ABSTRACT
Tuning the topology of two-dimensional (2D) covalent organic frameworks (COFs) is of paramount scientific interest but remains largely unexplored. Herein, we present a site-selective synthetic strategy that enables the tuning of 2D COF topology by simply adjusting the molar ratio of an amine-functionalized dihydrazide monomer (NH2 -Ah) and 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tribenzaldehyde (Tz). This approach resulted in the formation of two distinct COFs: a clover-like 2D COF with free amine groups (NH2 -Ah-Tz) and a honeycomb-like COF without amine groups (Ah-Tz). Both COFs exhibited good crystallinity and moderate porosity. Remarkably, the clover-shaped NH2 -Ah-Tz COF, with abundant free amine groups, displayed significantly enhanced adsorption capacities toward crystal violet (CV, 261â mg/g) and congo red (CR, 1560â mg/g) compared to the non-functionalized honeycomb-like Ah-Tz COF (123â mg/g for CV and 1340â mg/g for CR), underscoring the pivotal role of free amine functional groups in enhancing adsorption capacities for organic dyes. This work highlights that the site-selective synthetic strategy paves a new avenue for manipulating 2D COF topology by adjusting the monomer feeding ratio, thereby modulating their adsorption performances toward organic dyes.
ABSTRACT
Organic dyes are widely used in many important areas, but they also bring many issues for water pollution. To address the above issues, a reconstructed kaolinite hybrid compound (γ-AlOOH@A-Kaol) was obtained from raw kaolinite (Kaol) in this work. The product was then characterized by X-ray diffraction (XRD), Fourier-transform infrared (ATR-FTIR), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM), and the absorption properties of γ-AlOOH@A-Kaol for congo red were further studied. The results demonstrated that flower-like γ-AlOOH with nanolamellae were uniformly loaded on the surface of acid-treated Kaol with a porous structure (A-Kaol). In addition, the surface area (36.5 m2/g), pore volume (0.146 cm3/g), and pore size (13.0 nm) of γ-AlOOH@A-Kaol were different from those of A-Kaol (127.4 m2/g, 0.127 cm3/g, and 4.28 nm, respectively) and γ-AlOOH (34.1 m2/g, 0.315 cm3/g, and 21.5 nm, respectively). The unique structure could significantly enhance the sorption capacity for congo red, which could exceed 1000 mg/g. The reasons may be ascribed to the abundant groups of -OH, large specific surface area, and porous structure of γ-AlOOH@A-Kaol. This work provides an efficient route for comprehensive utilization and production of Kaol-based compound materials that could be used in the field of environmental conservation.
ABSTRACT
De novo design of peptides that bind specifically to functional proteins is beneficial for diagnostics and therapeutics. However, complex permutations and combinations of amino acids pose significant challenges to the rational design of peptides with desirable stability and affinity. Herein, we develop a computational-based evolution method, namely, peptidomimetics-driven recognition elements design (PepDRED), to derive hemoglobin-inspired peptidomimetics. PepDRED mimics the natural evolutionism pipeline to generate stable apovariant (AVs) structures for wild-type counterparts via automated point mutations and validates their efficiency through free binding energy analysis and per residue energy decomposition analysis. For application demonstration, we applied PepDRED to design de novo peptides to bind FhuA, a typical TonB-dependent transporter (TBDT). TBDTs are Gram-negative bacterial outer membrane proteins responsible for iron transport and vital for bacterial resistance. PepDRED generated a pool of AVs and proceeded to reach an optimized peptide, AV440, with a remarkable binding affinity of -21 kcal/mol. AV440 is â¼2.5-fold stronger than the existing FhuA inhibitor Microcin J25. Network energy analysis further unveils that incorporating methionine (M42) in the N-terminal region significantly enhances inter-residue contacts and binding affinity. PepDRED offers a prompt and efficient in silico approach to develop potent peptide candidates for target proteins.
