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Background The molecular diversity exhibited by diffuse large B-cell lymphoma (DLBCL) is a significant obstacle facing current precision therapies. However, scoring using the International Prognostic Index (IPI) is inadequate when fully predicting the development of DLBCL. Reprogramming lipid metabolism is crucial for DLBCL carcinogenesis and expansion, while a predictive approach derived from lipid metabolism-associated genes (LMAGs) has not yet been recognized for DLBCL. Methods Gene expression profiles of DLBCL were generated using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The LASSO Cox regression was used to construct an effective predictive risk-scoring model for DLBCL patients. The Kaplan-Meier survival assessment was employed to compare a given risk score with the IPI score and its impact on the survival of DLBCL patients. Functional enrichment examination was performed utilizing the KEGG pathway. After identifying hub genes via single-sample GSEA (ssGSEA), immunohistochemical staining and immunofluorescence were performed on lymph node samples from control and DLBCL patients to confirm these identified genes. Results Sixteen lipid metabolism- and survival-associated genes were identified to construct a prognostic risk-scoring approach. This model demonstrated robust performance over various datasets and emerged as an autonomous risk factor for predicting the development of DLBCL patients. The risk score could significantly distinguish the development of DLBCL patients from the low-risk and elevated-risk IPI classes. Results from the inhibitory immune-related pathways and lower immune scores suggested an immunosuppressive phenotype within the elevated-risk group. Three hub genes, MECR , ARSK , and RAN , were identified to be negatively correlated with activated CD8 T cells and natural killer T cells in the elevated-risk score class. Ultimately, it was determined that these three genes were expressed by lymphoma cells but not by T cells in clinical samples from DLBCL patients. Conclusion The risk level model derived from 16 lipid metabolism-associated genes represents a prognostic biomarker for DLBCL that is novel, robust, and may have an immunosuppressive role. It can compensate for the limitations of the IPI score in predicting overall survival and has potential clinical application value.

Very-high-cycle fretting fatigue (VHCFF) behavior at elevated temperatures is critical for the safety and longevity of aerospace components. This study investigates the VHCFF mechanisms of laser-clad IN718/20%WC composite coatings at 650 °C. Fatigue tests were conducted to generate S-N data, and the resulting wear and fracture morphologies were characterized. Crack initiation was found to preferentially occur in grains exhibiting higher Schmid factors, lower elastic moduli, and larger equivalent sizes. To simulate fretting fatigue, a crystal plasticity finite element model (CPFEM) incorporating the actual microstructure was developed. An improved fatigue indicator parameter (FIP) was proposed, which integrates multiple physically significant factors including plastic strain, dislocation density, elastic modulus, and grain size. Life predictions based on a critical FIP value demonstrated high accuracy, with 97.6% of the results falling within a ±3.5 scatter band of the experimental data, confirming the model’s effectiveness in predicting crack initiation life.

Extramedullary infiltration (EMI), as a concomitant symptom of acute myeloid leukemia (AML), is associated with low complete remission and poor prognosis in AML. However, the mechanism of EMI remains indistinct. Clinical trials showed that increased miR-29s were associated with a poor overall survival in AML [ 14 ]. Nevertheless, they were proved to work as tumor suppressor genes by encouraging apoptosis and inhibiting proliferation in vitro. These contradictory results led us to the hypothesis that miR-29s may play a notable role in the prognosis of AML rather than leukemogenesis. Thus, we explored the specimens of AML patients and addressed this issue into miR-29c&b2 knockout mice. As a result, a poor overall survival and invasive blast cells were observed in high miR-29c&b2-expression patients, and the wildtype mice presented a shorter survival with heavier leukemia infiltration in extramedullary organs. Subsequently, we found that the miR-29c&b2 inside leukemia cells promoted EMI, but not the one in the microenvironment. The analysis of signal pathway revealed that miR-29c&b2 could target HMG-box transcription factor 1 (Hbp1) directly, then reduced Hbp1 bound to the promoter of non-muscle myosin IIB (Myh10) as a transcript inhibitor. Thus, increased Myh10 encouraged the migration of leukemia cells. Accordingly, AML patients with EMI were confirmed to have high miR-29c&b2 and MYH10 with low HBP1. Therefore, we identify that miR-29c&b2 contribute to the poor prognosis of AML patients by promoting EMI, and related genes analyses are prospectively feasible in assessment of AML outcome.

