Influence of Social Distance on Foreign Language Effect in Moral Judgment.

Previous research has shown that moral choice depends on language, a phenomenon known as the moral foreign language effect (mFLE). The current study examines the influence of social distance on the mFLE. In Experiment 1, 200 participants were randomly assigned to either close or distant social distance in English or Chinese. In Experiment 2, 188 participants were randomly assigned to either English or Chinese and were presented with eight moral dilemmas, each with five different levels of social distance. After reading the dilemma, participants made a choice on a binary scale (Yes/No) in both Experiments 1 and 2 or on a more sensitive 100-point scale in Experiment 2. The results showed that the mFLE was present in distant social distance but absent in close social distance. Finally, a meta-analysis of the results from both studies confirmed the effect of social distance on the mFLE. These findings demonstrate that social distance might play an important role in moderating the mFLE in moral judgment.

Internal Dynamics and Modular Peripheral Binding in Stimuli-Responsive 3 : 2 Host:Guest Complexes.

Now that the chemistry of 1 : 1 host:guest complexes is well-established, it is surprising to note that higher stoichiometry (oligomeric) complexes, especially those with excess host, remain largely unexplored. Yet, proteins tend to oligomerize, affording new functions for cell machinery. Here, we show that cucurbit[n]uril (CB[n]) macrocycles combined with symmetric, linear di-viologens form unusual 3 : 2 host:guest complexes exhibiting remarkable dynamic properties, host self-sorting, and external ring-translocation. These results highlight the structural tunability of cucurbit[8]uril (CB[8]) based 3 : 2 host:guest complexes in water and their responsiveness toward several stimuli (chemicals, pH, redox).

Mitochondria-Targeting Multifunctional Fluorescent Probe toward Polarity, Viscosity, and ONOO- and Cell Imaging.

Abnormal changes occurring in the mitochondrial microenvironment are important markers indicating mitochondrial and cell dysfunction. Herein, we designed and synthesized a multifunctional fluorescent probe DPB that responds to polarity, viscosity, and peroxynitrite (ONOO-). DPB is composed of an electron donor (diethylamine group) and electron acceptor (coumarin, pyridine cations, and phenylboronic acid esters), in which the pyridine group with a positive charge is responsible for targeting to mitochondria. D-π-A structure with strong intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) properties give rise to respond to polarity and viscosity. The introduction of cyanogroup and phenylboronic acid esters increases the electrophilicity of the probe, which is prone to oxidation triggered by ONOO-. The integrated architecture satisfies the multiple response requirements. As the polarity increases, the fluorescence intensity of probe DPB at 470 nm is quenched by 97%. At 658 nm, the fluorescence intensity of DPB increases with viscosity and decreases with the concentration of ONOO-. Furthermore, the probe is not only successfully used to monitor mitochondrial polarity, viscosity, and endogenous/exogenous ONOO- level fluctuations but also to distinguish cancer cells from normal cells by multiple parameters. Therefore, as-prepared probe provides a reliable tool for better understanding of the mitochondrial microenvironment and also a potential approach for the diagnosis of disease.

Network pharmacology and molecular docking analysis on the mechanism of Cordyceps militaris polysaccharide regulating immunity through TLR4/TNF-α pathwayss.

The role of polysaccharide components in the immune system, especially immunomodulatory effects, has received increasing attention. In this context, in this study, network pharmacology was adopted to explore the hypothesis of a multitarget mechanism for immune modulation by Chrysalis polysaccharides. A total of 174 common targets were screened by network pharmacology, with the main ones being TNF, MAPK3, CASP3, VEGFA, and STAT3, mostly enriched in the Toll pathway. The molecular docking results showed that the polysaccharide fraction of Chrysalis binds well to TNF proteins. Besides, in vitro cellular assays were performed to verify the ability of Chrysalis polysaccharides to regulate macrophage polarization and to screen for macrophage surface receptors. Furthermore, in vivo experiments were conducted to prove the activation of TLR4 and TNF-α protein expression in mice by Chrysalis polysaccharide.

Protective Effect of Baicalin on Chlorpyrifos-Induced Liver Injury and Its Mechanism.

