Search

Coumarin acting as an optical probe was modified on ethylenediamine β-cyclodextrin, which not only enhanced its molecular binding affinity to glutathione (GSH) by a reversible Michael addition, showing 113 times more affinity than that of coumarin itself, but also achieved dynamic real-time sensing of glutathione in living HeLa cells.

ConspectusHyaluronic acid (HA), which contains multiple carboxyl, hydroxyl, and acetylamino groups and is an agent that targets tumors, has drawn great attention in supramolecular diagnosis and treatment research. It can not only assemble directly with macrocyclic host-guest complexes through hydrogen bonding and electrostatic interactions but also can be modified with macrocyclic compounds or functional guest molecules by an amidation reaction and used for further assembly. Macrocycles play a main role in the construction of supramolecular drug carriers, targeted imaging agents, and hydrogels, such as cyclodextrins and cucurbit[

Government supervision on vehicle recall has become a social focus in recent years with the rapid development of the automobile industry and the growing impact of public opinion in the recall process. Motivated by this, we apply the evolutionary game approach to study the interaction between the automakers and the governments in their vehicle recall and supervision behaviors under the impact of public opinion. The equilibrium outcomes when public opinion exists or not are analyzed. We find that the governments may choose weak or strong supervision under no supervision of public opinion, but the automakers always choose hiding vehicle defects in stable states; and the players’ optimal strategies may exhibit periodic fluctuations over time. Under public opinion supervision, the automakers may choose voluntary recall regardless of whether the governments choose strong or weak supervision. With a high public opinion supervision and low penalty for hiding defects, the governments may choose strong supervision even with sufficiently high supervision cost. Furthermore, although the players’ behaviors may also exhibit periodic fluctuations given a certain level of public opinion, the system will converge to the desired stable states under which voluntary recall is optimal for the automakers as public opinion increases. Our study highlights the role of public opinion in the players’ product recall and supervision behaviors.

Supplementary Data from Methylation Induced Gene Silencing of HtrA3 in Smoking-Related Lung Cancer

Purpose: Some 85% of lung cancers are smoking related. Here, we investigate the role of serine protease HtrA3 in smoking-related lung cancer.Experimental Design: We assess HtrA3 methylation and its corresponding expression in the human bronchial cell line BEAS-2B following cigarette smoke carcinogen treatment, in lung cancer cell lines and in primary lung tumors from light, moderate, and heavy smokers. We also show the effects of HtrA3 downregulation on MTT reduction and clonogenic survival with etoposide and cisplatin treatment and the corresponding effects of HtrA3 re-expression during treatment.Results: We show for the first time that HtrA3 expression is reduced or completely lost in over 50% of lung cancer cell lines and primary lung tumors from heavy smokers. Treatment of HtrA3-deficient cell lines with 5-aza-2′-deoxycytidine resulted in a dose-dependent increase in HtrA3 transcription. Further, sequence analysis of bisulfite-modified DNA from lung cancer cell lines and from primary lung tumors showed an increased frequency of methylation within the first exon of HtrA3 with a corresponding loss of HtrA3 expression, particularly in tumors from smokers. In BEAS-2B, treatment with the cigarette smoke carcinogen 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone resulted in HtrA3 downregulation with a corresponding increase in methylation. Additional studies indicate resistance to etoposide and cisplatin cytotoxicity as a functional consequence of HtrA3 loss. Finally, immunohistochemical analysis of primary lung tumors revealed a strong correlation between low HtrA3 expression and heavy smoking history.Conclusions: Collectively, these results suggest that cigarette smoke–induced methylation of HtrA3 could contribute to the etiology of chemoresistant disease in smoking-related lung cancer. Clin Cancer Res; 16(2); 398–409

A porous intramolecular D–A integrated carbon nitride with boosted photocatalytic activity was constructed via thermal melting followed by thermal copolymerization of m-aminophenol with urea.

