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Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects (15 mm in rats and 25 mm in humans), which can be improved by a beneficial intraluminal microenvironment. However, individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves. Herein, an aligned fibrin/functionalized self-assembling peptide (AFG/fSAP) interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly. The hydrogel possesses an aligned structure, high water content, appropriate mechanical properties and suitable biodegradation capabilities for nerve repair, which enhances the alignment and neurotrophin secretion of primary Schwann cells (SCs) in vitro, and successfully bridges a 15-mm sciatic nerve gap in rats in vivo. The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles. The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts. Moreover, the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve. Altogether, the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation., Graphical abstract Image 1, Highlights • A novel aligned interpenetrating nanofiber hydrogel is first constructed for peripheral nerve regeneration. • The aligned hydrogel presents synergistic topographical and biochemical cues for peripheral nerve regeneration. • Nerve conduits filled with the aligned hydrogel can repair the long-distance sciatic nerve defects in 12 weeks. • The function recovery facilitated by the aligned hydrogel is comparable with that of autografts. • The aligned hydrogel upregulates regeneration-related genes and activates the PI3K/Akt and MAPK signaling pathways.

Facial nerves are fragile and easily injured, for example, by traffic accidents or operations. Facial nerve injury drastically reduces the quality of life in affected patients, and its treatment presents clinical challenges. A promising therapeutic strategy includes nerve conduits with appropriate fillers capable of guiding nerve regeneration. In this study, a three-dimensional hierarchically aligned fibrin nanofiber hydrogel (AFG) assembled via electrospinning and molecular self-assembly was first used to mimic the architecture of the native fibrin cable, which is similar to the nerve extracellular matrix (ECM). AFG as a substrate in chitosan tubes (CST) was used to bridge a 7 mm-long gap in a rabbit buccal branch facial nerve defect model. The results showed that AFG and CST showed good compatibility to support the adhesion, activity, and proliferation of Schwann cells (SCs). Further morphological, histological, and functional analyses demonstrated that the regenerative outcome of AFG-prefilled CST was close to that of autologous nerve grafts and superior to that of CST alone or CSTs prefilled with random fibrin nanofiber hydrogel (RFG), which indicated that AFG-prefilled CST markedly improved axonal regeneration with enhanced remyelination and functional recovery, thus showing great potential for clinical application for facial nerve regeneration treatments.

The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration. Recently, using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention. Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials. In this study, we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ (RGI) and KLTWQELYQLKYKGI (KLT) to construct an artificial neurovascular microenvironment. The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma (PC12) cells and tube-like structures formation of human umbilical vein endothelial cells (HUVECs) in vitro, and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model. Using indirect co-culture models, we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs. When the two cells types were directly co-cultured on the dual-functionalized peptide hydrogel, the efficiency of cell-cell communication was enhanced, which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology, and HUVECs tube-like structure formation. In summary, the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Organic smart fluorophores (OSFs) are highly desirable over the past decades because of their potential applications in advanced photonic devices. However, it is still difficult and challenging to obtain such materials with tunable photophysical properties and high emission efficiency based on robust construction strategies. Therefore, we proposed a simple and efficient strategy for constructing OSFs by balancing the competition between intermolecular interactions and external stimuli via molecular structure design. In this work, four pyrene derivatives (T1-Py, T4-Py, T12-Py, and S12-Py) with tunable stimuli-responsive properties were designed and synthesized. The tunable intermolecular interactions in solution states were successfully demonstrated by the molecular structure and solution concentration-dependent luminescence properties. The effect of alkyl chain length on molecular packing in solid states was investigated by polarized optical microscopy and powder and single-crystal X-ray diffraction; the results show that with the increase in molecular chain length, the molecular packing of the compounds gradually changed from π-π stacked compact mode to X-crossing stacked loose mode, which leads to different stimuli-responsive phenomena of these compounds. The strategy provided herein facilitates the construction of multistimuli-responsive (thermochromism, mechanochromism, and vapochromism) OSFs with adjustable emission color. Harnessing the heat-responsive luminescence properties and great solubility of T12-Py, the optical information anticounterfeiting based on temperature was demonstrated by printing different concentrations of T12-Py solution on filter papers. Much more, this research may provide broad implications for the design of organic smart materials based on intermolecular interactions.

In this study, we recruited chitosan (CS) both for selenium nanoparticles (SeNPs) synthesis and for the development of a thermoresponsive nanocomposite hydrogel with the addition of glycerol phosphate (GP). Considering that SeNPs are toxic at high concentrations, five different ingredients of the nanocomposite hydrogel system with low concentrations of SeNPs (1.25-20 μg/mL) were prepared. The gelation conditions, structural characteristics, and mechanical properties of SeNPs-loaded thermosensitive CS/GP hydrogels were investigated. We also evaluated their antioxidizing activities and biocompatibility of the CS/GP/SeNPs hydrogels. Our study demonstrated that the incorporation of SeNPs in the hydrogel improved its mechanical properties, antioxidant activity, and degree of swelling. According to the properties of SeNPs and CS/GP thermosensitive hydrogels, the combination of these two technologies in an appropriate manner would be a promising antioxidant system for drug delivery and tissue engineering.

Chemotherapeutic resistance is a major obstacle in the control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we describe that sEV‐mediated TGF‐β1 intercellular transfer is involved in the drug‐resistant transmission. sEVs were isolated and characterized from both sensitive and resistant cells. sEVs derived from the resistant cells were incubated with the sensitive cells and resulted in transmitting the resistant phenotype to the recipient cells. Cytokine antibody microarray revealed that most metastasis‐associated cytokines present at the high levels in sEVs from the resistant cells compared with their levels in sEVs from the sensitive cells, particularly TGF‐β1 is enriched in sEVs from the resistant cells. The sEV‐mediated TGF‐β1 intercellular transfer led to increasing Smad2 phosphorylation and improving cell survival by suppressing apoptosis and enhancing cell mobility. Furthermore, sEV‐mediated drug‐resistant transmission by delivering TGF‐β1 was validated using a zebrafish xenograft tumor model. These results elaborated that sEV‐mediated TGF‐β1 intercellular transfer contributes to adriamycin resistance in BCa., Here, we show that small extracellular vesicles (sEVs) from adriamycin‐resistant breast cancer cells could confer resistance to adriamycin‐sensitive breast cancer cells. sEVs increased cell proliferation by inhibiting apoptosis and promoted cell mobility by enhancing EMT. sEV‐derived TGF‐β1 activated the TGF‐β1/Smad2 signaling pathway in recipient cells.

