Breaking of Lateral Symmetry in Two-Dimensional Crystallization-Driven Self-Assembly on a Surface.

Symmetry breaking is prevalent in nature and provides distinctive access to hierarchical structures for artificial materials. However, it is rarely explored in two-dimensional (2D) entities, especially for lateral asymmetry. Herein, we describe a unique symmetry breaking process in surface-initiated 2D living crystallization-driven self-assembly. The 2D epitaxial growth occurs only at one lateral side of the immobilized cylindrical micelle seeds, accessing unilateral platelets with the yield increasing with the seed length, the growth temperature, and poly(2-vinylpyridine) corona length (maximum = 92%). Generally, the tilted immobilization of seeds blocks one lateral side and triggers the lateral symmetry breaking, where the intensity and spatial arrangement of seed-surface interactions dictate the regulation. Segmented unilateral platelets with segmented corona regions are further fabricated with the addition of different blended unimers. Remarkably, discrete slope-like and dense blade-like platelet arrays grow off the surface when seeds are compactly aligned either with spherical micelles or themselves. This strategy provides nanoscale insights into the symmetry breaking in long-range self-assembly and would be promising for the design of innovative colloids and smart surfaces.

ACETYL-COA PRODUCTION BY OCTANOIC ACID ALLEVIATES ACUTE COMPARTMENT SYNDROME-INDUCED SKELETAL MUSCLE INJURY THROUGH REGULATING MITOPHAGY.

ABSTRACT: Background: Treatment of acute compartment syndrome (ACS)-induced skeletal muscle injury remains a challenge. Previous studies have shown that octanoic acid is a promising treatment for ACS owing to its potential ability to regulate metabolic/epigenetic pathways in ischemic injury. The present study was designed to investigate the efficacy and underlying mechanism of octanoic acid in ACS-induced skeletal muscle injury. Methods: In this study, we established a saline infusion ACS rat model. Subsequently, we assessed the protective effects of sodium octanoate (NaO, sodium salt of octanoic acid) on ACS-induced skeletal muscle injury. Afterward, the level of acetyl-coenzyme A and histone acetylation in the skeletal muscle tissue were quantified. Moreover, we investigated the activation of the AMP-activated protein kinas pathway and the occurrence of mitophagy in the skeletal muscle tissue. Lastly, we scrutinized the expression of proteins associated with mitochondrial dynamics in the skeletal muscle tissue. Results: The administration of NaO attenuated muscle inflammation, alleviating oxidative stress and muscle edema. Moreover, NaO treatment enhanced muscle blood perfusion, leading to the inhibition of apoptosis-related skeletal muscle cell death after ACS. In addition, NaO demonstrated the ability to halt skeletal muscle fibrosis and enhance the functional recovery of muscle post-ACS. Further analysis indicates that NaO treatment increases the acetyl-CoA level in muscle and the process of histone acetylation by acetyl-CoA. Lastly, we found NaO treatment exerts a stimulatory impact on the activation of the AMPK pathway, thus promoting mitophagy and improving mitochondrial dynamics. Conclusion: Our findings indicate that octanoic acid may ameliorate skeletal muscle injury induced by ACS. Its protective effects may be attributed to the promotion of acetyl-CoA synthesis and histone acetylation within the muscular tissue, as well as its activation of the AMPK-related mitophagy pathway.

Extracellular vesicles derived from human ESC-MSCs target macrophage and promote anti-inflammation process, angiogenesis, and functional recovery in ACS-induced severe skeletal muscle injury.

BACKGROUND: Acute compartment syndrome (ACS) is one of the most common complications of musculoskeletal injury, leading to the necrosis and demise of skeletal muscle cells. Our previous study showed that embryonic stem cells-derived mesenchymal stem cells (ESC-MSCs) are novel therapeutics in ACS treatment. As extracellular vesicles (EVs) are rapidly gaining attention as cell-free therapeutics that have advantages over parental stem cells, the therapeutic potential and mechanisms of EVs from ESC-MSCs on ACS need to be explored. METHOD: In the present study, we examined the protective effects in the experimental ACS rat model and investigated the role of macrophages in mediating these effects. Next, we used transcriptome sequencing to explore the mechanisms by which ESC-MSC-EVs regulate macrophage polarization. Furthermore, miRNA sequencing was performed on ESC-MSC-EVs to identify miRNA candidates associated with macrophage polarization. RESULTS: We found that intravenous administration of ESC-MSC-EVs, given at the time of fasciotomy, significantly promotes the anti-inflammation process, angiogenesis, and functional recovery of muscle in ACS. The beneficial effects were associated with ESC-MSC-EVs affecting macrophage polarization by delivering various miRNAs which regulate NF-κB, JAK/STAT, and PI3K/AKT pathways. Our data further illustrate that ESC-MSC-EVs mainly modulate macrophage polarization via the miR-21/PTEN, miR-320a/PTEN, miR-423/NLRP3, miR-100/mTOR, and miR-26a/TLR3 axes. CONCLUSION: Together, our results demonstrated the beneficial effects of ESC-MSC-EVs in ACS, wherein the miRNAs present in ESC-MSC-EVs regulate the polarization of macrophages.

