Paired Single-B-Cell Transcriptomics and Receptor Sequencing Reveal Activation States and Clonal Signatures That Characterize B Cells in Acute Myeloid Leukemia

BACKGROUND: Acute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML\u27s immunological microenvironment along with their interaction with ICB remains rather constrained. METHODS: We performed an extensive analysis that involved paired single-cell RNA and B-cell receptor (BCR) sequencing on 52 bone marrow aspirate samples. These samples included 6 from healthy bone marrow donors (normal), 24 from newly diagnosed AML patients (NewlyDx), and 22 from 8 relapsed or refractory AML patients (RelRef), who underwent assessment both before and after azacitidine/nivolumab treatment. RESULTS: We delineated nine distinct subtypes of B cell lineage in the bone marrow. AML patients exhibited reduced nascent B cell subgroups but increased differentiated B cells compared with healthy controls. The limited diversity of BCR profiles and extensive somatic hypermutation indicated antigen-driven affinity maturation within the tumor microenvironment of RelRef patients. We established a strong connection between the activation or stress status of naïve and memory B cells, as indicated by AP-1 activity, and their differentiation state. Remarkably, atypical memory B cells functioned as specialized antigen-presenting cells closely interacting with AML malignant cells, correlating with AML stemness and worse clinical outcomes. In the AML microenvironment, plasma cells demonstrated advanced differentiation and heightened activity. Notably, the clinical response to ICB was associated with B cell clonal expansion and plasma cell function. CONCLUSIONS: Our findings establish a comprehensive framework for profiling the phenotypic diversity of the B cell lineage in AML patients, while also assessing the implications of immunotherapy. This will serve as a valuable guide for future inquiries into AML treatment strategies

Interim position emission tomography-computed tomography during multimodality treatment of locally advanced esophageal cancer: a scoping review.

BACKGROUND Among cancers, esophageal cancer (EC) has one of the highest incidences and mortality in Asia. As recognized in many national guidelines, functional imaging performed with position emission tomography is recommended for patients with locally advanced disease. This review evaluated evidence for the use of fluorodeoxyglucose (FDG) interim positron emission tomography (PETint) in bimodality (chemoradiation) and trimodality (chemoradiation followed by surgery) management of locally advanced esophageal cancer (LAEC), with a focus on its prognostic and predictive value. METHODS The MEDLINE database was searched from January 1, 2001, to January 1, 2022, as part of a scoping review. References of selected articles were manually checked to identify other articles meeting the inclusion criteria; only original articles were included, and reviews, guidelines, letters, editorials, and case reports were excluded. RESULTS A total of 63 articles were included in this review. PET-computed tomography (PET-CT) is recognized as having a significant role in the assessment of treatment response. Studies on the predictive PETint suggest that it has a certain value, particularly for early response. Identification of poor responders or nonresponders soon after commencement of multimodality treatment allows for treatment modification. CONCLUSIONS The scoping review indicated variable utility for the prognostic value of PETint. There is a need to improve its accuracy, which can likely be achieved through greater standardization of measurements and reporting and testing as well as combination with other promising measures of response to residual disease

Plant biomass allocation and driving factors of grassland revegetation in a Qinghai-Tibetan Plateau chronosequence

Biomass allocation is a key factor in understanding how ecosystems respond to changing environmental conditions. The role of soil chemistry in the above- and belowground plant biomass allocation in restoring grassland is still incompletely characterized. Consequently, it has led to two competing hypotheses for biomass allocation: optimal partitioning, where the plants allocate biomass preferentially to optimize resource use; and the isometric hypothesis, which postulates that biomass allocation between roots and shoots is fixed. Here we tested these hypotheses over a chronosequence of alpine grasslandsion undergoing restoration in the Qinghai-Tibetan Plateau, these range from severely degraded to those with 18 years of revegetation with an intact grassland (as a reference). A high proportion of biomass was allocated to the roots in the revegetated grasslands, and more biomass to shoots in the degraded and intact grasslands. The grasslands gradually decreased their root to shoot ratio as revegetation continued, with the lowest value in year 18 of revegetation. Our results showed that aboveground biomass (AGB) was increased by available phosphorus (P), soil moisture, and negatively related to bulk density, while belowground biomass (BGB) was positively impacted by total P and negatively by nitrate nitrogen (N). The trade-off between them was positively associated with available P and nitrate-N, and soil nutrient availability is more linked to increased AGB relative to BGB. Our study indicates that biomass allocation is highly variable during the revegetation period from degraded grassland, and is linked with soil properties, thus supporting the optimal partitioning hypothesis.</p

The Effects of Ambient Temperature on Lumbar Disc Herniation: A Retrospective Study

