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Abstract The value and direction angle of the perpendicularity error of the thrust surface and bearing bush in hydrostatic thrust bearings directly affect the motion accuracy. In this paper, a rapid onsite measurement method and evaluation model for the value and direction angle of the perpendicularity error of the thrust surface and bearing bush in hydrostatic thrust bearings are presented. The method is validated by comparing experimental measurements with those obtained using a CMM. An analysis of the perpendicularity errors before and after correction shows that at different speeds (10 rpm, 30 rpm, and 50 rpm), the errors in the mean axial and tilt displacements of the thrust bearing are reduced by 68.41% and 35.44%, respectively.

To monitor the position and profile of therapeutic carbon beams in real-time, in this paper, we proposed a system called HiBeam-T. The HiBeam-T is a time projection chamber (TPC) with forty Topmetal-II- CMOS pixel sensors as its readout. Each Topmetal-II- has 72 × 72 pixels with the size of 83 μm × 83 μm. The detector consists of the charge drift region and the charge collection area. The readout electronics comprise three Readout Control Modules and one Clock Synchronization Module. This Hibeam-T has a sensitive area of 20 × 20 cm and can acquire the center of the incident beams. The test with a continuous 80.55 MeV/u 12C6+ beam shows that the measurement resolution to the beam center could reach 6.45 μm for unsaturated beam projections.

Abstract Cholesterol (Chol) fortifies packing and reduces fluidity and permeability of the lipid bilayer in vesicles (liposomes)-mediated drug delivery. However, under the physiological environment, Chol is rapidly extracted from the lipid bilayer by biomembranes, which jeopardizes membrane stability and results in premature leakage for delivered payloads, yielding suboptimal clinic efficacy. Herein, we report a Chol-modified sphingomyelin (SM) lipid bilayer via covalently conjugating Chol to SM (SM-Chol), which retains membrane condensing ability of Chol. Systemic structure activity relationship screening demonstrates that SM-Chol with a disulfide bond and longer linker outperforms other counterparts and conventional phospholipids/Chol mixture systems on blocking Chol transfer and payload leakage, increases maximum tolerated dose of vincristine while reducing systemic toxicities, improves pharmacokinetics and tumor delivery efficiency, and enhances antitumor efficacy in SU-DHL-4 diffuse large B-cell lymphoma xenograft model in female mice. Furthermore, SM-Chol improves therapeutic delivery of structurally diversified therapeutic agents (irinotecan, doxorubicin, dexamethasone) or siRNA targeting multi-drug resistant gene (p-glycoprotein) in late-stage metastatic orthotopic KPC-Luc pancreas cancer, 4T1-Luc2 triple negative breast cancer, lung inflammation, and CT26 colorectal cancer animal models in female mice compared to respective FDA-approved nanotherapeutics or lipid compositions. Thus, SM-Chol represents a promising platform for universal and improved drug delivery.

Abstract Epacadostat (EPA), the most advanced IDO1 inhibitor, in combination with PD-1 checkpoint inhibitor, has failed in a recent Phase III clinical trial for treating metastatic melanoma. Here we report an EPA nanovesicle therapeutic platform (Epacasome) based on chemically attaching EPA to sphingomyelin via an oxime-ester bond highly responsive to hydrolase cleavage. Via clathrin-mediated endocytosis, Epacasome displays higher cellular uptake and enhances IDO1 inhibition and T cell proliferation compared to free EPA. Epacasome shows improved pharmacokinetics and tumour accumulation with efficient intratumoural drug release and deep tumour penetration. Additionally, it outperforms free EPA for anticancer efficacy, potentiating PD-1 blockade with boosted cytotoxic T lymphocytes (CTLs) and reduced regulatory T cells and myeloid-derived suppressor cells responses in a B16-F10 melanoma model in female mice. By co-encapsulating immunogenic dacarbazine, Epacasome further enhances anti-tumor effects and immune responses through the upregulation of NKG2D-mediated CTLs and natural killer cells responses particularly when combined with the PD-1 inhibitor in the late-stage metastatic B16-F10-Luc2 model in female mice. Furthermore, this combination prevents tumour recurrence and prolongs mouse survival in a clinically relevant, post-surgical melanoma model in female mice. Epacasome demonstrates potential to synergize with PD-1 blockade for improved response to melanoma immunotherapy.

Over the past several decades, liposomes have been extensively developed and used for various clinical applications such as in pharmaceutical, cosmetic, and dietetic fields, due to its versatility, biocompatibility, and biodegradability, as well as the ability to enhance the therapeutic index of free drugs. However, some challenges remain unsolved, including liposome premature leakage, manufacturing irreproducibility, and limited translation success. This article reviews various aspects of liposomes, including its advantages, major compositions, and common preparation techniques, and discusses present U.S. FDA-approved, clinical, and preclinical liposomal nanotherapeutics for treating and preventing a variety of human diseases. In addition, we summarize the significance of and challenges in liposome-enabled nanotherapeutic development and hope it provides the fundamental knowledge and concepts about liposomes and their applications and contributions in contemporary pharmaceutical advancement.