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Chirality, a fundamental design feature at all levels of life organization, has shown great capability in guiding cell‐fate determination and tissue regeneration. Chirality‐directed differentiation programs involve remarkable changes in transcriptional networks, yet whether epigenetic regulatory events are also required is less well understood. Herein, by combining high‐throughput m6A MeRIP sequencing, RIP‐qPCR, and gene modulation techniques, it is demonstrated that biomimetic chiral nanofibrils can bidirectionally regulate wilms tumor 1 associated protein (WTAP)‐mediated m6A RNA methylation to guide macrophages polarization for tissue regeneration. The biomimic chiral nanofibril hydrogels are fabricated using a self‐assembly approach based on C2‐symmetric phenylalanine derivatives. In vitro and in vivo studies indicated that the L‐nanofibrils exhibit a greater propensity to promote M2‐macrophage polarization than D‐nanofibrils, thereby favoring osteogenesis. Then, m6A‐MeRIP sequencing revealed a unique chirality‐dependent m6A methylation level in macrophages, which was gated by a competitive pair of CCM3‐FAK through enantioselectively integrin recognition. L‐nanofibrils considerably suppressed WTAP‐mediated m6A methylation by promoting Itgα3‐FAK expression and paxillin‐driven mechanotransduction, whereas D‐nanofibrils induced WTAP‐mediated m6A methylation by favoring ItgαV‐CCM3 expression and suppressing mechanotransduction. Furthermore, the gain‐of‐function and loss‐of‐function experiments and RIP‐qPCR demonstrate that the WTAP expression could direct macrophage polarization via manipulating the functional molecule B7‐H3 (CD276). Thus, a mechano‐epigenetic mechanism of chirality‐mediated cell‐fate determination is unveiled, which holds remarkable promise in the realm of assisted regenerative material design. [ABSTRACT FROM AUTHOR]

• Four l -phenylalanine derived gelators were synthesized. • Left- and right-handed nanofibers with different sizes were obtained. • The handedness, helical pitch and diameter of the assemblies could be controlled by tuning the central aromatic groups structure. • π-π stacking among the central aromatic rings and H-bonds among the amide groups play vital roles in the formation of the self-assemblies. Constructing chiral supramolecular assemblies with controllable handedness has attracted much attention in materials science, biology and chemistry, owing to their outstanding photophysical properties and novel biological effects. Herein, four gelators derived from l -phenylalanine were synthesized and their gel formation and self-assembled nanostructures were investigated. It was found that the handedness, helical pitch and diameter of these self-assemblies were successfully controlled by tuning the structure of central aromatic groups. Left- and right-handed nanofibers with different dimensions were obtained, showing configuration-regulated assembly behavior. These self-assemblies were further characterized by CD, FTIR, SEM, and UV–vis, and the results suggested that the π-π stacking among the central aromatic rings and hydrogen bonds among the amide groups at the terminals play important roles in the formation of these self-assemblies. [ABSTRACT FROM AUTHOR]

Chiral transcription and enantioselective separation have garnered significant research interests and showed potential for a broad range of practical applications. Here, we present a novel and facile strategy for chiral templating and enantiomers resolution by coating metal-ion-mediated l -phenylalanine derivatives (LPF/M) with graphene oxide (GO) via simply mixing. The LPF/M hydrogels precipitate from the liquid by encapsulation of GO through coordination interactions and hydrogen bonds, making heterogeneous transfer and separation possible. The chirality inversion of the internal LPF/M nanostructure could be triggered by different addition of metal ions, which further provides means for controlled chiral transfer of guest molecules on the outer GO surfaces as demonstrated in the transcription of thioflavin T (ThT) and 3-aminopyridine (AP) at the supramolecular level. Changing the metal ions also provides control over enantiomer selectivity with outstanding efficiency and reproducibility, as revealed by the separation of racemic mixtures of phenylanine (>98%), lysine (>96%), and histidine (>97%). In addition, the resultant hybrid materials exhibit excellent environmental stability and reusability (more than 20 times) with significant separation efficiency. More importantly, the GO-coated LPF/M could determine the enantiomeric composition of various chiral substrates. The proposed strategy opens up a promising avenue for practical chiral separation application. Image 1 [ABSTRACT FROM AUTHOR]

