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Osteosarcoma stem cells (OSCs) contribute to the pathogenesis of osteosarcoma (OS), which is the most common malignant primary bone tumor. The significance and underlying mechanisms of action of proteoglycans (PGs) and glycosaminoglycans (GAGs) in OSC phenotypes and OS malignancy are largely unknown. This study aimed to investigate the role of PG/GAG biosynthesis and the corresponding candidate genes in OSCs and poor clinical outcomes in OS using scRNA-seq and bulk RNA-seq datasets of clinical OS specimens, accompanied by biological validation by in vitro genetic and pharmacological analyses. The expression of b-1,3-glucuronyltransferase 3 (B3GAT3), one of the genes responsible for the biosynthesis of the common core tetrasaccharide linker region of PGs, was significantly upregulated in both OSC populations and OS tissues and was associatedwith poor survival in patientswithOSwith high stemcell properties. Moreover, the genetic inactivation of B3GAT3 by RNA interference and pharmacological inhibition of PGbiosynthesis abrogated the self-renewal potential of OSCs. Collectively, these findings suggest a pivotal role for B3GAT3 and PG/GAG biosynthesis in the regulation of OSC phenotypes and OS malignancy, thereby providing a potential target for OSC-directed therapy. [ABSTRACT FROM AUTHOR]

T and B lymphocytes are crucial players in cellular and humoral immune responses. The development, activation and differentiation of T and B lymphocytes are regulated by the best characterized PI3K‐PI (3,4,5) P3‐AKT phosphoinositide signalling pathway. As a branch of the phosphoinositide signalling pathway, the lipid phosphatase INPP4B inhibits AKT activation through degrading the phosphoinositide signalling messenger PI (3,4) P2. However, the role of Inpp4b in T and B lymphocytes remains elusive. Here, we reported that Inpp4b was highly expressed in human and murine T‐ and B‐1 lymphocytes. Despite its higher expression in T lymphocytes, neither T cell development and homeostasis nor in vitro T cell activation and CD4+ T cell differentiation were altered upon loss of Inpp4b. Interestingly, combined direct phenotype analysis of Inpp4b conventional knockout mice and adoptive transfer studies revealed that ablation of Inpp4b intrinsically reduced peritoneal B‐1 cells rather B‐2 cells. Moreover, Inpp4b deficiency led to impaired thymus independent (TI) and thymus dependent (TD) antigens‐induced antibody production. Further in vitro analysis revealed that CD40‐mediated B cell proliferation was impaired upon ablation of Inpp4b. Our findings reveal that Inpp4b is required in regulating B‐1 cell numbers and B cell‐mediated antibody production. [ABSTRACT FROM AUTHOR]

Gray mold, caused by Botrytis cinerea, is one of the most devastating agricultural diseases during the pre and postharvest stages. This study aims to investigate the application of Bacillus subtilis as a bioagent against B. cinerea and reducing pre and postharvest disease as a replacement method to chemical pesticides. Five Botrytis isolates were molecularly confirmed and the virulent isolate BC2 was registered for the first time in the National Center of Biotechnology Information (NCBI) with accession number OP257237. The mycelial growth of B. cinerea was inhibited by up to 84% when treated with the bio agent bacterium using the double drawing method in Petri plates. Pre-harvest application of B. subtilis at a concentration of 108/ml CFU reduced postharvest -gray mold of tomato fruit during ripening stages in the greenhouse. Preharvest application of bioagent bacterium B. subtilis induced the levels of B-1, 3-glucanase and Polyphenol oxidase, indicating enhanced plant resistance to gray mold. Disease severity was decreased compared with control and extended the shelf life at 25 °C.The field application of the bio agent bacterium at the maturity of ripening in preharvest had a significant effect on increasing the level of polyphenol oxidase PPO and B-1, 3-glucanase, which are related to the enhancement of plant defenses and resistance. Additionally, it led to an increase in storage life and a reduction in post-harvest losses. The results demonstrated that preharvest application of bio agent bacterium Bacillus subtilis improved the quality of postharvest tomato fruit and significantly reduced gray mold incidence, all without the use of chemical pesticides. [ABSTRACT FROM AUTHOR]