A Nanotherapy of Octanoic Acid Ameliorates Cardiac Arrest/Cardiopulmonary Resuscitation-Induced Brain Injury via RVG29- and Neutrophil Membrane-Mediated Injury Relay Targeting.

Treatment of cardiac arrest/cardiopulmonary resuscitation (CA/CPR)-induced brain injury remains a challenging issue without viable therapeutic options. Octanoic acid (OA), a lipid oil that is mainly metabolized in the astrocytes of the brain, is a promising treatment for this type of injury owing to its potential functions against oxidative stress, apoptosis, inflammation, and ability to stabilize mitochondria. However, the application of OA is strictly limited by its short half-life and low available concentration in the target organ. Herein, based on our previous research, an OA-based nanotherapy coated with a neutrophil membrane highly expressing RVG29, RVG29-H-NPOA, was successfully constructed by computer simulation-guided supramolecular assembly of polyethylenimine and OA. The in vitro and in vivo experiments showed that RVG29-H-NPOA could target and be distributed in the injured brain focus via the relay-targeted delivery mediated by RVG29-induced blood-brain barrier (BBB) penetration and neutrophil membrane protein-induced BBB binding and injury targeting. This results in enhancements of the antioxidant, antiapoptotic, mitochondrial stability-promoting and anti-inflammatory effects of OA and exhibited systematic alleviation of astrocyte injury, neuronal damage, and inflammatory response in the brain. Due to their systematic intervention in multiple pathological processes, RVG29-H-NPOA significantly increased the 24 h survival rate of CA/CPR model rats from 40% to 100% and significantly improved their neurological functions. Thus, RVG29-H-NPOA are expected to be a promising therapeutic for the treatment of CA/CPR-induced brain injury.

Soft nanobrush-directed multifunctional MOF nanoarrays.

Controlled growth of well-oriented metal-organic framework nanoarrays on requisite surfaces is of prominent significance for a broad range of applications such as catalysis, sensing, optics and electronics. Herein, we develop a highly flexible soft nanobrush-directed synthesis approach for precise in situ fabrication of MOF nanoarrays on diverse substrates. The soft nanobrushes are constructed via surface-initiated living crystallization-driven self-assembly and their active poly(2-vinylpyridine) corona captures abundant metal cations through coordination interactions. This allows the rapid heterogeneous growth of MOF nanoparticles and the subsequent formation of MIL-100 (Fe), HKUST-1 and CUT-8 (Cu) nanoarrays with tailored heights of 220~1100 nm on silicon wafer, Ni foam and ceramic tube. Auxiliary functional components including metal oxygen clusters and precious metal nanoparticles can be readily incorporated to finely fabricate hybrid structures with synergistic features. Remarkably, the MIL-100 (Fe) nanoarrays doped with Keggin H3PMo10V2O40 dramatically boost formaldehyde selectivity up to 92.8% in catalytic oxidation of methanol. Moreover, the HKUST-1 nanoarrays decorated with Pt nanoparticles show exceptional sensitivity to H2S with a ppb-level detection limit.

A chronotherapeutics-applicable multi-target therapeutics based on AI: Example of therapeutic hypothermia.

Nowadays, the complexity of disease mechanisms and the inadequacy of single-target therapies in restoring the biological system have inevitably instigated the strategy of multi-target therapeutics with the analysis of each target individually. However, it is not suitable for dealing with the conflicts between targets or between drugs. With the release of high-precision protein structure prediction artificial intelligence, large-scale high-precision protein structure prediction and docking have become possible. In this article, we propose a multi-target drug discovery method by the example of therapeutic hypothermia (TH). First, we performed protein structure prediction for all protein targets of each group by AlphaFold2 and RoseTTAFold. Then, QuickVina 2 is used for molecular docking between the proteins and drugs. After docking, we use PageRank to rank single drugs and drug combinations of each group. The ePharmaLib was used for predicting the side effect targets. Given the differences in the weights of different targets, the method can effectively avoid inhibiting beneficial proteins while inhibiting harmful proteins. So it could minimize the conflicts between different doses and be friendly to chronotherapeutics. Besides, this method also has potential in precision medicine for its high compatibility with bioinformatics and promotes the development of pharmacogenomics and bioinfo-pharmacology.

