Search Results (5,239)

Chickpea (Cicer arietinum L.) is an important legume, valued for its nutritional and bioactive components. In this study, seven chickpea advanced breeding lines, an elite line, and a cultivar were evaluated under field conditions to assess superior agronomic performance, seed quality traits, nutritional composition, and phenolic profile. A combined approach was used, integrating field phenotyping, seed quality assays, and LC–MS-based phenolic profiling. Significant genotype-dependent variation was observed in plant height, biomass yield, and 1000-seed weight, with P9/14 and P10/14 advanced lines performing strongly in yield-related traits. Seed functional properties also differed, with P8/14 showing superior hydration and seed coat characteristics, while cv. Blanco Sinaloa exhibited the highest hydration and swelling capacities. Protein content ranged from 22.6% to 25.4%, with P9/14 being the most protein-rich advanced line. Phytochemical and antioxidant analyses revealed substantial differences among genotypes: Blanco Sinaloa and M-15370 showed the highest total phenolics and ABTS activity, whereas P14/14 exhibited the strongest DPPH scavenging capacity. LC–MS profiling identified six major phenolic subclasses, with isoflavones predominating and biochanin A and its derivatives being the most abundant compounds. Overall, the integration of agronomic, nutritional, and phytochemical data highlights the advanced lines P14/14 and P9/14 as promising candidates for future breeding programs aimed at enhancing chickpea nutritional quality and functional seed attributes. Full article

Mucus plugs are airway-obstructing accumulations of inspissated secretions frequently observed in obstructive lung diseases (OLDs), including chronic obstructive pulmonary disease (COPD), severe asthma, and cystic fibrosis. Their presence on chest CT is strongly associated with airflow limitation, reduced lung function, and increased mortality, making them emerging imaging biomarkers of disease burden and treatment response. However, manual delineation of mucus plugs is labor-intensive, subjective, and impractical for large cohorts, leading most prior studies to rely on coarse segment-level scoring systems that overlook lesion-level characteristics such as size, extent, and location. Automated plug-level quantification remains challenging due to substantial heterogeneity in plug morphology, overlap in attenuation with adjacent vessels and airway walls on non-contrast CT, and pronounced size imbalance in clinical datasets, which are typically dominated by small distal plugs. To address these challenges, we developed and validated a simulation-driven, annotation-free deep learning framework for automated detection and segmentation of airway mucus plugs on non-contrast chest CT. A total of 200 COPD CT scans were analyzed (98 plug-positive, 83 plug-negative, and 19 uncertain). Synthetic mucus plugs were generated within segmented airways by transferring voxel-intensity statistics from adjacent intrapulmonary vessels, preserving realistic morphology and texture while enabling controlled sampling of plug phenotypes. An nnU-Net trained exclusively on synthetic data (S-Model) was evaluated on an independent, expert-annotated test set and compared with an nnU-Net trained on manual annotations using 10-fold cross-validation (M-Model). The S-Model achieved significantly higher detection performance than the M-Model (sensitivity 0.837 [95% CI: 0.818–0.854] vs. 0.757 [95% CI: 0.737–0.776]; 1.91 false positives per scan vs. 3.68; p < 0.001), with performance gains most pronounced for medium-to-large plugs (≥6 mm). This simulation-driven approach enables accurate, scalable quantification of mucus plugs without voxel-wise manual annotation in thin-slice (<1.5 mm) non-contrast chest CT scans. While the framework could, in principle, be extended to other annotation-limited medical imaging tasks, its generalizability beyond this COPD cohort and imaging protocol has not yet been established, and future work is required to validate performance across diverse populations and scanning conditions. Full article