During nervous system development, an extracellular matrix (ECM) plays a pivotal role through surface topography and microenvironment signals in neurons and neurites maturation. Topography and microenvironment signals act as physical and chemical guiding cues, respectively, for neural tissue formation and reconstruction. Imposed surface topography can affect neural stem cells by promoting adhesion, spreading, alignment, morphological changes, and specific gene expression. Therefore, fabrication of a biomimetic construct or scaffold to support neurite outgrowth and axon extension is a crucial and common strategy for neural tissue regeneration. Here, we review recent developments in biomaterials modification for simulating the microenvironment to promote neural cell adhesion and growth. The subtopics include those of potential cellular mechanisms of topographical response, topography on cellular organization and function, contact guidance in neurite outgrowth and axon growth, ECM microenvironment as regulatory cues, as well as challenges and future perspectives of nerve conduits that are now in clinical trials and usage.

Radiotherapy (RT) is one of the main treatments for men with prostate cancer (PCa). To date, numerous sophisticated nano-formulations as radiosensitizers have been synthesized with inspiring therapeutic effects both in vitro and in vivo; however, almost all the attention has been paid on the enhanced dose deposition effect by secondary electrons of nanomaterials with high atomic numbers (Z); despite this, cell-cycle arrest, DNA damage, and also reactive oxygen species (ROS) production are critical working mechanisms that account for radiosensitization. Herein, an 'all-purpose' nanostrategy based on dose deposition enhancement, cell cycle arrest, and ROS production as prostate cancer radiosensitizer for potential clinical translation was proposed. The rather simple structure of docetaxel-loaded Au nanoparticles (NPs) with prostate specific membrane antigen (PSMA) ligand conjugation have been successfully synthesized. Enhanced cellular uptake achieved via the selective internalization of the NPs by PCa cells with positive PSMA expression could guarantee enhanced dose deposition. Moreover, the as-synthesized nanosystem could effectively arrest the cell cycle at G2/M phases, which would reduce the ability of DNA damage repair for more irradiation sensitive of the PCa cells. Moreover, the G2/M phase arrest would further promote cascade retention and the enrichment of NPs within the cells. Furthermore, ROS generation and double strand breaks greatly promoted by NPs under irradiation (IR) could also provide an underlying basis for effective radiosensitizers. In vitro and in vivo investigations confirmed the as-synthesized NPs as an effective nano-radiosensitizer with ideal safety. More importantly, all moieties within the present nanosystem have been approved by FDA for the purpose of PCa treatment, thus making it highly attractive for clinical translation.

This study reports the properties of immobilized MAS1-H108A lipase from marine Streptomyces sp. strain W007 on XAD1180 resin and its application in the synthesis of n-3 polyunsaturated fatty acids (PUFA)-rich triacylglycerols (TAG) for the first time. It was found that the optimal temperature and pH for both immobilized MAS1-H108A lipase and free lipase MAS1-H108A were 70 °C and 7.0, respectively. However, immobilized MAS1-H108A lipase exhibited higher thermostability when compared with free lipase MAS1-H108A. It was also interesting that both immobilized MAS1-H108A lipase and free lipase MAS1-H108A showed no regiospecificity in the hydrolysis of triolein. Subsequently, immobilized MAS1-H108A lipase and free lipase MAS1-H108A were employed to catalyze glycerolysis of n-3 PUFA-rich ethyl esters (EE) and esterification of n-3 PUFA with glycerol under vacuum in the solvent-free system. The results showed that n-3 PUFA-rich TAG were synthesized efficiently by non-regiospecific immobilized MAS1-H108A lipase and TAG contents separately reached 92.07% and 76.13% during the esterification and glycerolysis reactions, which were significantly higher than those (71.82% and 39.62%, respectively) obtained by free lipase MAS1-H108A. Besides, TAG exhibited similar n-3 PUFA composition to the substrate. These findings indicated that non-regiospecific immobilized MAS1-H108A lipase is a promising and efficient biocatalyst for the industrial synthesis of n-3 PUFA-rich TAG.

The regenerative capacity of the peripheral nervous system is closely related to the role that Schwann cells (SCs) play in construction of the basement membrane containing multiple extracellular matrix proteins and secretion of neurotrophic factors, including laminin (LN) and brain-derived neurotrophic factor (BDNF). Here, we developed a self-assembling peptide (SAP) nanofiber hydrogel based on self-assembling backbone Ac-(RADA)4-NH2 (RAD) dual-functionalized with laminin-derived motif IKVAV (IKV) and a BDNF-mimetic peptide epitope RGIDKRHWNSQ (RGI) for peripheral nerve regeneration, with the hydrogel providing a three-dimensional (3D) microenvironment for SCs and neurites. Methods: Circular dichroism (CD), atomic force microscopy (AFM), and scanning electron microscopy (SEM) were used to characterize the secondary structures, microscopic structures, and morphologies of self-assembling nanofiber hydrogels. Then the SC adhesion, myelination and neurotrophin secretion were evaluated on the hydrogels. Finally, the SAP hydrogels were injected into hollow chitosan tubes to bridge a 10-mm-long sciatic nerve defect in rats, and in vivo gene expression at 1 week, axonal regeneration, target muscular re-innervation, and functional recovery at 12 weeks were assessed. Results: The bioactive peptide motifs were covalently linked to the C-terminal of the self-assembling peptide and the functionalized peptides could form well-defined nanofibrous hydrogels capable of providing a 3D microenvironment similar to native extracellular matrix. SCs displayed improved cell adhesion on hydrogels with both IKV and RGI, accompanied by increased cell spreading and elongation relative to other groups. RSCs cultured on hydrogels with IKV and RGI showed enhanced gene expression of NGF, BDNF, CNTF, PMP22 and NRP2, and decreased gene expression of NCAM compared with those cultured on other three groups after a 7-day incubation. Additionally, the secretion of NGF, BDNF, and CNTF of RSCs was significantly improved on dual-functionalized peptide hydrogels after 3 days. At 1 week after implantation, the expressions of neurotrophin and myelin-related genes in the nerve grafts in SAP and Autograft groups were higher than that in Hollow group, and the expression of S100 in groups containing both IKV and RGI was significantly higher than that in groups containing either IKV or RGI hydrogels, suggesting enhanced SC proliferation. The morphometric parameters of the regenerated nerves, their electrophysiological performance, the innervated muscle weight and remodeling of muscle fibers, and motor function showed that RAD/IKV/RGI and RAD/IKV-GG-RGI hydrogels could markedly improve axonal regeneration with enhanced re-myelination and motor functional recovery through the synergetic effect of IKV and RGI functional motifs. Conclusions: We found that the dual-functionalized SAP hydrogels promoted RSC adhesion, myelination, and neurotrophin secretion in vitro and successfully bridged a 10-mm gap representing a sciatic nerve defect in rats in vivo. The results demonstrated the synergistic effect of IKVAV and RGI on axonal regrowth and function recovery after peripheral nerve injury.

