Recent progress of metal halide perovskite materials in heterogeneous photocatalytic organic reactions.

Photocatalytic technology is widely regarded as an important way to utilize solar energy and achieve carbon neutrality, which has attracted considerable attentions in various fields over the past decades. Metal halide perovskites (MHPs) are recognized as "superstar" materials due to their exceptional photoelectric properties, readily accessible and tunable structure, which made them intensively studied in solar cells, light-emitting diodes, and solar energy conversion fields. Since 2018, increased attention has been focused on applying the MHPs as a heterogeneous visible light photocatalyst in catalyzing organic synthesis reactions. In this review, we present an overview of photocatalytic technology and principles of heterogeneous photocatalysis before delving into the structural characteristics, stability, and classifications of MHPs. We then focus on recent developments of MHPs in photocatalyzing various organic synthesis reactions, such as oxidation, cyclization, C-C coupling etc., based on their classifications and reported reaction types. Finally, we discuss the main limitations and prospects regarding the application of metal halide perovskites in organic synthesis.

Myofiber directs macrophages IL-10-Vav1-Rac1 efferocytosis pathway in inflamed muscle following CTX myoinjury by activating the intrinsic TGF-ß signaling.

BACKGROUND: To explore the role of skeletal muscle specific TGF-ß signaling on macrophages efferocytosis in inflamed muscle caused by Cardiotoxin (CTX) injection. METHODS: CTX myoinjury was manipulated in TGF-ßr2flox/flox (control) mice or transgenic mice with TGF-ß receptor 2 (TGF-ßr2) being specifically deleted in skeletal muscle (SM TGF-ßr2-/-). Gene levels of TGF-ß signal molecules, special inflammatory mediators in damaged muscle or in cultured and differentiated myogenic precursor cells (MPC-myotubes) were monitored by transcriptome microarray or qRT-PCR. TGF-ß pathway molecules, myokines and embryonic myosin heavy chain in regenerating myofibers, the phenotype and efferocytosis of macrophages were evaluated by immunofluorescence, immunoblotting, Luminex, or FACS analysis. In vitro apoptotic cells were prepared by UV-irradiation. RESULTS: In control mice, TGF-ß-Smad2/3 signaling were significantly up-regulated in regenerating centronuclear myofibers after CTX-myoinjury. More severe muscle inflammation was caused by the deficiency of muscle TGF-ß signaling, with the increased number of M1, but the decreased number of M2 macrophages. Notably, the deficiency of TGF-ß signaling in myofibers dramatically affected on the ability of macrophages to conduct efferocytosis, marked by the decreased number of Annexin-V-F4/80+Tunel+ macrophages in inflamed muscle, and the impaired uptake of macrophages to PKH67+ apoptotic cells transferred into damaged muscle. Further, our study suggested that, the intrinsic TGF-ß signaling directed IL-10-Vav1-Rac1 efferocytosis signaling in muscle macrophages. CONCLUSIONS: Our data demonstrate that muscle inflammation can be suppressed potentially by activating the intrinsic TGF-ß signaling in myofibers to promote IL-10 dependent-macrophages efferocytosis. Video Abstract.

IRE1α arm of unfolded protein response in muscle-specific TGF-ß signaling-mediated regulation of muscle cell immunological properties.

Endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are involved in various muscle pathological states. The IRE1α arm of UPR can affect immunological properties of myofiber through restraining p38 mitogen-activated protein kinases (MAPK) activation under inflammatory milieu. However, the relevant pathway molecules regulating the initiation of the IRE1α arm in myofiber remain unclear. In this work, expression of transforming growth factor-beta (TGF-ß) and TGF-ß receptor II (TGF-ßr2), and UPR pathway activation were examined in cardiotoxin (CTX)-damaged mouse muscle, which revealed the activation of TGF-ß signaling and UPR in CTX-damaged muscle and in regenerating myofibers. Using control or transgenic mice with TGF-ßr2 deleted in skeletal muscle (SM TGF-ßr2-/-) and the derived primary differentiating myogenic precursor cells (MPCs) treated with/without ERS activator or inhibitor, IRE1α pathway inhibitor, or TGF-ß signaling activator, this study further revealed an essential role of intrinsic TGF-ß signaling in regulating muscle cell to express inflammation-related molecules including H-2Kb, H2-Eα, TLR3, and special myokines. TGF-ß signaling prompted UPR IRE1α arm and restrained p38 MAPK activation in myofiber under inflammatory milieu. This study uncovers a previously unrecognized function of TGF-ß signaling acting as an upstream factor controlling myofiber immune capacities in the inflamed state through the UPR-IRE1α-p38 MAPK pathway.

Muscle cytotoxicity and immuno-reactivity analysis of the porous carbon nanospheres fabricated by high temperature calcination.

