Design and prototype test of a high-sensitivity reentrant-cavity based Schottky pickup.

Schottky diagnostics is an important measure for the debunched beam during the injection phase of the Xi'an Proton Application Facility (XiPAF). The existing capacitive Schottky pickup has a relatively low sensitivity and a poor signal-to-noise ratio for the low-intensity beam. A resonant Schottky pickup based on the principle of a reentrant cavity is proposed. The effects of cavity geometric parameters on cavity properties are systematically studied. A prototype was built and tested to validate the simulation results. The prototype has a resonance frequency of 24.23 MHz, a Q value of 635, and a shunt impedance of 19.75 kΩ. The resonant Schottky pickup has the capability to detect as few as 2.3 × 106 protons with an energy of 7 MeV and a momentum spread of about 1% at the injection phase of XiPAF. The sensitivity is two orders of magnitude higher than the existing capacitive pickup.

Triple-Combination Immunogenic Nanovesicles Reshape the Tumor Microenvironment to Potentiate Chemo-Immunotherapy in Preclinical Cancer Models.

Immune checkpoint blockade (ICB) therapies have had a tremendous impact on cancer therapy. However, most patients harbor a poorly immunogenic tumor microenvironment (TME), presenting overwhelming de novo refractoriness to ICB inhibitors. To address these challenges, combinatorial regimens that employ chemotherapies and immunostimulatory agents are urgently needed. Here, a combination chemoimmunotherapeutic nanosystem consisting of a polymeric monoconjugated gemcitabine (GEM) prodrug nanoparticle decorated with an anti-programmed cell death-ligand 1 (PD-L1) antibody (αPD-L1) on the surface and a stimulator of interferon genes (STING) agonist encapsulated inside is developed. Treatment with GEM nanoparticles upregulates PD-L1 expression in ICB-refractory tumors, resulting in augmented intratumor drug delivery in vivo and synergistic antitumor efficacy via activation of intratumor CD8+ T cell responses. Integration of a STING agonist into the αPD-L1-decorated GEM nanoparticles further improves response rates by transforming low-immunogenic tumors into inflamed tumors. Systemically administered triple-combination nanovesicles induce robust antitumor immunity, resulting in durable regression of established large tumors and a reduction in the metastatic burden, coincident with immunological memory against tumor rechallenge in multiple murine tumor models. These findings provide a design rationale for synchronizing STING agonists, PD-L1 antibodies, and chemotherapeutic prodrugs to generate a chemoimmunotherapeutic effect in treating ICB-nonresponsive tumors.

The Potential of Calcium/Phosphate Containing MAO Implanted in Bone Tissue Regeneration and Biological Characteristics.

Micro arc oxidation (MAO) is a prominent surface treatment to form bioceramic coating layers with beneficial physical, chemical, and biological properties on the metal substrates for biomaterial applications. In this study, MAO treatment has been performed to modify the surface characteristics of AZ31 Mg alloy to enhance the biocompatibility and corrosion resistance for implant applications by using an electrolytic mixture of Ca3(PO4)2 and C10H16N2O8 (EDTA) in the solutions. For this purpose, the calcium phosphate (Ca-P) containing thin film was successfully fabricated on the surface of the implant material. After in-vivo implantation into the rabbit bone for four weeks, the apparent growth of soft tissues and bone healing effects have been documented. The morphology, microstructure, chemical composition, and phase structures of the coating were identified by SEM, XPS, and XRD. The corrosion resistance of the coating was analyzed by polarization and salt spray test. The coatings consist of Ca-P compounds continuously have proliferation activity and show better corrosion resistance and lower roughness in comparison to mere MAO coated AZ31. The corrosion current density decreased to approximately 2.81 × 10-7 A/cm2 and roughness was reduced to 0.622 µm. Thus, based on the results, it was anticipated that the development of degradable materials and implants would be feasible using this method. This study aims to fabricate MAO coatings for orthopedic magnesium implants that can enhance bioactivity, biocompatibility, and prevent additional surgery and implant-related infections to be used in clinical applications.

Controlled release of BMP-2 from titanium with electrodeposition modification enhancing critical size bone formation.

In this study, a porous Ti-alloy based implant with an interconnected channel structure (MAO-CaP-BMP2) is fabricated using a method combining 3D printing, microarc oxidation (MAO) treatment, and co-precipitation of Ca,P layer with BMP-2 technique. The macroporous structure with pore size of 600 µm made by 3D printing not only enhances the ingrowth of cells but also allows the formation of blood vessels inside the implant. As a result, the new bond formation is promoted. In addition, the microporous dioxide layer formed on the implant surface by MAO provides the sites for co-precipitation of Ca,P layer with BMP-2. The microstructure allows the prolonged release of BMP-2. Our results show that a sustained release of BMP-2 over 35 days is achieved for MAO-CaP-BMP2 group longer than Ti without MAO modification group and without Ca,P electrochemical deposition group. The slow release of BMP-2 at the bone/implant interface for a long period of time leads to enhancement of the osseointegration between the implant and surrounding bones. This result indicates that MAO-CaP-BMP2 is a good candidate of growth factor carrier. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. MAO-CaP-BMP2 modified Ti-alloy implant is both osteoinductive and osteoconductive which can create better osteogenesis and angiogenesis. As a result, it can enhance bone formation.

Differential Expression of Toll-Like Receptor Signaling Pathway Is Associated with Microscopic Polyangiitis in Peripheral Blood Neutrophils.

Constitutive or excessive activation of Toll-like receptor (TLR) signaling pathway can disrupt the body's immune tolerance to autoantigen, thus promoting the development of autoimmune disease. However, the expression profile of TLR signaling pathway in peripheral blood neutrophils in the pathogenesis of microscopic polyangiitis (MPA) remains unclear. Thus, improved understanding of the pathobiology of this disease may aid in the development of therapeutic targets for patients with MPA. In the present study, we assessed the expression of TLR signaling pathway-related genes in peripheral blood neutrophils in patients with MPA. PCR array analysis was performed on 20 patients with MPA and 12 healthy controls. Gene expression profile was performed using the human TLR for autoimmunity and inflammation PCR array of Genecopoeia, containing 84 genes related to TLR signaling pathway and six house-keeping genes. We then used quantitative real-time PCR to validate the array test. The array results identified 13 upregulated genes and 5 genes which were downregulated. The resulting qRT-PCR was consistent with the findings by PCR array. Our results suggest that peripheral blood neutrophils display changes in the expression of TLR signaling pathway-related genes associated with the pathogenesis of microscopic polyangiitis.

Analysis and fabrication of a prism film with roll-to-roll fabrication process.

A prism-based brightness enhancement film (BEF), has been investigated through computer-aided optical analysis and experiments in this study. The prism film was fabricated on a 100 microm thick PET film substrate using roll-to-roll (R2R) process with UV curable resins of different refractive indices. The results from both optical analysis and experiments showed that resins with higher refractive indices have better on-axis luminous gain. The prism structures fabricated on the substrate achieved a replication rate of 97.54% in this study. Compared with the 3M BEF, the prism films developed in this study are improved in on-axis luminous gains when the refractive index of the resin is higher than 1.53.