Multicharged cyclodextrin (CD) supramolecular assemblies, including those based on positively/negatively charged modified mono-6-deoxy-CDs, per-6-deoxy-CDs, and random 2,3,6-deoxy-CDs, as well as parent CDs binding positively/negatively charged guests, have been extensively applied in chemistry, materials science, medicine, biological science, catalysis, and other fields. In this review, we primarily focus on summarizing the recent advances in positively/negatively charged CDs and parent CDs encapsulating positively/negatively charged guests, especially the construction process of supramolecular assemblies and their applications. Compared with uncharged CDs, multicharged CDs display remarkably high antiviral and antibacterial activity as well as efficient protein fibrosis inhibition. Meanwhile, charged CDs can interact with oppositely charged dyes, drugs, polymers, and biomacromolecules to achieve effective encapsulation and aggregation. Consequently, multicharged CD supramolecular assemblies show great advantages in improving drug-delivery efficiency, the luminescence properties of materials, molecular recognition and imaging, and the toughness of supramolecular hydrogels, in addition to enabling the construction of multistimuli-responsive assemblies. These features are anticipated to not only promote the development of CD-based supramolecular chemistry but also contribute to the rapid exploitation of these assemblies in diverse interdisciplinary applications.

Drought stress adversely impacts crop development and yield. Maize frequently encounters drought stress during its life cycle. Improvement of drought tolerance is a priority of maize breeding programs. Here, we identified a novel transcription factor encoding gene, APETALA2 (AP2)/Ethylene response factor (ERF), which is tightly associated with drought tolerance in maize seedlings. ZmERF21 is mainly expressed in the root and leaf and it can be highly induced by polyethylene glycol treatment. Genetic analysis showed that the zmerf21 mutant plants displayed a reduced drought tolerance phenotype, accompanied by phenotypical and physiological changes that are commonly observed in drought conditions. Overexpression of ZmERF21 in maize significantly increased the chlorophyll content and activities of antioxidant enzymes under drought conditions. RNA-Seq and DNA affinity purification sequencing analysis further revealed that ZmERF21 may directly regulate the expression of genes related to hormone (ethylene, abscisic acid) and Ca signaling as well as other stress-response genes through binding to the promoters of potential target genes. Our results thereby provided molecular evidence of ZmERF21 is involved in the drought stress response of maize.

Ischemia-induced angiogenesis is critical for blood flow restoration and tissue regeneration, but the underlying molecular mechanism is not fully understood. ATG7 (autophagy related 7) is essential for classical degradative macroautophagy/autophagy and cell cycle regulation. However, whether and how ATG7 influences endothelial cell (EC) function and regulates post-ischemic angiogenesis remain unknown. Here, we showed that in mice subjected to femoral artery ligation, EC-specific deletion of

Motivated by the result of Chen-Liu-Ru [1], we investigate the value distribution properties for the generalized Gauss maps of weakly complete harmonic surfaces immersed in ℝn with ramification, which can be seen as a generalization of the results in the case of the minimal surfaces. In addition, we give an estimate of the Gauss curvature for the K-quasiconfomal harmonic surfaces whose generalized Gauss map is ramified over a set of hyperplanes.

Flowering time is an important agronomic trait that determines the distribution and adaptation of plants. The accurate prediction of flowering time in elite germplasm is critical for maize breeding. However, the molecular mechanisms underlying the photoperiod response remain elusive in maize. Here we cloned the flowering time-controlling gene, ZmNF-YC2, by map-based cloning and confirmed that ZmNF-YC2 is the nuclear transcription factor Y subunit C-2 protein and a positive regulator of flowering time in maize under long-day conditions. Our results show that ZmNF-YC2 promotes the expression of ZmNF-YA3. ZmNF-YA3 negatively regulates the transcription of ZmAP2. ZmAP2 suppresses the expression of ZMM4 to delay flowering time. We then developed a gene regulatory model of flowering time in maize using ZmNF-YC2, ZmNF-YA3, ZmAP2, ZMM4, and other key genes. The cascading regulation by ZmNF-YC2 of maize flowering time has not been reported in other species.

