Dynamic-group-aware networks for multi-agent trajectory prediction with relational reasoning.

Demystifying the interactions among multiple agents from their past trajectories is fundamental to precise and interpretable trajectory prediction. However, previous works mainly consider static, pairwise interactions with limited relational reasoning. To more comprehensively model interactions and reason relations, we propose DynGroupNet, a dynamic-group-aware network, which (i) models time-varying interactions in highly dynamic scenes; (ii) captures both pairwise and group-wise interactions; and (iii) reasons both interaction strength and category without direct supervision. Based on DynGroupNet, we further design a prediction system to forecast socially plausible trajectories with dynamic relational reasoning. The proposed prediction system leverages the Gaussian mixture model, multiple sampling and prediction refinement to promote prediction diversity for multiple future possibilities capturing, training stability for efficient model learning and trajectory smoothness for more realistic predictions, respectively. The proposed complex interaction modeling of DynGroupNet, future diversity capturing, efficient model training and trajectory smoothing of prediction system together to promote more accurate and plausible future predictions. Extensive experiments show that: (1) DynGroupNet can capture time-varying group behaviors, infer time-varying interaction category and interaction strength during prediction; (2) DynGroupNet significantly outperforms the state-of-the-art trajectory prediction methods by 28.0%, 34.9%, 13.0% in FDE on the NBA, NFL and SDD datasets.

Photoswitchable Quadruple Hydrogen-Bonding Motif.

Multiple hydrogen-bonding motifs serve as important building blocks for molecular recognition and self-assembly. Herein, a photoswitchable quadruple hydrogen-bonding motif featuring near-complete, reversible, and thermostable conversion between DADA and AADD arrays associated with an alteration of their dimerization constants by over 3 orders of magnitude is reported. The system is based on a diarylethene featuring a ureidopyrimidin-4-ol moiety, which upon photoinduced ring closure and associated loss of aromaticity undergoes enol-keto tautomerization to a ureidopyrimidinone moiety. The latter causes a transformation of the hydrogen-bonding arrays and significantly weakens the free energy of dimerization in the case of the closed isomer. This photoswitchable quadruple hydrogen-bonding motif should allow us to spatially and temporarily direct self-assembly and supramolecular polymerization processes by light.

Collaborative Uncertainty Benefits Multi-Agent Multi-Modal Trajectory Forecasting.

In multi-modal multi-agent trajectory forecasting, two major challenges have not been fully tackled: 1) how to measure the uncertainty brought by the interaction module that causes correlations among the predicted trajectories of multiple agents; 2) how to rank the multiple predictions and select the optimal predicted trajectory. In order to handle the aforementioned challenges, this work first proposes a novel concept, collaborative uncertainty (CU), which models the uncertainty resulting from interaction modules. Then we build a general CU-aware regression framework with an original permutation-equivariant uncertainty estimator to do both tasks of regression and uncertainty estimation. Furthermore, we apply the proposed framework to current SOTA multi-agent multi-modal forecasting systems as a plugin module, which enables the SOTA systems to: 1) estimate the uncertainty in the multi-agent multi-modal trajectory forecasting task; 2) rank the multiple predictions and select the optimal one based on the estimated uncertainty. We conduct extensive experiments on a synthetic dataset and two public large-scale multi-agent trajectory forecasting benchmarks. Experiments show that: 1) on the synthetic dataset, the CU-aware regression framework allows the model to appropriately approximate the ground-truth Laplace distribution; 2) on the multi-agent trajectory forecasting benchmarks, the CU-aware regression framework steadily helps SOTA systems improve their performances. Especially, the proposed framework helps VectorNet improve by 262 cm regarding the Final Displacement Error of the chosen optimal prediction on the nuScenes dataset; 3) in multi-agent multi-modal trajectory forecasting, prediction uncertainty is proportional to future stochasticity; 4) the estimated CU values are highly related to the interactive information among agents. The proposed framework can guide the development of more reliable and safer forecasting systems in the future.

