Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.

CD19-targeting chimeric antigen receptors (CARs) with CD28 and CD3ζ signaling domains have been approved by the US FDA for treating B cell malignancies. Mutation of immunoreceptor tyrosine-based activation motifs (ITAMs) in CD3ζ generated a single-ITAM containing 1XX CAR, which displayed superior antitumor activity in a leukemia mouse model. Here, we investigated whether the 1XX design could enhance therapeutic potency against solid tumors. We constructed both CD19- and AXL-specific 1XX CARs and compared their in vitro and in vivo functions with their wild-type (WT) counterparts. 1XX CARs showed better antitumor efficacy in both pancreatic and melanoma mouse models. Detailed analysis revealed that 1XX CAR-T cells persisted longer in vivo and had a higher percentage of central memory cells. With fluorescence resonance energy transfer (FRET)-based biosensors, we found that decreased ITAM numbers in 1XX resulted in similar 70-kDa zeta chain-associated protein (ZAP70) activation, while 1XX induced higher Ca2+ elevation and faster extracellular signal-regulated kinase (Erk) activation than WT CAR. Thus, our results confirmed the superiority of 1XX against two targets in different solid tumor models and shed light on the underlying molecular mechanism of CAR signaling, paving the way for the clinical applications of 1XX CARs against solid tumors.

Pentiptycene-based ladder polymers with configurational free volume for enhanced gas separation performance and physical aging resistance.

Polymers of intrinsic microporosity (PIMs) have shown promise in pushing the limits of gas separation membranes, recently redefining upper bounds for a variety of gas pair separations. However, many of these membranes still suffer from reductions in permeability over time, removing the primary advantage of this class of polymer. In this work, a series of pentiptycene-based PIMs incorporated into copolymers with PIM-1 are examined to identify fundamental structure-property relationships between the configuration of the pentiptycene backbone and its accompanying linear or branched substituent group. The incorporation of pentiptycene provides a route to instill a more permanent, configuration-based free volume, resistant to physical aging via traditional collapse of conformation-based free volume. PPIM-ip-C and PPIM-np-S, copolymers with C- and S-shape backbones and branched isopropoxy and linear n-propoxy substituent groups, respectively, each exhibited initial separation performance enhancements relative to PIM-1. Additionally, aging-enhanced gas permeabilities were observed, a stark departure from the typical permeability losses pure PIM-1 experiences with aging. Mixed-gas separation data showed enhanced CO2/CH4 selectivity relative to the pure-gas permeation results, with only ∼20% decreases in selectivity when moving from a CO2 partial pressure of ∼2.4 to ∼7.1 atm (atmospheric pressure) when utilizing a mixed-gas CO2/CH4 feed stream. These results highlight the potential of pentiptycene's intrinsic, configurational free volume for simultaneously delivering size-sieving above the 2008 upper bound, along with exceptional resistance to physical aging that often plagues high free volume PIMs.

Tyrosine-Conjugation Method for Evaluating BACE1 Activity Based on Silver Nanoparticles/Metal-Organic Framework Composites as Electrochemical Tags.

Beta-site secretase (BACE1) catalyzes the cleavage of amyloid precursor protein (APP), which process ultimately lead to plaque deposition in the brain of Alzheimer's disease (AD). Thus, accurate monitor of BACE1 activity is essential to screen inhibitors for AD treatment. This study develops a sensitive electrochemical assay for probing BACE1 activity based on silver nanoparticles (AgNPs) and tyrosine conjugation as tags and a marking method, respectively. An APP segment is firstly immobilized on aminated microplate reactor. Cytosine (C) rich sequence-templated AgNPs/Zr-based metal-organic framework (MOF) composite is modified by phenol groups, and then the prepared tag (ph-AgNPs@MOF) is captured in microplate surface by the conjugation reaction of phenolic groups between tyrosine and tag. After cleavage by BACE1, the solution containing ph-AgNPs@MOF tags is transferred to the screen-printed graphene electrode (SPGE) surface for voltammetric detection of AgNP signal. This sensitive detection for BACE1 provided an excellent linear relationship between 1 to 200 pM with a detection limit of 0.8 pM. Furthermore, this electrochemical assay is successfully applied for screening of BACE1 inhibitors. This strategy is also verified to be used for evaluation of BACE1 in serum samples.