The construction of supramolecular multivalent assemblies with unique photoluminescence behaviors and biological functions has become a research hot spot recently in the biomaterial field. Herein, we report an adaptive supramolecular assembly via a multivalent co-assembly strategy prepared in two stages by using an adamantane-connected pyrenyl pyridinium derivative (APA2), sulfonated aluminum phthalocyanine (PcS), and folic acid-modified β-cyclodextrin (FA-CD) for efficient dual-organelle targeted photodynamic cancer cell ablation. Benefiting from π-π and electrostatic interactions, APA2 and PcS could first assemble into non-fluorescent irregular nanoaggregates because of the heterodimer aggregation-induced quenching and then secondarily assemble with FA-CD to afford targeted spherical nanoparticles (NPs) with an average diameter of around 50 nm, which could be specifically taken up by HeLa cancer cells through endocytosis in comparison with 293T normal cells. Intriguingly, such multivalent NPs could adaptively disaggregate in an intracellular physiological environment of cancer cells and further respectively and selectively accumulate in mitochondria and lysosomes, which not only displayed near-infrared two-organelle localization in situ but also aroused efficient singlet oxygen generation under light irradiation to effectively eliminate cancer cells up to 99%. This supramolecular multivalent assembly with an adaptive feature in a specific cancer cell environment provides a feasible strategy for precise organelle-targeted imaging and an efficiently synergetic photodynamic effect in situ for cancer cell ablation.

The photoisomerization behavior of cyanostilbene molecules is a hotspot in supramolecular configuration transformation research. Here, we reported a cyanostilbene derivative that converted from the

In e-commerce, many online platforms operate as a reseller for some products and serve as a marketplace for others. Under both selling modes, the logistics service can be undertaken by the platform or the supplier. The combination between the selling mode and the logistics service strategy produces four typical scenarios: (a) the platform acts as a reseller and the supplier offers the logistics service, namely, the RS scenario; (b) the platform serves as a reseller and provides the logistics service, namely, the RP scenario; (c) the platform works as a marketplace and the supplier offers the logistics service, namely, the MS scenario; and (d) the platform operates as a marketplace and provides the logistics service, namely, the MP scenario. On this basis, this paper proposes an analytical model to examine how the selling mode choice interacts with the logistics service strategy. We find that the supplier's preference aligns with the improvement of the logistics service level. When the cost performance of the logistics service is high, the RP scenario will generate the highest logistics service level, in which the supplier will gain the highest profit; when the cost performance of the logistics service is low, the MS scenario will generate the highest logistics service level and give the supplier the highest profit. For the platform, as the logistics service's cost performance increases, his preferred scenario will evolve from MP to MS, and then to RP. Further, we examine the equilibrium scenario by considering the interactions between the supplier and the online platform. We find that the MS scenario will be the equilibrium when the logistics service's cost performance is in the medium range; otherwise, RP will become the equilibrium scenario.

A C3-symmetric acylhydrazone-based low molecular weight gelator (BHTP) bearing three pyridine units was synthesized and it was found to form a stable supramolecular gel in the mixture solvent of DMSO–H2O. The morphology of the gel as observed by FE-SEM showed a dense sheet structure. Hydrogen bonding and π–π stacking between the gelators were determined as the non-covalent interactions for the gelation, which were investigated thoroughly using XRD, UV-Vis, 1H NMR and FT-IR instruments. BHTP could form pH tolerant supramolecular gels in the widest range of pH values from 1 to 11. The DMSO–H2O (v : v = 1 : 1) gel exhibited selective response to OH− over a series of other anions through the color change from a white gel to a yellow solution, and the OH− response mechanism was proved by 1H NMR experiments. In solution, the lowest detection limit of BHTP for OH− was calculated to be as low as 1.62 × 10−7 M via UV-Vis titration experiments. Finally, encapsulation and controlled release of small molecules such as rhodamine B, crystal violet and methyl orange have been successfully carried out, demonstrating the potential for drug delivery application of this C3-symmetric supramolecular gel. This work opens a novel avenue for the preparation of supramolecular gel-based multiple functional smart materials.