Network pharmacology and bioinformatics analysis on the underlying mechanisms of baicalein against oral squamous cell carcinoma.

BACKGROUND AND AIMS: This study performed a network pharmacology analysis to explore the potential anticancer activity of baicalein against oral squamous cell carcinoma (OSCC). METHODS: The differentially expressed genes in OSCC were identified by the OSCC, and the key module related to OSCC was acquired by the weighted gene co-expression network analysis from GSE30784. Baicalein targets were obtained from GeneCards, SwissTargetPrediction and TCMSP (the traditional Chinese medicine systems pharmacology database and analysis platform) databases. Apart from GSE30784, OSCC-related genes were acquired from the Comparative Toxicogenomics Database and DisGeNET platform. The baicalein targets and OSCC-related genes were overlapped to acquire the drug-disease interaction genes. We input the candidate drug-disease interaction genes into the STRING database and created the protein-protein interaction network. The hub genes in the network were identified by cytoHubba. The expression levels of hub genes between cancer tissues and normal tissues were evaluated based on The Cancer Genome Atlas. Moreover, we performed the cancer immune infiltration analysis and evaluated the association between the expression of HIF1A and the abundance of infiltrating immune cells. The molecular docking between HIFA and baicalein was also performed and visualized. Additionally, the enrichment analysis was performed based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. RESULTS: After overlapping the candidate baicalein targets with OSCC-related genes, 34 candidate drug-disease interaction genes were obtained. cytoHubba identified the top 10 genes with high centrality measures from the network, including AKT1, CD44, EGFR, HIF1A, IGF1, MMP2, MYC, PTGS2, STAT3 and TP53. The enriched biological process terms included regulation of apoptotic signaling pathway, regulation of cysteine-type endopeptidase activity and cellular response to chemical stress. The top five enriched pathways comprised Kaposi sarcoma-associated herpesvirus infection, hepatitis C, p53 signaling pathway, Epstein-Barr virus infection and proteoglycans in cancer. The expression of HIF1A was positively associated with the infiltration levels of CD4 + T cells (cor = 0.131, p = 0.004) and dendritic cells (cor = 0.098, p = 0.03), whereas negatively associated with B cells (cor = -0.098, p = 0.03). CONCLUSION: Our results suggested that baicalein might be a candidate drug against OSCC. More studies are necessary to validate its anticancer effect and explore the underlying mechanisms.

Improving Photocatalytic Performance through the Construction of a Supramolecular Organic Framework.

A supramolecular organic framework-type photocatalyst, named TM-SOF, is constructed by the self-assembly of cucurbit[8]uril and a tetra-arm monomer containing four N, N'-dimethyl 2,5-bis(4-pyridinium)thiazolo[5,4-d]thiazole (MPT) moieties. Benefiting from the multivalent assembly, a photocatalytically active supramolecular MPT dimer can be stably formed in TM-SOF. In addition, TM-SOF exhibits better stability against temperature, substrate, and light irradiation. As a result, TM-SOF shows a significantly improved performance for the photocatalytic aerobic oxidation of aryl boronic acids and thioethers. It is anticipated that this line of research will provide a facile approach for fabricating high-performance supramolecular photocatalysis systems.

Molecular Engineering of Noncovalent Dimerization.

Dimers are probably the simplest model to facilitate the understanding of fundamental physical and chemical processes that take place in much-expanded systems like aggregates, crystals, and other solid states. The molecular interplay within a dimer differentiates it from the corresponding monomeric state and determines its features. Molecular engineering of noncovalent dimerization through applied supramolecular restrictions enables additional control over molecular interplay, particularly over its dynamic aspect. This Perspective introduces the recent effort that has been made in the molecular engineering of noncovalent dimerization, including supramolecular dimers, folda-dimers, and macrocyclic dimers. It showcases how the variation in supramolecular restrictions endows molecular-based materials with improved performance and/or functions like enhanced emission, room-temperature phosphorescence, and effective catalysis. We particularly discuss pseudostatic dimers that can sustain molecular interplay for a long period of time, yet are still flexible enough to adapt to variations. The pseudostatic feature allows for active species to decay along an alternate pathway, thereby spinning off emerging features that are not readily accessible from conventional dynamic systems.