Subject(s)
Escherichia coli Proteins , Peptidomimetics , Escherichia coli Proteins/metabolism , Escherichia coli/metabolism , Bacterial Outer Membrane Proteins/genetics , Peptides/metabolism , Protein Binding , Bacterial Proteins/chemistryABSTRACT
Osteoarthritis (OA) is a major health problem, characterized by progressive cartilage degeneration. Previous works have shown that mechanical loading can alleviate OA symptoms by suppressing catabolic activities. This study evaluated whether mechanical loading can enhance anabolic activities by facilitating the recruitment of stem cells for chondrogenesis. We evaluated cartilage degradation in a mouse model of OA through histology with H&E and safranin O staining. We also evaluated the migration and chondrogenic ability of stem cells using in vitro assays, including immunohistochemistry, immunofluorescence, and Western blot analysis. The result showed that the OA mice that received mechanical loading exhibited resilience to cartilage damage. Compared to the OA group, mechanical loading promoted the expression of Piezo1 and the migration of stem cells was promoted via the SDF-1/CXCR4 axis. Also, the chondrogenic differentiation was enhanced by the upregulation of SOX9, a transcription factor important for chondrogenesis. Collectively, the results revealed that mechanical loading facilitated cartilage repair by promoting the migration and chondrogenic differentiation of endogenous stem cells. This study provided new insights into the loading-driven engagement of endogenous stem cells and the enhancement of anabolic responses for the treatment of OA.
Subject(s)
Chondrogenesis , Osteoarthritis , Mice , Animals , Chondrogenesis/physiology , Cartilage/pathology , Stem Cells/metabolism , Cell Differentiation , Osteoarthritis/metabolism , Chondrocytes/metabolism , Cells, Cultured , Ion Channels/metabolismABSTRACT
Osteoarthritis (OA) is a whole joint disorder that is characterized by cartilage damage and abnormal remodeling of subchondral bone. Injecting adipose-derived stem cells (ASCs) into the knee joint cavity can assist in repairing osteoarthritic joints, but their ability to migrate to the damaged site is limited. Our previous studies have shown that knee loading can improve the symptoms of OA, but the effect and mechanism of knee loading on the migration of ASCs in OA remain unclear. We employed a mouse model of OA in the knee and applied knee loading (1 N at 5 Hz for 6 min/day for 2 weeks) after the intra-articular injection of ASCs. The cartilage and subchondral bone repair were assessed by histopathological analysis. Immunofluorescence assays were also used to analyze the migration of ASCs. Using cell cultures, we evaluated the migration of ASCs using the transwell migration and wound healing assays. In vivo experiments showed that knee loading promoted the migration of ASCs, increased the local SDF-1 level, and accelerated the repair of the OA-damaged sites. Mechanistically, the observed effects were blocked by the SDF-1/CXCR4 inhibitor. The in vitro results further revealed that knee loading promoted the migration of ASCs and the inhibition of SDF-1/CXCR4 significantly suppressed the beneficial loading effect. The results herein suggested that the migration of ASCs was enhanced by knee loading through the SDF-1/CXCR4 regulatory axis, and mechanical loading promoted the joint-protective effect of ASCs.
Subject(s)
Knee Joint , Osteoarthritis , Adipose Tissue , Animals , Mice , Signal Transduction , Stem CellsABSTRACT
Exosomes are important transporters of miRNAs, which play varying roles in the healing of the bone fracture. Angiogenesis is one of such critical events in bone healing, and we previously reported the stimulatory effect of mechanical loading in vessel remodeling. Focusing on type H vessels and exosomal miR-214-3p, this study examined the mechanism of loading-driven angiogenesis. MiRNA sequencing and qRT-PCR revealed that miR-214-3p was increased in the exosomes of the bone-losing ovariectomized (OVX) mice, while it was significantly decreased by knee loading. Furthermore, compared to the OVX group, exosomes, derived from the loading group, promoted the angiogenesis of endothelial cells. In contrast, exosomes, which were transfected with miR-214-3p, decreased the angiogenic potential. Notably, knee loading significantly improved the microvascular volume, type H vessel formation, and bone mineral density and contents, as well as BV/TV, Tb.Th, Tb.N, and Tb.Sp. In cell cultures, the overexpression of miR-214-3p in endothelial cells reduced the tube formation and cell migration. Collectively, this study demonstrates that knee loading promotes angiogenesis by enhancing the formation of type H vessels and downregulating exosomal miR-214-3p.
