Temperature‐dependent dual fluorescence and switchable circularly polarized luminescence (CPL) are two highly pursued but challenging properties for small organic molecules (SOMs). We herein disclose ...a triarylborane π‐system based on a 2,2′‐diamino‐6,6′‐diboryl‐1,1′‐binaphthyl scaffold that can serve as a versatile building block for achieving these two properties by simply choosing different amino groups. BNMe2‐BNaph with less bulky dimethylamino groups displays temperature‐dependent dual fluorescence, and can thus be used as a highly sensitive ratiometric fluorescence thermometer. On the other hand, BNPh2‐BNaph with bulky diphenylamino groups exhibits intense fluorescence in both solution and in the solid state. A change of solvent from nonpolar cyclohexane to highly polar MeCN not only shifts the CPL position to much longer wavelength but also inverts the CPL sign. In addition, the complexation of BNPh2‐BNaph with fluoride greatly enhances the CPL intensity.
The combination of two donor–π‐acceptor subunits in the 2,2′‐diamino‐6,6′‐diboryl‐1,1′‐binaphthyl scaffold generates a versatile building block for organic fluorophores exhibiting temperature‐dependent dual fluorescence and switchable circularly polarized luminescence.
In elderly people particularly in postmenopausal women, inadequate bone formation by osteoblasts originating from bone marrow mesenchymal stem cells (BMSCs) for compensation of bone resorption by ...osteoclasts is a major reason for osteoporosis. Enhancing osteoblastic differentiation of BMSCs is a feasible therapeutic strategy for osteoporosis. Here, bone marrow stromal cell (ST)-derived exosomes (STExos) are found to remarkably enhance osteoblastic differentiation of BMSCs
in vitro
. However, intravenous injection of STExos is inefficient in ameliorating osteoporotic phenotypes in an ovariectomy (OVX)-induced postmenopausal osteoporosis mouse model, which may be because STExos are predominantly accumulated in the liver and lungs, but not in bone. Hereby, the STExo surface is conjugated with a BMSC-specific aptamer, which delivers STExos into BMSCs within bone marrow. Intravenous injection of the STExo-Aptamer complex enhances bone mass in OVX mice and accelerates bone healing in a femur fracture mouse model. These results demonstrate the efficiency of BMSC-specific aptamer-functionalized STExos in targeting bone to promote bone regeneration, providing a novel promising approach for the treatment of osteoporosis and fracture.
A novel strategy to deliver therapeutic exosomes to bone is developed for the first time by conjugating a specific BMSC-targeting aptamer to the exosomal surface.
Due to the wet and dynamic environment of the oral cavity, the healing of intraoral wounds, such as tooth extraction wounds, requires stable and firm wound dressings. In clinical practice, cotton ...balls and gauzes, sponge plugs, or sutures are used to treat extraction wounds, but none of these means can continuously isolate the wound from the intraoral environment and facilitate ideal healing conditions. Herein, inspired by the natural extracellular matrix, a family of wound dressings is developed for intraoral wound repair. Infiltrating a ductile long‐chain hydrogel network into a prefabricated, sturdy macromolecular meshwork and in situ crosslinking endowed the composite hydrogel with controllable swelling behaviors and robust mechanical properties. The macromolecular meshwork functioned as the backbone to support the composite and restricts the swelling of the long‐chain hydrogel network. In vitro tests verified that this wound dressing can provide durable protection for intraoral wounds against complex irritations. Furthermore, accelerated wound healing occurred when the wound dressing is applied in vivo on a canine tooth extraction model, due to the effective reduction of acute inflammation. These results suggest that this family of bioinspired hydrogels has great potential for application as intraoral wound dressing.
An extracellular matrix‐mimicking hydrogel wound dressing is designed as tooth extraction adhesive wound dressing for intraoral application. The hydrogel exhibits excellent anti‐swelling efficiency, along with consistent mechanical and adhesive robustness in aqueous environments. In vitro and in vivo tooth extraction models demonstrate the stability of hydrogels as physical and antibacterial barriers for intraoral wounds, leading to continuous protection and effective healing acceleration.