The functions of acidic-rich domains in non-collagenous protein during biomineralization are thought to induce nucleation and control the growth of hydroxyapatite. The tripeptide Asp-Ser-Ser (DSS) repeats are the most common acidic-rich repeated unit in non-collagenous protein of dentin phosphoprotein, the functions of which have aroused extensive interests. In this study, biomimetic peptides (DSS)n (n = 2 or 3) were designed and fabricated into self-assembled monolayers (SAMs) on Au (111) surface as biomimetic organic templates to regulate hydroxyapatite (HAp) mineralization in 1.5 simulated body fluid (1.5 SBF) at 37 °C. The early mineralization processes and minerals deposited on the SAMs were characterized by X-ray diffraction, scanning electron microscope, and Fourier transform infrared spectroscopy analyses. The SAM-DSS9/DSS9G showed the highest capacity to induce HAp nucleation and growth, followed by SAM-DSS6/DSS6G, SAM-COOH, and SAM-OH. The SAM-(DSS)n had more negative zeta potentials than SAM-COOH surface, indicating that DSS repeats contributed to the biomineralization, which not only provided strong affinity with Ca2+ ions through direct electrostatic bonds, but more importantly influence surface electrostatic potentials of the assembled organic template for nucleation., Graphical abstract Image 1, Highlights • Biomimetic peptides designed from DPP and self-assembled to form SAMs. • Quantitative model for HAp mineralization regulated by non-collagenous protein. • Extra DSS repeat reduced the zeta potential on the SAM surface. • The nuclei quantity and mineral size on DSS9/DSS9G were always larger. • DSS repeats provided surface electrostatic potentials for stronger Ca2+ affinity.

Pulp regeneration is to replace the inflamed/necrotic pulp tissue with regenerated pulp-like tissue to rejuvenate the teeth. Self-assembling peptide hydrogels RADA16-I (Ac-(RADA16-I)4-CONH2) can provide a three-dimensional environment for cells. The stem cell factor (SCF) plays a crucial role in homing stem cells. Combining these advantages, our study investigated the effects of SCF-RADA16-I on adhesion, proliferation, and migration of human dental pulp stem cells (DPSCs) and the angiogenesis of human umbilical vein endothelial cells (HUVECs). The β-sheet and grid structure were observed by circular dichroism (CD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Cytoskeleton staining, living cell staining, cell viability, cell migration, angiogenesis, and western blot assays were performed, and the results indicated that all the SCF groups were superior to the corresponding non-SCF groups in cell adhesion, proliferation, migration, and angiogenesis. RADA16-I provided a three-dimensional environment for DPSCs. Besides, the SCF promoted HUVECs to form more vascular-like structures and release more vascular endothelial growth factor A. In summary, the SCF-loaded RADA16-I scaffold improved adhesion, proliferation, and migration of DPSCs and the formation of more vascular-like structures of HUVECs. SCF-RADA16-I holds promise for guided pulp regeneration, and it can potentially be applied widely in tissue engineering and translational medicine in the future.

Sequential administration and controlled release of different drugs are of vital importance for regulating cellular behaviors and tissue regeneration, which usually demands appropriate carriers like microspheres (MS) to control drugs releases. Electrospray has been proven an effective technique to prepare MS with uniform particle size and high drug-loading rate. In this study, we applied electrospray to simply and hierarchically fabricate sphere-in-sphere composite microspheres, with smaller poly(lactic-co-glycolic acid) MS (∼8–10 μm in diameter) embedded in a larger chitosan MS (∼250–300 μm in diameter). The scanning electron microscopy images revealed highly uniform MS that can be accurately controlled by adjusting the nozzle diameter or voltage. Two kinds of model drugs, bovine serum albumin and chlorhexidine acetate, were encapsulated in the microspheres. The fluorescence-labeled rhodamine-fluoresceine isothiocyanate (Rho-FITC) and ultraviolet (UV) spectrophotometry results suggested that loaded drugs got excellent distribution in microspheres, as well as sustained, slow release in vitro. In addition, far-UV circular dichroism and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) results indicated original secondary structure and molecular weight of drugs after electrospraying. Generally speaking, our research proposed a modified hierarchically electrospraying technique to prepare sphere-in-sphere composite MS with two different drugs loaded, which could be applied in sequential, multi-modality therapy.

Polycarboxylate ether (PCE) of different charge densities has been synthesized via free radical polymerization. The molecular structure is characterized by gel permeation chromatography (GP...

Autologous nerve transplantation, which is the gold standard for clinical treatment of peripheral nerve injury, still has many limitations. In this study, aligned chitosan fiber hydrogel (ACG) grafted with a bioactive peptide mixture consisting of RGI (Ac-RGIDKRHWNSQGG) and KLT (Ac-KLTWQELYQLKYKGIGG), designated as ACG-RGI/KLT, was used as nerve conduit filler to repair sciatic nerve defects in rats. Methods: Chitosan nanofiber hydrogel was prepared by a combination of electrospinning and mechanical stretching methods, and was then grafted with RGI and KLT, which are peptides mimicking brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), respectively. The physicochemical properties of ACG-RGI/KLT were fully characterized. In vitro, the distribution, proliferation, and secretory activity of Schwann cells were analyzed. Next, the in vivo repair potential for 15-mm rat sciatic nerve defects was examined. The recovery of regenerated nerve, muscle, and motor function was evaluated by neuromuscular histology, electrophysiology, and catwalk gait analysis. Results: We first constructed directionally aligned chitosan nanofiber hydrogel grafted with RGI/KLT peptide mixture (ACG-RGI/KLT). ACG-RGI/KLT oriented the Schwann cells, and promoted the proliferation and secretion of neurotrophic factors by Schwann cells. At an early injury stage, ACG-RGI/KLT not only enhanced nerve regeneration, but also promoted vascular penetration. At 12 weeks, ACG-RGI/KLT facilitated nerve regeneration and functional recovery in rats. Conclusions: Aligned chitosan nanofiber hydrogel grafted with RGI/KLT peptide provides an effective means of repairing sciatic nerve defects and shows great potential for clinical application.