Embryonic stem cell-derived mesenchymal stem cells alleviate skeletal muscle injury induced by acute compartment syndrome.

BACKGROUND: Acute compartment syndrome (ACS), a well-known complication of musculoskeletal injury, results in muscle necrosis and cell death. Embryonic stem cell-derived mesenchymal stem cells (ESC-MSCs) have been shown to be a promising therapy for ACS. However, their effectiveness and potentially protective mechanism remain unknown. The present study was designed to investigate the efficacy and underlying mechanism of ESC-MSCs in ACS-induced skeletal muscle injury. METHOD: A total of 168 male Sprague-Dawley (SD) rats underwent 2 h of intracompartmental pressure elevation by saline infusion into the anterior compartment of the left hindlimb to establish the ACS model. ESC-MSCs were differentiated from the human embryonic stem cell (ESC) line H9. A dose of 1.2 × 106 of ESC-MSCs was intravenously injected during fasciotomy. Post-ACS assessments included skeletal edema index, serum indicators, histological analysis, apoptosis, fibrosis, regeneration, and functional recovery of skeletal muscle. Then, fluorescence microscopy was used to observe the distribution of labeled ESC-MSCs in vivo, and western blotting and immunofluorescence analyses were performed to examine macrophages infiltration in skeletal muscle. Finally, we used liposomal clodronate to deplete macrophages and reassess skeletal muscle injury in response to ESC-MSC therapy. RESULT: ESC-MSCs significantly reduced systemic inflammatory responses, ACS-induced skeletal muscle edema, and cell apoptosis. In addition, ESC-MSCs inhibited skeletal muscle fibrosis and increased regeneration and functional recovery of skeletal muscle after ACS. The beneficial effects of ESC-MSCs on ACS-induced skeletal muscle injury were accompanied by a decrease in CD86-positive M1 macrophage polarization and an increase in CD206-positive M2 macrophage polarization. After depleting macrophages with liposomal clodronate, the beneficial effects of ESC-MSCs were attenuated. CONCLUSION: Our findings suggest that embryonic stem cell-derived mesenchymal stem cells infusion could effectively alleviate ACS-induced skeletal muscle injury, in which the beneficial effects were related to the regulation of macrophages polarization.

Lateral Gradient Ambidextrous Optical Reflection in Self-Organized Left-Handed Chiral Nematic Cellulose Nanocrystals Films.

Artificial photonic materials displaying ordered reflected color patterns are desirable in the field of photonic technologies, however, it is challenging to realize. Here we present that self-assembly of cellulose nanocrystals (CNC) in a tilted cuvette leads to the formation of rainbow color CNC films. We show that the self-organized CNC films enable simultaneous reflection of left-handed circularly polarized (LCP) and right-handed circularly polarized (RCP) light with lateral gradient transmittance ratio (LCP/RCP: 8.7-0.9) and the maximum reflectance value up to ca. 72%. This unique ambidextrous optical reflection arises from left-handed chiral photonic architectures with lateral gradient photonic bandgaps and nematic-like defects at the film-substrate interface and between left-handed photonic bandgap layers acting as a half-wavelength retarder. We demonstrate that the tilted angle self-assembly method provides a feasible step toward color patterning of CNC-based photonic films capable of ambidextrous optical reflection.

Endowing Zeolite LTA Superballs with the Ability to Manipulate Light in Multiple Ways.

Advances in zeolites research emerging from interdisciplinary efforts have opened new opportunities beyond conventional applications. Colloids drive much current research owing to their distinct collective behaviors, but so far, using zeolites as a colloidal building block to construct ordered superstructures remains unexplored. Herein we show that self-assembly of colloidal zeolite LTA superball (ZAS) by tilted-angle sedimentation forms macroscopic films with micro-mesoporosity and 3D long-range periodicity featuring a photonic band gap (PBG) that is tunable through the superball geometry and responds reversibly to chemical vapors. Remarkably, self-assembly of ZAS at elevated temperature forms 3D chiral photonic crystals that enable negative circular dichroism, selective reflection of right-handed circularly polarized (CP) light and left-handed CP luminescence based on PBG. We present a novel class of functional colloids and zeolite-based photonic crystals with the ability to manipulate light in several ways.