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. ...Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.
Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate ...abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF signaling promotes cystine uptake and biosynthesis of glutathione (GSH) to protect fibroblasts from ferroptosis. Lastly, low dose IKE together with etanercept, a TNF antagonist, induce ferroptosis in fibroblasts and attenuate arthritis progression in the CIA model. Our results thus imply that the combination of TNF inhibitors and ferroptosis inducers may serve as a potential candidate for RA therapy.
The Role of Autophagy in Osteoarthritis Duan, Ran; Xie, Hui; Liu, Zheng-Zhao
Frontiers in cell and developmental biology,
11/2020, Letnik:
8
Journal Article
Recenzirano
Odprti dostop
Chondrocytes are the only cell type in normal cartilage. The pathological changes of osteoarthritis (OA) mostly revolve around the apoptosis and dysfunction of chondrocytes. Autophagy, as an ...intracellular degradation system that maintains the steady state of energy metabolism in cells, has been shown to restore the function of damaged chondrocytes, alleviating the occurrence and progression of OA. In this review, we explored the relationship between autophagy and OA and the key molecules of autophagy pathway that regulate the progression of OA, providing new ideas for OA treatment by targeting autophagy.
Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular ...calcification often occurs with osteoporosis, a contradictory association called "calcification paradox". Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.
On Similarity Preserving Feature Selection Zhao, Zheng; Wang, Lei; Liu, Huan ...
IEEE transactions on knowledge and data engineering,
03/2013, Letnik:
25, Številka:
3
Journal Article
Recenzirano
In the literature of feature selection, different criteria have been proposed to evaluate the goodness of features. In our investigation, we notice that a number of existing selection criteria ...implicitly select features that preserve sample similarity, and can be unified under a common framework. We further point out that any feature selection criteria covered by this framework cannot handle redundant features, a common drawback of these criteria. Motivated by these observations, we propose a new "Similarity Preserving Feature Selection" framework in an explicit and rigorous way. We show, through theoretical analysis, that the proposed framework not only encompasses many widely used feature selection criteria, but also naturally overcomes their common weakness in handling feature redundancy. In developing this new framework, we begin with a conventional combinatorial optimization formulation for similarity preserving feature selection, then extend it with a sparse multiple-output regression formulation to improve its efficiency and effectiveness. A set of three algorithms are devised to efficiently solve the proposed formulations, each of which has its own advantages in terms of computational complexity and selection performance. As exhibited by our extensive experimental study, the proposed framework achieves superior feature selection performance and attractive properties.
In this study, we developed a novel biosensor based on highly exposed Pt nanoparticles (Pt NPs) decorated porous graphene (PG) for the reliable detection of extracellular hydrogen peroxide (H2O2) ...released from living cells. The commercially available low-cost hydrophilic CaCO3 spheres were used as template for preparing PG. The porous structure provided larger surface area and more active sites. Due to the porous structure of PG, the Pt NPs supported on PG were not secluded by aggregated graphene layers and were highly exposed to target molecules. Ultrafine Pt NPs were well dispersed and loaded on PG by a method of microwave assistance. Electrochemical performances of the Pt/PG nanocomposites modified glassy carbon electrode (GCE) were investigated. The electrocatalytic reduction of H2O2 showed a wide linear range from 1 to 1477μM, with a high sensitivity of 341.14μAmM−1cm−2 and a limit of detection (LOD) as low as 0.50μM. Moreover, the Pt/PG/GCE exhibited excellent anti-interference property, reproducibility and long-term storage stability. Because of these remarkable analytical advantages, the constructed sensor was used to determine H2O2 released from living cells with satisfactory results. The superior catalytic activity makes Pt/PG nanocomposites a promising candidate for electrochemical sensors and biosensors design.
•Construction of porous graphene with large surface area and porous structure.•Pt nanoparticles with small size and good dispersion supported on porous graphene.•Excellent sensing properties of Pt/porous graphene towards H2O2.•Sensitive detection of H2O2 released from living cells at Pt/porous graphene.
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