The triboelectric nanogenerator (TENG) has been invented as an important mechanical energy harvesting technology, but the further improvement of its triboelectric properties is still required to meet those of practical and functional devices. The tribo-charge surface density of contact materials is considered to be crucial for the performance of TENG. However, currently the enhancement of the tribo-charge surface density is realized either by the physical modification or by the chemical modification of triboelectric surfaces. Here, to maximize the output performance, we introduce a novel post-processed micro-patterned double-network polydimethylsiloxane triboelectric film, in which both chemical modification and physical modification are simultaneously realized in one step along with high controllability, for the first time. With rational selection of monomers and photo-masks, the Voc and Jsc values of the TENGs are enhanced 17.4 times and the output power is significantly enhanced by ∼189 times compared to the devices without modification. This is associated with the improved surface potential and contact area of the triboelectric layer, leading to enhanced tribo-charge surface density and subsequent enhanced device performance. Moreover, the fabricated TENG exhibits high sensitivity. This design principle offers a universal method to further improve the device performance of TENGs in a low-cost, rapidly yielding way.

In this study, the multifunctional carbon nitride based composite graphitic-C3N4 (g-C3N4)/TiO2/Ag was prepared through a simple and efficient vacuum freeze-drying route. TiO2 and Ag nanoparticles were demonstrated to decorate onto the surface of g-C3N4 sheet. In the ultraviolet–visible absorption test, a narrower band gap and red-shift of light absorption edge were observed for g-C3N4/TiO2/Ag compared to pristine g-C3N4 and single-component modified g-C3N4/TiO2. The photodegradation property of g-C3N4/TiO2/Ag was investigated toward the degradation of methylene blue (abbreviated as MB) under the irradiation of visible light. These results indicated that the degradation performance of organic dyes for g-C3N4/TiO2/Ag was obviously improved compared with g-C3N4/TiO2 and g-C3N4. The reaction rate constant of MB degradation for g-C3N4/TiO2/Ag was 4.24 times higher than that of pristine g-C3N4. In addition, such rationally constructed nanocomposite presented evidently enhanced antibacterial performance against the Gram-negative Escherichia coli. Concentration dependent antibacterial performance was systematically investigated. And 84% bacterial cell viability loss had been observed at 500 μg/mL g-C3N4/TiO2/Ag within 2 h visible light irradiation.

The building of a mature material library is critically important for the practical application of any smart responsive optoelectronic materials. For thermochromic luminophores, as an important category of smart materials, however, it remains challenging to achieve this target due to the complexity and limitations of existing construction mechanisms. Here, we propose a simple and efficient strategy for developing a thermochromic luminophore library by exploiting the synergistic effects between peripheral flexible chain-related molecular dynamics and molecular aggregation structure-related luminescence properties of donor–acceptor–donor type luminophores. The strategy provided herein facilitates the construction of a prototype thermochromic material library of 13 dyes with a luminescence color-switching window covering the whole visible region and a wide temperature-response range from 35 °C to 190 °C. Based on this material library and a nano ink preparation method, reversible information displays and twelfth-level data encryptions based on temperature changes are demonstrated.

Using 4-(5-(4-(dimesitylboranyl)phenyl)pyridin-2-yl)-N,N-diphenylaniline (BNpppy) as a cyclometalated ligand, 1,10-phenanthroline or 2,4-pentanedione (acac) as the ancillary ligand, respectively, two novel iridium(III) complexes (Ir-1 and Ir-2) were successfully synthesized and their photoelectric properties have been investigated in detail. The incorporation of electron-accepting dimesitylboron (Mes2B) moieties and electron-donating triphenylamine moieties into iridium(III) complexes has been demonstrated with benign photophysical and electronic properties. The solution-processed OLEDs were fabricated using these two iridium(III) complexes, respectively. The devices of Ir-2 show good performances compared to those of Ir-1 with a maximum luminance of 7916 cd m−2, a maximum external quantum efficiency (EQE) of 2.48% and a maximum current efficiency of 3.99 cd A−1. These results indicate that the introduction of a donor–acceptor type of ligand into transition metal complexes has potential applications in constructing an efficient emitter in OLEDs with excellent performances.

n-3 polyunsaturated fatty acid (PUFA)-rich lysophosphatidylcholine (LPC) with many beneficial effects was effectively synthesized by immobilized MAS1 lipase-catalyzed esterification of n-3 PUFA with sn-glycero-3-phosphatidylcholine (GPC) under vacuum in a solvent-free system. Immobilized MAS1 lipase was found to be a more suitable catalyst for the production of n-3 PUFA-rich LPC when compared with Novozym 435. The maximal GPC conversion and LPC content (93.12% and 90.77 mol %) were obtained under the optimized conditions (enzyme loading of 300 U/g substrate, temperature of 55 °C, and n-3 PUFA/GPC molar ratio of 20:1). Moreover, it was observed that 1-acyl-sn-glycero-3-lysophosphatidylcholine (sn-1 acyl LPC) was the main reaction product, as demonstrated by molecular docking. These results showed that immobilized MAS1 lipase had high phospholipase activity with a predominant specificity for the sn-1 hydroxyl position of GPC to efficiently synthesize highly pure n-3 PUFA-rich LPC from GPC for industrial application.

Neural stem cells (NSCs) play an important role in neural tissue engineering because of their capacity of self-renewal and differentiation to multiple cell lineages. The in vitro conventional neurosphere culture protocol has some limitations such as limited nutrition and oxygen penetration and distribution causing the heterogeneity of cells inside, inaccessibility of internal cells, and inhomogeneous cellular morphology and properties. As a result, cultivation as a monolayer is a better way to study NSCs and obtain a homogeneous cell population. The cadherins are a classical family of homophilic cell adhesion molecules mediating cell-cell adhesion. Here, we used a recombinant human E-cadherin mouse IgG Fc chimera protein that self-assembles on a hydrophobic polystyrene surface via hydrophobic interaction to obtain an E-cadherin-coated culture plate (ECP). The rat fetal NSCs were cultured on the ECP and routine tissue culture plate (TCP) from passage 2 to passage 5. NSCs on TCP formed uniform floating neurospheres and grew up over time, while cells on the ECP adhered on the bottom of the plate and exhibited individual cells with scattering morphology, forming intercellular connections between cells. The cell proliferation and differentiation behaviors that were evaluated by Cell Counting Kit-8 assay (CCK-8), immunofluorescence staining, and real-time quantitative polymerase chain reaction showed NSCs could maintain the capacity for self-renewal and ability to differentiate into neurons, oligodendrocytes, and astrocytes after the long-term in vitro cell culture and passaging. Therefore, our study indicated that hE-cad-Fc could provide a homogeneous environment for individual cells in monolayer conditions to maintain the capacity of self-renewal and differentiation by mimicking the cell–cell interaction.