Subject(s)
Bone Marrow Cells/metabolism , Exosomes/metabolism , Knee Joint , Mesenchymal Stem Cells/metabolism , MicroRNAs/metabolism , Neovascularization, Physiologic , Animals , Exosomes/genetics , Female , Knee Joint/blood supply , Knee Joint/metabolism , Mice , MicroRNAs/genetics , Weight-BearingABSTRACT
Gram-stain-positive, aerobic, non-spore-forming strains CCNWLXL 1-35T, CCNWLXL 12-2 and CCNWLXL 21-a, were isolated from wheat rhizosphere from Yangling, Shaanxi Province, China. Comparison of the 16S rRNA gene sequences showed that they belonged to the genus Arthrobacter and were closely related to Arthrobacter globiformis NBRC 12137T (97.95% similarity). Genomic relatedness analyses based on the average nucleotide identity and the genome-to-genome distance showed these strains constituted a single species. The major fatty acids was anteiso-C15:0. The polar lipids consist of diphosphatidylglycerol, phsophatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and glycolipid. The predominant menaquinone was MK-9. The peptidoglycan type was A4α. Thus, these strains were classified as representing a novel species in the genus Arthrobacter, for which the name Arthrobacter rhizosphaerae sp. nov. is proposed. The type strain is CCNWLXL 1-35T (=JCM 34638T, =CCTCC AB 2021087T) and additional strains are CCNWLXL 12-2 (=JCM 35018, =CCTCC AB 2021546), CCNWLXL 21-a (=JCM 35019, =CCTCC AB 2021545).
Subject(s)
Arthrobacter , Rhizosphere , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Soil Microbiology , TriticumABSTRACT
Selective adsorption of ligands on nanocrystal surfaces can affect oxidative etching. Here, we report the etching of palladium nanocrystals imaged using liquid cell transmission electron microscopy. The adsorption of surface ligands (i.e., iron acetylacetonate and its derivatives) and their role as inhibitor molecules on the etching process were investigated. Our observations revealed that the etching was dominated by the interplay between palladium facets and ligands and that the etching exhibited different pathways at different concentrations of ligands. At a low concentration of iron acetylacetonate (0.1 mM), rapid etching primarily at {100} facets led to a concave structure. At a high concentration (1.0 mM), the etch rate was decreased owing to a protective film of iron acetylacetonate on the {100} facets and a round nanoparticle was achieved. Ab initio calculations showed that the differences in adsorption energy of inhibitor molecules on palladium facets were responsible for the etching behavior.
Subject(s)
Nanoparticles , Palladium , Adsorption , Ligands , Microscopy, Electron, TransmissionABSTRACT
The calcineurin B-like-interacting protein kinase (CIPK) protein family plays a key role in the plant calcium ion-mediated signal transduction pathway, which regulates a plant's response to abiotic stress. Nitraria sibirica pall. (N. sibirica) is a halophyte with a strong tolerance for high salt environments, yet how it is able to deal with salt stress on a molecular level is still unknown. Due to their function as described in other plant species, CIPK genes are prime candidates for a role in salt stress signaling in N. sibirica. In this study, we identified and analyzed the phylogenetic makeup and gene expression of the N. sibirica CIPK gene family. A total of 14 CIPKs were identified from the N. sibirica genome and were clustered into seven groups based on their phylogeny. The promoters of NsCIPK genes contained multiple elements involved in hormonal and stress response. Synteny analysis identified a total of three pairs of synteny relationships between NsCIPK genes. Each gene showed its own specific expression pattern across different tissues, with the overall expression of CIPK6 being the lowest, and that of CIPK20 being the highest. Almost all CIPK genes tended to respond to salt, drought, and cold stress, but with different sensitivity levels. In this study, we have provided a general description of the NsCIPK gene family and its expression, which will be of great significance for further understanding of the NsCIPK gene family function.
Subject(s)
Gene Expression Regulation, Plant , Plant Proteins , Calcineurin/metabolism , Calcium/metabolism , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Protein Kinases/genetics , Protein Kinases/metabolism , Stress, Physiological/geneticsABSTRACT
Nitraria sibirica is a shrub that can survive in extreme drought environments. The auxin-response factors (ARFs) are a class of transcription factors that are widely involved in plant growth and development, as well as in the regulation of stress resistance. However, the genome-wide identification of the ARF gene family and its responses to environmental stresses, especially drought stress, in N. sibirica has not yet been reported. Here, we identified a total of 12 ARF genes in the genome of N. sibirica, which were distributed over 10 chromosomes and divided into three clades. Intragenome synteny analysis revealed one collinear gene pair in the ARF gene family, i.e., NsARF9a and NsARF9b. Cis-acting element analysis showed that multiple hormones and stress-responsive cis-acting elements were found in the promoters of NsARFs, suggesting that NsARFs may be involved in multiple biological processes. Quantitative real-time PCR (qRT-PCR) showed that many NsARFs had tissue-specific expression patterns, with the highest expression of NsARF16 in the seedlings of N. sibirica. In addition, most of the NsARFs that were upregulated under drought were independent of endogenous ABA biosynthesis, whereas the response of NsARF5 and NsARF7a to drought was disrupted by the ABA-biosynthesis inhibitor fluridone. These studies provide a basis for further research into how NsARFs in N. sibirica respond to hormonal signaling and environmental stresses.