Herein, we reported highly efficient light-harvesting amphiphilic supramolecular assemblies based on a tetraphenylethylene derivative (TPE-4Py), an amphiphilic sulfonatocalix[4]arene (SC4A-C6), and a sulfite fluorescent probe (SP). The obtained assemblies not only showed obvious signal amplification compared to SP alone, with an antenna effect of up to 28.1 based on highly efficient energy transfer of 75.2% from TPE-4Py/SC4A-C6 to SP, but also displayed an excellent ratiometric fluorescence signal output toward sulfites. Meanwhile, the assemblies showed no obvious cytotoxicity to A549 cells and could be used to sense sulfites in the cells. This strategy for constructing supramolecular assemblies not only resulted in a high-efficiency light-harvesting platform but also amplified the signal of the probe because of the high antenna effect and thus constitutes an effective method for fabricating fluorescent cell sensors.

Metabolism in the liver is dysregulated in obesity, contributing to various health problems including steatosis and insulin resistance. While the pathogenesis of lipid accumulation has been extensively studied, the protective mechanism against lipid challenge in the liver remains unclear. Here, we report that Src homology 3 domain binding kinase 1 (SBK1) is a regulator of hepatic lipid metabolism and systemic insulin sensitivity in response to obesity.Enhanced Sbk1 expression was found in the liver of high-fat diet (HFD)-induced obese mice and fatty acid (FA)-challenged hepatocytes. SBK1 knockdown in mouse liver cells augmented FA uptake and lipid accumulation. Similarly, liver-specific SBK1 knockout (Lsko) mice displayed more severe hepatosteatosis and higher expression of genes in FA uptake and lipogenesis than the Flox/Flox (Fl/Fl) control mice when fed the HFD. The HFD-fed Lsko mice also showed symptoms of hyperglycemia, poor systemic glucose tolerance, and lower insulin sensitivity than the Fl/Fl mice. On the other hand, hepatic Sbk1 overexpression alleviated the high-fructose diet-induced hepatosteatosis, hyperlipidemia, and hyperglycemia in mice. White adipose tissue browning was also observed in hepatic SBK1-overexpressed mice. Moreover, we found that SBK1 was a positive regulator of FGF21 in the liver during energy surplus conditions. Mechanistically, SBK1 phosphorylates the orphan nuclear receptor 4A1 (Nur77) on serine 344 to promote hepatic FGF21 expression and inhibit the transcription of genes involved in lipid anabolism.Collectively, our data suggest that SBK1 is a regulator of the metabolic adaption against obesity through the Nur77-FGF21 pathway.

This study considers a multi-period two-region repositioning problem with setup repositioning costs involved for vehicle sharing systems. We find that incorporating such costs can influence the total cost significantly and complicate the structure of the optimal policy. Moreover, we manage to partially characterize the optimal policy, and then develop an easy-to-implement heuristic policy. The performance of the heuristic policy and the influence of setup repositioning costs on policies are assessed numerically.

The aim of the paper is to deal with the algebraic dependence and uniqueness problem for meromorphic mappings by using the new second main theorem with different weights involved the truncated counting functions, and some interesting uniqueness results are obtained under more general and weak conditions where the moving hyperplanes in general position are partly shared by mappings from ℂn into ℙN (ℂ), which can be seen as the improvements of previous well-known results.