Carbon-based nanomaterials have a high specific surface area, biocompatibility, and controlled mesopore structures. These characteristics make carbon nanospheres excellent carriers for drugs, biological dyes, photosensitizers, etc. Nevertheless, little is known about the impact of topological features on the surface of carbon nanomaterials on their in vivo immunoreactivity. In this study, we fabricated mesoporous carbon nanoparticles (MCNs) and solvent-processable carbon vesicles (CVs) by high-temperature calcination. The hematoxylin and eosin (H&E) staining suggested CVs' relatively poor dispersion capacity compared to MCNs and carbon precursors (CPs), leading to more severe muscle inflammation and necrosis. Immunostaining and Fluorescence Activated Cell Sorter (FACS) analysis further showed that both MCNs and CVs triggered a transient immune response in transplanted muscle and muscle-draining lymph nodes, but did not alter muscle resistance to exogenous viruses. In conclusion, this study provides insights into how carbon nanoparticles modulate the activation of immune responses in vivo.

Regulatory T cells-centered regulatory networks of skeletal muscle inflammation and regeneration.

As the understanding of skeletal muscle inflammation is increasingly clarified, the role of Treg cells in the treatment of skeletal muscle diseases has attracted more attention in recent years. A consensus has been reached that the regulation of Treg cells is the key to completing the switch of inflammation and repair of skeletal muscle, whose presence directly determine the repairing quality of the injured skeletal muscle. However, the functioning process of Treg cells remains unreported, thereby making it necessary to summarize the current role of Treg cells in skeletal muscle. In this review, the characteristics, origins, and cellular kinetics of these Treg cells are firstly described; Then, the relationship between Treg cells and muscle satellite cells (MuSCs), conventional T cells (Tconv) is discussed (the former is involved in the entire repair and regeneration process, while the latter matters considerably in causing most skeletal muscle autoimmune diseases); Next, focus is placed on the control of Treg cells on the phenotypic switch of macrophages, which is the key to the switch of inflammation; Finally, factors regulating the functional process of Treg cells are analyzed, and a regulatory network centered on Treg cells is summarized. The present study summarizes the cell-mediated interactions in skeletal muscle repair over the past decade, and elucidates the central role of regulatory T cells in this process, so that other researchers can more quickly and comprehensively understand the development and direction of this very field. It is believed that the hereby proposed viewpoints and problems can provide fresh visions for the latecomers.

Regenerating myofiber directs Tregs and Th17 responses in inflamed muscle through the intrinsic TGF-ß signaling-mediated IL-6 production.

Transforming growth factor-ß (TGF-ß) is considered to be an important immune regulatory cytokine. However, it remains unknown whether and how the muscle fiber specific-TGF-ß signaling is directly involved in intramuscular inflammatory regulation by affecting T cells. Here, we addressed these in a mouse tibialis anterior muscle Cardiotoxin injection-induced injury repair model in muscle creatine kinase (MCK)-Cre control or transgenic mice with TGF-ß receptor II (TGF-ßr2) being specifically deleted in muscle cells (SM TGF-ßr2-/-). In control mice, TGF-ß2 and TGF-ßr2 were found significantly upregulated in muscle after the acute injury. In mutant mice, deficiency of TGF-ß signaling in muscle cells caused more serious muscle inflammation, with the increased infiltration of macrophages and CD4+ T cells at the degeneration stage (D4) and the early stage of regeneration (D7) after myoinjury. Notably, the loss of TGF-ß signaling in myofibers dramatically affected CD4+ T cell function and delayed T cells withdrawal at the later stage of muscle regeneration (D10 and D15), marked by the elevated Th17, but the impaired Tregs response. Furthermore, in vivo and in vitro, the intrinsic TGF-ß signaling affected immune behaviors of muscle cells and directed CD4+ T cells differentiation by impairing IL-6 production and release. It suggests that local muscle inflammation can be inhibited potentially by directly activating the TGF-ß signaling pathway in muscle cells to suppress Th17, but induce Tregs responses. Thus, according to the results of this study, we found a new idea for the control of local acute inflammation in skeletal muscle.NEW & NOTEWORTHY Myofiber mediates muscle inflammatory response through activating the intrinsic TGF-ß signaling. The specific TGF-ß signaling activation contributes to myofiber IL-6 production and directs muscle-specific Th17 and Treg cell responses.

The immuno-reactivity of polypseudorotaxane functionalized magnetic CDMNP-PEG-CD nanoparticles.

pH-magnetic dual-responsive nanocomposites have been widely used in drug delivery and gene therapy. Recently, a polypseudorotaxane functionalized magnetic nanoparticle (MNP) was developed by synthesizing the magnetic nanoparticles with cyclodextrin (CD) molecules (CDMNP) via polyethylene glycol (PEG) (CDMNP-PEG-CD). The purpose of this study was to explore the antigenicity and immunogenicity of the nanoparticles in vivo prior to their further application explorations. Here, nanoparticles were assessed in vivo for retention, bio-distribution and immuno-reactivity. The results showed that, once administered intravenously, CDMNP-PEG-CD induced a temporary blood monocyte response and was cleared effectively from the body through the urine system in mice. The introduction of ß-CD and PEG/ß-CD polypseudorotaxane on SiO2 magnetic nanoparticles (SOMNP) limited particle intramuscular dispersion after being injected into mouse gastrocnemius muscle (GN), which led to the prolonged local inflammation and muscle toxicity by CDMNP and CDMNP-PEG-CD. In addition, T cells were found to be more susceptible for ß-CD-modified CDMNP; however, polypseudorotaxane modification partially attenuated ß-CD-induced T cell response in the implanted muscle. Our results suggested that CDMNP-PEG-CD nanoparticles or the decomposition components have potential to prime antigen-presenting cells and to break the muscle autoimmune tolerance.