ALOX5 inhibition protects against dopaminergic neurons undergoing ferroptosis.

Oxidative disruption of dopaminergic neurons is regarded as a crucial pathogenesis in Parkinson's disease (PD), eventually causing neurodegenerative progression. (-)-Clausenamide (Clau) is an alkaloid isolated from plant Clausena lansium (Lour.), which is well-known as a scavenger of lipid peroxide products and exhibiting neuroprotective activities both in vivo and in vitro, yet with the in-depth molecular mechanism unrevealed. In this study, we evaluated the protective effects and mechanisms of Clau on dopaminergic neuron. Our results showed that Clau directly interacted with the Ser663 of ALOX5, the PKCα-phosphorylation site, and thus prevented the nuclear translocation of ALOX5, which was essential for catalyzing the production of toxic lipids 5-HETE. LC-MS/MS-based phospholipidomics analysis demonstrated that the oxidized membrane lipids were involved in triggering ferroptotic death in dopaminergic neurons. Furthermore, the inhibition of ALOX5 was found to significantly improving behavioral defects in PD mouse model, which was confirmed associated with the effects of attenuating the accumulation of lipid peroxides and neuronal damages. Collectively, our findings provide an attractive strategy for PD therapy by targeting ALOX5 and preventing ferroptosis in dopaminergic neurons.

Diagnostic efficacy of double-balloon enteroscopy in patients with suspected isolated small bowel Crohn's disease.

BACKGROUND: Owing to the development of double-balloon enteroscopy (DBE) and video capsule endoscopy (VCE) in recent years, direct visualization of the entire small intestinal mucosa has become possible. Because of the nonspecific symptoms and the anatomic location of the small bowel, diagnosis of isolated small bowel Crohn's disease (CD) remains a challenge. The aim of this research was to explore the value of DBE for isolated small bowel CD in situations where routine tests cannot confirm the diagnosis. METHODS: This study included patients with suspected isolated small bowel CD who were hospitalized in Shengjing Hospital from April 2014 to June 2018. We included patients presenting with chronic diarrhea, abdominal pain, abdominal mass, perianal lesions, and systemic symptoms including weight loss, fever, and anemia after excluding infection factors. Patients with purely colonic CD were excluded from this cohort. Patients with suspected isolated small bowel CD underwent DBE. RESULTS: In 16/18 patients, pathological findings were detected by DBE. In 12 of the cases, small bowel CD was confirmed. The remaining four patients were diagnosed with small bowel inflammation, duodenal carcinoma, ileum inflammation and small bowel ulcers. However, the diagnosis of CD was confirmed in 14/18 (78%) patients by taking into account the clinical presentation, endoscopic and histological results as well as the experimental treatment. DBE assisted in the diagnosis in 86% (12/14) of the patients. CONCLUSIONS: In the diagnosis of small bowel CD, DBE is a helpful tool. Before assessment with DBE, clinical features, colonoscopy, and CT were used to initially assess the intestine. According to the lesions indicated by CT, we chose the most appropriate endoscope insertion route, and combined the endoscopic characteristics and pathological results of DBE to confirm the diagnosis.

[Historical evolution of Coicis Semen processing methods].

