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Biomarkers for classifying and grading gliomas have been extensively explored, whereas populations in public databases were mostly Western/European. Based on public databases cannot accurately represent Chinese population. To identify molecular characteristics associated with clinical outcomes of lower-grade glioma (LGG) and glioblastoma (GBM) in the Chinese population, we performed whole-exome sequencing (WES) in 16 LGG and 35 GBM tumor tissues. TP53 (36/51), TERT (31/51), ATRX (16/51), EFGLAM (14/51), and IDH1 (13/51) were the most common genes harboring mutations. IDH1 mutation (c.G395A; p.R132H) was significantly enriched in LGG, whereas PCDHGA10 mutation (c.A265G; p.I89V) in GBM. IDH1-wildtype and PCDHGA10 mutation were significantly related to poor prognosis. IDH1 is an important biomarker in gliomas, whereas PCDHGA10 mutation has not been reported to correlate with gliomas. Different copy number variations (CNVs) and oncogenic signaling pathways were identified between LGG and GBM. Differential genomic landscapes between LGG and GBM were revealed in the Chinese population, and PCDHGA10, for the first time, was identified as the prognostic factor of gliomas. Our results might provide a basis for molecular classification and identification of diagnostic biomarkers and even potential therapeutic targets for gliomas.

This paper introduces an innovative segmentation model that extends the U-Net architecture with a Squeeze and Excitation (SE) mechanism, designed to enhance the detection of moving objects in video streams. By integrating this model into the ViBe motion detection algorithm, we have significantly improved detection accuracy and reduced false positive rates. Our approach leverages adaptive techniques to increase the robustness of the segmentation model in complex scenarios, without requiring extensive manual parameter tuning. Despite the notable improvements, we recognize that further training is necessary to optimize the model for specific applications. The results indicate that our method provides a promising direction for real-time motion detection systems that require high precision and adaptability to varying conditions.

Human T-cell leukemia virus type I (HTLV-I) is an oncogenic virus whose infection can cause diverse diseases, most notably adult T-cell leukemia/lymphoma (ATL or ATLL), an aggressive and fatal malignancy of CD4 T cells. The oncogenic ability of HTLV-I is mostly attributed to the viral transcriptional transactivator Tax. Tax alone is sufficient to induce specific tumors in mice depending on the promotor used to drive Tax expression, thereby being used to understand HTLV-I tumorigenesis and model the tumor types developed in Tax transgenic mice. Tax exerts its oncogenic role predominantly by activating the cellular transcription factor NF-κB. Here, we report that genetic deletion of NF-κB1, the prototypic member of the NF-κB family, promotes adrenal medullary tumors but suppresses neurofibromas in mice with transgenic Tax driven by the HTLV-I Long Terminal Repeat (LTR) promoter. The adrenal tumors are derived from macrophages. Neoplastic macrophages also infiltrate the spleen and lymph nodes, causing splenomegaly and lymphadenopathy in mice. Nevertheless, the findings could be human relevant, because macrophages are important target cells of HTLV-I infection and serve as a virus reservoir in vivo. Moreover, the spleen, lymph nodes and adrenal glands are the most common sites of tumor cell infiltration in HTLV-I-infected patients. These data provide new mechanistic insights into the complex interaction between Tax and NF-κB, therefore improving our understanding of HTLV-I oncogenic pathogenesis. They also expand our knowledge and establish a new animal model of macrophage neoplasms and adrenal tumors.

The excessive use of antibiotics has resulted in the contamination of the environment with antibiotic resistance genes (ARGs), posing a significant threat to public health. Wastewater treatment plants (WWTPs) are known to be reservoirs of ARGs and considered to be hotspots for horizontal gene transfer (HGT) between bacterial communities. However, most studies focused on the distribution and dissemination of ARGs in hospital and urban WWTPs, and little is known about their fate in industrial WWTPs. In this study, collected the 15 wastewater samples containing N,N-dimethylformamide (DMF) from five stages of the anaerobic anoxic aerobic (AAO) process in an industrial WWTPs. The findings revealed a stepwise decrease in DMF and chemical oxygen demand (COD) content with the progression of treatment. However, the number and abundances of ARGs increase in the effluents of biological treatments. Furthermore, the residues of DMF and the treatment process altered the structure of the bacterial community. The correlation analysis indicated that the shift in bacterial community structures might be the main driver for the dynamics change of ARGs. Interestingly, observed that the AAO process may acted as a microbial source and increased the total abundance of ARGs instead of attenuating it. Additionally, found that non-pathogenic bacteria had higher ARGs abundance than pathogenic bacteria in effluents. The study provides insights into the microbial community structure and the mechanisms that drive the variation in ARGs abundance in industrial WWTPs.

Colorectal cancer is the third leading cause of cancer-related mortality in the world--the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway.

There are contradictory observations about the different radiosensitivities of cancer stem cells and cancer non-stem cells. To resolve these contradictory observations, we studied radiosensitivities by employing breast cancer stem cell (CSC)-like MDA-MB231 and MDA-MB453 cells as well as their corresponding non-stem cells. CSC-like cells proliferate without differentiating and have characteristics of tumor-initiating cells [1]. These cells were exposed to γ-rays (1.25-8.75 Gy) and survival curves were determined by colony formation. A final slope, D(0), of the survival curve for each cell line was determined to measure radiosensitivity. The D(0) of CSC-like and non-stem MDA-MB-453 cells were 1.16 Gy and 1.55 Gy, respectively. Similar results were observed in MDA-MB-231 cells (0.94 Gy vs. 1.56 Gy). After determination of radiosensitivity, we investigated intrinsic cellular determinants which influence radiosensitivity including cell cycle distribution, free-radical scavengers and DNA repair. We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity, differential DNA repair capacity may be a greater determinant of radiosensitivity. Unlike non-stem cells, CSC-like cells have little/no sublethal damage repair, a low intracellular level of ataxia telangiectasia mutated (ATM) and delay of γ-H2AX foci removal (DNA strand break repair). These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells.