to our knowledge of the
cis
-regulatory sequences, the understanding of the 3D genome organization in human and other eukaryotes is still limited. Recent advances in technologies to map the 3D genome architecture have greatly accelerated the pace of discovery. Here, we review emerging concepts of chromatin organization in mammalian cells, discuss the dynamics of chromatin conformation during development, and highlight important roles for chromatin organization in cancer and other human diseases.
Organic dye based NIR‐II fluorescent probes, owing to their high signal‐to‐background ratio and deeper penetration, are highly useful for deep‐tissue high‐contrast imaging in vivo. However, it is ...still a challenge to design activatable NIR‐II fluorescent probes. Here, a novel class of polymethine dyes (NIRII‐RTs), with bright (quantum yield up to 2.03 %), stable, and anti‐solvent quenching NIR‐II emission, together with large Stokes shifts, was designed. Significantly, the novel NIR‐II dyes NIRII‐RT3 and NIRII‐RT4, equipped with a carboxylic acid group, can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast. As a proof of concept, a series of target‐activatable NIRII‐RT probes (NIRII‐RT‐pH, NIRII‐RT‐ATP and NIRII‐RT‐Hg) for pH, adenosine triphosphate (ATP), and metal‐ion detection, were synthesized. By applying the NIRII‐RT probe, the real‐time monitoring of drug‐induced hepatotoxicity was realized.
The presented work reports a new class of polymethine dyes (NIRII‐RTs) with bright, stable, and anti‐quenching NIR‐II emissions together with large Stokes shifts. Importantly, by introducing the carboxylic acid functional group, the novel dyes NIRII‐RT3 and NIRII‐RT4 can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Small‐molecule‐based second near‐infrared (NIR‐II) activatable fluorescent probes can potentially provide a high target‐to‐background ratio and deep tissue penetration. However, most of the reported ...NIR‐II activatable small‐molecule probes exhibit poor versatility owing to the lack of a general and stable optically tunable group. In this study, we designed NIRII‐HDs, a novel dye scaffold optimized for NIR‐II probe development. In particular, dye NIRII‐HD5 showed the best optical properties such as proper pKa value, excellent stability, and high NIR‐II brightness, which can be beneficial for in vivo imaging with high contrast. To demonstrate the applicability of the NIRII‐HD5 dye, we designed three target‐activatable NIR‐II probes for ROS, thiols, and enzymes. Using these novel probes, we not only realized reliable NIR‐II imaging of different diseases in mouse models but also evaluated the redox potential of liver tissue during a liver injury in vivo with high fidelity.
A series of O‐HD‐like dyes (NIRII‐HDs) with bright and stable NIR‐II emission together with proper pKa is reported. By decorating the tunable hydroxyl group, the novel NIR‐II dye NIRII‐HD5 can serve as an effective platform to design various activatable NIR‐II probes for reliable in vivo bioimaging with high contrast.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The quality and application of super-resolution fluorescence imaging greatly lie in the dyes' properties, including photostability, brightness, and Stokes shift. Here we report a synergistic strategy ...to simultaneously improve such properties of regular fluorophores. Introduction of quinoxaline motif with fine-tuned electron density to conventional rhodamines generates new dyes with vibration structure and inhibited twisted-intramolecular-charge-transfer (TICT) formation synchronously, thus increasing the brightness and photostability while enlarging Stokes shift. The new fluorophore YL578 exhibits around twofold greater brightness and Stokes shift than its parental fluorophore, Rhodamine B. Importantly, in Stimulated Emission Depletion (STED) microscopy, YL578 derived probe possesses a superior photostability and thus renders threefold more frames than carbopyronine based probes (CPY-Halo and 580CP-Halo), known as photostable fluorophores for STED imaging. Furthermore, the strategy is well generalized to offer a new class of bright and photostable fluorescent probes with long Stokes shift (up to 136 nm) for bioimaging and biosensing.
Organic fluorophores are indispensable tools in cells, tissue and in vivo imaging, and have enabled much progress in the wide range of biological and biomedical fields. However, many available dyes ...suffer from insufficient performances, such as short absorption and emission wavelength, low brightness, poor stability, small Stokes shift, and unsuitable permeability, restricting their application in advanced imaging technology and complex imaging. Over the past two decades, many efforts have been made to improve these performances of fluorophores. Starting with the luminescence principle of fluorophores, this review clarifies the mechanisms of the insufficient performance for traditional fluorophores to a certain extent, systematically summarizes the modified approaches of optimizing properties, highlights the typical applications of the improved fluorophores in imaging and sensing, and indicates existing problems and challenges in this area. This progress not only proves the significance of improving fluorophores properties, but also provide a theoretical guidance for the development of high‐performance fluorophores.
The review has clarified the reasons for the insufficient properties of fluorophores, including short absorption and emission wavelength, low brightness, poor stability, small Stokes shift, and unsuitable permeability, and summarizes the methods for optimizing these properties developed in recent years. The review will provide a theoretical guidance and helpful insights for the design of high‐performance fluorophores.