Chlorpyrifos (CPF) plays a vital role in the control of various pests in agriculture and household life, even though some studies have indicated that CPF residues pose a significant risk to human health. Baicalin (BA) is a flavonoid drug with an obvious effect on the prevention and treatment of liver diseases. In this study, the protective effect of BA in vitro and in vivo was investigated by establishing a CPF-induced AML12 cell damage model and a CPF-induced Kunming female mouse liver injury model. The AML12 cell damage model indicated that BA had a good positive regulatory effect on various inflammatory factors, redox indexes, and abnormal apoptosis factors induced by CPF. The liver injury model of female mice in Kunming showed that BA significantly improved the liver function indexes, inflammatory response, and fibrosis of mice. In addition, BA alleviated CPF-induced AML12 cell damage and Kunming female mouse liver injury by enhancing autophagy and regulating apoptosis pathways through Western blotting. Collectively, these data suggest that the potential mechanism of BA is a multi-target and multi-channel treatment for chlorpyrifos-induced liver injury.

Cyclodextrin-Derived ROS-Generating Nanomedicine with pH-Modulated Degradability to Enhance Tumor Ferroptosis Therapy and Chemotherapy.

Nowadays, destruction of redox homeostasis to induce cancer cell death is an emerging anti-cancer strategy. Here, the authors utilized pH-sensitive acetalated ß-cyclodextrin (Ac-ß-CD) to efficiently deliver dihydroartemisinin (DHA) for tumor ferroptosis therapy and chemodynamic therapy in a synergistic manner. The Ac-ß-CD-DHA based nanoparticles are coated by an iron-containing polyphenol network. In response to the tumor microenvironment, Fe2+ /Fe3+ can consume glutathione (GSH) and trigger the Fenton reaction in the presence of hydrogen peroxide (H2 O2 ), leading to the generation of lethal reactive oxygen species (ROS). Meanwhile, the OO bridge bonds of DHA are also disintegrated to enable ferroptosis of cancer cells. Their results demonstrate that these nanoparticles acted as a ROS generator to break the redox balance of cancer cells, showing an effective anticancer efficacy, which is different from traditional approaches.

Spermine-Responsive Intracellular Self-Aggregation of Gold Nanocages for Enhanced Chemotherapy and Photothermal Therapy of Breast Cancer.

Improving the precise accumulation and retention of nanomedicines in tumor cells is one of the keys to effective therapy of tumors. Herein, supramolecular peptides capped Au nanocages (AuNCs) that may self-aggregate into micron-sized clusters intracellularly in response to spermine (SPM), leading to specific accumulation and retention of AuNCs in SPM-overexpressed tumor cells, are developed. In this design, polydopamine (PDA) is in situ coated on the surface of AuNCs with doxorubicin (DOX) encapsulated. A small peptide, Phe-Phe-Val-Leu-Lys (FFVLK), is conjugated with PDA via esterification, and cucurbit[7]uril (CB[7]) is threaded onto the N-terminal Phe via host-guest interactions. Once the supramolecular peptide (CB[7]-FFVLK) capped AuNCs are internalized in SPM-overexpressed breast cancer cells, CB[7] can be competitively removed from FFVLK by SPM, due to the much higher binding affinity between CB[7] and SPM than that between CB[7] and Phe, leading to exposure of free FFVLK, which can subsequently self-assemble and induce the aggregation of AuNCs to micron-sized clusters, resulting in the significantly enhanced accumulation and retention of DOX-loaded AuNCs in tumor cells. Under NIR laser irradiation, the enhanced photothermal conversion of AuNCs aggregates, together with photothermia-induced release of DOX leads to synergistic photothermal therapy and chemotherapy against breast cancer.

Macrocycle-Surfaced Polymer Nanocapsules: An Emerging Paradigm for Biomedical Applications.

In the recent decade, macrocycle-surfaced polymer nanocapsules have been developed and studied as potential drug carriers. In particular, a unique group of these nanocapsules were constructed from a covalently self-assembled polymer network based on several classic macrocycles including cucurbituril, pillararene, and calixarene. The unique structure of these nanocapsules consists of a liquid or solid core and a shell laced with macrocycles in which the macrocycles not only act as the shell matrix of the nanocapsules but also allow further facile, modular functionalization via host-guest interactions with guest-tagged molecules. More interestingly, when a responsive cross-linker was introduced between the macrocycles, the payload inside the nanocapsules could be selectively released in the presence of typical hallmarks of certain diseases, which is of great interest for biomedical applications. In this Topical Review, macrocycle-surfaced polymer nanocapsules derived from covalently self-assembled polymer networks are introduced systemically with a focus on the molecular design and biomedical applications.

