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Introducing hydroxylapatite (HAp) into biomolecular materials is a promising approach to improve their bone regenerative capability. Thus a facile method needs to be developed to achieve this goal. Here we show that a simple air-plasma treatment of silk fibroin (SF) films for 5 min induced the formation of bone-like plate-shaped nano-HAp (nHAp) on their surface and the resultant material efficiently enhanced in vivo osteogenesis. The air-plasma-treated SF films (termed A-SF) presented surface nano-pillars and enhanced hydrophilicity compared to the pristine SF films (termed SF), making the A-SF and SF films induce the formation of plate-shaped/more-crystalline and needle-like/less-crystalline nHAp, respectively. The mineralized A-SF and SF films (termed A-SF-nHAp and SF-nHAp, respectively) and their non-mineralized counterparts were seeded with rat mesenchymal stem cells and subcutaneously implanted into the rat models. The A-SF-nHAp and A-SF films exhibited more efficient bone formation than the SF-nHAp and SF films in 4 weeks due to their unique nanotopography, with the A-SF-nHAp films being more efficient than the A-SF films. This work shows that a combination of the air-plasma treatment and the subsequent nHAp mineralization most efficiently promotes bone formation. Our plasma-based method is an attractive approach to enhance the bone regenerative capacity of protein-based biomaterials.

Although polymeric nanoconjugates (NCs) hold great promise for the treatment of cancer patients, their clinical utility has been hindered by the lack of efficient delivery of therapeutics to targeted tumor sites. Here, we describe an albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium barrier through a caveolae-mediated transcytosis pathway to better target cancer. The Alb-NC is prepared by nanoprecipitation of doxorubicin (Doxo) conjugates of poly(phenyl O -carboxyanhydrides) bearing aromatic albumin-binding domains followed by subsequent surface decoration of albumin. The administration of Alb-NCs into mice bearing MCF-7 human breast cancer xenografts with limited tumor vascular permeability resulted in markedly increased tumor accumulation and anti-tumor efficacy compared to their conventional counterpart PEGylated NCs (PEG-NCs). The Alb-NC provides a simple, low-cost and broadly applicable strategy to improve the cancer targeting efficiency and therapeutic effectiveness of polymeric nanomedicine.

Calcific aortic valve disease (CAVD) is the most frequent cardiac valve pathology. Its standard treatment consists of surgical replacement either with mechanical (metal made) or biological (animal tissue made) valve prostheses, both of which have glaring deficiencies. In the search for novel materials to manufacture artificial valve tissue, we have conducted a high-throughput screening with subsequent up-scaling to identify non-degradable polymer substrates that promote valve interstitial cells (VICs) adherence/growth and, at the same time, prevent their evolution toward a pro-calcific phenotype. Here, we provide evidence that one of the two identified ‘hit’ polymers, poly(methoxyethylmethacrylate- co -diethylaminoethylmethacrylate), provided robust VICs adhesion and maintained the healthy VICs phenotype without inducing pro-osteogenic differentiation. This ability was also maintained when the polymer was used to coat a non-woven poly-caprolactone (PCL) scaffold using a novel solvent coating procedure, followed by bioreactor-assisted VICs seeding. Since we observed that VICs had an increased secretion of the elastin-maturing component MFAP4 in addition to other valve-specific extracellular matrix components, we conclude that valve implants constructed with this polyacrylate will drive the biological response of human valve-specific cells.

Metabolic syndrome (MetS) includes central obesity, hypertension, insulin resistance, and dyslipidemia and is closely related to nonalcoholic fatty liver disease, atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus, involving multiple causative factors. Current drug therapies for intervention and amelioration of MetS are essential in clinical treatment of metabolic disease. In this report, we proposed an H + -modified montmorillonite (H-MMT) using an acid modification method with ultrafine structure and super absorption ability as a potential drug for MetS. Hamsters fed a high-fat diet were orally treated with H-MMT and simvastatin was applied as a control. H-MMT lowered lipids by decreasing intestinal absorption and promoting lipid excretion, subsequently preventing obesity, fatty liver, and hyperlipidemia. Moreover, H-MMT was significantly safer and better tolerated by the liver compared to simvastatin, which was hepatotoxic. In addition, we found that H-MMT had protective effects on gastric mucosal damage. Therefore, this versatile H-MMT provides a potential strategy to effectively improve MetS and provide gastric mucosal protection in clinical applications.

Biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) play important roles in various physiological and pathological processes, and due to their similar structures and reaction activities, it is still challenging to simultaneously discriminate between GSH and Cys/Hcy in vivo . Hence, a novel fluorescent probe for simultaneously discriminating GSH and Cys/Hcy in biological samples is highly desirable. Herein, we presented two enhanced fluorescent probes (Cy1 and Cy2) with doubly-activated dual emission for sensitive and discriminative detection of Cys/Hcy and GSH. The probes were constructed with IR-780 and NBD linked via an ether bond, which responds to GSH with near infrared (NIR) emission at 810 nm ( λ ex = 720 nm) and Cys/Hcy with visible green emission at 550 nm ( λ ex = 470 nm). The probe Cy2 is operable in human serum samples, thus holding promise for its diagnosis-related application. Notably, the results of fluorescence microscopy imaging indicated that Cy2 is suitable for visualization of exogenous and endogenous biothiols in living cells. Furthermore, desirable results were obtained when the probe Cy2 was applied for bioimaging in tumor-bearing mice and acute liver injury (ALI) mice models, which revealed encouraging clinical values of this probe.

Coronary stent implantation is an effective procedure for percutaneous coronary intervention treatment. However, its long-term safety and efficacy are still hindered by the in-stent restenosis and late thrombus formation. Herein, an anti-biofouling and endothelial cell selective zwitterionic hydrogel coating was developed to simultaneously enhance the nonspecific resistance and rapid re-endothelialization of the titanium surface. An endothelial cell selective peptide, REDV, could be simply conjugated on the zwitterionic carboxybetaine (CB) hydrogel to prepare the REDV/CB coating. It was found that the REDV/CB hydrogel layer maintained antifouling properties, which could inhibit the protein adsorption, bacterial adhesion, platelet activation and aggregation, and smooth muscle cell proliferation. More importantly, the co-culture study confirmed that the conjugated REVD peptide could specifically capture endothelial cells and promote their migration and proliferation, and simultaneously decrease the adhesion and proliferation of smooth muscle cells. Therefore, the antifouling and endothelial cell selective coating proposed in this work provides a promising strategy to develop an intravascular stent for promoted re-endothelialization and inhibited neointimal hyperplasia in clinical applications.

Silver sulfide quantum dots (Ag 2 S QDs) as a theragnostic agent have received much attention because they provide excellent optical and chemical properties to facilitate diagnosis and therapy simultaneously. Ag 2 S QDs possess brightness and photostability suitable for intense and stable bioimaging. It has been verified via in vitro and in vivo studies that Ag 2 S QDs do not cause serious toxicity, unlike the first generation of widely used heavy metal-based (cadmium or lead) QDs. In particular, Ag 2 S QDs emit in the near infrared-II region (NIR-II window) that enables deep tissue penetration and imaging. Furthermore, various chemotherapeutic agents and targeting moieties can be efficiently conjugated to the surface of Ag 2 S QDs due to advanced technologies in the relevant surface chemistry using covalent bonding, high affinity, and electrostatic interaction. In addition, Ag 2 S QDs themselves exhibit an anticancer activity based on the photothermal effect. Consequently, Ag 2 S QDs can function as both a therapeutic agent and an imaging agent in imaging-based diagnosis concurrently, which led to the creation of Ag 2 S theragnostic nanomaterials. In this review, the synthetic methods, physicochemical properties, bioconjugations, and bioapplications of Ag 2 S QD theragnostic nanomaterials are discussed in detail.