In this study, the heat transfer characteristics of nanofluids used in spray cooling systems were examined. Three nanofluids, i.e., Cu, CuO, and Al2O3, respectively, with volume fractions ranging from 0.1% to 0.5%, as well as different volume fractions of a surfactant Tween 20, were used. In addition, their contact angles were measured to examine the heat-transfer characteristics. Under the same experimental conditions, with the increase in the volume fraction of the Cu nanoparticles from 0.1% to 0.5%, the maximum heat flux qmax increased from 3.36 MW/m2 to 3.48 MW/m2 from the impinging central point to r = 30 mm (r is the distance from the impingement point), and the corresponding temperature of qmax increased from 400°C to 420°C. Results revealed that with increasing Tween 20 concentrations, the contact angle decreased because of the decrease in the surface tension of nanofluids and improvement of the wetting ability, and the corresponding qmax increased from 3.48 MW/m2 to 3.94 MW/m2 at the impact central point.

Supramolecular low molecular weight gels made from tetrathiafulvalene derivatives have attracted great interest for various applications. In this work, a novel organic gelator derived from tetrathiafulvalene containing an L-glutamine moiety was designed and synthesized, and the electron-donating property and self-assembly behavior of the gelator were studied. It could form a charge-transfer complex with F4TCNQ in solution. And the gelator showed good gelation properties in alkanes, aromatic solvents and CH2Cl2. The morphologies and structures of the formed gels were characterized by field-emission scanning electron microscopy and X-ray diffraction studies, and the results of FT-IR, 1H NMR and UV-Vis spectroscopy revealed that hydrogen-bonding and π–π interactions played important roles in the gelation process. Furthermore, the gel–sol transition could be regulated by chemical redox, in which the reversibility of the sol–gel transition depended directly on the nature of the gelatinized solvents. Interestingly, the gelator mixed with C60 could form a charge-transfer complex gel in toluene, and the gel–sol transition temperature was observed to increase gradually when adding up to one equivalent of C60 to the gelator. In addition, the gels obtained from toluene and n-hexane showed the ability to absorb the toxic dye rhodamine B from water, and this property suggests the potential utilization for the removal of toxic dye molecules from wastewater.

In the bone marrow, classical and plasmacytoid dendritic cells (DC) develop from the macrophage-DC precursor (MDP) through a common DC precursor (CDP) step. This developmental process receives essential input from the niche in which it takes place, containing endothelial cells (EC) among other cell types. Here we show that targeted deletion of serine/threonine kinase 11 (Stk11) encoding tumor suppressor liver kinase b1 (Lkb1) in mouse ECs but not DCs, results in disrupted differentiation of MDPs to CDPs, severe reduction in mature DC numbers and spontaneous tumorigenesis. In wild type ECs, Lkb1 phosphorylates polypyrimidine tract binding protein 1 (Ptbp1) at threonine 138, which regulates stem cell factor (Scf) pre-mRNA splicing. In the absence of Lkb1, exon 6 of Scf is spliced out, leading to the loss of Scf secretion. Adeno-associated-virus-mediated delivery of genes encoding either soluble Scf or the phosphomimetic mutant Ptbp1T138E proteins rescued the defects of MDP to CDP differentiation and DC shortage in the endothelium specific Stk11 knockout mice. In summary, endothelial Stk11 expression regulates DC differentiation via modulation of Scf splicing, marking the Stk11-soluble-Scf axis as a potential cause of DC deficiency syndromes.

A C3-symmetric acylhydrazone-based low molecular weight gelator (BHTP) bearing three pyridine units was synthesized and it was found to form a stable supramolecular gel in the mixture solvent of DMSO-H2O. The morphology of the gel as observed by FE-SEM showed a dense sheet structure. Hydrogen bonding and π-π stacking between the gelators were determined as the non-covalent interactions for the gelation, which were investigated thoroughly using XRD, UV-Vis, 1H NMR and FT-IR instruments. BHTP could form pH tolerant supramolecular gels in the widest range of pH values from 1 to 11. The DMSO-H2O (v : v = 1 : 1) gel exhibited selective response to OH- over a series of other anions through the color change from a white gel to a yellow solution, and the OH- response mechanism was proved by 1H NMR experiments. In solution, the lowest detection limit of BHTP for OH- was calculated to be as low as 1.62 × 10-7 M via UV-Vis titration experiments. Finally, encapsulation and controlled release of small molecules such as rhodamine B, crystal violet and methyl orange have been successfully carried out, demonstrating the potential for drug delivery application of this C3-symmetric supramolecular gel. This work opens a novel avenue for the preparation of supramolecular gel-based multiple functional smart materials.