Subject(s)
Indoleacetic Acids , Magnoliopsida , Gene Expression Profiling , Gene Expression Regulation, Plant , Hormones , Indoleacetic Acids/metabolism , Magnoliopsida/genetics , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Breast cancer, a common malignancy for women, preferentially metastasizes to bone and obesity elevates the chance of its progression. While mechanical loading can suppress obesity and tumor-driven osteolysis, its effect on bone-metastasized obese mice has not been investigated. Here, we hypothesized that mechanical loading can lessen obesity-associated bone degradation in tumor-invaded bone by regulating the fate of bone marrow-derived cells. In this study, the effects of mechanical loading in obese mice were evaluated through X-ray imaging, histology, cytology, and molecular analyses. Tumor inoculation to the tibia elevated body fat composition, osteolytic lesions, and tibia destruction, and these pathologic changes were stimulated by the high-fat diet (HFD). However, mechanical loading markedly reduced these changes. It suppressed osteoclastogenesis by downregulating receptor activator of nuclear factor Kappa-B ligand and cathepsin K and promoted osteogenesis, which was associated with the upregulation of OPG and downregulation of C/enhancer-binding protein alpha and proliferator-activated receptor gamma for adipogenic differentiation. Furthermore, it decreased the levels of tumorigenic genes such as Rac1, MMP9, and interleukin 1ß. In summary, this study demonstrates that although a HFD aggravates bone metastases associated with breast cancer, mechanical loading significantly protected tumor-invaded bone by regulating the fate of bone marrow-derived cells. The current study suggests that mechanical loading can provide a noninvasive, palliative option for alleviating breast cancer-associated bone metastasis, in particular for obese patients.
Subject(s)
Bone Marrow/pathology , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Cellular Microenvironment , Adipocytes/pathology , Adipogenesis , Adipose Tissue , Animals , Body Weight , Cancellous Bone/pathology , Cell Line, Tumor , Cell Proliferation , Female , Mice, Inbred BALB C , Mice, Obese , Osteoblasts/pathology , Osteoclasts/pathology , Osteogenesis , Osteolysis/complications , Osteolysis/pathology , Weight-BearingABSTRACT
Covalent organic frameworks (COFs) with efficient charge transport and exceptional chemical stability are emerging as an import class of semiconducting materials for opto-/electronic devices and energy-related applications. However, the limited synthetic chemistry to access such materials and the lack of mechanistic understanding of carrier mobility greatly hinder their practical applications. Herein, we report the synthesis of three chemically stable polyarylether-based metallophthalocyanine COFs (PAE-PcM, M = Cu, Ni, and Co) and facile in situ growth of their thin films on various substrates (i.e., SiO2/Si, ITO, quartz) under solvothermal conditions. We show that PAE-PcM COFs thin films with van der Waals layered structures exhibit p-type semiconducting properties with the intrinsic mobility up to â¼19.4 cm2 V-1 s-1 and 4 orders of magnitude of increase in conductivity for PAE-PcCu film (0.2 S m-1) after iodine doping. Density functional theory calculations reveal that the carrier transport in the framework is anisotropic, with the out-of-plane hole transport along columnar stacked phthalocyanine more favorable. Furthermore, PAE-PcCo shows the redox behavior maximumly contributes â¼88.5% of its capacitance performance, giving rise to a high surface area normalized capacitance of â¼19 µF cm-2. Overall, this work not only offers fundamental understandings of electronic properties of polyarylether-based 2D COFs but also paves the way for their energy-related applications.
