Genetic and epigenetic mechanisms of GPRC5D loss after anti-GPRC5D CAR T-cell therapy in multiple myeloma.

G protein-coupled receptor, class C, group 5, member D (GPRC5D) has emerged as a novel target for chimeric antigen receptor (CAR) T-cell therapy, demonstrating promising efficacy in multiple myeloma (MM). However, disease relapse is still common, and the mechanism of resistance remains poorly understood. In this study, we conducted whole-genome sequencing (WGS) and whole-genome bisulfite sequencing (WGBS) on MM samples from 10 patients who relapsed after GPRC5D CAR T-cell therapy.

Lymphocyte/monocyte to lactate dehydrogenase ratio prior to lymphodepletion impact the outcomes of patients with diffused large B cell lymphoma undergoing CAR-T cell therapy.

Factors associated with outcomes of chimeric antigen receptor (CAR)-T cell therapy in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have not been fully elucidated. We explored the impact of the prelymphodepletion (pre-LD) lymphocyte to monocyte ratio (LMR) and its ratio to lactate dehydrogenase (LDH) (LMR/LDH) on the efficacy and prognosis of 60 patients with R/R DLBCL undergoing CAR-T cell therapy. The optimal cutoff values for pre-LD LMR and LMR/LDH were 3.

Particle size of zero-valent iron affects the risks from antibiotic resistance genes in waste activated sludge during anaerobic digestion.

Zero-valent iron (ZVI) is the promising enhancer for sludge anaerobic digestion (AD) performance and for mitigating the proliferation of antibiotic resistance genes (ARGs). However, concerns about its size effects in shifting the behavior and risk of ARGs in sludge, during the AD process. Here, the metagenomics-based profile of ARGs, along with their potential (pathogenic) hosts in sludge were investigated, during mesophilic AD enhanced by ZVI with three different sizes.

Free fatty acid receptor-4 regulates T-cell-mediated allogeneic reaction through activating an aryl hydrocarbon receptor pathway.

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it.

Fluvastatin Promotes Treg Cell Production in Allogeneic Immune Reaction and Suppresses Inflammatory Response.

Introduction: Statins, a class of HMG-CoA reductase inhibitors, exhibit prophylactic benefits against immune rejection induced by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite the protective function is confirmed, the precise mechanism to induce immune tolerance of statin in the initial stages of transplantation remains incompletely understood. Given that Treg cells play a critical role in preventing graft versus host response and Foxp3 as a transcription factor of Treg can be induced by statins, we hypothesize that the immunosuppressive effects of statins are partially mediated through regulation of Treg cells expansion.

The aberrantly activated AURKB supports and complements the function of AURKA in CALR mutated cells through regulating the cell growth and differentiation.

Aurora kinase B (AURKB) was reported to assist Aurora kinase A (AURKA) to regulate cellular mitosis. AURKA has been found activated in myeloproliferative neoplasms (MPNs) patients with CALR gene mutation, however, it's unclear whether AURKB displays a compensatory function of AURKA in regulation of CALR mutant cell growth and differentiation. Here, we found that AURKB, similar with AURKA, was aberrantly activated in CALR mutant patients, and displayed a more tolerance to the aurora kinase inhibitor.

Inaticabtagene autoleucel in adult relapsed or refractory B-cell acute lymphoblastic leukemia.

Before November 2023, CD19 chimeric antigen receptor (CAR) T-cell therapies had not been approved in China for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), leaving a significant unmet need. In response, inaticabtagene autoleucel (Inati-cel), a novel CD19 CAR T-cell therapy with a distinct single-chain variable fragment (HI19α), was developed and showed promising efficacy in preliminary clinical research. We conducted a phase 2, single-arm, multicenter study of Inati-cel in adult CD19+ R/R B-ALL in China.

Assessing Frailty-Specific Treatment Effect in Cardiovascular Disease: A Systematic Review.

Background: Clinicians are increasingly considering using frailty assessments to individualize treatment for older patients. It remains uncertain whether interventions to reduce cardiovascular disease (CVD) events offer similar benefits between older adults with and without frailty.

Methods: A systematic literature search was undertaken in PubMed and Embase, adhering to PRISMA guidelines.

Strategies following failure of CAR-T-cell therapy in non-Hodgkin lymphoma.

Several CD19 CAR-T-cell drugs are approved for safety and efficacy in advanced B-cell cancers with encouraging results. However, primary refractory and relapse are common. We critically analyze long-term data on efficacy of CD19 CAR-T-cell therapies in B-cell non-Hodgkin lymphomas from clinical trials with those of so-called real world data.

Integrated analysis of single-cell and bulk RNA-sequencing identifies a metastasis-related gene signature for predicting prognosis in lung adenocarcinoma.