Background The adipocyte remodeling, including of the morphological change, might indicate special pathological function. Our previous study found that the morphological remodeling of larger marrow adipocytes into small marrow adipocytes correlates with a poor prognosis for acute myeloid leukemia (AML) patients. However, the mechanisms contributed to the marrow adipocyte remodeling are still poorly understood. Methods GDF15 expression was analyzed by RT-qPCR and western blotting assays in the leukemic cells. The enhancing and antibody neutralization tests in vitro were employed to evaluate the effect of GDF15 on the morphology of mature adipocytes. CCK8 test was used to detect the proliferation of leukemic cells after co-cultivation with small marrow adipocytes. Flow cytometry was used to analysis the proportion of cell cycle of leukemic cells. Immunofluorescence staining and linear analysis were applied to verify the GDF15 expression and the relationship between GDF15 and small marrow adipocytes in AML patients. Results In this study, we found that leukemic cell lines not only expressed significantly higher growth differentiation factor 15 (GDF15) than the other three cytokines associated with adipocyte differentiation in RNA level but also secreted GDF15 factor. Furthermore, the in vitro experiments demonstrated that GDF15 was involved in the conversion of small marrow adipocytes from larger marrow adipocytes. Correspondingly, the leukemic cells proliferated more rapidly through regulating the cell cycle when co-cultured with GDF15-induced small marrow adipocytes. The immunofluorescence staining on the bone marrow sections of AML patients further exhibited that GDF15 was partly produced by leukemic cells. The positive correlation between the concentration of GDF15 in the marrow aspirates and the number and the volume of small marrow adipocytes might suggest the contribution of GDF15 in AML patients ( r  = 0.72, r  = 0.67). Conclusions GDF15 secreted by leukemic cells was involved in the morphological remodeling of marrow adipocytes, which can in turn promote leukemic cell growth, indicating that GDF15 may be a promising treatment target for AML patients.

Abstract Background/Aims: Chemotherapy is still the main strategy used to prevent the relapse of acute myeloid leukaemia (AML). As the most abundant stromal component in bone marrow (BM), marrow adipocytes have been previously shown to promote leukaemogenesis. The present study was designed to further validate whether marrow adipocytes exert synergistic effects on strengthening chemotherapeutic efficacy and evaluate the underlying mechanism. Methods: A retrospective study of BM biopsies from 80 patients with AML in remission and 71 control subjects was applied to quantitatively analyse the marrow adipocyte volume. Toxicity tests were used to assess the effect of chemotherapy drugs on BM cells. The possible mechanisms by which chemotherapy regulated the reduced marrow adipocyte content were investigated using antibody neutralization experiments, with an emphasis on growth differentiation factor 15 (GDF15). Results: In our study, the marrow adipocyte content was obviously reduced in the AML- complete remission (CR) group compared with the control group (P<0.001). Moreover, patients with a reduced adipocyte content exhibited longer relapse-free survival (RFS) (P<0.001). We also confirmed that GDF15 was overexpressed in mononuclear cells (MNCs) after treatment with chemotherapy drugs and partially blocked mesenchymal stem cells (MSCs) adipogenesis. Intriguingly, this inhibitory effect on adipogenesis was rescued by treatment with a neutralizing anti-GDF15 antibody. Conclusion: Chemotherapy indirectly inhibited adipogenesis by promoting GDF15 secretion from BM MNCs, subsequently strengthening the efficacy of consolidation chemotherapy in patients with AML during CR.

The enhancement of mechanical properties in magnesium (Mg) alloys through the pre-setting of tensile twins (TTs) has been widely demonstrated. Nevertheless, the impact of the initial microstructure, particularly the initial distribution of grain size and orientation, on the microstructure and mechanical characteristics of pre-twinned Mg sheets demands further elucidation. Therefore, in this study, the corrugated wide limit alignment (CWLA) method was used to induce TTs at 200 °C in Mg sheets with different initial microstructures, which are named as-received-A (AR-A) with a strong basal texture and uniform equiaxial grains and as-received-B (AR-B) with a fiber texture and heterogeneous grains, respectively. The corresponding sheets after CWLA are named C200-A and C200-B, respectively. The experimental results indicate that both C200-A and C200-B developed a transverse direction (TD)-tilted texture, and the newly generated TD-tilted texture component significantly weakens the basal texture and refines the grains. In comparison with C200-B, the texture intensity of C200-A exhibited a more pronounced reduction, reaching 36 pct. This can be attributed to the fact that AR-A, characterized by fine equiaxed grains and a strong basal texture, is more conducive to the activation of TTs. The mechanical properties of C200-A were synergistically improved, with a 27 pct increase in ultimate tensile strength (UTS), a 50 pct increase in yielding strength (YS), and a 21 pct increase in elongation, and the homogeneous plastic deformation stage is increased significantly. The reason is the significant activation of basal < a > slip and the synergistic effect of multiple dynamic recrystallization (DRX) mechanisms to refine grain size by 41 pct. The elongation of C200-B decreased by 20 pct. The main reason is related to the DRX mechanism. The grain refinement of the coarse grain region mainly via continuous dynamic recrystallization (CDRX) and the accompanied abnormal grain growth of the fine grain region, causing grain homogenization. High plasticity due to the AR-B heterogeneous structure then disappears. Therefore, it is suggested that Mg sheets with fine equiaxed grains and strong basal texture is more readily accessible to obtain good comprehensive mechanical properties via pre-setting TTs.