Angiogenesis plays an important role in brain injury repair, which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area. As a major component of developing brain extracellular matrix, hyaluronic acid (HA) has attracted more attention as a supporting matrix for brain repair. In the present study, HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT (KLTWQELYQLKYKGI). The characterization of the hydrogel shows that it could provide a porous, three-dimensional scaffold structure, which has a large specific surface area available for cell adhesion and interaction. Compared with the unmodified HA hydrogel, the HA-KLT hydrogel could effectively promote the attachment, spreading and proliferation of endothelial cells in vitro. Furthermore, the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain. Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation. Moreover, they could efficiently inhibit the formation of glial scars at the injured sites. The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels, suggesting that HA-KLT hydrogel promoted angiogenesis in vivo. Collectively, the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.

Osteoporotic fracture is one of the most common bone diseases in middle and old age, as the most serious consequence of osteoporosis. Sclerostin single‐chain antibody fragments (SCL‐scFv) have been proven to promote bone formation by binding to scleroprotein, a natural antagonist of the Wnt pathway, but it is difficult to rule alone due to the weak permeability and immunogenicity. Herein, we prepared poly(lactic‐co‐glycolic acid) microspheres as a sustained‐release vehicle to prolong the activity of SCL‐scFv. The morphology of microspheres were uniform and nearly sphere, loading efficiency and encapsulation efficiency of SCL‐scFv microspheres were 6.28 ± 1.04% and 48.37 ± 8.11%, respectively. Approximately 90% of the SCL‐scFvs were released from the microspheres over 28 days with initial burst releasing (38%) in the first 4 days. Sustained‐release of active SCL‐scFv from microspheres promoted bone marrow mesenchymal stem cells osteogenic differentiation in vitro and enhanced fracture healing in ovariectomized rats by improving bone mass and bone formation in the fracture region. All these findings demonstrate that the microspheres are able to simultaneously achieve localized long‐term SCL‐scFv controlled release and effectively promote bone formation, which provides a promising approach for osteoporotic fracture.

The interference effect and lack of selectivity are the bottlenecks for dual-mode magnetic resonance imaging (MRI) contrast agent development. To address these challenges and overcome the single mode imaging contrast limitations, a novel MgMnAl-layered double hydroxide@iron oxide nanoparticle (MgMnAl-LDH@IO NP) has been successfully synthesized as a concurrently enhanced dual-mode contrast agent for MRI of tumor tissues with sensitive pH response and high efficacy. The attachment of iron oxide nanoparticles on the surface of MgMnAl-LDH NPs led to the increased local magnetic field intensity, inducing the concurrent enhancement of both T1 and T2 relaxivity. The in vitro MRI demonstrated that the MgMnAl-LDH@IO NP could act as a pH-sensitive contrast agent for both T1- and T2-weighted MR imaging (r1, 5.67 mM-1 s-1 under pH 5.0 and 1.98 mM-1 s-1 under pH 7.4; r2, 369.12 mM-1 s-1 under pH 5.0 and 225.29 mM-1 s-1 under pH 7.4). The biocompatibility of the dual-mode contrast agent was revealed by the cytotoxicity test on fibroblast cells. Further in vivo dual-mode MR imaging exhibited that the MgMnAl-LDH@IO NP showed clear T1- and T2-weighted MR imaging of tumor tissues in breast-tumor-bearing mice. The facile synthetic method, desirable biocompatibility, sensitive stimuli response, and concurrently enhanced T1/T2 MRI signals both in vitro and in vivo encourage the great potential biomedical and clinical applications of MgMnAl-LDH@IO NP in MR imaging with improved accuracy.

No pharmacological treatment is currently available to protect brain from neuronal damage after ischemic stroke. Recent studies found that enkephalin may play an important role in neuron regeneration. We assembled a homogeneous size vesicle constituted by transferrin, exosomes, and enkephalin. Immunofluorescence assay showed that transferrin was combined with the exosomes and enkephalin was packaged into the vesicle; thus this complex was called tar-exo-enkephalin.In vitrostudies were performed using rat primary hippocampal neurons and the results showed that enkephalin decreased p53 and caspase-3 levels to 47.6% and 67.2%, respectively, compared to neurons treated with glutamate, thus inhibiting neuron apoptosis caused by glutamate. Anin vivoexperiment in rats was also carried out using a transient middle cerebral artery occlusion (tMCAO)/reperfusion model and tar-exo-enkephalin treatment was performed after tMCAO. The results showed that tar-exo-enkephalin crossed the blood brain barrier (BBB) and decreased the levels of LDH, p53, caspase-3, and NO by 41.9, 52.6, 45.5, and 57.9% compared to the tMCAO rats, respectively. In addition, tar-exo-enkephalin improved brain neuron density and neurological score after tMCAO. These findings suggest that the use of exogenous enkephalin might promote neurological recovery after stroke.

A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.

n-3 polyunsaturated fatty acids (PUFA)-rich triacylglycerols (TAG) with many beneficial effects are still difficult to be synthesized efficiently and rapidly by current synthetic techniques. This study reports the fatty acid specificity of immobilized MAS1 lipase and its efficient synthesis of n-3 PUFA-rich TAG by esterification of glycerol with n-3 PUFA in natural deep eutectic solvents (NADES) systems. Immobilized MAS1 lipase showed the highest preference for capric acid [C10:0, the highest specificity constant (1/α)=1] whereas it discriminated strongly against docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) due to their lowest specificity constants (1/α=0.19 and 0.2). Moreover, the highest n-3 PUFA-rich TAG content (55.8%) with similar n-3 PUFA composition to the substrate was obtained in choline chloride/glycerol (CG) system. There was a 1.38-fold increase of TAG content in CG system compared with that in the solvent-free system. Interestingly, immobilized MAS1 lipase exhibited no regiospecificity in the solvent-free and various NADES systems. Besides, the potential reaction mechanism of immobilized MAS1 lipase-catalyzed esterification of glycerol with n-3 PUFA in NADES systems was described. It was found that the use of NADES as solvents could greatly enhance TAG content, and make it easy to separate the product. These results indicated that immobilized MAS1 lipase is a promising biocatalyst for the efficient synthesis of n-3 PUFA-rich TAG by esterification of glycerol with n-3 PUFA in NADES systems.