Salt stress is one of the main abiotic stresses that restrict crop production. Melatonin (MT), a signal molecule widely present in plants, plays an important role in regulating abiotic stress response. In this study, celery seedlings were used as experimental materials, and the control, salt stress, and exogenous MT treatment groups under salt stress were set up. Through phenotypic, physiological index determination, transcriptome sequencing, and expression analysis, the alleviation effects of MT on salt stress were comprehensively investigated. The results showed that exogenous MT treatment significantly reduced seedling growth inhibition caused by salt stress. Physiological measurements showed that MT significantly reduced malondialdehyde content, increased the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), promoted the accumulation of free proline and soluble protein, and increased photosynthetic parameters such as chlorophyll, ΦPSII, Fv/Fm, and ETR. Transcriptome analysis showed that MT regulates the expression of several genes associated with carbon metabolism, including β-amylase gene (AgBAM), sucrose-degrading enzyme genes (AgSUS, AgINV), and glucose synthesis-related genes (AgAG, AgEGLC, AgBGLU). The results of qRT-PCR verification were highly consistent with the transcriptome sequencing data, revealing that MT synergistically regulates starch and sucrose metabolic pathways, and effectively alleviates the damage of celery seedlings under salt stress at the molecular level. In summary, exogenous MT significantly improved the salt tolerance of celery by enhancing antioxidant capacity, maintaining photosynthetic function, promoting the accumulation of osmotic adjustment substances, and synergistically regulating carbon metabolism-related pathways. The concentration of 200 μM was identified as optimal, based on its most pronounced alleviating effects across the physiological parameters measured. This study provides an important theoretical basis for utilizing MT to enhance plant salt resistance. Full article

Geodiamolides are depsipeptides previously isolated from marine sponges that are able to disrupt cytoskeleton microfilaments, inhibit cell migration and invasion, and reverse the malignant phenotype of human breast cancer cell lines to polarized spheroid-like structures. Such cytotoxicity to different cellular targets in breast cancer cells suggests that these molecules might also act in other cancer types such as non-melanoma skin cancer (NMSC), one of the cancer types with high incidence worldwide. Thus, the goal of this work was to study the effects of the marine sponge depsipeptides Geodiamolide A and H (Geo A and Geo H) in human squamous cell carcinoma (A431, NMSC) in order to investigate their effects on cell proliferation and cell death. While no significant statistical difference was observed after Geo H treatment, an expressive dose-dependent reduction in A431 cell viability (IC₅₀ of 368 nM, MTT assay; p < 0.05) and proliferation pattern (real-time cell analysis assay) was shown after 48 h exposure with Geo A. The cell proliferation blockade was confirmed after 24 h of Geo A treatment at 500 nM, with a 46% (p < 0.0001) reduction in the total number of cells (cell counting) and G2/M phase cell cycle arrest. Other cytotoxic evidence such as DNA fragmentation, phosphatidylserine exposure (flow cytometry), and time-dependent plasma membrane damage (Trypan Blue) suggested cell death by apoptosis. Therefore, Geo A showed both cytostatic and cytotoxic effects on A431 cells. Taken together, these data point out Geo A as a promising therapeutic molecule for NMSC treatment and is the first depsipeptide (marine or terrestrial), to our knowledge, to target this type of cancer cell. Full article

Fruit size and pungency are key yield and quality traits in chili. This study combines high-throughput genotyping with bulk segregant analysis (BSA) to identify candidate SNPs and quantitative trait loci (QTLs) by analyzing extreme phenotypes from a Ghotki × Chakwal-4 F2 population. The traits were fruit length, diameter, length-to-diameter ratio, and weight, along with capsaicin content. Significant correlations were observed among length, diameter, and length-to-diameter ratio. A total of 534 single nucleotide polymorphisms (SNP) markers were used to develop genetic maps from 4315 to 6607 cM long. The SNP frequency data was pooled for the 25% of individuals showing extreme values for each measured trait, and bulk segregant analysis (BSA) was performed. BSA identified high-scoring SNPs associated with pungency (SNP 1_41308232; SNP 12_104377148), fruit length (SNP 1_92509300; SNP 6_218780813), and fruit weight (SNP 6_100989762 and SNP 6_138660974). Genetic mapping identified twelve pungency QTLs, three for fruit length, two for fruit diameter, two for the length-to-diameter ratio, and thirteen for fruit weight. Overlapping QTL regions on chromosome 6 influence fruit length, fruit width, and capsaicin content, indicating potential pleiotropy and offering promising targets for multi-trait selection in chili breeding. The study identifies key SNPs and QTLs that simultaneously influence chili fruit size and pungency, providing valuable targets for multi-trait breeding. Full article