Supramolecular biomaterials for bio-imaging and imaging-guided therapy.

Benefiting from their unique advantages, including reversibly switchable structures, good biocompatibility, facile functionalization, and sensitive response to biological stimuli, supramolecular biomaterials have been widely applied in biomedicine. In this review, the representative achievements and trends in the design of supramolecular biomaterials (mainly those derived from biomacromolecules) with specific macromolecules including peptides, deoxyribonucleic acid, and polysaccharides, as well as their applications in bio-imaging and imaging-guided therapy are summarized. This review will serve as an important summary and "go for" reference for explorations of the applications of supramolecular biomaterials in bio-imaging and image-guided therapy, and will promote the development of supramolecular chemistry as an emerging interdisciplinary research area.

Cucurbituril-Based Supramolecular Polymers for Biomedical Applications.

Supramolecular polymers (SPs) have attracted broad interest because of their intriguing features and functions. Host-guest interactions often impart tunable physicochemical properties, reversible hierarchical organization, and stimuli-responsiveness to SPs for diverse biomedical applications. Characterized by strong but dynamic interactions with guest molecules, cucurbit[n]uril (CB[n]) has shown great potential as an important building block of various functional polymers for biomedical applications. In this Minireview, we summarize the most recent examples regarding the design, fabrication, and biomedical applications of CB[n]-based supramolecular polymers (CSPs), which are categorized as noncovalent and covalent CSPs according to the interactions between the CB[n] and polymer backbones. The design principles of CSPs and their unique advantages for biomedical applications, as well as the developmental trends and future perspectives of this cross-disciplinary area are also discussed.

Self-Propelled Asymmetrical Nanomotor for Self-Reported Gas Therapy.

Gas therapy has emerged as a new therapeutic strategy in combating cancer owing to its high therapeutic efficacy and biosafety. However, the clinical translation of gas therapy remains challenging due to the rapid diffusion and limited tissue penetration of therapeutic gases. Herein, a self-propelled, asymmetrical Au@MnO2 nanomotor for efficient delivery of therapeutic gas to deep-seated cancer tissue for enhanced efficacy of gas therapy, is reported. The Au@MnO2 nanoparticles (NPs) catalyze endogenous H2 O2 into O2 that propels NPs into deep solid tumors, where SO2 prodrug is released from the hollow NPs owing to the degradation of MnO2 shells. Fluorescein isothiocyanate (FITC) is conjugated onto the surface of Au via caspase-3 responsive peptide (DEVD) and the therapeutic process of gas therapy can be optically self-reported by the fluorescence of FITC that is turned on in the presence of overexpressed caspase-3 as an apoptosis indicator. Au@MnO2 nanomotors show self-reported therapeutic efficacy and high biocompatibility both in vitro and in vivo, offering important new insights to the design and development of novel nanomotors for efficient payload delivery into deep tumor tissue and in situ monitoring of the therapeutic process.

Polyamine-Responsive Morphological Transformation of a Supramolecular Peptide for Specific Drug Accumulation and Retention in Cancer Cells.

The precise accumulation and extended retention of nanomedicines in the tumor tissue has been highly desired for cancer therapy. Here a novel supramolecular-peptide derived nanodrug (SPN) that can be transformed to microfibers in response to intracellular polyamine in cancer cells for significantly enhanced tumor specific accumulation and retention is developed. The supramolecular-peptide is constructed via the non-covalent interactions between cucurbit[7]uril (CB[7]) and Phe on Phe-Phe-Val-Leu-Lys-camptothecin conjugates (FFVLK-CPT, PC). The resultant amphiphilic supramolecular complex subsequently self-assembles into nanoparticles with a hydrodynamic diameter of 164.2 ± 3.7 nm. Upon internalization into spermine-overexpressed cancer cells, the CB[7]-Phe host-guest pairs can be competitively dissociated by spermine and can release free PC, which immediately form ß-sheet structures and subsequently reorganize into microfibers, leading to dramatically improved accumulation, retention, and sustained release of CPT in tumor cells for highly effective cancer therapy. Accordingly, this SPN exhibit rather low toxicity against non-cancerous cells due to the morphological stability and fast exocytosis of the nanodrugs in those cells without abundant spermine. This study reports the first supramolecular peptide capable of polyamine-responsive "nanoparticle-to-microfiber" transformation for specific tumor therapy with minimal side effects. This work also offers novel insights to the design and development of stimuli-responsive nanomaterials as precision medicine.

Supramolecular Tropism Driven Aggregation of Nanoparticles In Situ for Tumor-Specific Bioimaging and Photothermal Therapy.

Inorganic nanomedicine has attracted increasing attentions in biomedical sciences due to their excellent biocompatibility and tunable, versatile functionality. However, the relatively poor accumulation and retention of these nanomedicines in targeted tissues have often hindered their clinical translation. Herein, highly efficient, targeted delivery, and in situ aggregation of ferrocene (Fc)-capped Au nanoparticles (NPs) are reported to cucurbit[7]uril (CB[7])-capped Fe3 O4 NPs (as an artificial target) that are magnetically deposited into the tumor, driven by strong, multipoint CB[7]-Fc host-guest interactions (here defined as "supramolecular tropism" for the first time), leading to high tumor accumulation and retention of these NPs. The in vitro and in vivo studies demonstrate the precisely controlled, specific accumulation, and retention of Au NPs in the tumor cells and tissue via supramolecular tropism and in situ aggregation, which afford locally enhanced CT imaging of cancer and enable tumor-specific photothermal therapy attributed to the plasmonic coupling effects between adjacent Au NPs within the supramolecular aggregations. This work provides a novel concept of supramolecular tropism, which may drive targeted delivery and enable specific accumulation, retention, and activation of nanomedicine for improved bioimaging and therapy of cancer.

Selection of Planar Chiral Conformations between Pillar[5,6]arenes Induced by Amino Acid Derivatives in Aqueous Media.

Chiral α-amino acids play critical roles in the metabolic process in nearly all life forms. So far, chiral recognition of α-amino acids has mainly focused on the determination of l/d enantiomers. Herein, selection of planar chiral conformations between water-soluble pillar[5]arene WP5 and pillar[6]arene WP6 was observed due to α-side chain or ethyl ester moieties of l-α-amino acid ethyl ester hydrochlorides binding with WP5 and WP6, respectively. Therefore, α-side chain and ethyl ester moieties of l-α-amino acid ethyl ester hydrochlorides were recognized by observing the induced CD signal and its inversion. This is a rare example of being able to detect the chiral region around α-carbon of a chiral α-amino acid molecule.

N-Doped carbon dots for the fluorescence and colorimetry dual-mode detection of curcumin.

Nitrogen doped carbon dots (N-CDs) were synthesized by a one-step hydrothermal method with dopamine and ethylenediamine. The as-prepared N-CDs were characterized via transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), fluorescence spectrophotometer, UV-Vis spectrophotometry and Fourier transform infrared spectroscopy (FTIR). The average particle dimension of the as-prepared N-CDs was 2.68 nm, and the best excitation and emission wavelengths were 405 nm and 535 nm, separately. N-CDs exhibits excellent selectivity and sensitivity to detect the curcumin (Cur), attaining a wider linear range of 97.5 nM-67.9 µM and a limit of detection (LOD) of as low as 94 nM. Interestingly, N-CDs can also give responsive signals of a visible colour change (yellow to red). Moreover, a novel fluorescent/colorimetric dual-mode method has been successfully employed for the determination of Cur in real samples with good recoveries (94%-110%) and precision (RSD = 0.3-2.9%).

Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation.

The wide-spreading SARS-CoV-2 virus has put the world into boiling water for more than a year, however pharmacological therapies to act effectively against coronavirus disease 2019 (COVID-19) remain elusive. Chloroquine (CQ), an antimalarial drug, was found to exhibit promising antiviral activity in vitro and in vivo at a high dosage, thus CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity. Herein, we show that supramolecular formulation of CQ by a macrocyclic host, curcurbit[7]uril (CB[7]), reduced its non-specific toxicity and improved its antiviral activity against coronavirus, working in synergy with CB[7]. CB[7] was found to form 1:1 host-guest complexes with CQ, with a binding constant of ∼104 L/mol. The CQ-CB[7] formulation decreased the cytotoxicity of CQ against Vero E6 and L-02 cell lines. In particular, the cytotoxicity of CQ (60 µmol/L) against both Vero E6 cell line and L-02 cell lines was completely inhibited in the presence of 300 µmol/L and 600 µmol/L CB[7], respectively. Furthermore, the CB[7] alone showed astonishing antiviral activity in SARS-CoV-2 infected Vero E6 cells and mouse hepatitis virus strain A59 (MHV-A59) infected N2A cells, and synergistically improved the antiviral activity of CQ-CB[7], suggesting that CB[7]-based CQ formulation has a great potential as a safe and effective antiviral agent against SARS-CoV-2 and other coronavirus.

