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The Sine Cosine Algorithm (SCA) is one of the population-based metaheuristic optimization algorithms inspired by the oscillation and convergence properties of sine and cosine functions. The SCA smoothly transits from exploration to exploitation using adaptive range change in the sine and cosine functions. On the other hand, pressure vessel design is a complex engineering structural optimization problem, which aims to find the best possible design for a vessel that can withstand high pressure. This typically involves optimizing the material, shape, and thickness of the vessel to minimize welding, the material, and forming cost while ensuring it meets safety and performance requirements. This paper evaluates the performance of SCA for solving pressure vessel design problems. The result produced by SCA is compared with the results obtained by other well-known metaheuristic optimization algorithms, namely; ABC, ACO, BBO, CMA-ES, CS, DE, GA, GSA, GWO, HSA, PSO, SSO, TLBO and TSA. The experimental results demonstrated that SCA provides a competitive solution to other metaheuristic optimization algorithms with the advantage of having a simple structured search equation. Moreover, the performance of SCA is checked by different numbers of populations and the results indicated that the best possible population size should be 30 and 40. In addition to this, the SCA search agent success rate is checked for different numbers of populations and results show that the search agent success rate do not exceed 4.2%.

The Sine Cosine Algorithm (SCA) is one of the population-based metaheuristic optimization algorithms inspired by the oscillation and convergence properties of sine and cosine functions. The SCA smoothly transits from exploration to exploitation using adaptive range change in the sine and cosine functions. On the other hand, pressure vessel design is a complex engineering structural optimization problem, which aims to find the best possible design for a vessel that can withstand high pressure. This typically involves optimizing the material, shape, and thickness of the vessel to minimize welding, the material, and forming cost while ensuring it meets safety and performance requirements. This paper evaluates the performance of SCA for solving pressure vessel design problems. The result produced by SCA is compared with the results obtained by other well-known metaheuristic optimization algorithms, namely; ABC, ACO, BBO, CMA-ES, CS, DE, GA, GSA, GWO, HSA, PSO, SSO, TLBO and TSA. The experimental results demonstrated that SCA provides a competitive solution to other metaheuristic optimization algorithms with the advantage of having a simple structured search equation. Moreover, the performance of SCA is checked by different numbers of populations and the results indicated that the best possible population size should be 30 and 40. In addition to this, the SCA search agent success rate is checked for different numbers of populations and results show that the search agent success rate do not exceed 4.2%.

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state, and a distinct expression profile together with MBL cells compared to normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically-driven growth dynamics and together with its persistent presence suggests a central role in the normal-to-cancer transition.

Chronic lymphocytic leukemia (CLL) is characterized by disordered DNA methylation, suggesting these epigenetic changes might play a critical role in disease onset and progression. The methyltransferase DNMT3A is a key regulator of DNA methylation. Although DNMT3A somatic mutations in CLL are rare, we found that low DNMT3A expression is associated with more aggressive disease. A conditional knockout mouse model showed that homozygous depletion of Dnmt3a from B cells results in the development of CLL with 100% penetrance at a median age of onset of 5.3 months, and heterozygous Dnmt3a depletion yields a disease penetrance of 89% with a median onset at 18.5 months, confirming its role as a haploinsufficient tumor suppressor. B1a cells were confirmed as the cell of origin of disease in this model, and Dnmt3a depletion resulted in focal hypomethylation and activation of Notch and Myc signaling. Amplification of chromosome 15 containing the Myc gene was detected in all CLL mice tested, and infiltration of high-Myc-expressing CLL cells in the spleen was observed. Notably, hyperactivation of Notch and Myc signaling was exclusively observed in the Dnmt3a CLL mice, but not in three other CLL mouse models tested (Sf3b1-Atm, Ikzf3, and MDR), and Dnmt3a-depleted CLL were sensitive to pharmacologic inhibition of Notch signaling in vitro and in vivo. Consistent with these findings, human CLL samples with lower DNMT3A expression were more sensitive to Notch inhibition than those with higher DNMT3A expression. Altogether, these results suggest that Dnmt3a depletion induces CLL that is highly dependent on activation of Notch and Myc signaling. SIGNIFICANCE: Loss of DNMT3A expression is a driving event in CLL and is associated with aggressive disease, activation of Notch and Myc signaling, and enhanced sensitivity to Notch inhibition.

Leukemic relapse remains a major barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aggressive hematologic malignancies. The basis for relapse of advanced lymphoid malignancies remains incompletely understood and may involve escape from the graft-versus-leukemia (GvL) effect. We hypothesized that for patients with chronic lymphocytic leukemia (CLL) treated with allo-HSCT, leukemic cell-intrinsic features influence transplant outcomes by directing the evolutionary trajectories of CLL cells. Integrated genetic, transcriptomic, and epigenetic analyses of CLL cells from 10 patients revealed that the clinical kinetics of post-HSCT relapse are shaped by distinct molecular dynamics. Early relapses after allo-HSCT exhibited notable genetic stability; single CLL cell transcriptional analysis demonstrated a cellular heterogeneity that was static over time. In contrast, CLL cells relapsing late after allo-HSCT displayed notable genetic evolution and evidence of neoantigen depletion, consistent with marked single-cell transcriptional shifts that were unique to each patient. We observed a greater rate of epigenetic change for late relapses not seen in early relapses or relapses after chemotherapy alone, suggesting that the selection pressures of the GvL bottleneck are unlike those imposed by chemotherapy. No selective advantage for human leukocyte antigen (HLA) loss was observed, even when present in pretransplant subpopulations. Gain of stem cell modules was a common signature associated with leukemia relapse regardless of posttransplant relapse kinetics. These data elucidate the biological pathways that underlie GvL resistance and posttransplant relapse.

Shun Gao, 1, 2 Hubin Yin, 1, 3 Hang Tong, 1, 2 Kai Zhan, 1, 2 Guang Yang, 1, 2 Mohammad Arman Hossain, 1 Tinghao Li, 1, 2 Xin Gou, 1 Weiyang He 1 1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Central Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Weiyang HeDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong, Chongqing 400016, People’s Republic of ChinaEmail weiyang361@aliyun.comPurpose: NUSAP1 has been reported to be involved in the progression of several types of cancer. However, its expression and exact role in bladder cancer (BLCA) remains elusive. The aim of this study was to determine the expression and role of NUSAP1 in BLCA.Methods: Tissue microarray, real-time PCR, Western blot and immunohistochemistry assays were carried out to determine NUSAP1 expression in BLCA tissues and cells. The biological roles of NUSAP1 were investigated using CCK-8, EdU labeling, flow cytometry, Transwell, and wound healing assays. Additionally, the effect of NUSAP1 on epithelial-mesenchymal transition (EMT) was investigated by Western blotting and real-time PCR.Results: We found that NUSAP1 was upregulated in BLCA, and its expression was closely related to the poor prognosis of patients. Subsequently, we transfected 5637 and T24 cell lines with NUSAP1 siRNA and an NUSAP1 overexpression plasmid, respectively. NUSAP1 downregulation in 5637 cells inhibited cell proliferation, migration, and invasiveness and enhanced chemosensitivity to gemcitabine, while NUSAP1 overexpression in T24 cells resulted in the inverse effects. Moreover, NUSAP1 regulated EMT via the TGF-&a