CycC1;1-WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis.

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.

Chaperone Mimetic Strategy for Achieving Organic Room-Temperature Phosphorescence based on Confined Supramolecular Assembly.

The development of organic materials that deliver room-temperature phosphorescence (RTP) is highly interesting for potential applications such as anticounterfeiting, optoelectronic devices, and bioimaging. Herein, a molecular chaperone strategy for controlling isolated chromophores to achieve high-performance RTP is demonstrated. Systematic experiments coupled with theoretical evidence reveal that the host plays a similar role as a molecular chaperone that anchors the chromophores for limited nonradiative decay and directs the proper conformation of guests for enhanced intersystem crossing through noncovalent interactions. For deduction of structure-property relationships, various structure-related descriptors that correlate with the RTP performance are identified, thus offering the possibility to quantitatively design and predict the phosphorescent behaviors of these systems. Furthermore, application in thermal printing is well realized for these RTP materials. The present work discloses an effective strategy for efficient construction of organic RTP materials, delivering a modular model which is expected to help expand the diversity of desirable RTP systems.

Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB.

In brief: The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. Abstract: Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF-κB activity compared with wild-type controls. Finally, we applied a selective NF-κB inhibitor named PDTC to validate the role of NF-κB in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.

ABA functions in low phosphate-induced anthocyanin accumulation through the transcription factor ABI5 in Arabidopsis.

KEY MESSAGE: ABI5 functions in ABA-mediated anthocyanin accumulation in plant response to low phosphate. Low phosphate (LP)-induced anthocyanin biosynthesis and accumulation play an important role in plant adaptive response to phosphate starvation conditions. However, whether and how the stress phytohormone abscisic acid (ABA) participates in LP-induced anthocyanin accumulation remain elusive. Here, we report that ABA is required for LP-induced anthocyanin accumulation in Arabidopsis thaliana. Disrupting ABA DEFICIENT2 (ABA2), a key ABA-biosynthetic gene, or BETA-GLUCOSIDASE1 (BG1), a major gene implicated in converting conjugated ABA to active ABA, significantly impairs LP-induced anthocyanin accumulation, as LP-induced expression of the anthocyanin-biosynthetic genes Chalcone Synthase (CHS) is dampened in the aba2 and bg1 mutant. In addition, LP-induced anthocyanin accumulation is defective in the mutants of ABA signaling pathway, including ABA receptors, ABA Insensitive2, and the transcription factors ABA Insensitive5 (ABI5), suggesting a role of ABI5 in ABA-mediated upregulation of anthocyanin-biosynthetic genes in plant response to LP. Indeed, LP-induced expression of CHS is repressed in the abi5-7 mutant but further promoted in the ABI5-overexpressing plants compared to the wild-type. Moreover, ABI5 can bind to and transcriptionally activate CHS, and the defectiveness of LP-induced anthocyanin accumulation in abi5-7 can be restored by overexpressing CHS. Collectively, our findings illustrates that ABI5 functions in ABA-mediated LP-induced anthocyanin accumulation in Arabidopsis.

Pillar[5]arene Derivatives Embedded with Aggregation-Induced Emission Luminogens and Their Fluorescence Regulation.

Through McMurry coupling reaction, three meso-position functionalized pillar[5]arene derivatives (H-1, H-2, and H-3) have been successfully prepared by embedding aggregation-induced emission luminogens (AIEgens, diphenyldibenzofulvene (DPDBF) and tetraphenylethylene (TPE)) into the skeleton of supramolecular macrocycles. H-1, bearing [15 ]paracyclophane ([15 ]PCP) and DPDBF moiety, exhibits yellow emission and demonstrates obvious AIE effect. In order to further improve the host-guest properties of this type of structure, H-2 and H-3 are prepared by replacing the [15 ]PCP moiety with pillar[5]arene backbone, both of which show significant AIE effect and excellent host-guest complexation properties with pyrazine salt guest G-1 and 1,4-dicyanobutane G-2. Our findings indicate that G-1 can decrease the fluorescence intensity of the AIE macrocycles, while G-2 can increase their fluorescence intensity in solution.

Immunization effect of recombinant Lactobacillus casei displaying Aeromonas veronii Aha1 with an LTB adjuvant in carp.

