Controllable amorphization and morphology engineering on mixed-valence MOFs for ultra-fast and high-stability near-pseudocapacitance Li storage.

Coulombic efficiency (CE) and rate capability are crucial parameters for advanced secondary batteries. Herein, for the first time, we report controllable amorphization and morphology engineering on mixed-valence Fe(II,III)-MOFs from the crystalline to amorphous state and micro-clustered to hollow nano-spherical geometry through valence manipulation by a dissolved oxygen-mediated pathway. The disordered structure and the hollow nanostructure can endow the MOFs with the highest initial CE (>80%) to date for MOF electrodes, and ultrafast and super-stable near-pseudocapacitance lithium storage.

Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs.

Chimeric antigen receptor (CAR) T cells have been used to successfully treat various blood cancers, but adverse effects have limited their potential. Here, we developed chimeric adaptor proteins (CAPs) and CAR tyrosine kinases (CAR-TKs) in which the intracellular ζ T cell receptor (TCRζ) chain was replaced with intracellular protein domains to stimulate signaling downstream of the TCRζ chain. CAPs contain adaptor domains and the kinase domain of ZAP70, whereas CAR-TKs contain only ZAP70 domains.

Prediction Model and Nomogram of Early Recurrence of Hepatocellular Carcinoma after Ultrasound-guided Microwave Ablation.

Background: Ultrasound-guided microwave ablation (MWA) is recommended as a first-line treatment for early liver cancer due to its minimally invasive, efficient, and cost-effective nature. It utilizes microwave radiation to heat and destroy tumor cells as a local thermal therapy and offers the benefits of being minimally invasive, repeatable, and applicable to tumors of various sizes and locations. However, despite the efficacy of MWA, early recurrence after treatment remains a challenge, particularly when it occurs within a year and has a significant impact on the prognosis of the patient.

In Situ Flash Synthesis of Ultra-High-Performance Metal Oxide Anode through Shunting Current-Based Electrothermal Shock.

The synthesis of anode materials plays an important role in determining the production efficiency, cost, and performance of lithium-ion batteries (LIBs). However, a low-cost, high-speed, scalable manufacturing process of the anode with the desired structural feature for practical technology adoption remains elusive. In this study, we propose a novel method called in situ flash shunt-electrothermal shock (SETS) which is controllable, fast, and energy-saving for synthesizing metal oxide-based materials.

Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma.

Background: Although most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapeutic strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican-2 (GPC2) and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation.

The value of contrast-enhanced ultrasound quantitative parameters in the prognosis prediction of hepatocellular carcinoma after thermal ablation: a retrospective cohort study.

Background: The postoperative recurrence rate is the main factor affecting the prognosis of hepatocellular carcinoma (HCC) patients, this study sought to investigate the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the recurrence and the survival of HCC patients after thermal ablation.

Methods: The data of 97 patients with pathologically diagnosed HCC who underwent thermal ablation were retrospectively included in this study. The patients had an average age of 46.

Fabrication of an anion exchange membrane with textured structure for enhanced performance of direct borohydride fuel cells.

Developing electrolyte membranes with a simple preparation process and high performance is a top priority for the commercialization of fuel cells. Inspired by solar cell texturing to improve its conversion efficiency, this study prepares a textured membrane by increasing the roughness of a glass plate. The structures of the textured membrane and the flat membrane are characterized and compared.

Self-Assembly of a Graphene Oxide Liquid Crystal for Water Treatment.

Adsorbents, especially those with high removal efficiency, long life, and multi-purpose capabilities, are the most crucial components in an adsorption system. By taking advantage of the liquid-like mobility and crystal-like ordering of liquid crystal materials, a liquid crystal induction method is developed and applied to construct three-dimensional graphene-based adsorbents featuring excellent shape adaptability, a distinctive pore structure, and abundant surface functional groups. When the monoliths are used for water restoration, the large amount of residual oxygen-containing groups is more susceptible to electrophilic attack, thus contributing to cation adsorption (up to 705.

Murine allogeneic CAR T cells integrated before or early after posttransplant cyclophosphamide exert antitumor effects.

Relapse limits the therapeutic efficacy both of chimeric antigen receptor (CAR) T cells and allogeneic hematopoietic cell transplantation (allo-HCT). Patients may undergo these therapies sequentially to prevent or treat relapsed malignancy. However, direct integration of the 2 therapies has been avoided over concerns for potential induction of graft-versus-host disease (GVHD) by allogeneic CAR T cells.

Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in .

Reverse transcription quantitative PCR (RT-qPCR) is a technique widely used to investigate the expression of genes. An appropriate reference gene (RG) is essential for RT-qPCR analysis to obtain accurate and reliable results. plays an important role in afforestation as a bush.

An optimized bicistronic chimeric antigen receptor against GPC2 or CD276 overcomes heterogeneous expression in neuroblastoma.

Chimeric antigen receptor (CAR) T cell therapies targeting single antigens have performed poorly in clinical trials for solid tumors due to heterogenous expression of tumor-associated antigens (TAAs), limited T cell persistence, and T cell exhaustion. Here, we aimed to identify optimal CARs against glypican 2 (GPC2) or CD276 (B7-H3), which were highly but heterogeneously expressed in neuroblastoma (NB), a lethal extracranial solid tumor of childhood. First, we examined CAR T cell expansion in the presence of targets by digital droplet PCR.

CD19/22 CAR T cells in children and young adults with B-ALL: phase 1 results and development of a novel bicistronic CAR.