Polarization of macrophages in the trigeminal ganglion of rats with pulpitis.

BACKGROUND: Dental pulp tissues are rich in pain-related afferent nerve fibers, which originate from primary sensory neurons in the trigeminal ganglion (TG). The mechanisms of central nervous system (CNS) underlying ectopic pain following peripheral inflammation have been reported that the macrophages as inflammatory and immunologic mediators in the TG play an important role in the process of pulpitis and hyperalgesia. OBJECTIVE(S): To observe the polarization response and dynamic distribution of macrophages in the TG during the development of dental pulp inflammation. METHODS: A rat model of pulpitis was established using complete Freund's adjuvant (CFA). Hematoxylin-eosin (HE), immunohistochemistry (IHC), immunofluorescence (IF), toluidine blue (TB) staining, and RT-qPCR were performed to observe the expression of macrophage-related factors in the TG. RESULTS: The results of IHC staining showed that M2 macrophages labeled with CD206 were observed in the TG of both the control and CFA groups. The statistical analysis indicated that the number of CD206-positive macrophages in the TG increased significantly at 24 h after CFA-induced pulpitis, reached a peak at 2 weeks, and then returned to the normal level after 6 weeks. The ratio of M2/M1 in the CFA groups was significantly lower than that in the control group from 24 to 72 h, and this pattern was reversed at 2 weeks after CFA-induced pulpitis; then, the ratio increased significantly and was maintained at a high level for 4 weeks. RT-qPCR results showed that the expression of IL-10 in the TG increased significantly from 1 to 4 weeks after CFA-induced pulpitis. CONCLUSION: The trend of M2 macrophages was opposite to that of M1 macrophages in the TG during the process of pulpitis induced by CFA, which is consistent with the expression of macrophage-related cytokines. Macrophage polarization in the TG may participate in the neuroinflammation response induced by dental pulpitis.

Cucurbit[7]uril-Modulated H/D Exchange of α-Carbonyl Hydrogen: Deceleration in Alkali and Acceleration in Acid Conditions.

Supramolecular catalysis based on host-guest interactions has aroused much attention in past decades. Among the various strategies, modulation of the reactivity of key intermediates is an effective strategy to achieve high-efficiency supramolecular catalysis. Here, we report that by utilizing the host-guest interaction of cucurbit[7]uril (CB[7]), the reactivity of anionic enolate and cationic oxonium, the intermediates of H/D exchange of the α-carbonyl hydrogen in alkali and acid conditions, respectively, could be modulated effectively. On one hand, in alkaline conditions, both the electrostatic effect and the steric hindrance effect of CB[7] disfavored formation of the enolate anion intermediate. On the other hand, in acidic conditions, the oxonium was stabilized and the solvent effect was weakened by the electrostatic effect of CB[7]. As a result, the H/D exchange of 1-(4-acetylphenyl)-N,N,N-trimethylmethanaminium bromide is decelerated in alkaline and accelerated in acidic conditions. It is promising that the highly polar portals of CB[n] molecules together with their well-defined host-guest chemistry may be applied to modulate the reactivity of other kinds of ionic intermediates in an effective and convenient way, thus enriching the toolkit of supramolecular catalysis.

Transforming a Fluorochrome to an Efficient Photocatalyst for Oxidative Hydroxylation: A Supramolecular Dimerization Strategy Based on Host-Enhanced Charge Transfer.

