Eradicating cancer cells: struggle with a chameleon

Eradication of cancer stem cells to abrogate tumor growth is a new treatment modality. However, like normal cells cancer cells show plasticity. Differentiated tumor stem cells can acquire stem cell properties when they gain access to the stem cell niche. This indicates that eradicating of stem cells (emptying of the niche) alone will not lead to eradication of the tumor. Treatment should be directed to cancer stem cells ànd more mature cancer cells

CENPH Inhibits Rapamycin Sensitivity by Regulating GOLPH3-dependent mTOR Signaling Pathway in Colorectal Cancer

Background: Centromere protein H (CENPH) is known as a fundamental component of the active centromere complex, and its overexpression is correlated with poor prognosis in various solid tumors. mTOR inhibitor rapamycin has been shown to possess antitumor activity, as well as prevent intestinal tumorigenesis. However, the prognostic value of CENPH in colorectal cancer (CRC) and the role of CENPH in rapamycin sensitivity remain unknown. Materials and methods: The effect of CENPH on the cell proliferation, clonogenicity, and cell response to rapamycin in CRC were evaluated by MTT and/or colony formation assays. For the underlying mechanisms, the interaction between CENPH and GOLPH3 were detected by co-immunoprecipitation, GST pull-down, and His-tag pull-down assays, as well as the laser scanning confocal microscopy. The status of kinases in mTOR signaling was determined by Western blot. Finally, the clinical significance of CENPH was analyzed using public CRC datasets with CENPH transcripts and clinical information. Results: CENPH inhibited CRC malignant phenotypes, conferred reduced sensitivity to rapamycin, and attenuated both mTORC1 and mTORC2 in mTOR signaling pathway through the interaction with golgi phosphoprotein 3 (GOLPH3), which has been identified as a potential oncogene and modulates the response to rapamycin. Moreover, elevated levels of CENPH were detected in CRC tissues, compared with normal colorectal tissues. High levels of CENPH expression gradually decreased according to CRC tumor stages. Patients with high CENPH expression had favorable survival. Conclusions: Our results suggest that CENPH inhibits rapamycin sensitivity by regulating GOLPH3 dependent mTOR pathway. High CENPH expression is associated with better prognosis in CRC patients. Taken together, CENPH may serve as a potential predictor for rapamycin sensitivity and therapeutic target for CRC patients.National Natural Science Foundation of China [81272766, 81450028, 81672439, 81470129, 81402346, 81502137]; Beijing Natural Science Foundation [7162039, 7132054, 7172042]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [XM201309, ZYLX201701]; Peking University (PKU) 985 Special Funding for Collaborative Research with PKU Hospitals; Beijing Health System High-level Health Technical Personnel Training Program [2015-3-074]; Science Foundation of Peking University Cancer HospitalSCI(E)ARTICLE122163-2172

Point Cloud Completion Network Based on Multi-Dimensional Adaptive Feature Fusion and Informative Channel Attention Mechanism

With the continuous advancement of 3D perception technology, point cloud data has found increasingly widespread application. However, the presence of holes in point cloud data caused by device limitations and environmental interference severely restricts algorithmic performance, making point cloud completion a research topic of high interest. This study observes that most existing mainstream point cloud completion methods primarily focus on capturing global features, while often underrepresenting local structural details. Moreover, the generation process of complete point clouds lacks effective control over fine-grained features, leading to insufficient detail in the completed outputs and reduced data integrity. To address these issues, we propose a Set Combination Multi-Layer Perceptron (SCMP) module that enables the simultaneous extraction of both local and global features, thereby reducing the loss of local detail information. In addition, we introduce the Squeeze Excitation Pooling Network (SEP-Net) module, an informative channel attention mechanism capable of adaptively identifying and enhancing critical channel features, thus improving the overall feature representation capability. Based on these modules, we further design a novel Feature Fusion Point Fractal Network (FFPF-Net), which fuses multi-dimensional point cloud features to enhance representation capacity and progressively refines the missing regions to generate a more complete point cloud. Extensive experiments conducted on the ShapeNet-Part and MVP datasets compared to L-GAN and PCN showed average prediction error improvements of 1.3 and 1.4, respectively. The average completion errors on the ShapeNet-Part and MVP datasets are 0.783 and 0.824, highlighting the improved fine-detail reconstruction capability of our network. These results indicate that the proposed method effectively enhances point cloud completion performance and can further promote the practical application of point cloud data in various real-world scenarios

Monitoring Pre- and Post-Operative Immune Alterations in Patients With Locoregional Colorectal Cancer Who Underwent Laparoscopy by Single-Cell Mass Cytometry