PurposeThis article was designed to provide critical evidence into the relationship between ambient temperature and intensity of back pain in people with lumbar disc herniation (LDH).MethodsData concerning patient's age, gender, diagnostic logout, admission time, discharge time, residence area, and work area (residence area and work area were used to ensure research area) from 2017 to 2019 were obtained from the Neck-Shoulder and Lumbocrural Pain Hospital in Jinan, China. A total of 1,450 hospitalization records were collected in total. The distributed lag non-linear model (DLNM) was used to evaluate the relationship between lag–response and exposure to ambient temperature. Stratification was based on age and gender. Days 1, 5, 20, and 28 prior to admission were denoted as lags 0, 5, 20, and 28, respectively.ResultsAn average daily temperature of 15–23°C reduced the risk of hospitalization the most in men. Conversely, temperatures &lt;10°C drastically increased hospitalization in men, particularly in lags 0–5 and lags 20–28. Men aged between 40 and 50 years old showed less effect in pain sensation during ambient temperature.ConclusionHigh or low ambient temperature can increase the hospitalization risk of LDH, and sometimes, the temperature effect is delayed

COVID−19 hospitalization increases the risk of developing glioblastoma: a bidirectional Mendelian-randomization study

BackgroundAs a result of the COVID-19 pandemic, patients with glioblastoma (GBM) are considered a highly vulnerable population. Despite this, the extent of the causative relationship between GBM and COVID-19 infection is uncertain.MethodsGenetic instruments for SARS-CoV-2 infection (38,984 cases and 1,644,784 control individuals), COVID-19 hospitalization (8,316 cases and 1,549,095 control individuals), and COVID-19 severity (4,792 cases and 1,054,664 control individuals) were obtained from a genome-wide association study (GWAS) from European populations. A total of 6,183 GBM cases and 18,169 controls from GWAS were enrolled in our study. Their associations were evaluated by applying Mendelian randomization (MR) including IVW meta-analysis, MR-Egger regression, and weighted-median analysis. To make the conclusions more robust and reliable, sensitivity analyses were performed.ResultsOur results showed that genetically predicted COVID−19 hospitalization increases the risk of GBM (OR = 1.202, 95% CI = 1.035–1.395, p = 0.016). In addition, no increased risk of SARS-CoV-2 infection, COVID-19 hospitalization and severity were observed in patients with any type of genetically predicted GBM.ConclusionOur MR study indicated for the first time that genetically predicted COVID−19 hospitalization was demonstrated as a risk factor for the development of GBM

Insights into the ameliorative effect of ZnONPs on arsenic toxicity in soybean mediated by hormonal regulation, transporter modulation, and stress responsive genes

Arsenic (As) contamination of agricultural soils poses a serious threat to crop productivity and food safety. Zinc oxide nanoparticles (ZnONPs) have emerged as a potential amendment for mitigating the adverse effects of As stress in plants. Soybean crop is mostly grown on marginalized land and is known for high accumulation of As in roots than others tissue. Therefore, this study aimed to elucidate the underlying mechanisms of ZnONPs in ameliorating arsenic toxicity in soybean. Our results demonstrated that ZnOB significantly improved the growth performance of soybean plants exposed to arsenic. This improvement was accompanied by a decrease (55%) in As accumulation and an increase in photosynthetic efficiency. ZnOB also modulated hormonal balance, with a significant increase in auxin (149%), abscisic acid (118%), gibberellin (160%) and jasmonic acid content (92%) under As(V) stress assuring that ZnONPs may enhance root growth and development by regulating hormonal signaling. We then conducted a transcriptomic analysis to understand further the molecular mechanisms underlying the NPs-induced As(V) tolerance. This analysis identified genes differentially expressed in response to ZnONPs supplementation, including those involved in auxin, abscisic acid, gibberellin, and jasmonic acid biosynthesis and signaling pathways. Weighted gene co-expression network analysis identified 37 potential hub genes encoding stress responders, transporters, and signal transducers across six modules potentially facilitated the efflux of arsenic from cells, reducing its toxicity. Our study provides valuable insights into the molecular mechanisms associated with metalloid tolerance in soybean and offers new avenues for improving As tolerance in contaminated soils

Comprehensive Characterization of Ifnγ Signaling in Acute Myeloid Leukemia Reveals Prognostic and Therapeutic Strategies

Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated in sera of most newly diagnosed acute myeloid leukemia (AML) patients, its complex interplay in AML remains insufficiently understood. We aim to characterize these complex interactions through comprehensive bulk and single-cell approaches in bone marrow of newly diagnosed AML patients. We identify monocytic AML as having a unique microenvironment characterized by IFNγ producing T and NK cells, high IFNγ signaling, and immunosuppressive features. IFNγ signaling score strongly correlates with venetoclax resistance in primary AML patient cells. Additionally, IFNγ treatment of primary AML patient cells increased venetoclax resistance. Lastly, a parsimonious 47-gene IFNγ score demonstrates robust prognostic value. In summary, our findings suggest that inhibiting IFNγ is a potential treatment strategy to overcoming venetoclax resistance and immune evasion in AML patients