Aeromonas veronii is an important aquatic zoonotic, which elicits a range of diseases, such as haemorrhagic septicemia. To develop an effective oral vaccine against Aeromonas veronii infection in carp, the Aeromonas veronii adhesion (Aha1) gene was used as a target molecule to attach to intestinal epithelial cells. Two anchored recombinant. Lactic acid bacteria strains (LC-pPG-Aha1 1038 bp and LC-pPG-Aha1-LTB 1383 bp) were constructed by fusing them with the E. coli intolerant enterotoxin B subunit (LTB) gene and using Lactobacillus casei as antigen delivery vector to evaluate immune effects of these in carp. Western blotting and immunofluorescence were used to confirm that protein expression was successful. Additionally, levels of specific IgM in serum and the activities of ACP, AKP, SOD, LYS, C3, C4, and lectin enzymes-were assessed. Cytokines IL-10, IL-1ß, TNF-α, IgZ1, and IgZ2 were measured in the liver, spleen, kidney, intestines, and gills tissue by qRT-PCR, which showed an increasing trend compared with the control group (P < 0.05). A colonization assay showed that the two L. casei recombinants colonized the middle and hind intestines of immunized fish. When immunized carp were experimentally challenged with Aeromonas veronii the relative percentage protection of LC-pPG-Aha1 was 53.57%, and LC-pPG-Aha1-LTB was 60.71%. In conclusion, these results demonstrate that Aha1 is a promising candidate antigen when it is displayed on lactic acid bacteria (Lc-pPG-Aha1 and Lc-pPG-Aha1-LTB) seems promising for a mucosal therapeutic approach. We plan to investigate the molecular mechanism of the L. casei recombinant in regulating the intestinal tissue of carp in future studies.

GAS6-mediated dialogue between decidual stromal cells and macrophages is essential for early pregnancy maintenance by inducing M2-like polarization and cell proliferation of decidual macrophages.

Maternal immunotolerance towards the semi-allogeneic foetus is critical for normal pregnancy (NP). As a secretory protein, growth arrest-specific factor 6 (GAS6) promotes cancer progression by inducing the conversion of tumour-associated macrophages to an immunosuppressive M2-like phenotype. However, little is known about whether GAS6 regulates decidual macrophages (dMφs) in the early maternal-foetal interface. In this study, first-trimester decidual tissues were obtained from normal pregnant women undergoing elective terminations and patients with miscarriages. The expression of GAS6 and its receptors (AXL, TYRO3 and MERTK) in decidua and GAS6 secretion by decidual stromal cells (DSCs) was measured. Then, we investigated the effect of recombinant human GAS6 (rhGAS6) on dMφs isolated from NP and THP-1 cells, and revealed the underlying mechanism. Both the expression of GAS6 in DSCs and MERTK in dMφs, in addition to GAS6 secretion by DSCs, was found to be significantly decreased in miscarriage patients compared to that in NPs. Additionally, we observed that rhGAS6 polarized dMφs and THP-1 cells towards an M2-like phenotype, as evidenced by the up-regulated CD163 expression. Moreover, rhGAS6 enhanced the clearance of toxic cell-free haemoglobin by dMφs by up-regulating CD163 expression, and rhGAS6 also boosted cell proliferation of dMφs and THP-1 cells. Finally, we demonstrated that rhGAS6 stimulated CD163 expression and cell proliferation by activating the PI3K/Akt signalling pathway. Collectively, these findings suggest that GAS6-mediated dialogue between DSCs and dMφs is crucial for the establishment and maintenance of maternal-foetal immunotolerance, and decreased GAS6 secretion by DSCs may lead to the occurrence of miscarriage in the first trimester.

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water.

Herein, we have designed and fabricated a simple and efficient supramolecular self-assembled nanosystem based on host-guest interactions between water-soluble tetraphenylethylene-embedded pillar[5]arene ( m -TPEWP5) and ammonium benzoyl-ʟ-alaninate (G) in an aqueous medium. The obtained assembly of m -TPEWP5 and G showed aggregation-induced emission (AIE) via the blocking of intramolecular phenyl-ring rotations and functioned as an ideal donor. After the loading of eosin Y (EsY) as acceptor on the surface of the assembly of m -TPEWP5 and G, the worm-like nanostructures changed into nanorods, which facilitates a Förster resonance energy transfer (FRET) from the m -TPEWP5 and G assembled donor to the EsY acceptor present in the nanorod assembly. The system comprising m -TPEWP5, G and EsY displayed moderate FRET efficiency (31%) at a 2:1 molar ratio of donor-to-acceptor. Moreover, the obtained supramolecular nanorod assembly could act as a nanoreactor mimicking natural photosynthesis and exhibited a high catalytic efficiency for the photocatalytic dehalogenation reaction of various bromoketone derivatives with good yields in short reaction time in water.