Background/Objectives: This study systematically analyzed the concentration dynamics of human milk oligosaccharides (HMOs) and the distribution characteristics of secretory (Se) and Lewis (Le) phenotypes in China. Methods: A total of 1462 breast milk samples were collected from lactating mothers in six major regions of China, including Changchun, Lanzhou, Chengdu, Tianjin, Guangzhou, and Shanghai. We quantified 17 major HMOs by high-performance anion exchange chromatography-pulsed amperometric detection (HPAEC-PAD), and Se/Le phenotypes were determined to evaluate regional differences and distribution patterns. Results: Total HMO concentration in breast milk showed a significant downward trend within 200 days postpartum and stabilized after 200 to 400 days. Fucosylated HMOs accounted for the highest proportion $60.0–83.0\%$, among which 2′-FL had the largest concentration $903.4–2832.7 \mathrm{m}\mathrm{g}/\mathrm{L}$; acetylated HMOs $8.4–17.6\%$ and sialylated HMOs $8.2–25.3\%$ accounted for relatively lower proportions. This study further divided breast milk into four phenotypes based on HMO characteristics: 72.49% of the samples were Se+/Le+, 6.145% were Se+/Le−, 20.12% were Se−/Le+, and 1.24% were double negative (Se−/Le−). Se+ and Le+ phenotypes accounted for 78.7% and 92.6% of the total population, respectively. The total concentration of HMOs in breast milk of different phenotypes was significantly different, with the average total HMO concentration of Se+/Le+ breast milk being the highest (8342 mg/L), while that of Se−/Le− breast milk being the lowest (4532 mg/L). Se+ phenotype was associated with higher levels of fucosylated HMOs, including 2′-fucosyllactose (2′-FL) and lacto-N-fucopentaose I (LNFP I), and lower levels of lacto-N-tetraose (LNT) and sialyl-lacto-N-tetraose b (LST b) compared to other phenotypes. Most HMOs reached their highest concentrations during the colostrum (CM) and transitional milk (TM) stages, followed by a progressive decline with lactation, with phenotype-specific variations evident across all HMOs. Notably, certain HMOs, such as 3-FL, 3′-SL, DFL, and LNDFH II, exhibited distinct temporal patterns. Conclusions: This study revealed the Se/Le phenotype distribution and dynamic characteristics of HMOs in the Chinese mother-infant population, offering a valuable reference for global breast milk composition databases and infant nutrition research. Full article

Tumor-associated macrophages (TAMs) and dendritic cells (DCs) play pivotal roles in shaping the tumor immune microenvironment, often contributing to immunosuppression and therapy resistance. Recent advances in nanotechnology have enabled precise modulation of these immune populations, offering a promising avenue to enhance the efficacy of cancer immunotherapy. Nano-enabled platforms can reprogram TAMs from a pro-tumorigenic M2-like phenotype to an anti-tumorigenic M1-like state, thereby restoring their capacity to phagocytose tumor cells and produce pro-inflammatory cytokines. Concurrently, nanomaterials can enhance DC activation and antigen presentation, promoting robust T-cell priming and adaptive immune responses. Various nanocarriers, including liposomes, polymeric nanoparticles, and inorganic nanostructures, have been engineered to deliver immune modulators, nucleic acids, or tumor antigens selectively to TAMs and DCs within the tumor microenvironment. These strategies have demonstrated synergistic effects when combined with immune checkpoint blockade or cytokine therapy, resulting in improved tumor regression and long-term immunological memory in preclinical models. Despite these promising outcomes, challenges remain regarding nanomaterial biocompatibility, targeted delivery efficiency, and potential off-target immune activation. Ongoing research is focused on optimizing nanoparticle physicochemical properties, surface functionalization, and multi-modal delivery systems to overcome these limitations. This review highlights recent advances in nano-enabled modulation of TAMs and DCs, emphasizing mechanistic insights, therapeutic outcomes, and translational potential. By integrating nanotechnology with immunotherapy, these approaches offer a powerful strategy to overcome tumor immune evasion, paving the way for more effective and personalized cancer treatments. Full article