ABSTRACT
Osteoporotic osteoarthritis (OPOA) is a common bone disease mostly in the elderly, but the relationship between Osteoporotic (OP) and osteoarthritis (OA) is complex. It has been shown that knee loading can mitigate OA symptoms. However, its effects on OPOA remain unclear. In this study, we characterized pathological linkage of OP to OA, and evaluated the effect of knee loading on OPOA. We employed two mouse models (OA and OPOA), and conducted histology, cytology, and molecular analyses. In the OA and OPOA groups, articular cartilage was degenerated and Osteoarthritis Research Society International score was increased. Subchondral bone underwent abnormal remodeling, the differentiation of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts and chondrocytes was reduced, and migration and adhesion of pre-osteoclasts were enhanced. Compared to the OA group, the pathological changes of OA in the OPOA group were considerably aggravated. After knee loading, however, cartilage degradation was effectively prevented, and the abnormal remodeling of subchondral bone was significantly inhibited. The differentiation of BMSCs was also improved, and the expression of Wnt/ß-catenin was elevated. Collectively, this study demonstrates that osteoporosis aggravates OA symptoms. Knee loading restores OPOA by regulating subchondral bone remodeling, and may provide an effective method for repairing OPOA.
Subject(s)
Cartilage, Articular/metabolism , Osteoarthritis/therapy , Osteoporosis, Postmenopausal/therapy , Weight-Bearing , Wnt Signaling Pathway , Animals , Cartilage, Articular/pathology , Cell Adhesion , Cell Differentiation , Cell Movement , Cells, Cultured , Chondrocytes/cytology , Chondrocytes/metabolism , Chondrocytes/physiology , Female , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , Osteoarthritis/etiology , Osteoarthritis/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism , Osteoblasts/physiology , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/metabolismABSTRACT
Breast cancer is a serious health problem that preferentially metastasizes to bone. We have previously shown that bone loss can be prevented by mechanical loading, but the efficacy of ankle loading for metastasis-linked bone loss has not been investigated. This study showed that body weight was decreased after inoculation of tumor cells, but ankle loading restored a rapid weight loss. The nonloading group exhibited a decrease in bone volume/tissue volume (BV/TV), trabecular thickness, and trabecular number (all P < 0.01) as well as an increase in trabecular separation (P < 0.001). However, ankle loading improved those changes (all P < 0.05). Furthermore, although the nonloading group increased the tumor bearing as well as expression of IL-8 and matrix metalloproteinase 9, ankle loading decreased them. Induction of tumor in the bone elevated the osteoclast number (P < 0.05) as well as the levels of nuclear factor of activated T-cells cytoplasmic 1, NF-κB ligand, cathepsin K, and serum tartrate-resistant acid phosphatase type 5b, but ankle loading reduced osteoclast activity and those levels (all P < 0.05). Tumor bearing was positively correlated with the osteoclast number (P < 0.01) and negatively correlated with BV/TV and the osteoblast number (both P < 0.01). Collectively, these findings demonstrate that ankle loading suppresses tumor growth and osteolysis by inhibiting bone resorption and enhancing bone formation.-Yang, S., Liu, H., Zhu, L., Li, X., Liu, D., Song, X., Yokota, H., Zhang, P. Ankle loading ameliorates bone loss from breast cancer-associated bone metastasis.
Subject(s)
Bone Neoplasms/secondary , Bone Resorption/prevention & control , Mammary Neoplasms, Experimental/therapy , Animals , Body Weight , Bone Neoplasms/complications , Bone Neoplasms/pathology , Bone Resorption/etiology , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Mammary Neoplasms, Experimental/pathology , Mammary Neoplasms, Experimental/physiopathology , Mice , Mice, Inbred BALB C , Osteoblasts/pathology , Osteoclasts/pathology , Osteolysis , Stress, Mechanical , Tarsus, Animal , Tumor Burden , Weight-Bearing/physiologyABSTRACT
Osteoporosis is a major health problem, making bones fragile and susceptible to fracture. Previous works showed that mechanical loading stimulated bone formation and accelerated fracture healing. Focusing on the role of Wnt3a (wingless/integrated 3a), this study was aimed to assess effects of mechanical loading to the spine, using ovariectomized (OVX) mice as a model of osteoporosis. Two-week daily application of this novel loading (4 N, 10 Hz, 5 min/d) altered bone remodeling with an increase in Wnt3a. Spinal loading promoted osteoblast differentiation, endothelial progenitor cell migration, and tube formation and inhibited osteoclast formation, migration, and adhesion. A transient silencing of Wnt3a altered the observed loading effects. Spinal loading significantly increased bone mineral density, bone mineral content, and bone area per tissue area. The loaded OVX group showed a significant increase in the number of osteoblasts and reduction in osteoclast surface/bone surface. Though expression of osteoblastic genes was increased, the levels of osteoclastic genes were decreased by loading. Spinal loading elevated a microvascular volume as well as VEGF expression. Collectively, this study supports the notion that Wnt3a-mediated signaling involves in the effect of spinal loading on stimulating bone formation, inhibiting bone resorption, and promoting angiogenesis in OVX mice. It also suggests that Wnt3a might be a potential therapeutic target for osteoporosis treatment.-Li, X., Liu, D., Li, J., Yang, S., Xu, J., Yokota, H., Zhang, P. Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model.