Background: Metastasis has been documented as an independent and significant prognostic feature of lung adenocarcinoma (LUAD) patients. However, the underlying genetic and molecular mechanisms responsible for LUAD metastasis and their prognostic significance are not exactly defined.

Methods: The single-cell transcriptomic profiles of primary and metastatic LUAD samples were integrated as a whole dataset.

[Effects of Down-Regulation of on Differentiation and Apoptosis of MPN Cells with Gene Mutation and Survival of 6133/MPL Mice].

Objective: To investigate the effects of down-regulation of p21 activated kinase 1 (PAK1) on the proliferation, differentiation, and apoptosis of myeloproliferative neoplasm (MPN) cells (6133/MPL) with thrombopoietin receptor MPL mutation at codon 515 () and survival of 6133/MPL mice.

Methods: Interference with the protein level of in 6133/MPL cells was assessed using lentivirus-mediated shRNA transfection technology. CCK-8 assay was used to detect the effect of down-regulation of on the proliferation viability of 6133/MPL cells, and colony-forming ability was measured by cell counting.

Targeting GPRC5D for multiple myeloma therapy.

Given its nearly ubiquitous expression on plasma cells and limited expression on essential normal tissue, the G protein-coupled receptor class C group 5 member D (GPRC5D) presents a promising opportunity for utilization as an immunotherapy target in multiple myeloma (MM). The therapeutic strategies targeting GPRC5D, such as bispecific antibodies (BsAbs), chimeric antigen receptor (CAR) T cells, and antibody-drug conjugates (ADCs), have been prominently emphasized in relapsed/refractory MM (R/R MM) in recent years. Further clinical trials are necessary to confirm the long-term efficacy of GPRC5D-targeting immunotherapies alone, explore their potentials co-targeting with other specific antigens, or investigate their combinations with existing treatments to overcome MM resistance.

Comprehensive characterization of cytopenia after chimeric antigen receptor-T cell infusion in patients with relapsed or refractory multiple myeloma.

Background: Many studies have demonstrated the effectiveness of chimeric antigen receptor-T (CAR-T) cell therapy for relapsed or refractory multiple myeloma (RRMM), but the hematologic toxicity has not been well characterized.

Methods: A total of 111 adults with RRMM who received BCMA CAR-T cells, BCMA + CD19 CAR-T cells or tandem BCMA/CD19 dual-target (BC19) CAR-T cells infusion were enrolled. We characterized cytopenia and hematologic recovery at different time points after CAR-T-cell therapy, analyzed the effect of cytopenia on prognosis and identified the risk factors.

Clinical outcomes and microenvironment profiling in relapsed/refractory multiple myeloma patients with extramedullary disease receiving anti-BCMA CAR T-cell-based therapy.

Relapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T-cell activities in EMD have yet to be determined; how EMD-specific microenvironment influences the clinical outcomes of CAR T-cell therapy remains of great interest. In this prospective cohort study, patients with histologically confirmed extra-osseous EMD were enrolled and treated with combined anti-BCMA and anti-CD19 CAR T-cell therapy from May 2017 to September 2023.

Adsorption and uptake of functionalized nanoplastics (NPs) by wetland plant (Sphagnum): A unique pathway for polystyrene-NPs reduction in non-vascular plants.

Wetlands are sources and sinks for nanoplastics (NPs), where adsorption and uptake by plants constitute a crucial pathway for NPs accumulation. This study found that Sphagnum exhibited a high potential (~89.75 %) to intercept NPs despite the lack of root systems and stomata.

Anti-BCMA/GPRC5D bispecific CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, single-centre, phase 1 trial.

Background: Some challenges still exist with single-target B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapies due to variable or negative BCMA expression, although they have yielded remarkable efficacy in relapsed or refractory multiple myeloma. We developed anti-BCMA/GPRC5D bispecific CARs to mitigate the limitations and potentiate the functions of CAR T cells.

Methods: This single-arm, phase 1 trial was conducted at the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China).

Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation.

Efficient homing of infused hematopoietic stem and progenitor cells (HSPCs) into the bone marrow (BM) is the prerequisite for successful hematopoietic stem cell transplantation. However, only a small part of infused HSPCs find their way to the BM niche. A better understanding of the mechanisms that facilitate HSPC homing will help to develop strategies to improve the initial HSPC engraftment and subsequent hematopoietic regeneration.

[Prognostic Significance of Progression of Disease within 24 Months in Mantle Cell Lymphoma].

Objective: To investigate the effect of progression of disease within 24 months (POD24) on overall survival (OS) in patients with mantle cell lymphoma (MCL), and compare the clinical characteristics between POD24 and non-POD24 patients.

Methods: A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020. According to the occurrence of POD24, the patients were grouped for prognostic evaluation and clinical characteristics comparison.