Osteogenic peptides are often introduced to improve biological activities and the osteogenic ability of artificial bone materials as an effective approach. Covalent bindings between the peptide and the host material can increase the molecular interactions and make the functionalized surface more stable. However, covalent bindings through different functional groups can bring different effects on the overall bioactivities. In this study, carboxyl and amino groups were respectively introduced onto carbon nanotubes, a nanoreinforcement for synthetic scaffold materials, which were subsequently covalently attached to the RGD/BMP-2 osteogenic peptide. MC3T3-E1 cells were cultured on scaffolds containing peptide-modified carbon nanotubes. The results showed that the peptide through the amino group binding could promote cell functions more effectively than those through carboxyl groups. The mechanism may be that the amino group could bring more positive charges to carbon nanotube surfaces, which further led to differences in the peptide conformation, protein adsorption, and targeting osteogenic effects. Our results provided an effective way of improving the bioactivities of artificial bone materials by chemically binding osteogenic peptides.

Kümmell disease (KD) causes serious vertebral body collapse in patients. However, only a few case reports have been conducted and the number of patients with KD investigated was limited. Additionally, the frequently used poly(methyl methacrylate) (PMMA) bone cement for KD is limited by excessive modulus and poor biocompatibility. Herein, we aimed to modify PMMA bone cement with mineralized collagen (MC), and compare the clinical effects, image performance and finite element analysis between the modified bone cement and PMMA bone cement for the treatment of phase I and II KD. Thirty-nine KD patients treated with PMMA bone cement and 40 KD patients treated with MC-modified PMMA bone cement from June 2015 to March 2017 were retrospectively analyzed. The surgical procedure, intraoperative blood loss, hospital stay and complications were compared between different groups. Visual analog scale, Oswestry disability index, anterior vertebral height, posterior vertebral height, computed tomography value, adjacent vertebral re-fracture, Cobb angle and wedge-shaped correction angle were evaluated. Additionally, the representative sample was selected for finite element analysis. We found that the MC-modified PMMA bone cement could achieve the same effect as that of PMMA bone cement and was associated with better vertebral height restoration in the long term.

Background The activation of the NF-κB pathway plays a crucial role in the progression of breast cancer (BCa) and also involved in endocrine therapy resistance. On the contrary to the canonical NF-κB pathway, the effect of the noncanonical NF-κB pathway in BCa progression remains elusive. Methods BCa tumor tissues and the corresponding cell lines were examined to determine the correlation between RelB and the aggressiveness of BCa. RelB was manipulated in BCa cells to examine whether RelB promotes cell proliferation and motility by quantitation of apoptosis, cell cycle, migration, and invasion. RNA-Seq was performed to identify the critical RelB-regulated genes involved in BCa metastasis. Particularly, RelB-regulated MMP1 transcription was verified using luciferase reporter and ChIP assay. Subsequently, the effect of RelB on BCa progression was further validated using BCa mice xenograft models. Results RelB uniquely expresses at a high level in aggressive BCa tissues, particularly in triple-negative breast cancer (TNBC). RelB promotes BCa cell proliferation through increasing G1/S transition and/or decreasing apoptosis by upregulation of Cyclin D1 and Bcl-2. Additionally, RelB enhances cell mobility by activating EMT. Importantly, RelB upregulates bone metastatic protein MMP1 expression through binding to an NF-κB enhancer element located at the 5′-flanking region. Accordingly, in vivo functional validation confirmed that RelB deficiency impairs tumor growth in nude mice and inhibits lung metastasis in SCID mice.

As rarely large flake graphite (9 mesh) was recently exploited in China, it was innovatively developed as the raw material to prepare a novel wound dressing based on large expanded graphite (EG) in this work. The EG worms were prepared in an easy oxidative intercalation and thermal expansion method. Afterward, chitosan was grafted onto the surface of EG by chemical modification, forming CS-EG worms. CS-EG sponge dressings were then obtained by pressing a number of CS-EG worms together by external force. Due to the porous structure and large specific surface area, the produced CS-EG sponges exhibited outstanding adsorption capacity for wound exudate. They could also promote blood coagulation by adsorbing the blood cells and proteins quickly and effectively, showing excellent hemostatic performance. The eminent performances and the simple preparation process ensure the great application potential of CS-EG as a dressing material. This is also the first time to report the application of the traditional carbon material, EG, to act as a dressing material after chemical modification.

Protein therapeutics are increasingly used to treat various diseases, yet they often suffer from short serum half-lives. An emerging strategy to extend lifetime in vivo is to attach fatty acids onto proteins to increase their binding to human serum albumin (HSA). Herein, the genetic encoding of ϵ-N-heptanoyl-l-lysine (HepoK) is reported, which introduces a fatty-acid-containing amino acid into proteins with exquisite site-specificity and homogeneity, overcoming issues associated with existing chemical conjugation methods. The expression in E .coli and purification of HepoK-incorporated glucagon-like peptide-1 (GLP1) is demonstrated. GLP1(HepoK) showed stronger binding to HSA than GLP1(WT), without impairing the stimulation of the GLP1 receptor in cells. Moreover, GLP1(HepoK) decreased blood glucose level to the same level as GLP1(WT) in mice, showing longer-lasting effects than GLP1(WT). HepoK incorporation will also be useful for investigating the function of protein lipidation.

