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Semi-quantitative evaluation was performed on matching two-dimensional (2D) histology and microCT images. Reproducibility of the QMA was tested on eleven age-matched additional joints. The results indicate the QMA method is accurate and reproducible and that microCT-derived cartilage measurements are valid for the analysis of rat joints. The pathologic changes caused by transection of the ACL and medial meniscectomy were reflected in measurements of bone shape, cartilage morphology, and joint alignment. Furthermore, we were able to identify model-specific predictive parameters based on morphometric parameters measured with the QMA.The antiretroviral (ARV) cocktailrevolved the treatment of the human immunodeficiency virus (HIV) infection. Drug combinations have been also tested to treat other infectious diseases, including the recentcoronavirus disease 2019 (COVID-19) outbreak. To simplify administration fixed-dose combinationshave been introduced, however, oral anti-HIV therapy still struggles with low oral bioavailability of many ARVs.This work investigated the co-encapsulation of two clinically relevant ARV combinations,tipranavir (TPV)efavirenz (EFV) anddarunavir (DRV)efavirenz (EFV)ritonavir (RTV),within the core of β-casein (bCN) micelles. Encapsulation efficiency in both systems was ~100%. Cryo-transmission electron microscopy and dynamic light scattering of the ARV-loaded colloidaldispersions indicatefull preservation of the spherical morphology, and x-ray diffraction confirm that the encapsulated drugs are amorphous. To prolong the physicochemical stabilitythe formulations were freeze-driedwithout cryo/lyoprotectant, and successfully redispersed, with minor changes in morphology.Then, theARV-loaded micelles were encapsulated within microparticles of Eudragit® L100, which prevented enzymatic degradation and minimized drug release under gastric-like pH conditionsin vitro. At intestinal pH, the coating polymer dissolved and released the nanocarriers and content. Overall, our results confirm the promise of this flexible and modular technology platform for oral delivery of fixed dose combinations.Currently, there are no clinically available tissue adhesives that work effectively in the fluid-rich and highly dynamic environments of the human body, such as the urinary system. This is especially relevant to the management of vesico-vaginal fistula, and developing a high-performance tissue adhesive for this purpose could vastly expand urologists' surgical repertoire and dramatically reduce patient discomfort. Herein, we developed a water-immiscible mussel protein-based bioadhesive (imWIMBA) with significantly improved properties in all clinical respects, allowing it to achieve rapid and strong underwater adhesion with tunable rheological properties. We evaluated in vivo potential of imWIMBA for sealing thermally injured fistula tracts between the bladder and vagina. Importantly, the use of imWIMBA in the presence of prolonged bladder drainage resulted in perfect closure of the vesico-vaginal fistula in operated pigs. Thus, imWIMBA could be successfully used for many surgical applications and improve treatment efficacy when combined with conventional surgical methods. STATEMENT OF SIGNIFICANCE Vesico-vaginal fistula (VVF) is an abnormal opening between the bladder and the vagina, which is a stigmatized disease in many developing countries. Leakage of urine into internal organs can induce serious complications and delay wound repair. Conventional VVF treatment requires skillful suturing to provide a tension-free and watertight closure. In addition, there is no clinically approved surgical glue that works in wet and highly dynamic environments such as the urinary system. In this work, for potential clinical VVF closure and regeneration, we developed an advanced immiscible mussel protein-based bioglue with fast, strong, wet adhesion and tunable rheological properties. This regenerative immiscible bioglue could be successfully used for sealing fistulas and further diverse surgical applications as an adjuvant for conventional suture methods.On-demand therapy following effective tumor detection would considerably reduce the side effects of traditional chemotherapy. DT-diaphorase (DTD), whose level is strongly elevated in various tumors, is a cytosolic flavoenzyme that promotes intracellular reactive oxygen species (ROS) generation via the redox cycling of hydroquinones. Incorporation of the DTD-responsive substrate to the structures of the probe and prodrug may facilitate the tumor detection and therapy. Herein, we established an multifunctional drug delivery nanosystem (HTLAC) that rapidly responds to the DTD enzyme, leads to the early-stage precise detection and termination of tumors. Firstly, the synthesis of DTD-responsive withaferin A (DT-WA) and indocyanine green (DT-Cy5) was performed. In the presence of DTD, WA, which produces ROS in cells, was released from DT-WA, and the red fluorescence of DT-Cy5 was detected for tumor imaging. Additionally, these DTD enzyme reaction processes of DT-WA and DT-Cy5 induced ROS. The self-burst of ROS gene-WA) and indocyanine green (DT-Cy5) are synthesized, and observed more specifically toward DTD under physiological conditions. As the cell-penetrating peptide and hyaluronic acid functionalized liposome, the HTLAC not only induces antiproliferative activity by generating self-burst of ROS, but also effectively accumulate and restore its fluorescence at the tumor site because of the HA actively targeting tumor along with the prolonged presence in blood circulation. Besides, this enzyme-triggering nanosystem exhibited an effective tumor inhibition with a low systemic toxicity.With the advancement of nanochemistry, artificial nanozymes with high catalytic stability, low manufacturing and storage cost, and greater design flexibility over natural enzymes, have emerged as a next-generation nanomedicine. https://www.selleckchem.com/products/Nolvadex.html The catalytic activity and selectivity of nanozymes can be readily controlled and optimized by the rational chemical design of nanomaterials. This review summarizes the various chemical approaches to regulate the catalytic activity and selectivity of nanozymes for biomedical applications. We focus on the in-depth correlation between the physicochemical characteristics and catalytic activities of nanozymes from several aspects, including regulating chemical composition, controlling morphology, altering the size, surface modification and self-assembly. Furthermore, the chemically designed nanozymes for various biomedical applications such as biosensing, infectious disease therapy, cancer therapy, neurodegenerative disease therapy and injury therapy, are briefly summarized. Finally, the current challenges and future perspectives of nanozymes are discussed from a chemistry point of view.
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