Coicis Semen is widely used as a raw material which can be used as both medicine and food among people. According to the ancient monographs on materia medica and relevant documents on the processing specifications in various provinces and cities, herba logical study on the historical evolution of the processing methods of Coicis Semen was conducted in this paper from the aspects of collecting and processing methods of Coicis Semen, the processing methods in the past dynasties and the nature, flavour and efficacy of Coicis Semen. The results showed that the processing methods of Coicis Semen recorded in monographs on materia medica mainly included stir-frying, glutinous rice stir-frying, salt processing(including salt cooking and salt stir-frying), stir-frying with the earth scraped from the wall facing east, and ginger juice stir-frying, etc. Among them, stir-frying, and stir-frying with the earth scraped from the wall facing east are still used nowadays. The bran stir-frying is the improved version of glutinous rice stir-frying in order to be adaptive to the modern-day situation and the needs of the present. In addition, the ancient shell removal and kernel keeping method are also included in the processing procedures in modern local processing specifications, which are combined with frying to form a new method named "Fazhi" processing( "Fazhi" means a processing method of multiple procedures). The 2015 edition of Chinese Pharmacopoeia records that Coicis Semen is helpful to clear dampness and promote diuresis, strengthen the spleen and prevent diarrhea, eliminate impediment, discharge pus, resolve toxin and a mass, etc., which are consistent with those contained in ancient monographs on materia medica. After the "Fazhi" processing, the cold nature of Coicis Semen has been removed and its nature,flavour and meridian tropism have been changed, so its application scopes expanded. The results of this study clearly traced the history of the collecting and proces-sing of Coicis Semen, summarized the nature, flavour and efficacy of Coicis Semen contained in both ancient and modern literature, and provided a historical basis for the standardization of the subsequent processing technology of Coicis Semen, the clinical application of various processed products, and the further development and utilization of medicinal materials.

[Herbalogical study on original plant and medicinal and edible values of Citri Sarcodactylis Fructus].

Citri Sarcodactylis Fructus is a both medicinal and edible species specified by the China Ministry of Health, with a long history in China. According to the ancient monographs about materia medica, it was found that the records of the Citri Sarcodactylis Fructus on the original plants were confused. This paper reviewed the ancient monographs about materia medica, and made a summarization and textual research on the name, origin, habitat, processing methods, medicinal properties and clinicacy efficacy of Citri Sarcodactylis Fructus based the comprehensive analysis on modern literatures and authoritative books of Chinese herbal medicine. The results indicated that there were many bynames of Citri Sarcodactylis Fructus. Before the Yuan Dynasty, there was a mixed use of Citri Sarcodactylis Fructus and Citri Fructus, which were not distinguished from each other in terms of nature and taste until the Yuan dynasty. Citri Sarcodactylis Fructus was a varietas of Citri Fructus. The main shape of the original plant of Citri Sarcodactylis Fructus is "like a human hand with fingers" as recorded in ancient monographs about materia medica. The main places of origin of Citri Sarcodactylis Fructus were Guangdong, Zhejiang, Fujian, Sichuan, which were relatively stable. There were fewer records about medicinal proces-sing methods of Citri Sarcodactylis Fructus. Only steaming and baking methods were found in ancient monographs about materia medica, and the steaming method could reduce the irritability of Citri Sarcodactylis Fructus. The processing of therapeutic dietary of Citri Sarcodactylis Fructus was widely used in folk, which was represented by Chaozhou Laoxianghuang, a traditional succade made of Citri Sarcodactylis Fructus. According to the 2015 edition of Chinese Pharmacopoeia, Citri Sarcodactylis Fructus had effects in soothing liver and regulating gas, relieving pain in the stomach, eliminating dampness and resolving phlegm, which was basically consistent with the descriptions in ancient monographs about materia medica. This paper defined the original plant of Citri Sarcodactylis Fructus, and sorted out and summarized the processing methods, nature and taste of Citri Sarcodactylis Fructus, so as to provide data support for the standardization of the processing technology and the development and utilization of Citri Sarcodactylis Fructus.

Hierarchically Porous Co/Cox My (M = P, N) as an Efficient Mott-Schottky Electrocatalyst for Oxygen Evolution in Rechargeable Zn-Air Batteries.