Prader–Willi (PWS) and Angelman (AS) syndromes were the first examples in humans with errors in genomic imprinting, usually from de novo 15q11-q13 deletions of different parent origin (paternal in PWS and maternal in AS). Dozens of genes and transcripts are found in the 15q11-q13 region, and may play a role in PWS, specifically paternally expressed SNURF-SNRPN and MAGEL2 genes, while AS is due to the maternally expressed UBE3A gene. These three causative genes, including their encoding proteins, were targeted. This review article summarizes and illustrates the current understanding and cause of both PWS and AS using strategies to include the literature sources of key words and searchable web-based programs with databases for integrated gene and protein interactions, biological processes, and molecular mechanisms available for the two imprinting disorders. The SNURF-SNRPN gene is key in developing complex spliceosomal snRNP assemblies required for mRNA processing, cellular events, splicing, and binding required for detailed protein production and variation, neurodevelopment, immunodeficiency, and cell migration. The MAGEL2 gene is involved with the regulation of retrograde transport and promotion of endosomal assembly, oxytocin and reproduction, as well as circadian rhythm, transcriptional activity control, and appetite. The UBE3A gene encodes a key enzyme for the ubiquitin protein degradation system, apoptosis, tumor suppression, cell adhesion, and targeting proteins for degradation, autophagy, signaling pathways, and circadian rhythm. PWS is characterized early with infantile hypotonia, a poor suck, and failure to thrive with hypogenitalism/hypogonadism. Later, growth and other hormone deficiencies, developmental delays, and behavioral problems are noted with hyperphagia and morbid obesity, if not externally controlled. AS is characterized by seizures, lack of speech, severe learning disabilities, inappropriate laughter, and ataxia. This review captures the clinical presentation, natural history, causes with genetics, mechanisms, and description of established laboratory testing for genetic confirmation of each disorder. Three separate searchable web-based programs and databases that included information from the updated literature and other sources were used to identify and examine integrated genetic findings with predicted gene and protein interactions, molecular mechanisms and functions, biological processes, pathways, and gene-disease associations for candidate or causative genes per disorder. The natural history, review of pathophysiology, clinical presentation, genetics, and genetic-phenotypic findings were described along with computational biology, molecular mechanisms, genetic testing approaches, and status for each disorder, management and treatment options, clinical trial experiences, and future strategies. Conclusions and limitations were discussed to improve understanding, clinical care, genetics, diagnostic protocols, therapeutic agents, and genetic counseling for those with these genomic imprinting disorders. Full article

Whole-genome duplication (WGD) is a powerful evolutionary force, yet the mechanisms by which neopolyploids achieve transcriptomic stability and phenotypic success remain poorly understood. This study investigated the phenotypic and transcriptomic consequences of ploidy changes in the flatworm Macrostomum lignano, a “successful” neopolyploid model. We exploited two established sublines derived from the inbred DV1 line: the euploid DV1_8 (hidden tetraploid, SSL₁L₂) and the aneuploid DV1_10 (hidden hexaploid, SSL₁L₁L₂L₂). By integrating whole-genome sequencing (WGS)-informed normalization with RNA-seq analysis, we differentiated true regulatory shifts from gene-dosage effects. We revealed that while most genes scale linearly with ploidy, 1308 genes exhibited a nonlinear aneuploidy-induced transcriptional response. The remarkable trans-acting effects were observed across subgenome S encoded by disomic small chromosomes. Differentially expressed genes (DEGs) were enriched in pathways essential for homeostasis and growth: mTOR signaling, ubiquitin-mediated proteolysis, and the Hippo/Wnt pathways. Phenotypes of the DV1_10 worms exhibited increased body size, enhanced cell proliferation, and higher viability in comparison to the DV1_8 worms (60.25% vs. 21.5%). These findings suggest that M. lignano possesses mechanisms for dosage compensation to mitigate the deleterious effects of aneuploidy. Ultimately, this study demonstrates how genomic plasticity and rewiring of the transcriptome may facilitate the evolutionary success of animal neopolyploids. Full article