Transformable Honeycomb-Like Nanoassemblies of Carbon Dots for Regulated Multisite Delivery and Enhanced Antitumor Chemoimmunotherapy.

Tumor fibrotic stroma forms complex barriers for therapeutic nanomedicine. Although nanoparticle vehicles are promising in overcoming biological barriers for drug delivery, fibrosis causes hypoxia, immunosuppression and limited immunocytes infiltration, and thus reduces antitumor efficacy of nanosystems. Herein, we report the development of cancer-associated fibroblasts (CAFs) responsive honeycomb-like nanoassemblies of carbon dots (CDs) to spatially program the delivery of multiple therapeutics for enhanced antitumor chemoimmunotherapy. Doxorubicin (DOX) and immunotherapeutic enhancer (Fe ions) are immobilized on the surface of CDs, whereas tumor microenvironment modifier (losartan, LOS) is encapsulated within the mesopores. The drugs-loaded nanoassemblies disassociate into individual CDs to release LOS to mitigate stroma and hypoxia in response to CAFs. The individual CDs carrying DOX and Fe ion efficiently penetrate deep into tumor to trigger intensified immune responses. Our in vitro and in vivo studies show that the nanoassemblies exhibit effective T cells infiltration, tumor growth inhibition and lung metastasis prevention, thereby providing a therapeutic platform for desmoplasia solid tumor.

Synthesis and Bioactivity of Guanidinium-Functionalized Pillar[5]arene as a Biofilm Disruptor.

Due to the inherent resistance of bacterial biofilms to antibiotics and their serious threat to global public health, novel therapeutic agents and strategies to tackle biofilms are urgently needed. To this end, we designed and synthesized a novel guanidinium-functionalized pillar[5]arene (GP5) that exhibited high antibacterial potency against Gram-negative E. coli (BH101) and Gram-positive S. aureus (ATCC25904) strains. More importantly, GP5 effectively disrupted preformed E. coli biofilms by efficient penetration through biofilm barriers and subsequent destruction of biofilm-enclosed bacteria. Furthermore, host-guest complexation between GP5 and cefazolin sodium, a conventional antibiotic that otherwise shows negligible activity against biofilms, exhibited much enhanced, synergistic disruption activity against E. coli biofilms, thus providing a novel supramolecular platform to effectively disrupt biofilms.

Supramolecular Polymerization-Induced Nanoassemblies for Self-Augmented Cascade Chemotherapy and Chemodynamic Therapy of Tumor.

The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H2 O2 level in tumor tissues. Herein, we developed a supramolecular nanoparticle via a simple one-step supramolecular polymerization-induced self-assembly process using platinum (IV) complex-modified ß-cyclodextrin-ferrocene conjugates as supramolecular monomers. The supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H2 O2 in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H2 O2 in the tumor tissue. Thus, the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapy via the self-augmented cascade radical generation and drug release. In addition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.

Guest Exchange by a Partial Energy Ratchet in Water.

Molecular machines are ubiquitous in nature and function away from equilibrium by consuming fuels to produce appropriate work. Chemists have recently excelled at mimicking the fantastic job performed by natural molecular machines with synthetic systems soluble in organic solvents. In efforts toward analogous systems working in water, we show that guest molecules can be exchanged in the synthetic macrocycle cucurbit[7]uril by involving kinetic traps, and in such a way as modulating energy wells and kinetic barriers using pH, light, and redox stimuli. Ditolyl-viologen can also be exchanged using the best kinetic trap and interfaced with alginate, thus affording pH-responsive blue, fluorescent hydrogels. With tunable rate and binding constants toward relevant guests, cucurbiturils may become excellent ring molecules for the construction of advanced molecular machines working in water.