Remission durability following single-antigen targeted chimeric antigen receptor (CAR) T-cells is limited by antigen modulation, which may be overcome with combinatorial targeting. Building upon our experiences targeting CD19 and CD22 in B-cell acute lymphoblastic leukemia (B-ALL), we report on our phase 1 dose-escalation study of a novel murine stem cell virus (MSCV)-CD19/CD22-4-1BB bivalent CAR T-cell (CD19.22.

Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design.

Background: Successful development of chimeric antigen receptor (CAR) T cell immunotherapy for children and adults with relapsed/refractory acute myeloid leukemia (AML) is highly desired given their poor clinical prognosis and frequent inability to achieve cure with conventional chemotherapy. Initial experiences with CD19 CAR T cell immunotherapy for patients with B-cell malignancies highlighted the critical impact of intracellular costimulatory domain selection (CD28 vs 4-1BB (CD137)) on CAR T cell expansion and in vivo persistence that may impact clinical outcomes. However, the impact of costimulatory domains on the efficacy of myeloid antigen-directed CAR T cell immunotherapy remains unknown.

CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial.

Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease.

Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis.

Metastasis is the leading cause of cancer-related deaths, and greater knowledge of the metastatic microenvironment is necessary to effectively target this process. Microenvironmental changes occur at distant sites prior to clinically detectable metastatic disease; however, the key niche regulatory signals during metastatic progression remain poorly characterized. Here, we identify a core immune suppression gene signature in pre-metastatic niche formation that is expressed predominantly by myeloid cells.

Perforin-deficient CAR T cells recapitulate late-onset inflammatory toxicities observed in patients.

Late-onset inflammatory toxicities resembling hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) occur after chimeric antigen receptor T cell (CAR T cell) infusion and represent a therapeutic challenge. Given the established link between perforin deficiency and primary HLH, we investigated the role of perforin in anti-CD19 CAR T cell efficacy and HLH-like toxicities in a syngeneic murine model. Perforin contributed to both CD8+ and CD4+ CAR T cell cytotoxicity but was not required for in vitro or in vivo leukemia clearance.

Inhibitory effect of 5-FU loaded ultrasound microbubbles on tumor growth and angiogenesis.

The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU) combined with targeted microbubbles to establish a molecular targeted ultrasound response microbubble for neovascular cells.

Bilayer Anion-Exchange Membrane with Low Borohydride Crossover and Improved Fuel Efficiency for Direct Borohdyride Fuel Cell.

The development of membranes with low fuel crossover and high fuel efficiency is a key issue in direct borohydride fuel cells (DBFCs). In previous work, we produced a poly(vinyl alcohol) (PVA)-anion-exchange resin (AER) membrane with a low fuel crossover and a low fuel efficiency by introducing Co ions. In this work, a bilayer membrane was designed to improve the fuel efficiency and cell performance.

CD4/CD8 T-Cell Selection Affects Chimeric Antigen Receptor (CAR) T-Cell Potency and Toxicity: Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial.

Purpose: Patients with B-cell acute lymphoblastic leukemia who experience relapse after or are resistant to CD19-targeted immunotherapies have limited treatment options. Targeting CD22, an alternative B-cell antigen, represents an alternate strategy. We report outcomes on the largest patient cohort treated with CD22 chimeric antigen receptor (CAR) T cells.

Clonal expansion of CAR T cells harboring lentivector integration in the CBL gene following anti-CD22 CAR T-cell therapy.

Reexpansion of CAR T cells led to further investigations which confirmed the clonal nature of this expansion.

Low-temperature pseudomorphic transformation of polyhedral MIL-88A to lithium ferrite (LiFeO) in aqueous LiOH medium toward high Li storage.

The ability to develop novel nanomaterials, and to precisely manufacture their functional structures at the nano- and microscales would benefit many emerging device applications. Herein, as a first example, we describe the exploration of feasibility for the morphological replacement of an iron-based MOF bearing trimeric FeIII-O clusters, MIL-88A preform, with a polyhedral architecture of around 0.4 × 1.

Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence.

Purpose: Chimeric antigen receptor T-cell (CART) therapy targeting CD22 induces remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, the majority of post-CD22 CART remissions are short and associated with reduction in CD22 expression. We evaluate the implications of low antigen density on the activity of CD22 CART and propose mechanisms to overcome antigen escape.

Chimeric Antigen Receptors Incorporating D Domains Targeting CD123 Direct Potent Mono- and Bi-specific Antitumor Activity of T Cells.

Chimeric antigen receptor (CAR) T cell therapies have demonstrated impressive initial response rates in hematologic malignancies. However, relapse rates are significant, and robust efficacies in other indications, such as solid tumors, will likely require novel therapeutic strategies and CAR designs. To that end, we sought to develop simple, highly selective targeting domains (D domains) that could be incorporated into complex, multifunctional therapeutics.

Preclinical Development of Bivalent Chimeric Antigen Receptors Targeting Both CD19 and CD22.

Despite high remission rates following CAR-T cell therapy in B-ALL, relapse due to loss of the targeted antigen is increasingly recognized as a mechanism of immune escape. We hypothesized that simultaneous targeting of CD19 and CD22 may reduce the likelihood of antigen loss, thus improving sustained remission rates. A systematic approach to the generation of CAR constructs incorporating two target-binding domains led to several novel CD19/CD22 bivalent CAR constructs.