A unique fluorescent supramolecular assembly was constructed using coumarin-modified β-cyclodextrin as a reversible ratiometric probe and an adamantane-modified cyclic arginine–glycine–aspartate peptide as a cancer-targeting agent via host–guest inclusion complexation. Importantly, the coumarin-modified β-cyclodextrin not only showed higher sensitivity than the parent coumarin derivatives owing to the presence of numerous hydroxyl groups on the cyclodextrin but also provided a hydrophobic cavity for encapsulation of a cancer-targeting agent. The assembly showed a reversible and fast response to biothiols with a micromolar dissociation constant, as well as outstanding cancer cell permeability, which can be used for high-efficiency real-time monitoring of biothiols in cancer cells. This supramolecular assembly strategy endows the fluorescent probe with superior performance for dynamic sensing of biothiols., A unique fluorescent supramolecular assembly was constructed from coumarin-modified β-cyclodextrin and an adamantane-modified cyclic arginine–glycine–aspartate peptide for high-efficiency real-time monitoring of biothiols in cancer cells.

The influence of cooling models and moving velocity on the temperature variation and cooling rate through the thickness of a metal plate is experimentally investigated. In this investigation, the cooling process is divided into four stages: a starting stage (I), a rapid cooling stage (II), a slow cooling stage (III) and a stopping stage (IV). Based on the curves, cooling rate, temperature difference, the heat transfer coefficient and center temperature curves are discussed. The results indicate that the cooling model and moving velocity influence the heat transfer on the surface, and affects the cooling rate through the thickness by changing the temperature difference. When the flow rates of nozzles 1, 2 and 3 are set to be V1, V2 and V3 respectively, the highest heat transfer is observed when V1 > V2 > V3. Under this cooling model, the maximum temperature difference occurs at the time of transition from the rapid cooling stage (II) to the slow cooling stage (III). In the slow cooling stage (III), increased moving velocity improves the synchronization of the heat transfer and decreases the maximum heat flux. As well, the speed of motion affects the internal heat conduction and cooling rate by affecting surface heat transfer.

Autophagy is of key importance for eliminating aggregated proteins during the maintenance of cellular proteostasis in response to endoplasmic reticulum (ER) stress. However, the upstream signaling that mediates autophagy activation in response to ER stress is incompletely understood. In this study, in vivo and in vitro approaches were utilized that include gain- and loss-of-function assays and mouse livers and human cell lines with tunicamycin-induced pharmacological ER stress. We report that calreticulin, a quality control chaperone that binds to misfolded glycoproteins for refolding in the ER, is induced under ER stress. Calreticulin overexpression stimulated the formation of autophagosomes and increased autophagic flux. Interestingly, calreticulin was sufficient for attenuating ER stress in tunicamycin- or thapsigargin-treated HeLa cells, whereas lentivirus-mediated shRNA calreticulin knockdown exacerbated ER stress. Mechanistically, we noted that calreticulin induces autophagy by interacting with microtubule-associated protein 1A/1B-light chain 3 (LC3). Confocal microscopy revealed that the colocalization of calreticulin and LC3 at the autophagosome was enhanced under ER stress conditions. Importantly, a conserved LC3-interacting region was necessary for calreticulin-mediated stimulation of autophagy and for reducing ER stress. These findings indicate a calreticulin-based mechanism that couples ER stress to autophagy activation, which, in turn, attenuates cellular stress, likely by alleviating the formation of aberrantly folded proteins. Pharmacological or genetic approaches that activate calreticulin–autophagy signaling may have potential for managing ER stress and related cellular disorders.

