CD28 costimulation augments CAR signaling in NK cells via the LCK/CD3Z/ZAP70 signaling axis.

Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being a key component. Yet, the impact of costimulatory domains on the downstream signaling and subsequent functionality of CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated the impact of various costimulatory domains on CAR-NK cell activity, using a CD70-targeting CAR. We found that CD28, a costimulatory molecule not inherently present in mature NK cells, significantly enhanced the antitumor efficacy and long-term cytotoxicity of CAR-NK cells both in vitro and in multiple xenograft models of hematologic and solid tumors. Mechanistically, we showed that CD28 linked to CD3Z creates a platform that recruits critical kinases, such as LCK and ZAP70, initiating a signaling cascade that enhances CAR-NK cell function. Our study provides insights into how CD28 costimulation enhances CAR-NK cell function and supports its incorporation in NK-based CARs for cancer immunotherapy.

Strong, highly porous and sustainable nanocellulose foam made using bioderived hyperbranched crosslinker for thermal insulation and sound absorption.

This paper reports an environment-friendly biobased foam made with cellulose nanofiber (CNF) and a biobased hyperbranched crosslinker, glycerol succinic anhydride (GSA). As a biobased hyperbranched crosslinker, carboxyl-terminated GSA is synthesized through a straightforward esterification process involving glycerol and succinic anhydride. The GSA-crosslinked CNF (GSA/CNF) foam is prepared using a facile, sustainable, cost-effective, and efficient solvent-exchange method. The resulting foam exhibits notable characteristics, including improved dimensional stability, remarkably low density (13.41 mg/cm3) with high porosity (>99 %), and exceptional compressive strength (494 kPa) and modulus (452 kPa). Further, the foam offers outstanding sound absorption capabilities with a coefficient of 0.986 at 2 kHz and remarkably low thermal conductivity (30.18 mW/mK), significantly lower than commonly used and reported porous materials, indicating its potential as an efficient, environmentally friendly sound absorption and thermal insulation material.

Environment-friendly, high-performance cellulose nanofiber-vanillin epoxy nanocomposite with excellent mechanical, thermal insulation and UV shielding properties.

With the increased demand for biobased epoxy thermosets as an alternative to petroleum-based materials in various fields, developing environment-friendly and high-performance natural fiber-biobased epoxy nanocomposites is crucial for industrial applications. Herein, an environment-friendly nanocomposite is reported by introducing cellulose nanofiber (CNF) in situ interaction with lignin-derived vanillin epoxy (VE) monomer and 4, 4´-diaminodiphenyl methane (DDM) hardener that serves as a multifunctional platform. The CNF-VE nanocomposite is fabricated by simply dispersing the CNF suspension to the VE and DDM hardener solution through the in-situ reaction, and its mechanical properties and thermal insulation behavior, wettability, chemical resistance, and optical properties are evaluated with the CNF weight percent variation. The well-dispersed CNF-VE nanocomposite exhibited high tensile strength (∼127.78 ± 3.99 MPa) and strain-at-break (∼16.49 ± 0.61 %), haziness (∼50 %) and UV-shielding properties. The in situ loading of CNF forms covalent crosslinking with the VE and favors improving the mechanical properties along with the homogeneous dispersion of CNF. The CNF-VE nanocomposite also shows lower thermal conductivity (0.26 Wm-1K-1) than glass. The environment-friendly and high-performance nanocomposite provides multiple platforms and can be used for building materials.

Increased expression of CD70 in relapsed acute myeloid leukemia after hypomethylating agents.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While induction chemotherapy leads to remission in most patients, a significant number will experience relapse. Therefore, there is a need for novel therapies that can improve remission rates in patients with relapsed and refractory AML. CD70 is the natural ligand for CD27 (a member of the TNF superfamily) and appears to be a promising therapeutic target. Consequently, there is considerable interest in developing chimeric antigen receptor (CAR) T-cell therapy products that can specifically target CD70 in various neoplasms, including AML. In this study, we employed routine diagnostic techniques, such as immunohistochemistry and flow cytometry, to investigate the expression of CD70 in bone marrow samples from treatment-naïve and relapsed AML patients after hypomethylating agents (HMA). Also, we evaluated the impact of HMA on CD70 expression and examined CD70 expression in various leukemic cell subsets and normal hematopoietic progenitors.

Advanced hydrostable, recyclable and degradable cellulose hybrid films as renewable alternatives to synthetic plastics.

Strong, tough and sustainable materials are in high demand in various engineering applications. We demonstrate a potential sustainable hybrid film made from natural cellulose and a biobased slurry. Through a simple and scalable approach, cellulose can be processed into an advanced material with over 2.8 and 9.2-fold increase in dry strength and toughness after curing and a 728-fold increase in wet strength, respectively. In addition, these hybrid composite films display an outstanding antioxidant activity surpassing 90 %, along with excellent ultraviolet radiation shielding and thermal insulation properties. Further, the hybrid films can be fabricated by integrating all-natural materials and still guarantee their unique functionality. We also demonstrate the feasibility of a circular bioeconomy by recycling the hybrid film using a green, deep eutectic solvent to fabricate a recycled hybrid film that displays excellent mechanical and optical properties. When recycling is unsuitable or economical, the hybrid film can naturally degrade in the soil under 6 months. These encouraging findings suggest the promise of cellulose hybrid films as a renewable, low-cost, tough, and strong material with the potential to replace nonrenewable synthetic plastics and products.

Single-, Dual-, and Multi-Stimuli-Responsive Nanogels for Biomedical Applications.

In recent years, stimuli-responsive nanogels that can undergo suitable transitions under endogenous (e.g., pH, enzymes and reduction) or exogenous stimuli (e.g., temperature, light, and magnetic fields) for on-demand drug delivery, have received significant interest in biomedical fields, including drug delivery, tissue engineering, wound healing, and gene therapy due to their unique environment-sensitive properties. Furthermore, these nanogels have become very popular due to some of their special properties such as good hydrophilicity, high drug loading efficiency, flexibility, and excellent biocompatibility and biodegradability. In this article, the authors discuss current developments in the synthesis, properties, and biomedical applications of stimulus-responsive nanogels. In addition, the opportunities and challenges of nanogels for biomedical applications are also briefly predicted.