Subject(s)
Bone Remodeling , Neovascularization, Physiologic , Osteoporosis, Postmenopausal/metabolism , Weight-Bearing , Wnt3A Protein/metabolism , Animals , Bone Density , Cells, Cultured , Female , Humans , Mice , Mice, Inbred C57BL , Osteoblasts/cytology , Osteoblasts/metabolism , Osteogenesis , Osteoporosis, Postmenopausal/etiology , Osteoporosis, Postmenopausal/therapy , Ovariectomy/adverse effects , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Wnt3A Protein/geneticsABSTRACT
Osteoarthritis (OA) is a disease characterized by cartilage damage and abnormal remodeling of subchondral bone. Our previous study showed that in the early stage of OA, knee loading exerts protective effects by suppressing osteoclastogenesis through Wnt signaling, but little is known about loading effects at the late OA stage. Endoplasmic reticulum (ER) stress and autophagy are known to be involved in the late OA stage. We determined the effects of mechanical loading on ER stress and autophagy in OA mice. One hundred seventy-four mice were used for a surgery-induced OA model. In the first set of experiments, 60 mice were devoted to evaluation of the role of ER stress and autophagy in the development of OA. In the second set, 114 mice were used to assess the effect of knee loading on OA. Histologic, cellular, microcomputed tomography, and electron microscopic analyses were performed to evaluate morphologic changes, ER stress, and autophagy. Mechanical loading increased phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and regulated expressions of autophagy markers LC3II/I and p62. Osteoarthritic mice also exhibited an elevated ratio of calcified cartilage to total articular cartilage (CC/TAC), and synovial hyperplasia with increased lining cells was found. At the early disease stage, subchondral bone plate thinning and reduced subchondral bone volume fraction (B.Ar/T.Ar) were observed. At the late disease stages, subchondral bone plate thickened concomitant with increased B.Ar/T.Ar. Mice subjected to mechanical loading exhibited resilience to cartilage destruction and a correspondingly reduced Osteoarthritis Research Society International score at 4 and 8 wk, as well as a decrease in synovitis and CC/TAC. While chondrocyte numbers in the OA group was notably decreased, mechanical loading restored chondrogenic differentiation. These results demonstrate that mechanical loading can retard the pathologic progression of OA at its early and late stages. The observed effects of loading are associated with the regulations of ER stress and autophagy.-Zheng, W., Li, X., Liu, D., Li, J., Yang, S., Gao, Z., Wang, Z., Yokota, H., Zhang, P. Mechanical loading mitigates osteoarthritis symptoms by regulating endoplasmic reticulum stress and autophagy.