Background/Objectives: Simple urinary tract infections (sUTIs) are common in women and increasingly affected by multidrug-resistant (MDR) Escherichia coli. Extended-spectrum β-lactamase (ESBL) and AmpC producers restrict oral treatment options and promote carbapenem use. This study aimed to (i) describe the etiology and antimicrobial susceptibility of sUTIs in women of reproductive age in Oman, (ii) determine the prevalence of ESBL/AmpC-producing E. coli, (iii) evaluate nitroxoline, fosfomycin, mecillinam, and temocillin against ESBL and non-ESBL E. coli, and (iv) characterize circulating clones and resistance/virulence determinants using whole-genome sequencing (WGS). Methods: In this multicentric study (September 2022–August 2023), 795 uropathogens from 762 women (15–50 years) with sUTI were collected from four Omani hospitals. Identification and susceptibility testing of E. coli (n = 489) and Klebsiella pneumoniae (n = 140) using BD Phoenix and MALDI-TOF MS was performed (CLSI 2022). Thirty ESBL-producing and 82 non-ESBL E. coli underwent phenotypic ESBL/AmpC testing and evaluation of mecillinam, temocillin, nitroxoline, and fosfomycin. WGS was performed on 26 isolates (23 ESBL, 3 wild type) and analyzed for MLST, and SNP phylogeny using ResFinder, CARD, PlasmidFinder, VirulenceFinder. Statistical significance was set at p < 0.05. Results: E. coli (62%) and K. pneumoniae (18%) were the predominant pathogens. E. coli showed high susceptibility to nitrofurantoin (~97%), carbapenems, aminoglycosides, and piperacillin–tazobactam, but reduced susceptibility to cephalosporins, fluoroquinolones, cotrimoxazole, and ampicillin. ESBL prevalence ranged from 38–51%; AmpC producers were rare (4.6%). Mecillinam, nitroxoline, and fosfomycin exhibited 100% activity against both ESBL and non-ESBL isolates; temocillin showed 89.3% activity in ESBL strains. WGS identified 15 sequence types dominated by ST-131, ST-1193, ST-73, and ST-174, with blaCTX-M-15 as the major ESBL genotype. Conclusions: sUTIs in Oman show a high burden of ESBL-producing E. coli. Nitrofurantoin, mecillinam, fosfomycin, temocillin, and nitroxoline would be effective carbapenem-sparing oral options. Continuous phenotypic and genomic surveillance are crucial to guide antimicrobial therapy and stewardship. Full article

Background/Objectives: Neuroblastoma cells are phenotypically plastic, transitioning between mesenchymal and adrenergic states. Core functional genes (e.g., YAP1) mark the mesenchymal state, which is linked to unfavorable prognosis. We and others previously demonstrated relapse-specific Hippo-YAP pathway activation in matched primary/relapsed neuroblastomas. Here we explored the role of YAP1 in neuroblastoma aggressiveness and response to therapy. Methods: RT-qPCR and immunoblotting assessed YAP1 expression in neuroblastoma cell lines. RNA-sequencing detected YAP1-dependent gene signatures in Tet-ON SK-N-AS and SH-EP neuroblastoma cell models expressing wildtype YAP1 or constitutively activated YAP1^S127A. Data from cell models were compared with our published YAP1 expression data from neuroblastomas. Efficacy of commonly used chemotherapeutics was comparatively analyzed in the cell models. Results: YAP1 expression showed marked variability across a panel of neuroblastoma cell lines, assessed by mRNA analysis in 10 cell lines and protein analysis in a subset of 9 cell lines. RNA sequencing in constitutively activated YAP1^S127A mutant and wildtype YAP1 models detected 2162 and 1837 significantly differentially expressed genes in the SK-N-AS and SH-EP backgrounds, respectively. Continuously activating YAP1 in SK-N-AS cells upregulated mesenchymal signature genes and mesenchymal-associated transcription factors. Gene expression influenced by YAP1 activity in the cell models significantly overlapped with YAP1-associated genes (e.g., CYR61 and SPRY4) in published tumor data. Functionally, YAP1^S127A expression rendered neuroblastoma cells resistant to chemotherapy. Conclusions: Findings corroborate the idea of a mechanistic role for YAP1 in neuroblastoma adrenergic to mesenchymal reprogramming and therapy resistance. The YAP1-mediated plastic switch towards a mesenchymal expression state in neuroblastoma cells may provide the molecular basis for novel therapeutic avenues. Full article

The transcription factor IRF5 maintains macrophages in the pro-inflammatory M1 state. We assessed the effects of siRNA-mediated knockdown of Irf5 on murine bone marrow-derived macrophages (BMDM) in M0, M1 and M2 states. Knockdown of Irf5 in M1 macrophages made them phenotypically similar to M2 macrophages, which was reflected in the decreased expression of the M1 marker iNOS, increased expression of the M2 marker CD206, increased mitochondrial content and respective morphological changes. Interestingly, the M2 phenotype was also affected by the reduction in Irf5. Using atomic force microscopy (AFM), we showed that Irf5 knockdown increases plasma membrane roughness, particularly in M2 macrophages. AFM-based stiffness measurements indicated that Irf5 knockdown altered macrophage elasticity, potentially influencing their functional behavior. Our data suggest a complex role of IRF5 in macrophage polarization, supporting its dual role as a transcriptional activator and repressor both in M1 and M2 states, and highlight the importance of IRF5 in the maintenance of metabolic and functional properties of macrophages. Full article