Immobilization of membrane proteins on solid supports with high stability, favorable reusability and prevention of contamination is of great interest in nanobiology and medicine. Cell membrane coating technology enables the membrane proteins associated with their surrounding membranes to co-immobilize onto the solid matrix, largely enhancing the loading efficiency and conserving the bioactivity of the membrane proteins. Herein, we systematically illustrate the mechanism of cell membrane immobilization on porous silica beads, facilitating the fabricated biomimic carriers applied for chromatography. Rabbit red blood cell membranes were obtained via a low permeability swelling method. Batch immobilization studies were carried out to investigate the effects of the pore size of porous silica beads and incubation time on cell membrane immobilization. The absorption behavior of cell membranes could be well described by a pseudo-second-order kinetic model and the Freundlich model (a multilayer adsorption process) at 298 K, demonstrating an insertion/self-fusion mechanism involved in cell membrane coating onto the surface of porous silica beads. The insertion/self-fusion mechanism was further confirmed by confocal imaging and transmission electron microscopy.

Prodrug strategy especially in the field of chemotherapy of cancers possesses significant advantages reducing the side toxicity of anticancer drugs. However, high-efficiency delivery and in situ activation of prodrugs for tumor growth suppression are still a great challenge. Herein, we report rationally engineered pH-responsive endosomolytic polymeric micelles for the delivery of an oxidation-activable prodrug into the cytoplasm of cancer cells and amplification of intracellular oxidative stress for further prodrug activation. The prepared block copolymers consist of a poly(ethylene glycol) (PEG) block and a segment grafted by endosomolytic moieties and acetal linkage-connected cinnamaldehyde groups. The amphiphilic diblock copolymers can self-assemble to form micelles in water for loading the oxidation-activable phenylboronic pinacol ester-caged camptothecin prodrug (ProCPT). The obtained micelles can release free cinnamaldehyde under acidic conditions in tumor tissues and endo/lysosomes followed by efficient endosomal escape, which further induces enhancement of intracellular reactive oxygen species (ROS) to activate the prodrugs. Simultaneously, intracellular glutathione (GSH) can be reduced by quinone methide that was produced during prodrug activation. The ProCPT-loaded micelles can finally achieve efficient tumor accumulation and retention as well as effective tumor growth inhibition. More importantly, hematological and pathological analysis of toxicity reveals that the ProCPT-loaded micelles do not cause obvious toxic side effects toward important organs of mice. A positive immunomodulatory microenvironment in tumor tissue and serum can be detected after treatment with ProCPT-loaded micelles. Therefore, the endosomolytic ProCPT-loaded micelles exert synergistic therapeutic effects toward tumors through amplification of intracellular oxidative stress and activation of the prodrugs.

A novel photosensitizer carbazolyl-BODIPY (Cz-BODIPY) with an orthogonal donor–acceptor structure was developed for photodynamic therapy (PDT). The photosensitizer Cz-BODIPY showed strong singlet oxygen sensitizing capability ( Φ Δ = 0.68 in MeOH), excellent water solubility in dilute solution, and high photostability. The photosensitizer Cz-BODIPY exhibited negligible dark cytotoxicity and high phototoxicity (IC 50 0.45 μM). Cz-BODIPY could induce cell apoptosis upon light illumination. Three cell states including living cells, apoptotic cells, and dead cells in the PDT process of Cz-BODIPY were determined via the Hoechst 33342/PI dual staining assays. The ROS (reactive oxygen species) generation in living cells during the PDT process of Cz-BODIPY was captured by the ROS detector, dihydroethidium (DHE). The photosensitizer Cz-BODIPY could be assimilated by zebrafish to generate ROS and diminish the integrity of zebrafish tissue upon light illumination. Tumor cell growth could be inhibited by Cz-BODIPY upon light illumination. The photosensitizer Cz-BODIPY displayed potential in real PDT application.