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.

Evolution of the Asian summer monsoon and regional karst ecological environment since the middle ages in Southwest China.

The frequent droughts and floods, closely associated with the Asian summer monsoon (ASM), has profoundly affected the ecological environment and economy in East Asia. While changes in the ASM are closely related to precipitation patterns, the specific mechanism still requires further investigation. This study utilized stalagmite records from the Feilong Cave in southwest China to reconstruct the evolution of the ASM since the Medieval Warm Period (MWP).

Millennial-scale climate variability of the Asian summer monsoon over the last 690,000 years: insights from cave records.

The Asian summer monsoon (ASM) is an important component of the global climate system. Cave oxygen isotope (δO) records from the region have well characterized the ASM millennial-scale climate variability (MCV) over the last 640 ka, with especially detailed insights for the most recent 60 ka, but little is known about ASM variability beyond the U-Th dating limit of ∼640 ka. Furthermore, questions remain regarding the climatic significance of millennial-scale ASM variability recorded among various climate archives, particularly in the context of the "orbital-scale paradox".

Recent centennial drought on the Tibetan Plateau is outstanding within the past 3500 years.

Given growing concerns about global climate change, it is critical to understand both historical and current shifts in the hydroclimate, particularly in regions critically entwined with global circulation. The Tibetan Plateau, the Earth's largest and highest plateau, is a nexus for global atmospheric processes, significantly influencing East Asian hydroclimate dynamics through the synergy of the Asian Monsoon and the Westerlies. Yet, understanding historical and recent hydroclimate fluctuations and their wide-ranging ecological and societal consequences remains challenging due to short instrumental observations and partly ambiguous proxy reconstructions.

Exploring the relationship between MGAT2 and glioblastoma: A Mendelian Randomization and bioinformatics approach.

Background: Mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase 2 (MGAT2) and tumors' relevant research was in full swing recently. Therefore, we employed Mendelian Randomization (MR) alongside bioinformatics to thoroughly investigate the possible relationship between MGAT2 and glioblastoma (GBM).

Methods: We utilized the summary statistics of genome-wide association studies (GWAS) for MGAT2 (N = 35,559 from deCODE) and glioblastoma (N = 379,155 from FinnGen).

[Fever Characteristics and Biomarker Changes of CRS in Patients with Relapsed/Refractory Multiple Myeloma after CAR-T Cell Therapy].

Objective: To investigate the correlation of the clinical characteristics, fever characteristics, serum biomarkers with cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma (R/R MM) treated with chimeric antigen receptor T cell (CAR-T) immunotherapy.

Methods: 104 R/R MM patients who received CAR-T cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to November 2021 were included, and the correlations of their clinical characteristics, fever characteristics, serum biomarkers with the severity of CRS were analyzed.

Results: Among 104 R/R MM patients receiving CAR-T treatment, no CRS was observed in 8 cases (7.

Spatial correlation network structure of operational efficiency and its driving factors: A case study of star-rated hotels in China.

Accurately grasping the spatial network correlation structure of operational efficiency in star-rated hotels and its influencing factors is of great significance for promoting high-quality coordinated development of star-rated hotels and the regional tourism reception industry. Using a comprehensive approach integrating the Super-DEA model, modified gravity model, and social network analysis to explore the evolving characteristics of spatial network structure in operational efficiency of provincial star-rated hotels in China from 2013 to 2022, and their underlying mechanisms. The results indicate that: (1) During the study period, the average operational efficiency of star-rated hotels in China was 0.

Lamination-based organoid spatially resolved transcriptomics technique for primary lung and liver organoid characterization.

Spatial-transcriptomics technologies have demonstrated exceptional performance in characterizing brain and visceral organ tissues, as well as brain and retinal organoids. However, it has not yet been proven whether spatial transcriptomics can effectively characterize primary tissue-derived organoids, as the standardized tissue sectioning or slicing methods are not applicable for such organoids. Herein, we present a technique, lamination-based organoid spatially resolved transcriptomics (LOSRT), for organoid-spatially resolved transcriptomics based on organoid lamination.

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.

Triple oxygen isotope reveals insolation-forced tropical moisture cycles.

Tropical oceans are the main global water vapor and latent heat sources, but their responses to radiative forcing remain unclear. Here, we investigate oceanic moisture dynamics of the western tropical Pacific (WTP) over the past 210,000 years through an approach of planktonic foraminiferal triple oxygen isotope (Δ'O). The Δ'O record is dominated by the precession cycles (~23,000 years), with lower values reflecting higher humidity in concert with higher Northern Hemisphere summer insolation.

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.

Mercury deposition in central China from the Last Glacial Maximum to the early Holocene recorded in an accurately-dated stalagmite.

Characterization of transport pathways and depositional changes in Mercury (Hg) and their connection to climatic and environmental changes on various time scales are crucial for better understanding the anthropogenic impacts on the global Hg cycle in the Anthropocene epoch. In this study, we examined Hg variations recorded in a stalagmite from central China, covering the period from 25.5 to 10.

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).

Microplastics footprint in nature reserves-a case study on the microplastics in the guano from Yancheng Wetland Rare Birds National Nature Reserve, China.

Bio-ingestion of microplastics poses a global threat to ecosystems, yet studies within nature reserves, crucial habitats for birds, remain scarce despite the well-documented ingestion of microplastics by avian species. Located in Jiangsu Province, China, the Yancheng Wetland Rare Birds Nature Reserve is home to diverse bird species, including many rare ones. This study aimed to assess the abundance and characteristics of microplastics in common bird species within the reserve, investigate microplastic enrichment across different species, and establish links between birds' habitat types and microplastic ingestion.

Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial.

Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells.

Associations of granulocyte colony-stimulating factor with toxicities and efficacy of chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell acute lymphoblastic leukemia.

Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We present a retrospective study of 67 patients with R/R B-ALL who received anti-CD19 CAR T-cell therapy, 41 (61.2%) patients received G-CSF (G-CSF group), while 26 (38.

Complex association of body mass index and outcomes in patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy.

Background Aims: Chimeric antigen receptor-T (CAR-T) cells have exhibited remarkable efficacy in treating refractory or relapsed multiple myeloma (R/R MM). Although obesity has a favorable value in enhancing the response to immunotherapy, less is known about its predictive value regarding the efficacy and prognosis of CAR-T cell immunotherapy.

Methods: We conducted a retrospective study of 111 patients with R/R MM who underwent CAR-T cell treatment.

Hydroclimatic changes on multiple timescales since 7800 y BP in the winter precipitation-dominated Central Asia.

Central Asia (CA) is one of the world's most significant arid regions, which is markedly impacted by global warming. A better understanding of the dynamical processes governing its Holocene climate variability is critical for a better understanding of possible future impacts of climate change in the region. To date, most of the existing CA paleoclimate records are from the summer precipitation-dominated eastern CA (ECA), with few records from the winter precipitation-dominated western CA (WCA).

Impact of IRGM gene promoter polymorphisms on susceptibility to chronic HBV infection.

The autophagy gene immunity-related GTPase M (IRGM) can affect the immune response against intracellular pathogens. The study was performed to determine any possible association between three IRGM single-nucleotide polymorphisms (SNPs) (rs4958842, rs4958843 and rs4958846) and chronic hepatitis B virus (HBV) infection. A total of 171 chronic HBV-infected individuals and 171 healthy controls were collected.