Search

Background: Blast transformation is a rare but well-recognized event in Philadelphia-negative myeloproliferative neoplasms associated with a poor prognosis. Secondary acute myeloid leukemias evolving from myeloproliferative neoplasms are characterized by a unique set of cytogenetic and molecular features distinct from de novo disease. t(8;21) (q22;q22.1); RUNX1::RUNX1T1, one of the most frequent cytogenetic abnormalities in de novo acute myeloid leukemia, is rarely observed in post-myeloproliferative neoplasm acute myeloid leukemia. Here we report a case of secondary acute myeloid leukemia with t(8;21) evolving from JAK2-mutated essential thrombocythemia. Case presentation: The patient was a 74-year-old Japanese woman who was referred because of thrombocytosis (platelets 1046 × 109/L). Bone marrow was hypercellular with increase of megakaryocytes. Chromosomal analysis presented normal karyotype and genetic test revealed JAK2 V617F mutation. She was diagnosed with essential thrombocythemia. Thrombocytosis had been well controlled by oral administration of hydroxyurea; 2 years after the initial diagnosis with ET, she presented with leukocytosis (white blood cells 14.0 × 109/L with 82% of blasts), anemia (hemoglobin 91 g/L), and thrombocytopenia (platelets 24 × 109/L). Bone marrow was hypercellular and filled with 80% of myeloperoxidase-positive blasts bearing Auer rods. Chromosomal analysis revealed t(8;21) (q22;q22.1) and flow cytometry presented positivity of CD 13, 19, 34, and 56. Molecular analysis showed the coexistence of RUNX1::RUNX1T1 chimeric transcript and heterozygous JAK2 V617F mutation in leukemic blasts. She was diagnosed with secondary acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 evolving from essential thrombocythemia. She was treated with combination chemotherapy with venetoclax and azacytidine. After the first cycle of the therapy, blasts disappeared from peripheral blood and decreased to 1.4% in bone marrow. After the chemotherapy, RUNX1::RUNX1T1 chimeric transcript disappeared, whereas mutation of JAK2 V617F was still present in peripheral leukocytes. Conclusions: To our best knowledge, the present case is the first one with JAK2 mutation preceding the acquisition of t(8;21). Our result suggests that t(8;21); RUNX1::RUNX1T1 can be generated as a late event in the progression of JAK2-mutated myeloproliferative neoplasms. The case presented typical morphological and immunophenotypic features associated with t(8;21) acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

By virtue of reversible energy dissipation and good ionic conductivity, metal ions have been extensively introduced to construct hydrogels. However, the traditional soaking method to prepare metal ions coordination hydrogels (MI‐HG) faces the challenge of diffusion and combination of metal ions, leading to weak mechanical properties. Inspired by the leather mineral tanning mechanism, a strategy that controls the accessibility of hydrogels by pickling and basifying processes thus significantly improving the strength and toughness of MI‐HG is proposed. To achieve this, polyvinyl alcohol/poly(acrylamide‐co‐acrylic acid) (PVA/PAM‐co‐PAA) hydrogels‐bearing ligands similar to those of leather collagen are fabricated. Zr4+, Cr3+, Al3+, and Fe3+ commonly used for mineral tanning are chosen as the metal source. The results demonstrate that the mechanical properties of the products (MI‐HGTanning) are significantly promoted, especially for Cr3+ and Zr4+. For example, the tensile strength of Zr‐HGTanning and toughness of Cr‐HGTanning reach 7.79 ± 0.41 Mpa and 28.01 ± 3.1 MJ m−3, approximately three and seven times that of their soaking samples. From macro to micro characterization and by theoretical simulation, the mineral tanning mechanism of metal ions first permeating and then effectively combining with carboxylates, thus improving the mechanical performance of MI‐HGTanning is deciphered, the products of which are promised applications in flexible force sensors. [ABSTRACT FROM AUTHOR]

Inorganic biomaterials are used in various orthopedic and dental implants. Nevertheless, they cause clinical issues such as loosening of implants and patient morbidity. Therefore, inspired by mussel adhesive proteins, we aimed to design an adhesive and dimer-forming highly active bone morphogenetic protein-2 (BMP-2) using bioorthogonal chemistry, in which recombinant DNA technology was combined with enzymatic modifications, to achieve long-term osseointegration with titanium. The prepared BMP-2 exhibited substantially higher binding activity than wild-type BMP-2, while the adhered BMP-2 was more active than soluble BMP-2. Therefore, the adhesive BMP-2 was immobilized onto titanium wires and screws and implanted into rat bones, and long-term osteogenesis was evaluated. Adhesive BMP-2 promoted the mechanical binding of titanium to bones, enabling efficient bone regeneration and effective stabilization of implants. Thus, such adhesive biosignaling proteins can be used in regenerative medicine. [ABSTRACT FROM AUTHOR]

Advanced nucleic acid amplification techniques require separating test samples into numerous units (digitalization), which enables higher sensitivity and accuracy than traditional methods. Reagent partition tools are commercially available, but are usually complex and expensive, hindering mass adoption. Herein, the fabrication of a large‐scale micro‐through‐hole array on glass substrates for an advanced digital nucleic acid amplification technique (NAAT) is demonstrated. To meet the requirement of hole quantities (over tens of thousands) for valid nucleic acid statistics, ultrafast Bessel pulses with continuous translation of the glass substrate are applied. A single‐shot Bessel pulse can lead to a single hole, and 100 holes can be produced per second (scalable to thousands per second). Experiments using the fabricated chips show that the performance meets the NAAT requirements. This work provides a highly efficient and low‐cost scheme for reagent partitioning that promotes the wide accessibility of advanced digital NAATs as well as a variety of other applications. [ABSTRACT FROM AUTHOR]

