It is of great significance to track the platinum drugs in real time with super‐resolution to elucidate their mechanism of action, such as their behavior and distribution in live cells. Such ...information is required for further drug development. However, it is always challenging to design platinum complexes suitable for such research. Herein, we design a luminescent building block (L) for metal complexes and a dinuclear platinum complex (Pt2L) for super‐resolution imaging. Because of its super‐large Stokes shift and excellent photophysical properties, Pt2L is capable of serving as an ideal candidate for super‐resolution imaging with extremely low luminescence background and high photobleaching resistance. Moreover, upon light stimulation, a matter flux of Pt2L escaping from autolysosomes to nucleus was observed, which represents a new transportation path. Utilizing the photoactivated escape properties, we can regulate the nuclear accessibility of Pt2L form autolysosomes with photo‐selectivity, which provides a new way to improve the targeting of platinum drugs.
A multiple‐color platinum complex (Pt2L) with super‐large Stokes shift was designed for super‐resolution imaging, showing an extremely low luminescence background and high photobleaching resistance. Moreover, upon light stimulation, a matter flux of Pt2L escaping from autolysosomes to the nucleus is detected, which represents a new transportation path.
Abstract
In the last few years, the survival of patients with castration-resistant prostate cancer (CRPC) has significantly improved as a result of the development of second-generation androgen ...deprivation therapies such as abiraterone and second-generation antagonists such as enzalutamide. However, CRPC patients rapidly develop resistance to these drugs, in many cases because of reactivation of the therapeutic target, the androgen receptor (AR) transcription factor. Several mechanisms responsible for AR transcriptional reactivation have been demonstrated, including mutation, amplification, and rearrangement of the AR gene, transcriptional compensation by alternative steroid receptors, and mutation or copy number alteration of genes encoding AR coregulators. In addition, CRPC tumors display elevated expression of truncated AR variants (AR-Vs) that can arise from alternative splicing or underlying AR gene rearrangements. In this review, we discuss general mechanisms of resistance to androgen/AR-targeted therapies, with a focus on the role of AR-Vs in conferring resistance to abiraterone or enzalutamide in CRPC patients.
We review the role of androgen receptor variants (AR-Vs) arising from alternative splicing and genome rearrangements in resistance to AR-targeted therapies in castration-resistant prostate cancer.
The ability to precisely control the subcellular distribution of luminous materials presents unprecedented advantages for understanding cell biology and disease therapy. We introduce a luminescence ...tool for subcellular distribution imaging and differentiation of live and dead cells, utilizing cationic organoplatinum(II) complexes that exhibit well‐defined monomeric to aggregate nanostructures along with concentration‐dependent switchable luminescence from green to red due to assembly via PtII⋅⋅⋅PtII and π–π stacking interactions. One of the complexes was chosen to demonstrate the unique lysosome‐to‐nucleus subcellular re‐distribution and imaging capability in live and dead cells, respectively, which represents the first example to discriminate the subcellular localization of platinum(II) complexes through differential luminescence response. These new findings facilitate the fundamental understanding of self‐assembly behaviors of platinum(II) complexes for potential subcellular detection assays.
The aggregation affinities of the platinum(II) complexes enable them to exhibit well‐defined monomeric to aggregate nanostructures along with concentration‐dependent switchable luminescence from green to red, attributed to the extent of PtII⋅⋅⋅PtII and π–π stacking interactions. The platinum(II) complex is applied to manifest the unique lysosome‐to‐nucleus subcellular re‐distribution and imaging capability in live and dead cells.
Platinum(II) complexes as supramolecular luminescent materials have received considerable attention due to their unique planar structures and fascinating photophysical properties. However, the ...molecular design of platinum(II) complexes with impressive circularly polarized luminescence properties still remains challenging and rarely explored. Herein, we reported a series of cyclometalated platinum(II) complexes with benzaldehyde and its derived imine-containing alkynyl ligands to investigate their phosphorescent, chiroptical, and self-assembly behaviors. An isodesmic growth mechanism is found for their temperature-dependent self-assembly process. The chiral sense of the enantiomers can be transferred from the chiral alkynyl ligands to the cyclometalated platinum(II) dipyridylbenzene N^C^N chromophore and further amplified through supramolecular assembly via intermolecular noncovalent interactions. Notably, distinctive phosphorescent properties and nanostructured morphologies have been found for enantiomers
and
. Their intriguing self-assembled nanostructures and phosphorescence behaviors are supported by crystal structure determination,
H NMR, emission, and UV-vis absorption spectroscopy, scanning electron microscopy, and X-ray powder diffraction studies.
...67% reported feeling confident with their decision for admission. ...some respondents advocated for standardization of patient care. Early evidence suggests fewer readmissions, better overall pain ...control, and higher quality of life 12,13. Pain management in SCD is an example in which individual social decision-making heavily impacts clinical decision-making and patient outcomes.
Key points
Leptin is a potent respiratory stimulant.
A long functional isoform of leptin receptor, LepRb, was detected in the carotid body (CB), a key peripheral hypoxia sensor. However, the effect ...of leptin on minute ventilation (VE) and the hypoxic ventilatory response (HVR) has not been sufficiently studied.
We report that LepRb is present in approximately 74% of the CB glomus cells.
Leptin increased carotid sinus nerve activity at baseline and in response to hypoxia in vivo.
Subcutaneous infusion of leptin increased VE and HVR in C57BL/6J mice and this effect was abolished by CB denervation.
Expression of LepRb in the carotid bodies of LepRb deficient obese db/db mice increased VE during wakefulness and sleep and augmented the HVR.