The mechanism of electron transmission in combined nanoiron-bacteria denitrification cannot be explained by the classic model, in which an Fe0 H2-nitrate transferring chain is proposed. In this study, we used characteristic techniques and electrochemical analysis to investigate the necessity of molecular hydrogen for the combined denitrifying system using commercial nanoiron with Alcaligenes eutrophus, and to analyze its potential electron donor. Based on our results, nitrate removal and its by-products (NO2− and NH4+) generation was not significantly affected by residual H2 gas, indicating that H2 was not necessary for hydrogenotrophic denitrification. As to the potential electron donor analysis, nanoscale zero-valent iron did not appear to be the electron donor due to its high level of toxicity (83% mortality using nanoiron versus 36% in the control cells). In addition, when iron oxides (Fe3O4, Fe2O3 and FeOOH on the nanoiron surface) and free ferrous ions [Fe2+(aq)] were present alone, they were not utilized by the bacteria to degrade nitrate. According to the results of electrochemical analysis, adsorbed ferrous iron [Fe2+(ad)] on ferric oxides might be the electron donor in this kind of nitrate removal.

Various artificial materials have been fabricated as alternatives to autologous nerve grafts in peripheral nerve regeneration, and these afford positive recovery effects without the disadvantages of the gold standard. In this study, we prepared a three-dimensional functionalized self-assembling peptide nanofiber hydrogel containing two neurotrophic peptides (CTDIKGKCTGACDGKQC and RGIDKRHWNSQ derived from nerve growth factor and brain-derived neurotrophic factor, respectively) that reflected the structure and properties of the neural extracellular matrix. The material was used to promote axonal regrowth and functional recovery. Scanning electron microscopy revealed a three-dimensional porous matrix within the hydrogel. Circular dichroism spectroscopy and atomic force microscopy confirmed that the peptides displayed a β-sheet structure and self-assembled into long nanofibers. Rheology measurements and atomic force microscopy indicated that the elasticity of the peptide hydrogels was close to that of the nerve tissue matrix. In vitro work with Schwann cells and dorsal root ganglia showed that the hydrogels exhibited good cell compatibility. Furthermore, the hydrogel containing CTDIKGKCTGACDGKQC and RGIDKRHWNSQ promoted the neurite outgrowth of PC12 cells significantly compared to non-functionalized peptide. In vivo, the hydrogels were placed into chitosan tubes and used to bridge 10 mm long sciatic nerve defects in rats. We found that the combination of CTDIKGKCTGACDGKQC and RGIDKRHWNSQ accelerated axonal regeneration and afforded good functional recovery, suggesting that they synergistically facilitate peripheral nerve regeneration.

Lipopolysaccharide (LPS), a characteristic component of the outer membrane of Gram-negative bacteria, can be used as an effective biomarker to detect bacterial contamination. Here, we reported a 293/hTLR4A-MD2-CD14 cell-based fluorescent biosensor to detect and identify LPS, which is carried out in a 96-well microplate which is nondestructive, user-friendly, and highly efficient. The promoter sequence of the critical signaling pathway gene ZC3H12A (encoding MCPIP1 protein) and enhanced green fluorescence protein (EGFP) were combined to construct a recombinant plasmid, which was transferred into 293/hTLR4A-MD2-CD14 cells through lipid-mediated, DNA-transfection way. LPS was able to bind to TLR4 and coreceptors-induced signaling pathway could result in green fluorescent protein expression. Results show that stable transfected 293/hTLR4A-MD2-CD14 cells with LPS treatment could be directly and continually observed under a high content screening imaging system. The novel cell-based biosensor detects LPS at low concentration, along with the detection limit of 0.075 μg/mL. The cell-based biosensor was evaluated by differentiating Gram-negative and Gram-positive bacteria and detecting LPS in fruit juices as well. This proposed fluorescent biosensor has potential in sensing LPS optically in foodstuff and biological products, as well as bacteria identification, contributing to the control of foodborne diseases and ensurance of public food safety with its high throughput detection way.

Molybdenum disulfide (MoS2), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes (IOMS NCs) via the integration of MoS2 (MS) film onto iron oxide (IO) nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose (2-DG), a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG-modified PEGylated NCs (IOMS-PEG-2DG NCs) acted as drug-carriers for doxorubicin (DOX), which could be easily loaded within the NCs. The obtained IOMS-PEG(DOX)-2DG NCs exhibited a T2 relaxivity coefficient of 48.86 (mM)−1·s−1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG(DOX)-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 min at a low power density of 0.5 W·cm−2, a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.

To assess the relationship between metal ion-mediated microstructures and the macro-performance, Cu- and Zn-doped α-Fe2O3 nanoparticles were prepared via a solvothermal method. The morphologies of the as-synthesized nanoparticles were investigated by scanning electron microscopy and transmission electron microscopy. The results revealed that the sizes and morphologies could be regulated by doping with divalent cations. The structures of the as-synthesized nanoparticles were characterized by X-ray diffraction and Raman spectroscopy, indicating that Cu2+ and Zn2+ ions had diffused into the lattice of α-Fe2O3 matrix. The magnetization behaviors of these nanoparticles were measured to analyze the effect of doping on α-Fe2O3. Furthermore, the catalytic activities of Cu- and Zn-doped α-Fe2O3 nanoparticles demonstrated that the high-temperature decomposition temperature of ammonium perchlorate could be lowered by 115 °C and 107 °C, respectively, compared to that of ammonium perchlorate without catalyst. The enhanced catalytic activity could be attributed to the defect structure induced by doping with divalent cations.

Hyperthermia has been considered as a promising healing treatment in bone regeneration. We designed a tissue engineering hydrogel based on magnetic nanoparticles to explore the characteristics of hyperthermia for osteogenic regeneration. This nanocomposite hydrogel was successfully fabricated by incorporating magnetic Fe3O4 nanoparticles into chitosan/polyethylene glycol (PEG) hydrogel, which showed excellent biocompatibility and were able to easily achieve increasing temperatures under an alternative magnetic field (AMF). With uniformly dispersed nanoparticles, the composite hydrogel resulted in high viability of mesenchymal stem cells (MSCs), and the elevated temperature contributed to the highest osteogenic differentiation ability compared with direct heat treatment applied under equal temperatures. Therefore, the nanoheat stimulation method using the magnetic nanocomposite hydrogel under an AMF may be considered as an alternative candidate in bone tissue engineering regenerative applications.