Chinese college students' ability to recognize facial expressions based on their meaning-in-life profiles: An eye-tracking study.

OBJECTIVE: People can be categorized into one of four meaning-in-life profiles: High Presence High Search (HPHS), High Presence Low Search (HPLS), Low Presence High Search (LPHS), and Low Presence Low Search (LPLS).The main goal of this study is to provide a theoretical explanation for why Chinese people with different meaning-in-life profiles have different mental health levels than Western people, based on their emotional-cognitive-processing ability. METHOD: We adopted eye-movement analysis and recognition-judgment experimental paradigm concerning absolute-recognition judgment and relative-recognition judgment in our study. Moreover, we applied a multifactor and multilevel mixed-experimental design. We selected 118 participants for the experiments from the 788 Chinese college students who responded. RESULTS: Our results showed that HPHS individuals preferred positive-emotion pictures, LPLS individuals preferred negative-emotion pictures, HPLS individuals preferred positive- and neutral-emotion pictures, and LPHS individuals preferred neutral-emotion pictures. Moreover, HPHS individuals were better at accurately processing facial expression from pictures, while LPLS individuals lacked such ability. The fine-processing ability of HPLS and LPHS individuals was lower than that of HPHS yet higher than that of LPLS individuals. Moreover, the features of HPLS individuals were closer to HPHS, while those of LPHS individuals were closer to LPLS. CONCLUSIONS: Our findings support the hypothesis that meaning-in-life profiles have different immediate processing abilities and preferences regarding facial expression recognition and different emotional-cognitive-processing ability.

Influence of weight management on the prognosis of steatohepatitis in chronic hepatitis B patients during antiviral treatment.

BACKGROUND: Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment. METHODS: In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72. RESULTS: A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P > 0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P < 0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/m2 (Asian criteria) [odds ratio (OR): 0.414; 95% confidence interval (95% CI): 0.190-0.899; P = 0.012] and weight gain (OR: 0.187; 95% CI: 0.050-0.693; P = 0.026) were less likely to have NASH resolution. Among patients without NASH at baseline, 22 (3.7%) developed NASH. Baseline BMI ≥ 23 kg/m2 (OR: 12.506; 95% CI: 2.813-55.606; P = 0.001) and weight gain (OR: 5.126; 95% CI: 1.674-15.694; P = 0.005) were predictors of incident NASH. CONCLUSIONS: Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation.

Role of Functionalized Pillararene Architectures in Supramolecular Catalysis.

The many useful features possessed by pillararenes (PAs; e.g. rigid, capacious, and hydrophobic cavities, as well as exposed functional groups) have led to a tremendous increase in their popularity since their first discovery in 2008. In this Minireview, we emphasize the use of functionalized PAs and their assembled supramolecular materials in the field of catalysis. We aim to provide a fundamental understanding and mechanism of the role PAs play in catalytic process. The topics are subdivided into catalysis promoted by the PA rim/cavity, PA-based nanomaterials, and PA-based polymeric materials. To the best of our knowledge, this is the first overview on PA-based catalysis. This Minireview not only summarizes the fabrications and applications of PAs in catalysis but also anticipates future research efforts in applying supramolecular hosts in catalysis.

Insight into functionalized-macrocycles-guided supramolecular photocatalysis.

Due to the unique characteristics of macrocycles (e.g., the ease of modification, hydrophobic cavities, and specific guest recognition), they can provide a suitable environment to realize photocatalysis via noncovalent interactions with different substrates. In this minireview, we emphasized the photochemical transformation and catalytic reactivity of different guests based on the binding with various macrocyclic hosts as well as on the role of macrocyclic-hosts-assisted hybrid materials in energy transfer. To keep the clarity of this review, the macrocycles are categorized into the most commonly used supramolecular hosts, including crown ethers, cyclodextrins, cucurbiturils, calixarenes, and pillararenes. This minireview not only summarizes the role that macrocycles play in photocatalytic reactions but also clarifies the photocatalytic mechanisms. Finally, the future research efforts and new pathways to apply macrocycles and supramolecular hybrid materials in photocatalysis are also discussed.

Supramolecular Strategies for Controlling Reactivity within Confined Nanospaces.