Abstract: Butterfly wing skeleton is a widely used hard-template in recent years for fabricating photonic crystal structures. However, the smallest construction units for the most species of butterflies are commonly larger than ∼50nm, which greatly hinders their applications in designing much smaller functional parts down to real “nano scale”. This work indicates, however, that hollow ZrO2 nanowires with ∼2.4μm in length, ∼35nm in diameter and ∼12nm in wall thickness can be synthesized via the selection of suitable butterfly bio-templates followed by heat processing. Especially, the successful fabrication of these naturally cross-linked ZrO2 nanotubes suggests a new optional approach in fabricating assembled nano systems. [Copyright &y& Elsevier]

Abstract: A sonochemical method was introduced to synthesize SnO2 nanoparticles in the pores of mesoporous carbon without any other agents. The nitrogen adsorption measurement and transmission electron microscopy results revealed that the SnO2 nanoparticles with the average particle size of around 10nm were homogeneous distribution in the matrix. The aggregation of SnO2 was hindered by the three-dimensioned porous frameworks, resulting in a relatively large surface area of 362m2 g−1, which is beneficial for lithium-ion storage in batteries. The resultant composites with 43% SnO2 exhibited a high reversible capacity of 200mAhg−1 even after 300 cycles, which is 186% higher than that of the initial mesoporous carbon matrix. This strategy is expected to incorporate other functional nanoparticles inside mesoporous carbon for many applications. [Copyright &y& Elsevier]

Abstract: Using ultrasonication we succeed in a controlled incorporation of TiO2 nanoparticles on the graphene layers homogeneously in a few hours. The average size of the TiO2 nanoparticles was controlled at around 4–5nm on the sheets without using any surfactant, which is attributed to the pyrolysis and condensation of the dissolved TiCl4 into TiO2 by ultrasonic waves. The photocatalytic activity of the resultant graphene–TiO2 composites containing 25wt.% TiO2 is better than that of commercial pure TiO2. This is partly due to the extremely small size of the TiO2 nanoparticles and partly due to the graphene–TiO2 composite structure consisting of homogeneous dispersion of crystalline TiO2 nanoparticles on the graphene sheets. As the graphene in the composites has a very good contact with the TiO2 nanoparticles it enhances the photo-electron conversion of TiO2 by reducing the recombination of photo-generated electron–hole pairs. [Copyright &y& Elsevier]

Understanding the influence of the molecular architecture on the self-assembly and properties of supramolecular organogel materials is necessary for elucidating the structure-property relationship. Although conventional gelation motifs (e.g., amides, long alkyl side chains, and steroidal groups) have been considered essential for the effective gel process, the lack of gelation motifs hinders the development and self-assembly of non-conventional gelators. Herein, coumarin-based derivatives (1–12) without a conventional gelation motif were designed and synthesised by inducing a one-step reaction that entails fine-tuning the molecular architecture, particularly the position of the nitrogen atom in pyridine, the substitution position of pyridine, and the placement of methyl in coumarin. A previous gelation study revealed that 7-substituted coumarin-based derivatives with methyl (1–4) are highly efficient gelators that can self-assemble to form different nanostructures, and gelate various polar protic solvents. After small-scale modification of the molecular structures, Derivatives 5–6 self-assembled and only formed gels in the alcohol phase, whereas gels were not formed by Derivatives 7–12 in various solvents. Interestingly, the fluorescence property of these gels was significantly influenced by the dielectric constant and viscosity of the solvent. Furthermore, differences in the self-assembly and fluorescence of gelators were numerically investigated by performing density functional theory calculations and all-atom molecular dynamics simulations. This study provides a foundation for the development of a low-cost, non-conventional supramolecular organogel system with minimal building blocks, a modifiable self-assembly pathway, and alterable properties. [ABSTRACT FROM AUTHOR]

How to maintain high catalytic activity and stability in the process of biocatalysis is crucial, inspiring strategies to construct an appropriate catalytic microenvironment. Considering the lipase's inherent chirality and the necessity for a delicate hydrophilic-hydrophobic equilibrium, we crafted a chiral, nonaqueous catalytic microenvironment via the in situ coassembly of Boc-F L F L -NHNH 2 (Bfl) and lipase. Benefiting from the chirality and distinct Bfl-lipase interactions, the lipase@Bfl supramolecular hybrid amplifies biological functionalities and can serve as a versatile and highly efficient catalyst. Kinetic investigations and molecular docking simulations uncover the strong lipase-substrate affinity and lipase-Bfl interactions, explaining the enhanced biological effects, catalytic activity, and stability. Our study establishes a suitable microenvironment to address the chirality and hydrophobicity during catalysis and highlights the potential of artificial chiral scaffolds and catalytic medium for enhancing lipase activity.

