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Folate is an essential nutrient for nearly all organisms. While the physiological function and mechanism aspects of folate have been extensively and deeply investigated in Eukarya, related researches in Bacteria remains poorly understood. In this study, we focus on physiological functions of folate in Lactiplantibacillus plantarum by employing a combination of genetics, biochemistry and microscopy approaches. Deletion of the genes folE, folP, or both folE and folK in the folate biosynthesis pathway generated the mutant strains ΔfolE, ΔfolP, and ΔfolKE, respectively. Folate production in ΔfolE, ΔfolKE, and ΔfolP decreased to 51 %, 32 %, and 74 % of the wild-type level, respectively. Simultaneous deletion folE and folK distinctly extended the glutamate tail of folate. These mutants exhibited severely impaired growth capacity under normal conditions. Notably, only ΔfolP cells precipitated in liquid culture. All mutant strains displayed increased cell length, with the extent of elongation correlating to intracellular folate levels. It is noticed that DNA content was increased along with the cell size in deletion mutants. Additionally, 12 % of ΔfolKE cells and 4 % of ΔfolP cells exhibited abnormal lysis, characterized by granular cytoplasm. These findings provide significant insights into the physiological roles of folate in Bacteria., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The aim of this study is to explore the role of the IL-10/STAT3 pathway in the upregulation of natural killer group 2, member D (NKG2D) ligands (MICA and ULBP2) induced by Bruton's tyrosine kinase (BTK) inhibitors in non-germinal center B-cell-like diffuse large B-cell lymphoma cells. The expression levels of NKG2D ligands and the IL-10/STAT3 pathway in SUDHL4, U2932, and OCI-LY3 cells were analyzed using western blotting. After stimulation of the B-cell receptor signaling pathway with IgM antibodies, the expression levels of NKG2D ligands, as well as IL-10 and phosphorylated STAT3 (p-STAT3) were significantly reduced. In contrast, treatment with ibrutinib produced effects opposite to those induced by IgM antibodies. Additionally, treatment of U2932 and OCI-LY3 cells with the STAT3 inhibitor (STAT3-IN-1) led to an increase in NKG2D ligand expression and a decrease in IL-10 levels. When IL-10 neutralizing antibodies were introduced, p-STAT3 levels decreased, and NKG2D ligand expression increased. Similar outcomes were observed when the BTK inhibitors ACP-196 and BGB-3111 were administered. Our findings suggest that the IL-10/STAT3 pathway plays a key role in the upregulation of NKG2D ligands induced by BTK inhibitors in U2932 and OCI-LY3 cells., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To characterize the occurrence of SRSF2 mutations in chronic myelomonocytic leukemia(CMML) patients and their correlation with other gene mutations and some clinical characteristics., Methods: The clinical data of 43 CMML patients diagnosed in Changzhou No.2 People's Hospital and Wuxi No.2 People's Hospital were retrospectively analyzed, and gene mutations detection was performed using next-generation sequencing (NGS)., Results: Among the 43 CMML patients the SRSF2 mutation detection rate was 39.5%(17/43). These mutations clustered collectively at the proline 95 residue in the splicing factor SRSF2 . The other genes with mutation rate greater than 15% were ASXL1 (48.8%), TET2 (41.9%), NRAS (30.2%), RUNX1 (25.6%), and SETBP1 (16.3%). Among SRSF2 - mutated patients, the most common co-mutation was ASXL1 , followed by TET2 . The median age of SRSF2 mutant patients was significantly higher than that of the wild type (68 vs 51.5, P < 0.001), but there was not statistically significant differences in gender, peripheral leukocytes, hemoglobin, platelets, karyotype, and blast cell compared to the wild-type (all P >0.05). Notably, 4 out of the 6 SRSF2 mut ASXL1 mut CMML patients developed leukemia transformation, and 1 out of 10 SRSF2 wt ASXL1 wt CMML patients developed leukemia transformation, with statistically significant difference in leukemia transformation rates (66.7% vs 10%, P =0.036)., Conclusion: SRSF2 mutations have a high incidence in CMML, occurring frequently in older patients, and often coexisting with ASXL1 and TET2 mutations. Patients with CMML carrying both SRSF2 mut ASXL1 mut double mutations have a higher risk of acute leukemia transformation.

Objective: To investigate the expression and clinical significance of CD30 in patients with diffuse large B-cell lymphoma (DLBCL)., Methods: A retrospective analysis was conducted on 124 cases of primary DLBCL diagnosed at Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2018 to July 2020. The expression of CD30 in patients with DLBCL was detected by immunohistochemical method, and the clinicopathological characteristics were analyzed and compared between CD30 + and CD30 - groups. Kaplan-Meier analysis was used for survival analysis. The relationship between CD30 expression and clinical features and prognosis were analyzed., Results: Among the 124 patients with DLBCL, 19 patients expressed CD30, and the positive rate is 15.32%. The clinico-pathological characteristics of CD30 + in patients with DLBCL were characterized by low age, more common in males, fewer extranodal lesions, lower international prognostic index (IPI), GCB type being more common in Hans subtype, and achieving better therapeutic effects ( P < 0.05). However, there were no significant statistical differences in B-symptoms ( P =0.323), Ann Arbor staging ( P =0.197), Eastern Cooperative Oncology Group (ECOG) score ( P =0.479), lactate dehydrogenase (LDH) ( P =0.477), and the involvement of bone marrow ( P =0.222). There were significant differences in OS and PFS between the CD30 + and CD30 - groups (χ 2 =5.653, P =0.017; χ 2 ＝4.109， P =0.043), the CD30 + group had a better prognosis than that of the CD30 - group. The results of subgroup analysis showed that the CD30 + group in the IPI score=1-2, LDH elevated group had a better prognosis ( P < 0.05). In the subgroups of Ann Arbor staging III-IV ( P =0.055) and non GCB type ( P =0.053), the CD30 + group had a good prognosis trend, but the difference was not statistically significant. The results of univariate analysis showed that the good prognosis of DLBCL patients was closely related to CD30 + expression, no B-symptoms, early Ann Arbor staging, low ECOG score, normal LDH, low IPI score, fewer extranodal involvement, and obtaining the best therapeutic effect as CR (all P <0.05). COX multivariate regression analysis showed that the presence of B-symptoms and achieving the best therapeutic effect as Non-CR were independent risk factors affecting the prognosis of DLBCL patients ( P < 0.05)., Conclusion: The CD30 + expression in DLBCL patients indicates a good prognosis and has certain diagnostic value in evaluating the prognosis of DLBCL patients.

A polymer-free technique for generating nanopatterns on both synthesized and exfoliated graphene sheets is proposed and demonstrated. A low-energy (5-30 keV) scanning electron beam with variable repetition rates is used to etch suspended and unsuspended graphene sheets on designed locations. The patterning mechanisms involve a defect-induced knockout process in the initial etching stage and a heat-induced curling process in a later stage. Rough pattern edges appear due to inevitable stochastic knockout of carbon atoms or graphene structure imperfection and can be smoothed by thermal annealing. By using this technique, the minimum feature sizes achieved are about 5 nm for suspended and 7 nm for unsuspended graphene. This study demonstrates a polymer-free direct nanopatterning approach for graphene., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)