Nuclear pore complex (NUP) is the main transport channel between cytoplasm and nucleoplasm, which plays an important role in stress response. The function of NUPs was widely reported in yeast and vertebrate but rarely in plants. Here, we identified a nuclear pore complex (ZmNUP58), that is tightly associated with drought and salt tolerance phenotype accompanied with phenotypic and physiological changes under drought and salt stress. The overexpression of ZmNUP58 in maize (Zea mays L.) significantly promotes both chlorophyll content and activities of antioxidant enzymes under drought- and salt-stressed conditions. RNA-Seq analysis showed that ZmNUP58 could regulate the expression of genes related to phytohormone synthesis and signaling, osmotic adjustment substances, antioxidant enzyme system, cell wall biosynthesis, glucose metabolism and aquaporin. The results provide novel insights into the regulatory role of ZmNUP58 in improving drought and salt tolerance through regulating phytohormone and other stress response genes in maize.

Serine/threonine protein phosphatases play essential roles in plants. PP2C has diverse functions related to development and stress response, while little is known about the functions of PP2C genes with respect to a variety of stresses in maize. In the present study, three ZmPP2C genes, ZmPP2C55, ZmPP2C28, and ZmPP2C71, were identified. Subcellular localization demonstrated that ZmPP2C28 and ZmPP2C71 were nuclear proteins, and ZmPP2C55 was located in both the nucleus and cytoplasm. qRT–PCR analysis showed that ZmPP2C55, ZmPP2C28, and ZmPP2C71 were expressed in roots, leaves and stems, and the three genes were responsive to drought, salt, high-temperature stress and exogenous ABA treatment. To explore the function of the ZmPP2C gene, ZmPP2C55-overexpressing transgenic lines were generated. The transgenic plants exhibited higher RWC, proline content, POD and SOD activities, GSH content and GSH/GSSG ratio and lower MDA content, electrolyte leakage and GSSG content compared with WT plants under natural stress treatment when seedlings were at the three-leaf. Our results illustrated that the overexpression of ZmPP2C55 positively enhanced tolerance to drought stress.

Constructing ultralong organic phosphorescent materials possessing a high quantum yield is challenging. Herein, assemblies of purely organic supramolecular pins composed of alkyl-bridged phenylpyridinium salts and cucurbit[8]uril (CB[8]) are reported. Different from "one host with two guests" and "head-to-tail" binding, the binding formation of supramolecular pins is "one host with one guest" and "head-to-head," which overcomes electrostatic repulsion and promotes intramolecular charge transfer. The supramolecular pin 1/CB[8] displays afterglow with high phosphorescence quantum yield (99.38%) after incorporation into a rigid matrix, which is the highest yield reported to date for phosphorescent materials. Moreover, multicolor photoluminescence can be obtained by different excitation wavelengths and ratios of host to guest. Owing to the redshift of the absorption, the supramolecular pins are applied for targeted phosphorescence imaging of mitochondria. This work will provide a reasonable supramolecular strategy to achieve redshifted and efficient phosphorescence both in the solid state and in aqueous solution.

Acquisition and maintenance of vascular smooth muscle cell (VSMC) fate are important for vascular development and homeostasis; however, little is known about the key determinant for VSMC fate and vascular homeostasis. We found that VSMC-specific Lkb1 ablation in Lkb1flox/flox;Tagln-Cre mice caused severe vascular abnormalities and embryonic lethality. VSMC-specific deletion of Lkb1 in tamoxifen-inducible Lkb1flox/flox;Myh11-Cre/ERT2 mice progressively induced aortic/arterial dilation, aneurysm, rupture, and premature death. Single-cell RNA sequencing and imaging-based lineage tracing showed that Lkb1-deficient VSMCs underwent dynamic transcriptional reprogramming and transformed gradually from early modulated VSMCs to fibroblast-like, chondrocyte-like, and even osteocyte-like cells. VSMC transformation followed by extracellular matrix remodeling and inflammatory cell infiltration contributed to the arterial aneurysm formation in tamoxifen-induced Lkb1flox/flox;Myh11-Cre/ERT2 mice. Finally, we found that VSMC-specific Lkb1 ablation resulted in decreased vascular contractility, hypotension, and impaired responses to angiotensin II and vessel injury in vivo. Lkb1 is therefore a key determinant of mouse VSMC fate that prevents VSMC reprogramming and sustains vascular homeostasis. Our findings have important implications for understanding the pathogenesis of aortic aneurysm.

The construction of supramolecular assembly whose singlet oxygen (1O2) generation capability can be controllably regulated in water still remains challenging. Herein, a novel cyclodextrin secondary assembly was fabricated from the photochromic-switch moiety diarylethene-bridged dicyclodextrin, the adamantane-polypyridyl ruthenium photosensitizer, and the cancer-cell-targeting ligand β-cyclodextrin-grafted hyaluronic acid, which not only possessed cancer-cell-targeting ability but also served as cell imaging and photodynamic therapy agents with noninvasive controllability. In virtue of the multivalent interactions between the three components, they could self-assemble in two stages to form uniform spherical nanoparticles (OF-NPs) with average diameters of about 80 nm, as indicated by scanning electron microscopy, high-resolution transmission electron microscopy, atomic force microscopy, and dynamic light scattering. Significantly, the prepared OF-NPs exhibited excellent photochromic performance and can transform into their ring-closed form (CF-NPs), accompanied by the efficient energy transfer from donor 2 to CF-1 and gradual quenching of 1O2 generation. Cellular imaging experiments showed that OF-NPs could specifically target the mitochondria of A549 cancer cells, while CF-NPs displayed a negligible red fluorescence signal in A549 cells due to the energy-transfer process. Furthermore, in vitro cytotoxicity tests revealed that upon irradiation with 450 nm light, OF-NPs with 10 μM concentration displayed a remarkable higher cytotoxicity with the cell death rate of up to 88% toward A549 cancer cells, which was approximately 4.4 times higher than that of CF-NPs. Additionally, the apoptosis rate of A549 cells induced by OF-NPs under light irradiation was 4.68 times higher than that of CF-NPs. These well-designed cyclodextrin secondary assemblies successfully achieve noninvasive control over the generation of 1O2 both in water and in cancer cells by irradiation at distinct wavelengths and are further applied in targeted PDT, which avoid the inadvertent photosensitizer activation and provide a new approach for cancer therapy with more safety and high efficiency.

Developing high performance fluorescent chemosensor for Al

Purely organic room-temperature phosphorescence has attracted attention for bioimaging but can be quenched in aqueous systems. Here we report a water-soluble ultralong organic room-temperature phosphorescent supramolecular polymer by combining cucurbit[n]uril (CB[7], CB[8]) and hyaluronic acid (HA) as a tumor-targeting ligand conjugated to a 4-(4-bromophenyl)pyridin-1-ium bromide (BrBP) phosphor. The result shows that CB[7] mediated pseudorotaxane polymer CB[7]/HA–BrBP changes from small spherical aggregates to a linear array, whereas complexation with CB[8] results in biaxial pseudorotaxane polymer CB[8]/HA–BrBP which transforms to relatively large aggregates. Owing to the more stable 1:2 inclusion complex between CB[8] and BrBP and the multiple hydrogen bonds, this supramolecular polymer has ultralong purely organic RTP lifetime in water up to 4.33 ms with a quantum yield of 7.58%. Benefiting from the targeting property of HA, this supramolecular polymer is successfully applied for cancer cell targeted phosphorescence imaging of mitochondria., Room-temperature phosphorescence has attracted attention for bioimaging, but quenching in aqueous systems is an issue. Here, the authors report on the synthesis of a water soluble organic phosphorescent polymer and demonstrate application is cancer cell targeting and imaging.