B-1 lymphocytes exhibit specialized roles in host defense against multiple pathogens. Despite the fact that CD19+CD93+B220lo/- B cells have been identified as B-1 progenitors, the definition for B-1 progenitors remains to be elucidated as CD19+CD93+B220+ B cells are capable to give rise to B-1 cells. Given that transcription factor Bhlhe41 is highly and preferentially expressed in B-1 cells and regulates B-1a cell development, we generated a transgenic mouse model, Bhlhe41dTomato-Cre, for fate mapping and functional analysis of B-1 cells. Bhlhe41dTomato-Cre mice efficiently traced Bhlhe41 expression, which was mainly restricted to B-1 cells in B-cell lineage. We showed an efficient and specific Cremediated DNA recombination in adult B-1 cells and neonatal B-1 progenitors rather than B-2 cells by flow cytometric analysis of Bhlhe41dTomato-Cre/+Rosa26EYFP mice. Treatment of Bhlhe41dTomato-Cre/+Rosa26iDTR mice with diphtheria toxin revealed a robust efficacy of B-1 cell depletion. Interestingly, using Bhlhe41dTomato-Cre mice, we demonstrated that neonatal B-1 progenitors (CD19+CD93+B220lo/-) expressed Bhlhe41 andwere identical to well-defined transitional B-1a progenitors (CD19+CD93+B220lo/-CD5+), which only gave rise to peritoneal B-1a cells. Moreover, we identified a novel population of neonatal splenic CD19hidTomato+B220hiCD43loCD5lo B cells, which differentiated to peritoneal B-1a and B-1b cells. Bhlhe41 deficiency impaired the balance between CD19hidTomato+B220lo/-CD5hi and CD19hidTomato+B220hiCD5lo cells. Hence, we identified neonatal CD19hidTomato+B220hiCD43loCD5lo B cells as novel transitional B-1 progenitors. Bhlhe41dTomato-Cre/+ mouse can be used for fate mapping and functional studies of B-1 cells in host-immune responses. [ABSTRACT FROM AUTHOR]

B-1 lymphocytes exhibit specialized roles in host defense against multiple pathogens. Despite the fact that CD19+CD93+B220lo/- B cells have been identified as B-1 progenitors, the definition for B-1 progenitors remains to be elucidated as CD19+CD93+B220+ B cells are capable to give rise to B-1 cells. Given that transcription factor Bhlhe41 is highly and preferentially expressed in B-1 cells and regulates B-1a cell development, we generated a transgenic mouse model, Bhlhe41dTomato-Cre, for fate mapping and functional analysis of B-1 cells. Bhlhe41dTomato-Cre mice efficiently traced Bhlhe41 expression, which was mainly restricted to B-1 cells in B-cell lineage. We showed an efficient and specific Cre-mediated DNA recombination in adult B-1 cells and neonatal B-1 progenitors rather than B-2 cells by flow cytometric analysis of Bhlhe41dTomato-Cre/+Rosa26EYFP mice. Treatment of Bhlhe41dTomato-Cre/+Rosa26iDTR mice with diphtheria toxin revealed a robust efficacy of B-1 cell depletion. Interestingly, using Bhlhe41dTomato-Cre mice, we demonstrated that neonatal B-1 progenitors (CD19+CD93+B220lo/-) expressed Bhlhe41 and were identical to well-defined transitional B-1a progenitors (CD19+CD93+B220lo/-CD5+), which only gave rise to peritoneal B-1a cells. Moreover, we identified a novel population of neonatal splenic CD19hidTomato+B220hiCD43loCD5lo B cells, which differentiated to peritoneal B-1a and B-1b cells. Bhlhe41 deficiency impaired the balance between CD19hidTomato+B220lo/-CD5hi and CD19hidTomato+B220hiCD5lo cells. Hence, we identified neonatal CD19hidTomato+B220hiCD43loCD5lo B cells as novel transitional B-1 progenitors. Bhlhe41dTomato-Cre/+ mouse can be used for fate mapping and functional studies of B-1 cells in host-immune responses.