100-kyr climate cycles caused by 2.4-Myr eccentricity-modulated carbon cycles.

Earth's climate has been dominated by ~100-kyr glacial cycles over the past ~800 ka, yet the mechanism remains debated. Here, we present correlation analyses of spectral power ratios of global records spanning the past 2.7 Ma, revealing a persistent anticorrelation between ~21-kyr and ~100-kyr power ratios, but no significant relationship between ~41-kyr and ~100-kyr power ratios.

Interstadial diversity of East Asian summer monsoon linked to changes of the Northern Westerlies.

During the last glacial period, the iconic Greenland ice-core records provide evidence of interstadial warmings with various durations ranging from a century to millennia. However, whether differences in interstadial duration are mirrored by distinct hydroclimate responses in the tropics remains unclear. Here we present four speleothem δO records from the Indian summer monsoon (ISM) and East Asian summer monsoon (EASM) regions, spanning both short and long interstadials during the last glacial period.

Summer and nonsummer climatic signals in speleothem δO revealed by loess microcodium δO in East Asia.

Speleothem δO records from central southern China have long been regarded as a key benchmark for Asian summer monsoon intensity. However, the similar δO minima observed among precession minima and their link to seasonal precipitation mixing remains unclear. Here, we present a 400,000-y record of summer precipitation δO from loess microcodium, which captures distinct precession cycles similar to those seen in speleothem δO records, particularly during glacial periods.

A comprehensive stalagmite investigation distinguishing anthropogenic and natural signals in Madagascar between 1680 and 1860.

Disentangling anthropogenic from natural induced changes is difficult, but crucial to accurately assess the specific environmental impacts of humans' actions versus climate in the paleoclimate records. Here we combine a new set of proxies, including stable isotopes, element concentrations (mainly Mg, Sr, and U), and detailed mineralogy to better distinguish the impacts of these two factors in the stalagmite records. We studied the period between 1680 and 1860 CE because of the known historical events in Madagascar history (e.

Integrative multi-omics analysis reveals BEST1 as a potential tumor-associated gene in gliomas.

Background: The newest glioma classification in WHO 2021 emphasizes the importance of gene mutations in the glioma molecular pathogenesis. Our research aims to look for new glioma-related genes that have the potential to be therapeutic targets.

Methods: We applied Mendelian randomization and colocalization analysis to identify the target genes.

Asian summer monsoon variability across Termination II and implications for ice age terminations.

The detailed anatomy of Termination I (TI) is well depicted, but whether changes across Termination II (TII) resemble TI remains controversial. Here we present high-resolution Asian monsoon records covering TII using Shima Cave stalagmites from China. Correlating marine and ice-core records to our U/Th-dated records via millennial-scale variabilities, we find an initial CO rise from 139 ± 1 ka BP concordant with boreal summer insolation increase, which was followed by a major rise phase of CO between 135.

Complex association of mean corpuscular volume and outcomes in patients with aplastic anemia treated with cyclosporine A plus androgen or cyclosporine A alone.

The aim of this study was to explore the prognostic value of mean corpuscular volume (MCV) in newly diagnosed aplastic anemia (AA) patients treated with cyclosporine A (CsA) plus androgen or CsA alone. The clinical data of 181 newly diagnosed patients with aplastic anemia from April 2008 to September 2020 in the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. According to the MCV levels, the patients were divided into a high-MCV group (107/181) and a normal-MCV group (74/181).

The impact of antibiotic use on outcomes of relapsed/refractory multiple myeloma patients treated with CAR-T therapy.

Background: In recent years, chimeric antigen receptor (CAR)-T cell therapy has achieved tremendous efficacy in relapsed/refractory multiple myeloma (R/R MM). However, the impact of antibiotic (ATB) use on R/R MM patients treated with CAR-T is still not known. The aim of our study was to analyse the influence of ATB on the clinical outcomes of R/R MM patients treated with CAR-T cells.

Nephrotoxicity of CAR-T therapy in patients with relapsed and refractory multiple myeloma.

Objective: Chimeric antigen receptor T (CAR-T) cell therapy has achieved impressive efficacy in treating relapsed and refractory multiple myeloma (R/R MM). Nephrotoxicity after CAR-T cell therapy has rarely been reported.

Methods: We investigated the occurrence and clinical outcomes of acute kidney injury (AKI) in 111 patients with R/R MM after CAR-T cell therapy.

Anti-GPRC5D CAR T-cell therapy as a salvage treatment in patients with progressive multiple myeloma after anti-BCMA CAR T-cell therapy: a single-centre, single-arm, phase 2 trial.

Background: For patients with multiple myeloma progression after anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, the optimal salvage treatment strategies remain unclear. GPRC5D-directed CAR T cell might be a potential option. The aim of this trial was to investigate the activity and safety of anti-GPRC5D CAR T cells in patients with progressive multiple myeloma after anti-BCMA CAR T-cell therapy.

Decoding mitochondrial stress genes in DCM: towards precision diagnosis and therapy.

Background: Mitochondrial oxidative stress (ROS) is a crucial factor in the pathogenesis of dilated cardiomyopathy (DCM). Despite its significance, robust biomarkers for assessing its role remain scarce. This study investigates ROS mechanisms in DCM and identifies associated biomarkers, offering fresh insights into diagnosis and treatment.

Effect of metachronous primary and secondary solid cancers in patients with multiple myeloma: a retrospective study from a single-center.

Statement Of Translational Relevance: Effects of metachronous primary malignant solid tumor (MPMST) on survival risk and prognosis of multiple myeloma (MM) and differences between MPMST occurring before and after MM remains unclear. Use of well-characterized clinical information of individual patient, we found that older patients with MM (≥ 65 years) had a higher risk of developing MPMST. Patients with MM and MPMST including male patients, aged ≥ 65 years and those with ISS stage III had a worse prognosis.

Astrocyte-secreted cues promote neural maturation and augment activity in human forebrain organoids.

Brain organoids have been proposed as suitable human brain model candidates for a variety of applications. However, the lack of appropriate maturation limits the transferability of such functional tools. Here, we present a method to facilitate neuronal maturation by integrating astrocyte-secreted factors into hPSC-derived 2D and 3D neural culture systems.

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 and whole-genome bisulfite sequencing 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.