Surgical excision is currently the principal therapy for locoregional colorectal cancer (CRC). However, surgical trauma leads to controlled tissue damage, causing profound alterations in host immunity and, in turn, affecting post-operative outcomes. Surgery-induced immune alterations in CRC remain poorly defined. Here, single-cell mass cytometry was applied to serial blood samples collected pre-operatively, and on days 1, 3, and 7 post-operatively from 24 patients who underwent laparoscopic surgical resection of CRC to comprehensively monitor the perioperative phenotypic alterations in immune cells and dynamics of immune response. Characterization of immune cell subsets revealed that the post-operative immune response is broad but predominantly suppressive, supported by the decreases in total frequencies of circulating T cells and natural killer (NK) cells, as well as decreased HLA-DR expression on circulating monocytes. The proportion of T cells significantly decreased on day 1 and recovered to the pre-surgical level on day 3 after surgery. The frequency of monocytes was significantly elevated on day 1 after surgery and declined to baseline level on day 3. NK cells temporarily contracted on post-operative day 3. T cells, monocytes, DCs, NK cells, and B cells were partitioned into phenotypically different single-cell clusters. The dynamics of single-cell clusters were different from those of the bulk lineages. T cell clusters in the same response phase fluctuate inconsistently during the perioperative period. Comparing to the baseline levels, the frequencies of CD11b(+)CD33(+)CD14(+)CD16(−) classical monocytes expanded followed by contraction, whereas CD11b(+)CD33(+)CD14(high)CD16(low) intermediate monocytes remained unchanged; HLA-DR expression in monocytes were significantly reduced; the frequencies of intermediate CD56(bright)CD16(+) NK cell subsets increased; and the percentage of memory B lymphocytes were elevated after surgery. Post-operative pro- and anti-inflammatory cytokines were both altered. Furthermore, perioperative immune perturbations in some of the cell subsets were unrecovered within seven days after surgery. Chronological monitoring major immune lineages provided an overview of surgery-caused alterations, including cell augments and contractions and precisely timed changes in immune cell distribution in both innate and adaptive compartments, providing evidence for the interaction between tumor resection and immune modulation.</jats:p

Hybrid Cross-Feature Interaction Attention Module for Object Detection in Intelligent Mobile Scenes

Object detection is one of the fundamental tasks in computer vision, holding immense significance in the realm of intelligent mobile scenes. This paper proposes a hybrid cross-feature interaction (HCFI) attention module for object detection in intelligent mobile scenes. Firstly, the paper introduces multiple kernel (MK) spatial pyramid pooling (SPP) based on SPP and improves the channel attention using its structure. This results in a hybrid cross-channel interaction (HCCI) attention module with better cross-channel interaction performance. Additionally, we bolster spatial attention by incorporating dilated convolutions, leading to the creation of the cross-spatial interaction (CSI) attention module with superior cross-spatial interaction performance. By seamlessly combining the above two modules, we achieve an improved HCFI attention module without resorting to computationally expensive operations. Through a series of experiments involving various detectors and datasets, our proposed method consistently demonstrates superior performance. This results in a performance improvement of 1.53% for YOLOX on COCO and a performance boost of 2.05% for YOLOv5 on BDD100K. Furthermore, we propose a solution that combines HCCI and HCFI to address the challenge of extremely small output feature layers in detectors, such as SSD. The experimental results indicate that the proposed method significantly improves the attention capability of object detection in intelligent mobile scenes. © 2023 by the authors

Clinical significance of circulating immune cells in left- and right-sided colon cancer

Background Left-sided and right-sided colon cancers (LCCs and RCCs, respectively) differ in their epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and prognosis. Notably, immune response gene expression profiles have been shown to differ between patients with LCC and patients with RCC. The immune system plays an important role in tumor immunosurveillance, and there is increasing evidence that peripheral blood immune cells have a profound influence on tumor prognosis. This study aimed to determine the clinical significance of circulating immune cells with respect to colon tumor locations. Methods Different types of circulating immune cells were separated and analysed based on their surface markers by flow cytometry. We compared the numbers of dendritic cells (DCs) and T cell subsets in the peripheral blood of 94 patients with RCC or LCC and analysed the proportions of these immune cells in relation to tumor stage, tumor differentiation and lymphatic metastasis. Results We show that at later tumor stages, patients with LCC had higher levels of circulating myeloid DCs (P = 0.049) and plasmacytoid DCs (P = 0.018) than patients with RCC. In poorly differentiated tumors, LCC patients had significantly higher amount of plasmacytoid DCs (P = 0.036), CD4+ memory T (Tm) cells (P = 0.012), CD4+ T cells (P = 0.028), Tm cells (P = 0.014), and regulatory T cells (P = 0.001) than RCC patients. The levels of circulating CD4+ T cells, Tm cells and CD4+ Tm cells were significantly elevated at later stages in patients with LCC or RCC, while these cells decreased in poorly differentiated tumors in patients with RCC. Moreover, CD4+ Tm cell and CD4+ T cell levels are significantly associated with lymph node metastasis in patients with LCC and RCC. Discussion Circulating immune cells were associated with tumor location, tumor stage and tumor differentiation, and can be used to predict lymphatic metastasis in patients with colon cancer. This variation in systemic immunity could contribute to the differential prognosis of patients with colon cancer

A comparative study of several enhanced energy operators for vibration exciter bearing fault diagnosis

Abstract Rolling bearings of the vibration exciter are prone to failure due to long-term high amplitude alternating impact loads, causing economic losses and threatening production safety. The heavy environmental noise during the operation of the vibration exciter and the high vibration level generated by the eccentric block make the weak bearing fault features submerged and difficult to extract. Teager–Kaiser energy operator is a popular method for extracting bearing fault features. However, it has poor noise-robustness and low accuracy of frequency estimation of the exciter with heavy noise and multiple disturbances. Therefore, three enhanced energy operators—symmetric higher-order analytical energy operator (SHAEO), multi-resolution symmetric difference energy operator (MSDAEO), and symmetric higher-order frequency weighted energy operator (SHFWEO) have been introduced. This paper compares and studies the three energy operators through theoretical analysis and vibration exciter bearing fault diagnosis experiments. The results show that MSDAEO has the most outstanding noise robustness, but has the minimum effect on improving the signal-to-interference ratio (SIR) of the signal among the three energy operators. SHFWEO has the most prominent performance on improving SIR but is sensitive to the signal energy. SHAEO can increase the amplitude of the signal, and its ability to improve signal SIR is higher than MSDAEO but lower than SHFWEO. Its ability to improve signal SNR is the weakest among the three. Finally, the characteristics of preprocessing methods that can be jointly used by the three energy operators in different application scenarios are presented