Nanospaces are ubiquitous in the realm of biological systems and are of significant interest among supramolecular chemists. Understanding chemical behavior within nanospaces offers new perspectives on biological phenomena in nature and opens the way to highly unusual and selective forms of catalysis. Supramolecular chemistry exploits weak, yet effective, intermolecular interactions such as hydrogen bonding, metal-ligand coordination, and the hydrophobic effect to assemble nano-sized molecular architectures, providing reactions with remarkable rate acceleration, substrate specificity, and product selectivity. In this minireview, the focus is on the strategies that supramolecular chemists use to emulate the efficiency of biological processes, and elucidating how chemical reactivity is efficiently controlled within well-defined nanospaces. Approaches such as orientation and proximity of substrate, transition-state stabilization, and active-site incorporation will be discussed.

A Supramolecular Artificial Light-Harvesting System with Two-Step Sequential Energy Transfer for Photochemical Catalysis.

An artificial light-harvesting system with sequential energy-transfer process was fabricated based on a supramolecular strategy. Self-assembled from the host-guest complex formed by water-soluble pillar[5]arene (WP5), a bola-type tetraphenylethylene-functionalized dialkyl ammonium derivative (TPEDA), and two fluorescent dyes, Eosin Y (ESY) and Nile Red (NiR), the supramolecular vesicles achieve efficient energy transfer from the AIE guest TPEDA to ESY. ESY can function as a relay to further transfer the energy to the second acceptor NiR and realize a two-step sequential energy-transfer process with good efficiency. By tuning the donor/acceptor ratio, bright white light emission can be successfully achieved with a CIE coordinate of (0.33, 0.33). To better mimic natural photosynthesis and make full use of the harvested energy, the WP5⊃TPEDA-ESY-NiR system can be utilized as a nanoreactor: photocatalyzed dehalogenation of α-bromoacetophenone was realized with 96 % yield in aqueous medium.

Cadmium-induced genome-wide DNA methylation changes in growth and oxidative metabolism in Drosophila melanogaster.

BACKGROUND: Cadmium (Cd)-containing chemicals can cause serious damage to biological systems. In animals and plants, Cd exposure can lead to metabolic disorders or death. However, for the most part the effects of Cd on specific biological processes are not known. DNA methylation is an important mechanism for the regulation of gene expression. In this study we examined the effects of Cd exposure on global DNA methylation in a living organism by whole-genome bisulfite sequencing (WGBS) using Drosophila melanogaster as model. RESULTS: A total of 71 differentially methylated regions and 63 differentially methylated genes (DMGs) were identified by WGBS. A total of 39 genes were demethylated in the Cd treatment group but not in the control group, whereas 24 showed increased methylation in the former relative to the latter. In most cases, demethylation activated gene expression: genes such as Cdc42 and Mekk1 were upregulated as a result of demethylation. There were 37 DMGs that overlapped with differentially expressed genes from the digital expression library including baz, Act5C, and ss, which are associated with development, reproduction, and energy metabolism. CONCLUSIONS: DNA methylation actively regulates the physiological response to heavy metal stress in Drosophila in part via activation of apoptosis.

A Branched Tripeptide with an Anion-Binding Motif as a New Delivery Carrier for Efficient Gene Transfection.

Branched and dendrimeric cationic peptides have shown better transfection efficiency than linear peptides, owing to their superior capacity for inducing DNA condensation. We have designed and synthesized two analogously guanidinocarbonylpyrrole-substituted (GCP-substituted) branched cationic tripeptides that provide extremely strong electrostatic attraction towards DNA. Both ligands 1 and 2 can bind to DNA and form condensed complexes, owing to the branched structure and high positive charges, as demonstrated by isothermal titration calorimetry (ITC), ζ potential and atomic force microscopy (AFM). After the replacement of the carboxylate group by an amide group, binding of ligand 2 to DNA shows exothermic enthalpy and positive entropy changes relative to ligand 1. Rational interpretation would suggest that ligand 2 might aid the translocation of plasmid pF143 to HEK 293T cells, showing high gene transfection efficiency. This work therefore provides a facile way, by modifying a branched cationic tripeptide with GCP, to turn a peptide even a tripeptide into an efficient gene transfection vector.

Supramolecular vesicles based on pillar[n]arenes: design, construction, and applications.