Nobiletin (NOB), a citrus polymethoxy flavonoid, has been reported to exhibit anti-inflammatory, anti-cancer, and anti-insulin resistance activities. Although the anti-inflammatory activity of NOB already reported, its involvement in lung protection has not been reported. Thus, this study aimed to investigate the anti-inflammatory response of NOB in lipopolysaccharide (LPS)-stimulated A549 cells and LPS-induced acute lung injury (ALI) in mice. The animals were pre-treated with NOB (5, 10, and 20 mg/kg) or DEX (5 mg/kg) at 12 and 1 h before intranasal instillation of LPS. The severity of pulmonary injury was evaluated 6 h after LPS administration. Results suggested that treatment with NOB dramatically attenuated lung histopathological changes, wet-to-dry (W/D) ratio, myeloperoxidase (MPO) activity, the numbers of inflammatory cells, and TNF-α, IL-6, and NO in BALF induced by LPS. Furthermore, NOB also significantly inhibited the expression of iNOS and the phosphorylation of NF-κBp65 and IκBα. In vitro, NOB inhibited NF-κB activation and TNF-α, IL-6 production in LPS-stimulated A549 cells. Taken together, these results indicated that NOB exhibited a protective effect on ALI, and the possible mechanism is involved in inhibiting NF-κB activation, subsequently inhibiting LPS-induced inflammatory response.

Taking inspiration from the characteristics and the limitations of flexible organic thin-film transistor (OTFT) devices, a novel surface modification method was proposed to modify the gate insulator to tune the mechanical compatibility and adhesion energy between gate insulator and semiconductor layer for high performance flexible OTFT devices. The surface modification method aimed to form a polymer network structure within the cross-linked polymer film by photo-polymerization of the liquid monomers which were infused into the cross-linked polymer film. The formation of double-network structure significantly improved the electrical performance of the flexible devices. The charge mobility increased from 0.17 cm2V−1s−1 to 1.52 cm2V−1s−1 and on/off current ratio increased by one or two orders of magnitude. During the bending tests, the devices modified with double-network dielectric structure exhibited excellent mechanical stability even after hundreds of successive bending cycles along with different bending radius. For instance, the mobility of the devices modified with methyl methacrylate only reduced by 2% after 500 successive bending cycles with a bending radius of 10 mm. It is ascribed to the improvement of mechanical compatibility and decrease of adhesion energy between gate insulator and semiconductor with the double network dielectric structure. More importantly, this work is a unique example to demonstrate the importance of mechanical compatibility and adhesion energy between gate insulator and semiconductor on the mechanical stability of flexible OTFT. Furthermore, these results clearly demonstrated that this method is a promising tool to tune the semiconductor/dielectric interface, especially the mechanical compatibility and adhesion energy between semiconductor layer and dielectric layer, which has great potential for high performance flexible OTFTs with excellent mechanical stability.

In the past decade, iron oxide nanoparticles (IONPs) have attracted more and more attention for their excellent physicochemical properties and promising biomedical applications. In this review, we summarize and highlight recent progress in the design, synthesis, biocompatibility evaluation and magnetic theranostic applications of IONPs, with a special focus on cancer treatment. Firstly, we provide an overview of the controlling synthesis strategies for fabricating zero-, one- and three-dimensional IONPs with different shapes, sizes and structures. Then, the in vitro and in vivo biocompatibility evaluation and biotranslocation of IONPs are discussed in relation to their chemo-physical properties including particle size, surface properties, shape and structure. Finally, we also highlight significant achievements in magnetic theranostic applications including magnetic resonance imaging (MRI), magnetic hyperthermia and targeted drug delivery. This review provides a background on the controlled synthesis, biocompatibility evaluation and applications of IONPs as cancer theranostic agents and an overview of the most up-to-date developments in this area.

Even small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP). We hypothesized that increased recruitment of endogenous stem cells by the composite scaffold could enhance cartilage regeneration. Methods: To test our hypothesis, in vitro proliferation, attachment and chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) were tested to confirm the bioactivities of the functionalized peptide hydrogel. The composite scaffold was then implanted into full-thickness cartilage defects on rabbit knee joints for cartilage repair, in comparison with microfracture or other sample groups. Stem cell recruitment was monitored by dual labeling with CD29 and CD90 under confocal microcopy at 1 week after implantation, followed by chondrogenic differentiation examined by qRT-PCR. Repaired tissue of the cartilage defects was evaluated by histological and immunohistochemistry staining, microcomputed tomography (micro-CT) and magnetic resonance imaging (MRI) at 3 and 6 months post-surgery. Macroscopic and histological scoring was done to evaluate the optimal in vivo repair outcomes of this composite scaffold. Results: The functionalized SAP hydrogels could stimulate rabbit MSC proliferation, attachment and chondrogenic differentiation during in vitro culture. At 7 days after implantation, increased recruitment of MSCs based on CD29+ /CD90+ double-positive cells was found in vivo in the composite hydrogel scaffold, as well as upregulation of cartilage-associated genes (aggrecan, Sox9 and type II collagen). After 3 and 6 months post-surgery, the articular cartilage defect in the composite scaffold-treated group was fully covered with cartilage-like tissue with a smooth surface, which was similar to the surrounding native cartilage, according to the results of histological and immunohistochemistry staining, micro-CT and MRI analysis. Macroscopic and histological scoring confirmed that the quality of cartilage repair was significantly improved with implantation of the composite scaffold at each timepoint, in comparison with microfracture or other sample groups. Conclusion: Our findings demonstrated that the composite scaffold could enhance endogenous stem cell homing and chondrogenic differentiation and significantly improve the therapeutic outcome of chondral defects. The present study provides a promising approach for in vivo cartilage repair without cell transplantation. Optimization of this strategy may offer great potential and benefits for clinical application in the future.

Understanding the intrinsic relationship between photoluminescence (PL) properties and fine crystal structure is essential for developing excellent cerium doped Y3Al5O12 (YAG:Ce) nanophosphors. Herein, we studied the crystal structure evolution of YAG:Ce nanophosphors with calcination temperature via multiple characterization techniques, and focused on clarifying the local structure of Ce3+ activator by advanced quantitative 27Al magic angle spinning nuclear magnetic resonance (27Al MAS NMR) spectroscopy. The results showed that the crystallinity of the YAG:Ce nanophosphors was improved and the lattice constant monotonously decreased with rising calcination temperature. Especially, as the calcination temperature increased from 830 to 1030 °C, more Ce3+ ions entered the first sphere of AlO6 groups and the symmetry of AlO4 species gradually increased in YAG:Ce nanophosphors, which caused the decrease of geometrical distortion surrounding Ce3+ activators. Due to the variations of fine structure, the PL intensity obviously increased with calcination temperature while its position remained constant. When the calcination temperature further increased to 1080 °C, CeO2 impurity formed in the nanophosphor, resulting in the increase of the quenching centers.