Tailoring composition and morphology of electrocatalysts is of great importance in improving their catalytic performance. Herein, a salt-templated strategy is proposed to construct novel multicomponent Co/Cox My (M = P, N) hybrids with outstanding electrocatalytic performance for the oxygen evolution reaction (OER). The obtained Co/Cox My hybrids present porous sheet-like architecture consisting of many hierarchical secondary building-units. The synthetic strategy depends on a facile and effective dissolution-recrystallization-pyrolysis process under NH3 atmosphere of the precursors, which does not involve any surfactant or long-time hydrothermal pretreatment. That is different from the conventional methods for the synthesis of hierarchical nitrides/phosphides. Benefitting from unique composition/structure-dependent merits, the Co/Cox My hybrids as a typical Mott-Schottky electrocatalyst exhibit good OER performance in an alkaline medium compared with their counterparts, as evidenced by a low overpotential of 334 mV at 10 mA cm-2 and a small Tafel slope of 79.2 mV dec-1 , as well as superior long-term stability. More importantly, the Co/Cox My +Pt/C achieves higher voltaic efficiency and several times longer cycle life than conventional RuO2 +Pt/C catalysts in rechargeable Zn-air batteries. It is envisioned that the present work can provide a new avenue for the development of Mott-Schottky electrocatalysts for sustainable energy storage.

Tailoring Interfacial Nanoparticle Organization through Entropy.

The ability to tailor the interfacial behaviors of nanoparticles (NPs) is crucial not only for the design of novel nanostructured materials with superior properties and of interest for many promising applications such as water purification, enhanced oil recovery, and innovative energy transduction, but also for a better insight into many biological systems where nanoscale particles such as proteins or viruses can interact and organize at certain interfaces. As a class of emerging building blocks, Janus NPs consisting of two compartments of different chemistry or polarity are ideal candidates to generate tunable and stable interfacial nanostructures because of the asymmetric nature. However, precise control over such interfacial nanostructures toward a controllable order and even responses to various external stimuli still remains a great challenge as the interfaces do not simply serve as a scaffold but rather induce complex enthalpic and entropic interactions. In this Account, we focus on our efforts on exploiting entropy strategies based on computational design to tailor the spatial distribution and ordering of NPs at the interfaces of various systems. First, we introduce the physical principle of entropic ordering, being the theoretical basis of entropy-directed interfacial self-assembly. The typical types of entropy, which have been harnessed to manipulate the interfacial NP organization, are then summarized, including conformational entropy, shape entropy, and rotational and vibrational entropy. Next, we describe the emerging pathways in the development of novel environmentally responsive systems which involve the use of entropy to access the stimuli-responsive behaviors of interfacial nanostructures. Taking one step further, how molecular architectures can be tailored to tune the entropic contributions to the interfacial self-assembly is demonstrated, through identifying the effects of various intrinsic properties of block segments, such as chain length and stiffness, on entropy-governed precise organization of Janus NPs at block copolymer interfaces. Finally, we detail some key factors for tailoring interfacial organization through entropy. In summary, entropy strategies offer a promising and abundant framework for precisely programming the structural organization of NPs at interfaces. We discuss future directions to signify the framework in tailoring the interfacial organization of NPs. We hope that this Account will promote further efforts toward fundamental research and the wide applications of designed interfacial assemblies in new types of functional nanomaterials and beyond.

Plastic Crystal-to-Crystal Transition of Janus Particles under Shear.

Colloidal Janus spheres in the bulk typically spontaneously assemble into plastic crystalline phases, while particle orientations exhibit glasslike dynamics without long-range order. Through Brownian dynamics simulations, we demonstrate that shear can trigger a phase transition from an isotropic crystal with orientational disorder to an orientationally ordered crystal with lamellae along the shear direction. This nonequilibrium transition is accompanied with the orientational ordering following a nucleation and growth mechanism. By performing a phenomenological extension of free energy analysis, we reveal that the nucleation originates from the orientation fluctuations induced by shear. The growth of the orientationally crystalline cluster is examined to be disklike, captured by developing a lattice model with memoryless state functions. These findings bring new insights into the mechanisms for the ordering transition of anisotropic particles at nonequilibrium states.

Highly-Branched Palladium Nanodandelions: Simple, Fast, and Green Fabrication with Superior Oxygen Reduction Property.