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Tumor‐specific, hypoxia‐activated prodrugs have been developed to alleviate the side effects of chemotherapy drugs. However, the release efficiency of hypoxia‐activated prodrugs is restricted by the ...degree of tumor hypoxia, which further leads to poor cancer treatment effects. On the other hand, oxygen is consumed gradually in photodynamic therapy (PDT), which aggravates hypoxia at the tumor site. In this study, we combined hypoxia‐activated prodrugs with PDT agents to promote the prodrugs release, thereby improving their bioavailability and therapeutic effects. As a proof of concept, a mitochondria‐targeted molecular prodrug, CS‐P, was designed and synthesized. It can be selectively activated by tumor hypoxia to release chemotherapeutic drugs and photosensitizers, and then further discharge drugs after light irradiation. The design strategy proposed in this paper provides a new idea for enhancing hypoxia‐activated prodrug release and real‐time monitoring prodrug release.
A mitochondria‐targeted molecular prodrug, namely CS‐P, was designed and synthesized to demonstrate the feasibility of using the PDT process to effectively promote the release of hypoxia‐activated drugs. The experimental results indicated that CS‐P can be selectively activated by tumor hypoxia to release chemotherapeutic drugs and photosensitizers, and then further release chemotherapeutic drugs after light irradiation. The design strategy proposed provides a new idea for enhancing hypoxia‐activated prodrugs release.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The second near‐infrared (NIR‐II) fluorescent imaging shows great potential for deep tissue analysis at high resolution in living body owing to low background autofluorescence and photon scattering. ...However, reversible monitoring of redox homeostasis using NIR‐II fluorescent imaging remains a challenge due to the lack of appropriate probes. In this study, a series of stable and multifunctional NIR‐II dyes (NIR‐II Cy3s) were constructed based on trimethine skeleton. Significantly, introducing the 1,4‐diethyl‐decahydroquinoxaline group to the NIR‐II Cy3s not only effectively increased the wavelength, but also served as an effective response site for HClO, which can be restored by reactive sulfur species (RSS). Based on this, NIR‐II Cy3s were used for reversible monitoring of HClO/RSS‐mediated redox processes in the pathophysiology environment. Finally, NIR‐II Cy3‐988 was successfully utilized for assessment of the redox environments and drug treatment effects in acute inflammation model.
We report a new class of trimethine skeleton NIR‐II fluorophores (NIR‐II Cy3s) with improved stability over traditional heptamethine NIR‐II fluorophores and emission above 1000 nm. The NIR‐II Cy3s can reversibly respond to HClO and reactive sulfur species (RSS) and can serve as an effective platform for the reversible monitoring of the HClO/RSS‐mediated redox process in a pathophysiology environment. Finally, we applied NIR‐II Cy3‐988 to the reversible assessment of the redox environment and dynamic effect of drug treatment in an acute inflammation model and of redox potential changes during liver injury and repair.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Fluorescent dyes have enabled much progress in the broad range of biomedical fields. However, many commercially available dyes suffer from small Stokes shifts, resulting in poor signal-to-noise ratio ...and self-quenching on current microscope configurations. In this work, we have developed a general method to significantly increase the Stokes shifts of common fluorophores. By simply appending a 1,4-diethyl-decahydro-quinoxaline (DQ) moiety onto the conjugated structure, we introduced a vibronic backbone that could facilely expand the Stokes shifts, emission wavelength, and photostability of 11 different fluorophores by more than 3-fold. This generalizable method could significantly improve the imaging efficiency of commercial fluorophores. As a demonstration, we showed that the DQ derivative of hemicyanine generated 5-fold signal in mouse models over indocyanine green. Furthermore, the DQ-modified fluorophores could pair with their parent molecules to conduct one-excitation, multiple emission imaging, allowing us to study the cell behavior more robustly. This approach shows promise in generating dyes suitable for super-resolution microscopy and second window near-infrared imaging.
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IJS, KILJ, NUK, PNG, UL, UM
The cyanine fluorophores, a kind of classic organic fluorophores, are famous for their high extinction coefficient, simple synthetic route, and relatively long absorption and emission wavelengths. ...Moreover, the excellent biocompatibility and low toxicity in biological samples make cyanine fluorophores show excellent application value in the biomedical field, especially in Near-Infrared II (NIR-II) sensing and imaging. In this review, we briefly outline the history, characteristics, and current state of development of cyanine fluorophores. In particular, we described the application of cyanine fluorophores in NIR-II sensing and imaging. We hope this review can help researchers grab the latest information in the fast-growing field of cyanine fluorophores for NIR-II sensing and imaging.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Two‐photon imaging is an emerging tool for biomedical research and clinical diagnostics. Electron donor–acceptor (D–A) type molecules are the most widely employed two‐photon scaffolds. However, ...current D–A type fluorophores suffer from solvatochromic quenching in aqueous biological samples. To address this issue, we devised a novel class of D–A type green fluorescent protein (GFP) chromophore analogues that form a hydrogen‐bond network in water to improve the two‐photon efficiency. Our design results in two‐photon chalcone (TPC) dyes with 0.80 quantum yield and large two‐photon action cross section (210 GM) in water. This strategy to form hydrogen bonds can be generalized to design two‐photon materials with anti‐solvatochromic fluorescence. To demonstrate the improved in vivo imaging, we designed a sulfide probe based on TPC dyes and monitored endogenous H2S generation and scavenging in the cirrhotic rat liver for the first time.
Turn bane into a boon: A unique class of two‐photon dyes with anti‐solvatochromic fluorescence, optically tunable groups, high fluorescence quantum yields, and large two‐photon action cross sections in water are developed. Their use for in vivo imaging, was demonstrated in the monitoring of endogenous H2S generation and scavenging in the cirrhotic rat liver.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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