We conclude that leptin acts on LepRb in the CBs to stimulate breathing and HVR, which may protect against sleep disordered breathing in obesity.
Leptin is a potent respiratory stimulant. The carotid bodies (CB) express the long functional isoform of leptin receptor, LepRb, but the role of leptin in CB has not been fully elucidated. The objectives of the current study were (1) to examine the effect of subcutaneous leptin infusion on minute ventilation (VE) and the hypoxic ventilatory response to 10% O2 (HVR) in C57BL/6J mice before and after CB denervation; (2) to express LepRb in CB of LepRb‐deficient obese db/db mice and examine its effects on breathing during sleep and wakefulness and on HVR. We found that leptin enhanced carotid sinus nerve activity at baseline and in response to 10% O2 in vivo. In C57BL/6J mice, leptin increased VE from 1.1 to 1.5 mL/min/g during normoxia (P < 0.01) and from 3.6 to 4.7 mL/min/g during hypoxia (P < 0.001), augmenting HVR from 0.23 to 0.31 mL/min/g/ΔFIO2 (P < 0.001). The effects of leptin on VE and HVR were abolished by CB denervation. In db/db mice, LepRb expression in CB increased VE from 1.1 to 1.3 mL/min/g during normoxia (P < 0.05) and from 2.8 to 3.2 mL/min/g during hypoxia (P < 0.02), increasing HVR. Compared to control db/db mice, LepRb transfected mice showed significantly higher VE throughout non‐rapid eye movement (20.1 vs. −27.7 mL/min respectively, P < 0.05) and rapid eye movement sleep (16.5 vs 23.4 mL/min, P < 0.05). We conclude that leptin acts in CB to augment VE and HVR, which may protect against sleep disordered breathing in obesity.
Key points
Leptin is a potent respiratory stimulant.
A long functional isoform of leptin receptor, LepRb, was detected in the carotid body (CB), a key peripheral hypoxia sensor. However, the effect of leptin on minute ventilation (VE) and the hypoxic ventilatory response (HVR) has not been sufficiently studied.
We report that LepRb is present in approximately 74% of the CB glomus cells.
Leptin increased carotid sinus nerve activity at baseline and in response to hypoxia in vivo.
Subcutaneous infusion of leptin increased VE and HVR in C57BL/6J mice and this effect was abolished by CB denervation.
Expression of LepRb in the carotid bodies of LepRb deficient obese db/db mice increased VE during wakefulness and sleep and augmented the HVR.
We conclude that leptin acts on LepRb in the CBs to stimulate breathing and HVR, which may protect against sleep disordered breathing in obesity.
A new class of amphiphilic spiropyran derivatives has been designed and synthesized. Their photophysical and photochromic properties have been investigated. Under UV light irradiation, the ...ring-closed hydrophobic spiropyrans have been shown to undergo photoinduced ring-opening to give the zwitterionic ring-opened merocyanine forms, which resulted in the amphiphilic properties of the compounds. These compounds were also found to display self-assembly behavior with the formation of H-aggregation in organic solvents under UV irradiation to give different morphologies with diverse nano-structures, leading to promising candidates for the design of a new class of small-molecule photo-responsive materials. The H-aggregate formation has been further supported by computational studies and noncovalent interaction (NCI) analysis of the dimer of the merocyanine form. This represents the first demonstration of the use of NCI analysis on the role played by noncovalent interactions in H-aggregate formation of the spiropyran derivatives.
H-Aggregate formation of photochromic spiropyran derivatives
via
photoswitchable amphiphilicity.
Here we report the first two-dimensional (2D) supramolecular polymer, which has varying structure and function arising from the perturbation of noncovalent metal···metal interactions in response to ...acid–base stimuli. This 2D assembly possesses a positively charged, honeycomb-like nanostructure consisting of trinuclear alkynylplatinum(II) terpyridine complexes appended with acid-sensitive dimethylamino groups. Upon addition of acids and bases, reversible switching mediated by protonation and deprotonation of dimethylamino and dimethylammonium moieties intrinsically alters the positive charge density of the constituent cationic units, which causes interior cavities to adaptively adjust their size, accompanied by drastic photoluminescence changes. When water molecules pass through the membranes obtained from 2D supramolecular polymers, the permeating flux can also be tuned by the pH values of the buffer media. This work paves the way toward supramolecularly engineered 2D smart materials with stimuli-responsive properties.
A series of platinum(II) calix4arene‐based molecular tweezers was synthesized. The studies of the host–guest association with a charge‐neutral cyclometalated platinum(II) complex showed a drastic ...color change and the turning on of near‐infrared emission resulting from Pt⋅⋅⋅Pt and π–π interactions. Control of the host–guest assembly process by varying the solvent composition can lead to a change from discrete host and guest molecules to high‐ordered host–guest oligomers with the formation of sheet‐like nanostructures, demonstrating a rare example of three‐state supramolecular host–guest system with high solubility in solvents of diverse polarity. The change in host–guest assembly behaviors could be probed by drastic color changes from yellow to orange to green. The present study provides insights into the systematic design of solvent‐responsive molecular materials using molecular tweezers‐directed host–guest assembly, with potential applications in colorimetric sensing of changes in the micro‐environment.
The host–guest assembly process of a platinum(II) tweezers–guest system can be controlled by varying the solvent composition. The change in the assembly behavior from discrete host and guest molecules to high‐ordered host–guest oligomers can be probed by drastic changes in the color from yellow to orange to green, demonstrating a three‐state supramolecular system with potential application as a colorimetric micro‐environment sensor.
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