Controllable synthesis of highly-branched metallic structures is of great interest and broad significance for their unique properties of superior conductivity, high porosity, low density, etc., that promote the development of high-efficiency electrocatalysts. Herein, a simple, rapid and green method for the synthesis of highly-branched palladium nanodandelions with flexible ultrafine tentacles and bumpy superficial atomic steps is investigated, without the demand of elevated temperature, seed, template, prolonged reaction time and any organically toxic reducing agent from previously reported highly-branched nanostructures. For the first time, N,N'-methylenebisacrylamide (MBAA) serves as the only additive to simultaneously cover the functions of coordinating agent, reducing agent, and structure-directing agent, facilitating the strategy of intramolecular coordination and self-reduction. Derived from their plentiful ultrafine tentacles, porosity due to the highly-branched structure, and abundant surface atom steps, the Pd nanodandelions exhibit a more positive half-wave of 0.863 V (vs. RHE), optimized specific kinetic activity of 3.0 mA cm-2 at 0.9 V, and better cycle stability with a maintenance of 77.8 % after 20000 s for the oxygen reduction reaction (ORR), when compared to commercial Pd black. The architectural design of highly-branched metallic structures, as well as the smart fabrication strategy, may hold great promise for exploring a variety of functional nanomaterials.

Entropic Effects in Polymer Nanocomposites.

Polymer nanocomposite materials, consisting of a polymer matrix embedded with nanoscale fillers or additives that reinforce the inherent properties of the matrix polymer, play a key role in many industrial applications. Understanding of the relation between thermodynamic interactions and macroscopic morphologies of the composites allow for the optimization of design and mechanical processing. This review article summarizes the recent advancement in various aspects of entropic effects in polymer nanocomposites, and highlights molecular methods used to perform numerical simulations, morphologies and phase behaviors of polymer matrices and fillers, and characteristic parameters that significantly correlate with entropic interactions in polymer nanocomposites. Experimental findings and insight obtained from theories and simulations are combined to understand how the entropic effects are turned into effective interparticle interactions that can be harnessed for tailoring nanostructures of polymer nanocomposites.

Unveiling the Role of tBP-LiTFSI Complexes in Perovskite Solar Cells.

Lead halide-based perovskite materials have been applied as an intrinsic layer for next-generation photovoltaic devices. However, the stability and performance reproducibility of perovskite solar cells (PSCs) needs to be further improved to match that of silicon photovoltaic devices before they can be commercialized. One of the major bottlenecks that hinders the improvement of device stability/reproducibility is the additives in the hole-transport layer, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and 4- tert-butylpyridine (tBP). Despite the positive effects of these hole-transport layer additives, LiTFSI is hygroscopic and can adsorb moisture to accelerate the perovskite decomposition. On the other hand, tBP, the only liquid component in PSCs, which evaporates easily, is corrosive to perovskite materials. Since 2012, the empirical molar ratio 6:1 tBP:LiTFSI has been wildly applied in PSCs without further concerns. In this study, the formation of tBP-LiTFSI complexes at various molar ratios has been discovered and investigated thoroughly. These complexes in PSCs can alleviate the negative effects (decomposition and corrosion) of individual components tBP and LiTFSI while maintaining their positive effects on perovskite materials. Consequently, a minor change in tBP:LiTFSI ratio results in huge influences on the stability of perovskite. Due to the existence of uncomplexed tBP in the 6:1 tBP:LiTFSI mixture, this empirical tBP-LiTFSI molar ratio has been demonstrated not as the ideal ratio in PSCs. Instead, the 4:1 tBP:LiTFSI mixture, in which all components are complexed, shows all positive effects of the hole-transport layer components with dramatically reduced negative effects. It minimizes the hygroscopicity of LiTFSI, while lowering the evaporation speed and corrosive effect of tBP. As a result, the PSCs fabricated with this tBP:LiTFSI ratio have the highest average device efficiency and obviously decreased efficiency variation with enhanced device stability, which is proposed as the golden ratio in PSCs. Our understanding of interactions between hole-transport layer additives and perovskite on a molecular level shows the pathway to further improve the PSCs' stability and performance reproducibility to make them a step closer to large-scale manufacturing.

Mesoscale Graphene-like Honeycomb Mono- and Multilayers Constructed via Self-Assembly of Coclusters.