Amino acid-derived self-assembled nanofibers comprising supramolecular chiral hydrogels with unique physiochemical characteristics are highly demanded biomaterials for various biological applications. However, their narrow functionality often limits practical use, necessitating the development of biomaterials with multiple features within a single system. Herein, chiral co-assembled hybrid hydrogel systems termed LPH-EGCG and DPH-EGCG were constructed by co-assembling L/DPFEG gelators with epigallocatechin gallate (EGCG) followed by cross-linking with polyvinyl alcohol (PVA) and hyaluronic acid (HA). The developed hybrid hydrogels exhibit superior mechanical strength, self-healing capabilities, and adhesive properties, owing to synergistic non-covalent interactions. Integrating hydrophilic polymers enhances the system's capacity to demonstrate favorable swelling characteristics. Furthermore, the introduction of EGCG facilitated the hybrid gels to display notable antibacterial properties against both Gram-positive and Gram-negative bacterial strains, alongside showcasing strong antioxidant capabilities. In vitro investigation demonstrated enhanced cell adhesion and migration with the LPH-EGCG system in comparison to DPH-EGCG, thus emphasizing the promising prospects of these hybrid hydrogels in advanced tissue engineering applications.

Tumor-derived exosomes (TDEs) induced extracellular microenvironment has recently been validated to be critical for tumor progression and metastasis, however, remodeling it for oncotherapy still remains a major challenge due to difficulty in regulation of TDEs secretion. Herein, the supramolecular chiral nanofibers, composed of L/D -phenylalanine derivates (L/D-Phe) and linear hyaluronic acid (HA), are successfully employed to construct TDEs induced anti-tumor extracellular microenvironment. The left-handed L-Phe @HA nanofibers significantly inhibit TDEs secretion into extracellular microenvironment, which results in suppression of tumor proliferation and metastasis in vitro and vivo. Biological assays and theoretical modeling reveal that these results are mainly attributed to strong adsorption of the key exosomes transporters (Ras-related protein Rab-27A and synaptosome-associated protein 23) on left-handed L-Phe @HA nanofibers via enhanced stereoselective interaction, leading to degradation and phosphorylated dropping of exosomes transporters. Subsequently, transfer function of exosomes transporters is limited, which causes remarkable inhibition of TDEs secretion. These findings provide a promising novel insight of chiral functional materials to establish an anti-tumor extracellular microenvironment via regulation of TDEs secretion., (© 2024 Wiley‐VCH GmbH.)

Although chemotherapy has the potential to induce tumor immunotherapy via immunogenic cell death (ICD) effects, how to control the intensity of the immune responses still deserves further exploration. Herein, a controllable ultrasound (US)-triggered chemo-immunotherapy nanoagonist is successfully synthesized by utilizing the pH and reactive oxygen species (ROS) dual-responsive PEG-polyphenol to assemble sonosensitizer zinc oxide (ZnO) and doxorubicin (DOX). The PZnO@DOX nanoparticles have an intelligent disassembly to release DOX and zinc ions in acidic pH conditions. Notably, US irradiation generates ROS by sonodynamic therapy and accelerates the drug release process. Interestingly, after the PZnO@DOX+US treatment, the injured cells release double-stranded DNA (dsDNA) from the nucleus and mitochondria into the cytosol. Subsequently, both the dsDNA and zinc ions bind with cyclic GMP-AMP synthase and activate the stimulator of interferon genes (STING) pathway, resulting in the dendritic cell maturation, ultimately promoting DOX-induced ICD effects and antigen-specific T cell immunity. Therefore, chemotherapy-induced immune responses can be modulated by non-invasive control of US., (© 2024 Wiley‐VCH GmbH.)