Subject(s)
Autophagy , Endoplasmic Reticulum Stress , Osteoarthritis/metabolism , Stress, Mechanical , Animals , Cartilage, Articular/metabolism , Cells, Cultured , Eukaryotic Initiation Factor-2/metabolism , Female , Mice , Mice, Inbred C57BL , Microtubule-Associated Proteins/metabolism , Sequestosome-1 Protein/metabolismABSTRACT
AIM: Hormonal and nutritional disorders are the main causes of obesity and non-alcoholic fatty liver disease, especially in the elderly and in postmenopausal women. Although physical activity might alleviate these disorders, the elderly may often have difficulty in carrying out physical exercise. The purpose of this study was to investigate the therapeutic effect of knee loading, a new form of physical stimulation, on the symptoms of obesity and fatty liver. METHODS: Using ovariectomized mice fed a high-fat diet, we evaluated the effect of knee loading that applies gentle cyclic loads to the knee. Female C57BL/6 mice were divided into five groups: control (SCD), high-fat diet (HF), HF with loading (HF + L), HF with ovariectomy (HF + OVX), and HF + OVX with loading (HF + OVX + L). Except for SCD, mice underwent sham operation or ovariectomy and were maintained on HF diet. After 6 weeks, the mice in the HF + L and HF + OVX + L groups were treated with knee loading for 6 weeks. RESULTS: Compared to the obesity groups (HF and HF + OVX), knee loading significantly decreased a gain in body weight, liver weight, and white adipose tissue (all P < 0.01). It also reduced the lipid level in the serum (P < 0.01) and histological severity of hepatic steatosis (P < 0.01). Furthermore, knee loading downregulated biomarkers related to endoplasmic reticulum (ER) stress (GRP78, p-eIF2α, and ATF4) and altered biomarkers in autophagy (LC3 and p62). CONCLUSIONS: Knee loading suppressed obesity-associated metabolic alterations and hepatic steatosis. These effects with knee loading might be associated with suppression of ER stress and promotion of autophagy.
ABSTRACT
Atomically ordered intermetallic nanoparticles (iNPs) have sparked considerable interest in fuel cell applications by virtue of their exceptional electronic and structural properties. However, the synthesis of small iNPs in a controllable manner remains a formidable challenge because of the high temperature generally required in the formation of intermetallic phases. Here we report a general method for the synthesis of PtZn iNPs (3.2 ± 0.4 nm) on multiwalled carbon nanotubes (MWNT) via a facile and capping agent free strategy using a sacrificial mesoporous silica (mSiO2) shell. The as-prepared PtZn iNPs exhibited ca. 10 times higher mass activity in both acidic and basic solution toward the methanol oxidation reaction (MOR) compared to larger PtZn iNPs synthesized on MWNT without the mSiO2 shell. Density functional theory (DFT) calculations predict that PtZn systems go through a "non-CO" pathway for MOR because of the stabilization of the OH* intermediate by Zn atoms, while a pure Pt system forms highly stable COH* and CO* intermediates, leading to catalyst deactivation. Experimental studies on the origin of the backward oxidation peak of MOR coincide well with DFT predictions. Moreover, the calculations demonstrate that MOR on smaller PtZn iNPs is energetically more favorable than larger iNPs, due to their high density of corner sites and lower-lying energetic pathway. Therefore, smaller PtZn iNPs not only increase the number but also enhance the activity of the active sites in MOR compared with larger ones. This work opens a new avenue for the synthesis of small iNPs with more undercoordinated and enhanced active sites for fuel cell applications.
ABSTRACT
The facile pyrolysis of a bipyridyl metal-organic framework, MOF-253, produces N-doped porous carbons (Cz-MOF-253), which exhibit excellent catalytic activity in the Knoevenagel condensation reaction and outperform other nitrogen-containing MOF-derived carbons. More importantly, by virtue of their high Lewis basicity and porous nature, Cz-MOF-253-supported Pd nanoparticles (Pd/Cz-MOF-253-800) show excellent performance in a one-pot sequential Knoevenagel condensation-hydrogenation reaction.
ABSTRACT
Nitrones are key intermediates in organic synthesis and the pharmaceutical industry. The heterogeneous synthesis of nitrones with multifunctional catalysts is extremely attractive but rarely explored. Herein, we report ultrasmall platinum nanoclusters (PtNCs) encapsulated in amine-functionalized Zr metal-organic framework (MOF), UiO-66-NH2 (Pt@UiO-66-NH2 ) as a multifunctional catalyst in the one-pot tandem synthesis of nitrones. By virtue of the cooperative interplay among the selective hydrogenation activity provided by the ultrasmall PtNCs and Lewis acidity/basicity/nanoconfinement endowed by UiO-66-NH2 , Pt@UiO-66-NH2 exhibits remarkable activity and selectivity, in comparison to Pt/carbon, Pt@UiO-66, and Pd@UiO-66-NH2 . Pt@UiO-66-NH2 also outperforms Pt nanoparticles supported on the external surface of the same MOF (Pt/UiO-66-NH2 ). To our knowledge, this work demonstrates the first examples of one-pot synthesis of nitrones using recyclable multifunctional heterogeneous catalysts.