Intracellular calcium dynamics is key to regulating various physiological events. Myotube formation by myoblast fusion is controlled by the release of Ca 2+ from the endoplasmic reticulum (ER), and the calpain (CAPN) family is postulated to be an executioner of the process. However, the activation of a specific member of the family or its physiological substrates is unclear. In this study, we explore the involvement of a CAPN in myoblast differentiation. Time-course experiments showed that the reduction in potential substrates of calpains, c-Myc and STAT3 (signal transducer and activator of transcription 3) and generation of STAT3 fragments occurred multiple times at an early stage of myoblast differentiation. Inhibition of the ER Ca 2+ release suppressed these phenomena, suggesting that the reduction was dependent on the cleavage by a CAPN. CAPN5 knockdown suppressed the reduction. In vitro reconstitution assay showed Ca 2+ - and CAPN5-dependent degradation of c-Myc and STAT3. These results suggest the activation of CAPN5 in differentiating myoblasts. Fusion of the Capn5 knockdown myoblast efficiently occurred; however, the upregulation of muscle-specific proteins (myosin and actinin) was suppressed. Myofibrils were poorly formed in the fused cells with a bulge where nuclei formed a cluster, suggesting that the myonuclear positioning was abnormal. STAT3 was hyperactivated in those fused cells, possibly inhibiting the upregulation of muscle-specific proteins necessary for the maturation of myotubes. These results suggest that the CAPN5 activity is essential in myoblast differentiation., Competing Interests: Conflict of interest The authors declare no conflicts of interest with the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The development of bone implants through bioinspired immobilization of growth factors remains a key issue in the generation of biological interfaces, especially in enhancing osteodifferentiation ability. In this study, we developed a strategy for surface functionalization of poly(lactide-glycolide) (PLGA) and hydroxyapatite (HA) composite substrates through site-specific conjugation of bone morphogenetic protein 2 containing 3,4-hydroxyphenalyalanine (DOPA-BMP2) mediated by tyrosinase and sortase A (SrtA). Firstly, the growth factor BMP2-LPETG containing LPETG motif was successfully expressed in Escherichia coli through recombinant DNA technology. The excellent binding affinity of binding growth factor (DOPA-BMP2) was achieved by converting the tyrosine residue (Y) of YKYKY-GGG peptide into DOPA (X) by tyrosinase, which bound to the substrates. Then its GGG motif was specifically bound to the end of BMP2-LPETG mediated by SrtA. Therefore, the generated bioactive DOPA-BMP2/PLGA/HA substrates significantly promoted the osteogenic differentiation of MC3T3-E1 cells. Thanks to this microbial-assisted engineering approach, our work presents a facile and highly site-specific strategy to engineer biomimetic materials for orthopedics and dentistry by effectively delivering growth factors, peptides, and other biomacromolecules., (© 2024 Wiley Periodicals LLC.)

During surveillance of Staphylococcus aureus in lesions from patients with atopic dermatitis (AD), we isolated Staphylococcus argenteus , a species registered in 2011 as a new member of the genus Staphylococcus and previously considered a lineage of S. aureus . Genome sequence comparisons between S. argenteus isolates and representative S. aureus clinical isolates from various origins revealed that the S. argenteus genome from AD patients closely resembles that of S. aureus causing skin infections. We previously reported that 17%-22% of S. aureus isolated from skin infections produce staphylococcal enterotoxin Y (SEY), which predominantly induces T-cell proliferation via the T-cell receptor (TCR) Vα pathway. Complete genome sequencing of S. argenteus isolates revealed a gene encoding a protein similar to superantigen SEY, designated as SargEY, on its chromosome. Population structure analysis of S. argenteus revealed that these isolates are ST2250 lineage, which was the only lineage positive for the SEY-like gene among S. argenteus . Recombinant SargEY demonstrated immunological cross-reactivity with anti-SEY serum. SargEY could induce proliferation of human CD4 + and CD8 + T cells, as well as production of TNF-α and IFN-γ. SargEY showed emetic activity in a marmoset monkey model. S arg EY and SET (a phylogenetically close but uncharacterized SE) revealed their dependency on TCR Vα in inducing human T-cell proliferation. Additionally, TCR sequencing revealed other previously undescribed Vα repertoires induced by SEH. S arg EY and SEY may play roles in exacerbating the respective toxin-producing strains in AD., Importance: Staphylococcus aureus is frequently isolated from active lesions of atopic dermatitis (AD) patients. We reported that 17%-22% of S. aureus isolated from AD patients produced a novel superantigen staphylococcal enterotoxin Y (SEY). Unlike many S . aureus superantigens that activate T cells via T-cell receptor (TCR) Vß, SEY activates T cells via TCR Vα and stimulates cytokine secretion. Staphylococcus argenteus was isolated from AD patients during the surveillance for S. aureus . Phylogenetic comparison of the genome indicated that the isolate was very similar to S. aureus causing skin infections. The isolate encoded a SEY-like protein, designated SargEY, which, like SEY, activated T cells via the TCR Vα. ST2250 is the only lineage positive for SargEY gene. ST2250 S. argenteus harboring a superantigen SargEY gene may be a novel staphylococcal clone that infects human skin and is involved in the exacerbation of AD., Competing Interests: The authors declare no conflict of interest.