The development of non-covalent synthetic strategy to fabricate efficient photocatalysts is of great importance in theranostic and organic materials. Herein, a fluorochrome N,N'-dimethyl 2,5-bis(4-pyridinium)thiazolo[5,4-d]thiazolediiodide (MPT) was transformed into an efficient photocatalyst through supramolecular dimerization in the cavity of cucurbit[8]uril (CB[8]). The host-enhanced charge transfer interaction within the supramolecular dimer 2MPT-CB[8] dramatically promoted intersystem crossing to produce triplet. In addition, the staggered conformation of 2MPT-CB[8] facilitated the energy transfer and electron transfer of the triplet. As a result, 2MPT-CB[8] could serve as a high-efficiency photocatalyst for the oxidative hydroxylation of arylboronic acids. This supramolecular dimerization strategy enriches the supramolecular engineering of functional π-systems. It is anticipated that this strategy can be extended to fabricate various π-systems with tailor-made functions.

A Self-Degradable Supramolecular Photosensitizer with High Photodynamic Therapeutic Efficiency and Improved Safety.

Concerning that the residues of photosensitizers (PS) may cause serious side effects under light, it is of great significant to timely switch-off PS after photodynamic therapy (PDT). Herein, we proposed a supramolecular strategy to regulate the activity of PS, fabricating a supramolecular PS with improved reactive oxygen species (ROS) generation efficiency and accelerated self-degradation ability. During PDT treatment, the supramolecular PS exhibited good therapeutic efficiency as well as reduced dark toxicity. Moreover, the supramolecular PS could be degraded by ROS generated by itself and lose its PDT activities once PDT treatment finished. In this way, the side effects of PDT can be reduced without sacrificing the therapeutic efficiency. This work provides a novel strategy for smarter PDT beacon to further improve the safety of PDT treatment.

Cucurbit[n]urils for Supramolecular Catalysis.

The control over chemical reactivity and selectivity are always pursued. Using non-covalent interactions to achieve efficient and selective catalysis is an essential goal of supramolecular catalysis. Supramolecular catalysis based on cucurbit[n]urils (CB[n]s) possesses distinct characteristics for the unique structure of CB[n]s. CB[n]s are a family of pumpkin-shaped host molecules with various molecular sizes, rigid structures, electronegative portals and wealthy host-guest chemistry. Herein, we summarize the three major mechanisms of CB[n]s based supramolecular catalysis. Owing to the structural properties of CB[n]s, CB[n]s can serve as nanoreactors and steric hindrance to modulate the reactivity of substrates. They can also catalyze the reactions by modulating the reactivity of ionized intermediates. Recent progresses on the CB[n]s based supramolecular catalysis are introduced in this Minireview and the future development in this field is discussed. It is anticipated that this review provides insights into the mechanism of CB[n]s based supramolecular catalysis and may help scientists find new opportunities in this field.

Tough and Multi-Recyclable Cross-Linked Supramolecular Polyureas via Incorporating Noncovalent Bonds into Main-Chains.

Covalent thermosets generally exhibit robust mechanical properties, while they are fragile and lack the ability to be reprocessed or recycled. Herein, a new strategy of incorporating noncovalent bonds into main-chains is developed to construct tough and multi-recyclable cross-linked supramolecular polyureas (CSPU), which are prepared via the copolymerization of diisocyanate monomers, noncovalently bonded diamine monomers linked by quadruple hydrogen bonds, and covalent diamine/triamine monomers. The CSPU exhibit remarkable solvent resistance and outstanding mechanical properties owing to the covalent cross-linking via triamine monomer. Through the incorporation of 9.7% and 14.6% quadruple hydrogen bonded diamine monomer, the transparent CSPU films are endowed with superior toughness of 74.17 and 124.17 MJ m-3 , respectively. Impressively, even after five generations of recycling processes, the mechanical properties of reprocessed CSPU can recover more than 95% of their original properties, displaying excellent multiple recyclablity. As a result, the superior toughness, remarkable solvent resistance, high transparency, and excellent multiple recyclability are well-combined in the CSPU. It is highly anticipated that this line of research will provide a facile and general method to construct various cross-linked polymer materials with superior recyclability and mechanical properties.