Critical-size defects (CSDs) of the craniofacial bones cause aesthetic and functional complications that seriously impact the quality of life. The transplantation of human dental pulp stem cells (hDPSCs) is a promising strategy for bone tissue engineering. Chirality is commonly observed in natural biomolecules, yet its effect on stem cell differentiation is seldom studied, and little is known about the underlying mechanism. In this study, supramolecular chiral hydrogels were constructed using L/ d -phenylalanine (L/D-Phe) derivatives. The results of alkaline phosphatase expression analysis, alizarin red S assay, as well as quantitative real-time polymerase chain reaction and western blot analyses suggest that right-handed D-Phe hydrogel fibers significantly promoted osteogenic differentiation of hDPSCs. A rat model of calvarial defects was created to investigate the regulation of chiral nanofibers on the osteogenic differentiation of hDPSCs in vivo . The results of the animal experiment demonstrated that the D-Phe group exhibited greater and faster bone formation on hDPSCs. The results of RNA sequencing, vinculin immunofluorescence staining, a calcium fluorescence probe assay, and western blot analysis indicated that L-Phe significantly promoted adhesion of hDPSCs, while D-Phe nanofibers enhanced osteogenic differentiation of hDPSCs by facilitating calcium entry into cells and activate the MAPK pathway. These results of chirality-dependent osteogenic differentiation offer a novel therapeutic strategy for the treatment of CSDs by optimising the differentiation of hDPSCs into chiral nanofibers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Tissue engineering (TE), as a new interdisciplinary discipline, aims to develop biological substitutes for repairing damaged tissues and organs. For the success of tissue regeneration, such biomaterials need to support the physiological activities of cells and allow the growth and maturation of tissues. Naturally, this regulation is achieved through the dynamic remodeling of the extracellular matrix (ECM) of cells. In recent years, chiral supramolecular hydrogels have shown higher application potential in the TE field than traditional polymer hydrogels due to their dynamic noncovalent interactions, adjustable self-assembly structure, and good biocompatibility. These advantages make it possible to construct hydrogels under physiological conditions with structure and function similar to those of the natural ECM. Meanwhile, the chiral characteristics of hydrogels play an important role in regulating cellular activities such as differentiation, adhesion, and proliferation, which is beneficial for tissue formation. In this review, a brief introduction is presented to highlight the importance of chiral fiber supramolecular hydrogels for TE at first. Afterward, the considerations for chiral supramolecular hydrogel design, as well as the influence of external stimuli on chiral hydrogel construction, are discussed. Finally, the potential application prospects of these materials in TE and the significant contribution made by our group in this field are summarized. This review not only helps to reveal the importance of chiral properties in TE but also provides new strategies for TE research based on chiral bionic microenvironments. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Biology-Inspired Nanomaterials > Peptide-Based Structures Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2022 Wiley Periodicals LLC.)

Because any perturbation in the number of oxidation sites associated with the polymeric backbone can cause changes in the electrical properties, the stability of electrical properties has strongly prevented the wide adoption of most conducting polymers for commercialization, e.g., polyanilines (PANI). Herein, we showed that aniline dimers (AD) had more stable conductivity during redox due to their determinately separate oxidization or reduction units. Instead of intramolecular charge transfer as PANI, AD could serve as effective transfer units to facilitate intermolecular charge-carrier transmission due to low band-gap formation induced by the J-aggregation of AD, ensuring efficient conductivity. Typically, the electrical properties of AD-derived materials will still be stable after 10,000 redox cycles under a high operating voltage, far surpassing PANI under equivalent conditions. Meanwhile, the AD-derived materials could act as effective conducting and sensing layers with good stability. This approach opened an avenue for improving the stability of conductive polymers., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Cancer recurrence remains a major challenge after primary tumor excision, and the inflammation of tumor-caused wounds can hinder wound healing and potentially promote tumor growth. Herein, a chiral L-phenylalanine-based (LPFEG) supramolecular hydrogel system encapsulated with polydopamine nanoparticles (PDA-NPs) has been developed in order to prevent tumor relapse after surgery and promote wound repair. PDA-NPs allow for near-infrared (NIR) light-triggered photothermal therapy, especially, it can scavenge free radicals in the surgical wound. LPFEG can mimic native extracellular matrix (ECM) structure to create a chiral microenvironment that enhances fibroblast adhesion, proliferation, and new tissue regeneration. With anticancer drug doxorubicin (DOX) loaded into the composite hydrogel, the antitumor effect is significantly enhanced by the integration of chemo-photothermal therapy both in vitro and in vivo. The PDA-based chiral supramolecular composite hydrogel as an effective postoperative adjuvant possesses promising applicable prospects in inhibiting tumor recurrence and accelerating wound healing after operation. STATEMENT OF SIGNIFICANCE: After primary tumor excision, cancer recurrence remains a severe concern, and the inflammation induced by tumor-related wounds can delay wound healing. Herein, we designed a chiral L-phenylalanine-based (LPFEG) supramolecular hydrogel platform that was co-assembled with polydopamine nanoparticles (PDA-NPs). Among them, PDA-NPs can offer photothermal therapy and scavenge free radicals in surgical wounds. LPFEG can create a chiral microenvironment that promotes fibroblast adhesion, proliferation, and new tissue regeneration. Furthermore, with anticancer drug doxorubicin (DOX) loaded into the composite hydrogel, the antitumor effect is considerably boosted. Therefore, the PDA-based chiral supramolecular hydrogel shows high application potential as a postoperative adjuvant in preventing tumor relapse as well as accelerating wound healing after surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/ d - phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)