Honeycomb structure endows graphene with extraordinary properties. But could a honeycomb monolayer superlattice also be generated via self-assembly of colloids or nanoparticles? Here we report the construction of mono- and multilayer molecular films with honeycomb structure that can be regarded as self-assembled artificial graphene (SAAG). We construct fan-shaped molecular building blocks by covalently connecting two kinds of clusters, one polyoxometalate and four polyhedral oligomeric silsesquioxanes. The precise shape control enables these complex molecules to self-assemble into a monolayer 2D honeycomb superlattice that mirrors that of graphene but on the mesoscale. The self-assembly of the SAAG was also reproduced via coarse-grained molecular simulations of a fan-shaped building block. It revealed a hierarchical process and the key role of intermediate states in determining the honeycomb structure. Experimental images also show a diversity of bi- and trilayer stacking modes. The successful creation of SAAG and its stacks opens up prospects for the preparation of novel self-assembled nanomaterials with unique properties.

How Implementation of Entropy in Driving Structural Ordering of Nanoparticles Relates to Assembly Kinetics: Insight into Reaction-Induced Interfacial Assembly of Janus Nanoparticles.

The ability to understand and exploit entropic contributions to ordering transition is of essential importance in the design of self-assembling systems with well-controlled structures. However, much less is known about the role of assembly kinetics in entropy-driven phase behaviors. Here, by combining computer simulations and theoretical analysis, we report that the implementation of entropy in driving phase transition significantly depends on the kinetic process in the reaction-induced self-assembly of newly designed nanoparticle systems. In particular, such systems comprise binary Janus nanoparticles at the fluid-fluid interface and undergo phase transition driven by entropy and controlled by the polymerization reaction initiated from the surfaces of just one component of nanoparticles. Our simulations demonstrate that the competition between the reaction rate and the diffusive dynamics of nanoparticles governs the implementation of entropy in driving the phase transition from randomly mixed phase to intercalated phase in these interfacial nanoparticle mixtures, which thereby results in diverse kinetic pathways. At low reaction rates, the transition exhibits abrupt jump in the mixing parameter, in a similar way to first-order, equilibrium phase transition. Increasing the reaction rate diminishes the jumps until the transitions become continuous, behaving as a second-order-like phase transition, where a critical exponent, characterizing the transition, can be identified. We finally develop an analytical model of the blob theory of polymer chains to complement the simulation results and reveal essential scaling laws of the entropy-driven phase behaviors. In effect, our results allow for further opportunities to amplify the entropic contributions to the materials design via kinetic control.

Optimal Reactivity and Improved Self-Healing Capability of Structurally Dynamic Polymers Grafted on Janus Nanoparticles Governed by Chain Stiffness and Spatial Organization.

Structurally dynamic polymers are recognized as a key potential to revolutionize technologies ranging from design of self-healing materials to numerous biomedical applications. Despite intense research in this area, optimizing reactivity and thereby improving self-healing ability at the most fundamental level pose urgent issue for wider applications of such emerging materials. Here, the authors report the first mechanistic investigation of the fundamental principle for the dependence of reactivity and self-healing capabilities on the properties inherent to dynamic polymers by combining large-scale computer simulation, theoretical analysis, and experimental discussion. The results allow to reveal how chain stiffness and spatial organization regulate reactivity of dynamic polymers grafted on Janus nanoparticles and mechanically mediated reaction in their reverse chemistry, and, particularly, identify that semiflexible dynamic polymers possess the optimal reactivity and self-healing ability. The authors also develop an analytical model of blob theory of polymer chains to complement the simulation results and reveal essential scaling laws for optimal reactivity. The findings offer new insights into the physical mechanism in various systems involving reverse/dynamic chemistry. These studies highlight molecular engineering of polymer architecture and intrinsic property as a versatile strategy in control over the structural responses and functionalities of emerging materials with optimized self-healing capabilities.

Ligand-Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics.

Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on the functionality of attached ligands. Understanding how the ligands interact with the receptors in cell membrane and its further effect on the cellular uptake of dendrimer-like soft nanoparticles is thereby a key issue for their better application in nanomedicine. However, the essential mechanism and detailed kinetics for the ligand-receptor interaction-mediated transmembrane transport of such unconventional nanoparticles remain poorly elucidated. Here, using coarse-grained simulations, we present the very first study of molecular mechanism and kinetics behaviors for the transmembrane transport of dendrimer-like soft nanoparticles conjugated with ligands. A phase diagram of interaction states is constructed through examining ligand densities and membrane tensions that allows us to identify novel endocytosis mechanisms featured by the direct wrapping and the penetration-extraction vesiculation. The results provide an in-depth insight into the diffusivity of receptors and dendrimer in the membrane plane and demonstrate how the ligand density influences receptor diffusion and uptake kinetics. It is interesting to find that the ligand-conjugated dendrimers present superdiffusive behaviors on a membrane, which is revealed to be driven by the random fluctuation dynamics of the membrane. The findings facilitate our understanding of some recent experimental observations and could establish fundamental principles for the future development of such important nanomaterials for widespread nanomedical applications.

Entropy-mediated mechanical response of the interfacial nanoparticle patterning.

The precise organization of nano-objects into well-defined patterns at interfaces is an outstanding challenge in the field of nanocomposites toward technologically important materials and devices. Herein, by means of computer simulations we show novel mechanomutable nanocomposites designed by binary mixtures of tethered Janus nanoparticles at the interface of a binary fluid mixture under mechanical pressure. Our simulations demonstrate that the nanoparticle organization in the systems undergo reversible transition between random state and long-ranged intercalation state, controlled by various structural parameters of the tethered chains and the applied pressure. The dynamical mechanism during the transition is explored through examining the diffusion trajectories of the nanoparticles confined at the interfaces. We provide a theoretical analysis of the lateral pressure induced by the tethered chains, which is fully supported by simulation data and reveals that the compression-induced transition is fundamentally attributed to the entropic effect from the tethered chains. Our study leads to a class of interface-reactive nanomaterials in which the transfer and recovery of interfacial nanopatterning presents precise and tunable mechanical responses.

A Filled-Honeycomb-Structured Crystal Formed by Self-Assembly of a Janus Polyoxometalate-Silsesquioxane (POM-POSS) Co-Cluster.

Clusters with diverse structures and functions have been used to create novel cluster-assembled materials (CAMs). Understanding their self-assembly process is a prerequisite to optimize their structure and function. Herein, two kinds of unlike organo-functionalized inorganic clusters are covalently linked by a short organic tether to form a dumbbell-shaped Janus co-cluster. In a mixed solvent of acetonitrile and water, it self-assembles into a crystal with a honeycomb superstructure constructed by hexagonal close-packed cylinders of the smaller cluster and an orderly arranged framework of the larger cluster. Reconstruction of these structural features via coarse-grained molecular simulations demonstrates that the cluster crystallization and the nanoscale phase separation between the two incompatible clusters synergistically result in the unique nano-architecture. Overall, this work opens up new opportunities for generating novel CAMs for advanced future applications.

Immunoproteasome Subunit Low Molecular Mass Peptide 2 (LMP2) Deficiency Ameliorates LPS/Aß1-42-Induced Neuroinflammation.

Low molecular mass peptide 2 (LMP2) is the ß1i subunit of immunoproteasome (iP) which plays a key role in neuroinflammatory responses, and inhibition of iP exhibits a high neuroprotective action against neurodegenerative diseases. Since neuroinflammation has been shown to be involved in the development and progression of Alzheimer's disease (AD), the aim of this study was to evaluate the anti-inflammatory role of LMP2 deficiency in AD in vivo and in vitro. Here, we found that LMP2 was upregulated in the brains of 5 × FAD and APP/PS1 mice and increased with age in C57/BL6 mice. We showed that the lack of LMP2 significantly decreased NLRP3 expression and downstream cytokine release in microglia, resulting in partially blocking Aß1-42- or LPS-induced inflammation in vivo and in vitro, which ameliorated cognitive deficits in aged rats and D-galactose + Aß1-42-treated rats. These results suggest that LMP2 contributes to the regulation of LPS-or Aß-driven innate immune responses by diminishing NLRP3 expression and clarify that inhibition of iP function may mediate the inflammatory-related cognitive phenotype.