Host-Guest Interactions between Oxaliplatin and Cucurbit[7]uril/Cucurbit[7]uril Derivatives under Pseudo-Physiological Conditions.

Compared with conventional drug delivery systems (DDSs), DDSs based on host-guest interactions possess unique advantages, such as high selectivity, tunable binding ability, and controllable release of drugs. It is important to study the host-guest interactions between the carrier and drug under physiological conditions for constructing DDSs. In this work, we have studied the host-guest interaction between cucurbit[7]uril (CB[7]) and oxaliplatin (OxPt), a clinical antitumor drug, in the cell culture medium. The results show that amino acids such as phenylalanine in the 1640 culture medium can partially occupy the cavity of CB[7], which leads to the decrease of enthalpy changes of the host-guest interaction between OxPt and CB[7]. In addition, inorganic salts such as NaCl in the medium reduce the enthalpy change and increase the entropy change of the binding because of the preorganization of the portal of CB[7] and sodium cation. As a result, the binding constant of CB[7] with OxPt in the 1640 culture medium is 1/20 of that in pure water. When CB[7] is modified at the terminal of star-type PEG to construct the star-PEGylated CB[7], it is shown that the molecular weight and topological structure of the PEG polymer backbone exhibit little effect on the host-guest interactions between CB[7] and OxPt. This study enriches the host-guest chemistry of cucurbiturils and may provide guidance for constructing novel DDSs based on host-guest interactions with high loading and releasing efficiency.

Tuning the stability of organic radicals: from covalent approaches to non-covalent approaches.

Organic radicals are important species with single electrons. Because of their open-shell structure, they are widely used in functional materials, such as spin probes, magnetic materials and optoelectronic materials. Owing to the high reactivity of single electrons, they often serve as a key intermediate in organic synthesis. Therefore, tuning the stability of radicals is crucial for their functions. Herein, we summarize covalent and non-covalent approaches to tune the stability of organic radicals through steric effects and tuning the delocalization of spin density. Covalent approaches can tune the stability of radicals effectively and non-covalent approaches benefit from dynamicity and reversibility. It is anticipated that the further development of covalent and non-covalent approaches, as well as the interplay between them, may push the fields forward by enriching new radical materials and radical mediated reactions.

Cucurbit[7]uril promoted Fenton oxidation by modulating the redox property of catalysts.

The redox property of a ferrocene derivative, the catalyst of Fenton oxidation, is modulated by the host-guest complexation of cucurbit[7]uril. The supramolecularly modulated catalyst significantly accelerates the catalytic oxidation of dye chromophores, thus providing a way to avoid product inhibition and broadening the range of substrates.

A Supramolecular Radical Dimer: High-Efficiency NIR-II Photothermal Conversion and Therapy.

Photothermal therapy at the NIR-II biowindow (1000-1350 nm) is drawing increasing interest because of its large penetration depth and maximum permissible exposure. Now, the supramolecular radical dimer, fabricated by N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole radical cation (MPT.+ ) and cucurbit[8]uril (CB[8]), achieves strong absorption at NIR-II biowindow. The supramolecular radical dimer (2MPT.+ -CB[8]) showed highly efficient photothermal conversion and improved stability, thus contributing to the strong inhibition on HegG2 cancer cell under 1064 nm irradiation even penetrating through chicken breast tissue. This work provides a novel approach to construct NIR-II chromophore by tailor-made assembly of organic radicals. It is anticipated that this study provides a new strategy to achieve NIR-II photothermal therapy and holds promises in luminescence materials, optoelectronic materials, and also biosensing.

A supramolecular radical cation: folding-enhanced electrostatic effect for promoting radical-mediated oxidation.