The Thickness of Surface Grafting Layer on Bio-materials directly Mediates the Immuno-reacitivity of Macrophages in vitro.

Introducing the surface grafting layers to regulate bio-compatibility and bio-function is an important step in the tissue engineering field. However, whether the thickness variation of the introduced biomimetic layer impacts the behavior of the adhered immune effector cells is yet to be dissected fully. In this study, we used a surface-induced atom transfer radical polymerization (SI-ATRP) method to synthetize and graft poly-phenoxyethyl methacrylate (PHEMA) brushes having different lengths on the glass substrates. Primary murine peritoneal macrophages were collected and cultured on the PHEMA brushes and we investigated the influence of polymer brushes having different lengths on macrophages phenotype and function. Our results demonstrated that the thicker brushes (200 nm and 450 nm) are superior to the thinner layers (50 nm) for macrophages survival, proliferation, cell elongation and migration. Moreover, the thicker brushes are more beneficial for macrophage's activities and functions, presented by the increased production of M1-associated cytokines IL-6 and MCP-1, the elevated cell phagocytosis and the activation molecule F4/80 expression, and the reduced macrophages apoptosis in thicker brushes-sustained macrophages. Our data suggests that the thickness of the substrate grafting layer directly impacts macrophages recruitment and pro-inflammatory function, which is important in determining the intrinsic immuno-compatibilities of the surface modified-biomaterials and mediates material-host interactions in vivo.

The IRE1α Arm of UPR Regulates Muscle Cells Immune Characters by Restraining p38 MAPK Activation.

Skeletal muscle repair and systemic inflammation/immune responses are linked to endoplasmic reticulum stress (ER stress) pathways in myopathic muscle, and muscle cells play an active role in muscular immune reactions by exhibiting immunological characteristics under persistent proinflammation stimuli. Whether ER stress affects the intrinsic immunological capacities of myocytes in the inflammatory milieu, as it does to immune cells, and which arms of the unfolded protein response (UPR) mainly participate in these processes remain mostly unknown. We investigated this issue and showed that inflammatory stimuli can induce the activation of the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) arms of the UPR in myocytes both in vivo and in vitro. UPR stressor administration reversed the increased IFN-γ-induced expression of the MHC-II molecule H2-Ea, the MHC-I molecule H-2K b , toll-like receptor 3 (TLR3) and some proinflammatory myokines in differentiated primary myotubes in vitro. However, further IRE1α inhibition thoroughly corrected the trend in the UPR stressor-triggered suppression of immunobiological molecules. In IFN-γ-treated myotubes, dramatic p38 MAPK activation was observed under IRE1α inhibitory conditions, and the pharmacological inhibition of p38 reversed the immune molecule upregulation induced by IRE1α inhibition. In parallel, our coculturing system verified that the ovalbumin (OVA) antigen presentation ability of inflamed myotubes to OT-I T cells was enhanced by IRE1α inhibition, but was attenuated by further p38 inhibition. Thus, the present findings demonstrated that p38 MAPK contributes greatly to IRE1α arm-dependent immunobiological suppression in myocytes under inflammatory stress conditions.

The thickness of poly-phenoxyethyl methacrylate brush interferes with cellular behavior and function of myofibers.

Introducing or grafting molecules onto biomaterial surfaces to regulate muscle cell destination via biophysical cues is one of the important steps for biomaterial design in muscle tissue engineering. Therefore, it is important to understand the interaction between myoblasts and myofibers with substrates modified by biomimetic layer with different thicknesses. In this study, we used a surface-induced atom transfer radical polymerization method to synthetize and graft poly-phenoxyethyl methacrylate (PHEMA) brushes having different lengths on the glass substrates. C2C12 myoblasts were seeded on the PHEMA brushes and differentiated using horse serum, for analyzing the sensibility of muscle cells to feel environment changing, and further investigating whether the depths of grafting layer on the biomaterial surface are important factors in regulating muscle cell behaviors. Our results demonstrated that on the thicker PHEMA brushes surface (200 and 450 nm), C2C12 myoblasts showed a better survival and proliferation and were favorable for cell fusion and myotube formation. Furthermore, myofibers survived on the thicker brushes were more functional and upregulated cytoskeleton proteins (tubulin, vimentin, and vinculin) and FAK levels, and enhanced the expression levels for mechanical stress molecules (HGF, NOS-1, and c-Met). These results suggest that grafting thickness of PHEMA layer on the substrate led to the myoblasts/myofiber behavior change, which would be valuable for the design and preparation of the modified layer on muscle tissue engineering scaffolds. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1264-1272, 2019.