Synergistic Chemical Synthesis and Self-Assembly Lead to Three-Dimensional b-Oriented MFI Superstructures with Selective Adsorption and Luminescence Properties.

Higher-order organization of inorganic nanoparticles with hierarchical architectures and tailored functionality is crucial in the nanofabrication of advanced materials. Here we demonstrate that three-dimensional b-oriented MFI superstructures can be organized by synergistic chemical synthesis and self-assembly. The organization is accomplished by vapor treatment of tetrapropylammonium hydroxide (TPAOH)-coated inorganic/bacterial cellulose scaffolds. TPA+ acts to direct nucleation and to mediate crystal morphology leading to oriented assembly of MFI crystals along crystallographic b-axis, whereas bacterial cellulose holds the oriented assembly together forming three-dimensional superstructures with macroporosity. Self-supporting monoliths of the macroporous MFI show outstanding selective adsorption for para-xylene and high adsorption capacity for volatile organic compounds. Incorporating luminescent molecules imparts the macroporous monoliths the new property of adsorption tunable luminescence that may act as an optical sensor indicating the level of adsorption. The current work opens a novel space for rational organization of hierarchical materials with tailored architectures and multifunctionality.

Hierarchical TiO2/C nanocomposite monoliths with a robust scaffolding architecture, mesopore-macropore network and TiO2-C heterostructure for high-performance lithium ion batteries.

Engineering hierarchical structures of electrode materials is a powerful strategy for optimizing the electrochemical performance of an anode material for lithium-ion batteries (LIBs). Herein, we report the fabrication of hierarchical TiO2/C nanocomposite monoliths by mediated mineralization and carbonization using bacterial cellulose (BC) as a scaffolding template as well as a carbon source. TiO2/C has a robust scaffolding architecture, a mesopore-macropore network and TiO2-C heterostructure. TiO2/C-500, obtained by calcination at 500 °C in nitrogen, contains an anatase TiO2-C heterostructure with a specific surface area of 66.5 m(2) g(-1). When evaluated as an anode material at 0.5 C, TiO2/C-500 exhibits a high and reversible lithium storage capacity of 188 mA h g(-1), an excellent initial capacity of 283 mA h g(-1), a long cycle life with a 94% coulombic efficiency preserved after 200 cycles, and a very low charge transfer resistance. The superior electrochemical performance of TiO2/C-500 is attributed to the synergistic effect of high electrical conductivity, anatase TiO2-C heterostructure, mesopore-macropore network and robust scaffolding architecture. The current material strategy affords a general approach for the design of complex inorganic nanocomposites with structural stability, and tunable and interconnected hierarchical porosity that may lead to the next generation of electrochemical supercapacitors with high energy efficiency and superior power density.

A bioscaffolding strategy for hierarchical zeolites with a nanotube-trimodal network.

Hierarchical zeolite monoliths with multimodal porosity are of paramount importance as they open up new horizons for advanced applications. So far, hierarchical zeolites based on nanotube scaffolds have never been reported. Inspired by the organization of biominerals, we have developed a novel precursor scaffolding-solid phase crystallization strategy for hierarchical zeolites with a unique nanotube scaffolding architecture and nanotube-trimodal network, where biomolecular self-assembly (BSA) provides a scaffolding blueprint. By vapor-treating Sil-1 seeded precursor scaffolds, zeolite MFI nanotube scaffolds are self-generated, during which evolution phenomena such as segmented voids and solid bridges are observed, in agreement with the Kirkendall effect in a solid-phase crystallization system. The nanotube walls are made of intergrown single crystals rendering good mechanical stability. The inner diameter of the nanotube is tunable between 30 and 90 nm by varying the thickness of the precursor layers. Macropores enclosed by cross-linked nanotubes can be modulated by the choice of BSA. Narrow mesopores are formed by intergrown nanocrystals. Hierarchical ZSM-5 monoliths with nanotube (90 nm), micropore (0.55 nm), mesopore (2 nm) and macropore (700 nm) exhibit superior catalytic performance in the methanol-to-hydrocarbon (MTH) conversion compared to conventional ZSM-5. BSA remains intact after crystallization, allowing a higher level of organization and functionalization of the zeolite nanotube scaffolds. The current work may afford a versatile strategy for hierarchical zeolite monoliths with nanotube scaffolding architectures and a nanotube-multimodal network leading to self-supporting and active zeolite catalysts, and for applications beyond.