Supramolecular vesicles have attracted considerable attention due to their advantages of facile construction, high-cargo-loading capacity, and good biocompatibility. Pillar[n]arenes are a unique family of supramolecular macrocycles, exhibiting excellent features and broad applications due to their intrinsic topology and high functionality. In the past decade, the construction of pillar[n]arene-based supramolecular vesicles has been continuously attempted and developed rapidly. In this review, we mainly summarize the significant advancements of such supramolecular vesicles in the last three years. By showing some representative examples, the design strategies, construction methods, and potential applications of these dynamic nanocarriers are discussed in detail. In particular, the responsiveness of such vesicles to various external stimuli and their applications in drug delivery are highlighted. The outstanding performance of pillar[n]arene-based supramolecular vesicles would definitely enrich the family of supramolecular vesicles and promote the development of dynamic supramolecular materials.

Probiotics may not prevent the deterioration of necrotizing enterocolitis from stage I to II/III.

BACKGROUND: Probiotic therapy can reduce the incidence of NEC. Therapeutic use of probiotics after NEC diagnosis reduces the severity of NEC in preterm infants or full-term infants is unclear. To evaluate the effect of probiotics on preventing the deterioration of necrotizing enterocolitis (NEC) from stage I to II/III. METHODS: A retrospective matched cohort study was performed. Included patients were ultimately divided into two groups: the probiotic treatment group (probiotics were used ≥4 days) and the no probiotic treatment group. The differences in deterioration trends between the two groups were compared. Additionally, the risk factors associated with the deterioration of NEC were further analyzed with a case-control study. RESULTS: A total of 231 infants met the inclusion criteria. Eighty-one pairs were matched according to similar gestational age and birth weight. Before matching, we found that the rate of deterioration of NEC from stage I to II/III in the group with probiotic treatment was similar to that in the group without probiotic treatment (23.1% [25/108] vs 26.0% [32/123], P = 0.614). After matching, the rate of deterioration of NEC between the two groups still had no significant difference (21.0% [17/81] vs 27.2% [22/81], P = 0.358). Logistic regression analysis showed that sepsis after NEC was an independent risk factor for NEC deteriorating from stage I to II/III (OR 2.378, 95% CI 1.005-5.628, P = 0.049). CONCLUSION: Probiotics may not prevent the deterioration of NEC from stage I to II/III in infants, but this conclusion should be treated with caution.

From Supramolecular Vesicles to Micelles: Controllable Construction of Tumor-Targeting Nanocarriers Based on Host-Guest Interaction between a Pillar[5]arene-Based Prodrug and a RGD-Sulfonate Guest.

The targeting ability, drug-loading capacity, and size of the drug nanocarriers are crucial for enhancing the therapeutic index for cancer therapy. Herein, the morphology and size-controllable fabrication of supramolecular tumor-targeting nanocarriers based on host-guest recognition between a novel pillar[5]arene-based prodrug WP5-DOX and a Arg-Gly-Asp (RGD)-modified sulfonate guest RGD-SG is reported. The amphiphilic WP5-DOX⊃RGD-SG complex with a molar ratio of 5:1 self-assembles into vesicles, whereas smaller-sized micelles can be obtained by changing the molar ratio to 1:3. This represents a novel strategy of controllable construction of supramolecular nanovehicles with different sizes and morphologies based on the same host-guest interactions by using different host-guest ratios. Furthermore, in vitro and in vivo studies reveal that both these prodrug nanocarriers could selectively deliver doxorubicin to RGD receptor-overexpressing cancer cells, leading to longer blood retention time, enhanced antitumor efficacy, and reduced systematic toxicity in murine tumor model, suggesting their potential application for targeted drug delivery.

Multiresponsive Supramolecular Theranostic Nanoplatform Based on Pillar[5]arene and Diphenylboronic Acid Derivatives for Integrated Glucose Sensing and Insulin Delivery.

A closed-loop "smart" insulin delivery system with the capability to mimic pancreatic cells will be highly desirable for diabetes treatment. This study reports a multiple stimuli-responsive insulin delivery platform based on an explicit supramolecular strategy. Self-assembled from a well-designed amphiphilic host-guest complex formed by pillar[5]arene and a diphenylboronic acid derivative and loaded with insulin and glucose oxidase, the obtained insulin-GOx-loaded supramolecular vesicles can selectively recognize glucose, accompanied by the structure disruption and efficient release of the entrapped insulin triggered by the high glucose concentration as well as the in situ generated H2 O2 and acid microenvironment during the GOx-promoted specific oxidation of glucose into gluconic acid. Moreover, such a "smart" supramolecular theranostic nanoplatform is able to function as both a glucose sensor and a controlled insulin delivery actuator. In vivo experiments further demonstrate that this smart supramolecular nanocarrier shows fast response to hyperglycemic circumstances and can effectively regulate the glucose levels in a mouse model of type I diabetes.