Background: The ACE Y215C mutation is a common, functionally damaging missense variant (~1.5% allele frequency) associated with reduced plasma ACE levels and increased Alzheimer’s disease (AD) risk. In CHO and HEK cell models, this mutation caused a ~3–6-fold decrease in ACE surface expression, soluble ACE levels, and ACE enzymatic activity compared to those of wild-type ACE. Methods: Circulating ACE levels and activity were measured in EDTA plasma obtained from 84 carriers of the ACE Y215C mutation using a set of mAbs to the ACE. The mAbs 5B3/1G12 binding ratio was revealed as a sensitive marker for the circulating Y215C ACE mutant. Whole-exome and whole-genome sequencing (WES/WGS) were performed to identify genetic variants potentially modifying circulating ACE levels. In parallel, published sequencing and proteomic data from 35,559 Icelanders participants were analyzed to identify genes influencing ACE shedding. Sequence comparison was performed between carriers with elevated and reduced ACE concentrations to identify the potential protective variants that may compensate for decreased ACE levels due to the Y215C mutation itself. Results: Most carriers of the Y215C ACE mutation demonstrated significantly decreased ACE levels (median is 62% of control ACE levels). However, substantial inter-individual variability was observed in plasma ACE activity among carriers. Comparative sequencing analysis revealed 9648 variants unique to individuals with elevated ACE, mapping to 5779 protein-coding genes and enriched for pathways related to intracellular and transmembrane transport. Conclusions: The presence of the damaging ACE mutation Y215C does not invariably result in low plasma ACE or, likely, elevated AD risk. Therefore, combined blood ACE phenotyping and whole-exome sequencing are recommended to more accurately assess ACE-related AD susceptibility in mutation carriers. Full article

Background and Objectives: This study compared functional performance, gait performance, and dynamic balance between Coronal Plane Alignment of the Knee (CPAK) Type I and Type II patients undergoing unilateral total knee arthroplasty (TKA). Materials and Methods: We included 162 consecutive patients scheduled for unilateral TKA between January 2022 and August 2025. Patients were classified according to CPAK type; 42 were Type I and 33 were Type II. Preoperative assessments included demographic data, Korean Knee Score, and WOMAC. Functional performance was evaluated using the Timed Up and Go (TUG) test and the 4 m walk test. Isokinetic knee extensor and flexor strength (60°/s), hip abductor strength, and bilateral thigh circumferences measured 5 cm and 15 cm proximal to the patella were assessed. Dynamic balance asymmetry was evaluated using the POSTUROMED device. Inter-limb differences were calculated by comparing the operated and non-operated limbs. Results: No significant between-group differences were observed in clinical scores, knee extensor, or flexor strength deficits, hip abductor strength deficits, or thigh circumference differences. However, CPAK Type II patients demonstrated significantly better functional performance, with faster TUG (p = 0.014) and 4 m walk test times (p = 0.022). Dynamic balance outcomes were also significantly better in the Type II group (p = 0.042). Conclusions: Despite similar patient-reported clinical scores and muscle strength, patients with the CPAK Type II phenotype exhibited superior gait performance and dynamic balance compared with those with Type I following unilateral TKA. Full article

Chronic lymphocytic leukemia (CLL) is a dynamic malignancy in which intraclonal subfractions differ in activation history and responsiveness to microenvironmental signals. Here, we investigated the expression and inducibility of IL-12 family receptor subunits (IL-23R, IL-12Rβ1, IL-12Rβ2) and the related receptor complexes in recirculating CLL cells, with a focus on CXCR4/CD5-defined fractions: the proliferative fraction (PF; CXCR4^dim/CD5^bright; most recently divided, tissue-emigrated cells) and the resting fraction (RF; CXCR4^bright/CD5^dim; older, quiescent cells). At baseline, IL-12Rβ1 was enriched in the PF and was associated with a higher proportion of cells expressing IL-23R and IL-12R receptor complexes. Concomitantly, RT-qPCR disclosed higher IL-12Rβ1 mRNA levels. Following antigen-independent activation with CpG or CpG + IL-15, there was a marked increase in IL-23R and IL-12Rβ1 but not in IL-12Rβ2 surface expression, resulting in preferential upregulation of the IL-23R complex over the IL-12R complex. Fraction-specific analyses showed stronger induction of IL-23R and IL-23R complex expression in PF compared with RF. These findings identify an intraclonal bias toward IL-23 responsiveness in the CLL cells with a phenotype of recently divided, tissue-emigrated cells and suggest the IL-23/IL-23R axis as a potential therapeutic target. Full article