Doxorubicin is an important class of anthracycline antitumor antibiotics produced by Streptomyces peucetius. The doxorubicin fermentation yield of the wild-type strain was very low, so it could not be produced directly by fermentation at an industrial scale due to the high cost. In the present study, S. peucetius SIPI-7-14 was obtained from SIPI-14 through several rounds of doxorubicin resistance screening. Then, the ketoreductase gene dnrU was knocked out to reduce (13S)-13-dihydrodaunorubicin production, and the resistance gene drrC was overexpressed to further enhance resistance to doxorubicin. The resulting engineered strain S. peucetius △U1/drrC produced 1128 mg/L doxorubicin, a 102.1% increase compared to that of SIPI-14. Then, fermentation medium was optimized using the response surface method. In the optimized fermentation medium, the yield of doxorubicin was increased to 1406 mg/L in shake flask on the 7th day. Furthermore, batch culture was carried out in a 10 L fermenter, and the concentration of doxorubicin reached 1461 mg/L after 7 days of culture, which was the highest yield reported to date, indicating the potential for industrial production of doxorubicin by fermentation.

In this paper, deep learning and image processing technologies are combined, and an automatic sampling robot is proposed that can completely replace the manual method in the three-dimensional space when used for the autonomous location of sampling points. It can also achieve good localization accuracy, which solves the problems of the high labor intensity, low efficiency, and poor scientific accuracy of the manual sampling of mineral powder. To improve localization accuracy and eliminate non-linear image distortion due to wide-angle lenses, distortion correction was applied to the captured images. We solved the problem of low detection accuracy in some scenes of Single Shot MultiBox Detector (SSD) through data augmentation. A visual localization model has been established, and the image coordinates of the sampling point have been determined through color screening, image segmentation, and connected body feature screening, while coordinate conversion has been performed to complete the spatial localization of the sampling point, guiding the robot in performing accurate sampling. Field experiments were conducted to validate the intelligent sampling robot, which showed that the maximum visual positioning error of the robot is 36 mm in the x-direction and 24 mm in the y-direction, both of which meet the error range of less than or equal to 50 mm, and could meet the technical standards and requirements of industrial sampling localization accuracy.

Poor sleep has been associated with risk of hypertension, but previous studies were limited by treating one or two sleep factors as predictor. Our previous study has developed a sleep factor questionnaire (SFQ) to comprehensively assess wide range of sleep characteristics including sleep duration, sleep quality, light at night (LAN) exposure, night/shift work, daytime napping, and frequency of nighttime waking, insomnia, and snoring. In this cross-sectional study we used the SFQ to evaluated the associations between these sleep domains and hypertension. Comparing with the subjects who slept 7–8 h, subjects with sleep duration 6–7 h (OR = 1.42, 95% CI: 1.01, 2.00), 8–9 h (OR = 1.60, 95% CI: 1.07, 2.40), and over 9 h (OR = 2.39, 95% CI: 1.60, 3.58) had an increased prevalence of hypertension. The associations were significant among individuals under 45 years sleeping 6–7 h and those over 45 years sleeping over 8 h. The OR of prevalent hypertension was 0.80 (95% CI: 0.62, 0.97) for habitual daytime napping compared with never napping, and the association was also significant among individuals over 45 years old. Moreover, among subjects with sleep duration 7–8 h, habitual daytime napping may decrease prevalent hypertension (OR = 0.635, 95% CI: 0.437, 0.924). In conclusion, our data suggested a positive association between both short (6–7 h) and long sleep duration and hypertension, and a preventive pattern for habitual daytime napping among over 45 years old and hypertension. Moreover, interaction analysis indicated that habitual midday nap may decrease prevalent hypertension among subjects with sleep duration 7–8 h.