We report a supramolecular strategy to promote radical-mediated Fenton oxidation by the rational design of a folded host-guest complex based on cucurbit[8]uril (CB[8]). In the supramolecular complex between CB[8] and a derivative of 1,4-diketopyrrolo[3,4-c]pyrrole (DPP), the carbonyl groups of CB[8] and the DPP moiety are brought together through the formation of a folded conformation. In this way, the electrostatic effect of the carbonyl groups of CB[8] is fully applied to highly improve the reactivity of the DPP radical cation, which is the key intermediate of Fenton oxidation. As a result, the Fenton oxidation is extraordinarily accelerated by over 100 times. It is anticipated that this strategy could be applied to other radical reactions and enrich the field of supramolecular radical chemistry in radical polymerization, photocatalysis, and organic radical battery and holds potential in supramolecular catalysis and biocatalysis.

Highly Efficient Supramolecular Catalysis by Endowing the Reaction Intermediate with Adaptive Reactivity.

A new strategy of highly efficient supramolecular catalysis is developed by endowing the reaction intermediate with adaptive reactivity. The supramolecular catalyst, prepared by host-guest complexation between 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) and cucurbit[7]uril (CB[7]), was used for biphasic oxidation of alcohols. Cationic TEMPO+ , the key intermediate, was stabilized by the electrostatic effect of CB[7] in aqueous phase, thus promoting the formation of TEMPO+ and inhibiting side reactions. Moreover, through the migration into the organic phase, TEMPO+ was separated from CB[7] and recovered the high reactivity to drive a fast oxidation of substrates. The adaptive reactivity of TEMPO+ induced an integral optimization of the catalytic cycle and greatly improved the conversion of the reaction. This work highlights the unique advantages of dynamic noncovalent interactions on modulating the activity of reaction intermediates, which may open new horizons for supramolecular catalysis.

The fabrication of a supra-amphiphile for dissipative self-assembly.

Dissipative self-assembly is a challenging but attractive field of supramolecular science, because it generally concerns complex systems but is more close to the self-assembly of living bodies. In this article, we realized dissipative self-assembly by coupling a supra-amphiphile with a chemical oscillator. The supra-amphiphile was fabricated with iodine and a double hydrophilic block copolymer containing PEG segments, as the non-covalent interaction between PEG and iodine could turn PEG hydrophobic, leading to the formation of the supra-amphiphile. The self-assembly and disassembly of the supra-amphiphile could be controlled by varying the concentration of iodine. Therefore, the dissipative self-assembly of the supra-amphiphile was realized when it was coupled with the IO3--NH3OH+-OH- chemical oscillator, which was able to produce iodine periodically. Meanwhile, the kinetic data of the self-assembly and disassembly of the supra-amphiphile could be estimated by the theoretical simulation of the chemical oscillations. This line of research promotes the self-assembly of supra-amphiphiles one step forward from thermodynamic statics to a dissipative system, and also suggests a new strategy to investigate the kinetics of stimuli-responsive molecular self-assembly.

Tuning the surface activity of gemini amphiphile by the host-guest interaction of cucurbit[7]uril.

This research is aimed to develop an effective supramolecular route for tuning the surface activity of the surfactant. To this end, cationic gemini amphiphiles and cucurbit[7]uril (CB[7]) were complexed in water, and each hydrophobic chain of the gemini amphiphiles was bound with a CB[7]. The steric hindrance of CB[7] prevented the two hydrophobic chains from getting closed to each other, leading a significant change of surface activity. Before supramolecular complexation, the surface activity of the gemini amphiphile is relatively high, which can generate the foams easily. However, the foam generated by gemini amphiphile can be destructed by adding CB[7], suggesting that the suface activity is lowed after the supramolecular complexation. The surface activity can recover after adding 1-adamantanamine hydrochloride, which has a stronger ability to bind CB[7]. Therefore, a controllable foaming and defoaming process can be realized. It is highly anticipated that supramolecular chemistry for tuning amphiphilicity of surfactants may find application in the fields that fast foaming and defoaming are needed.