USP1 Promotes Cholangiocarcinoma Progression by Deubiquitinating PARP1 To Prevent Its Proteasomal Degradation

Despite its involvement in various cancers, the function of the deubiquitinase USP1 (ubiquitin-specific protease 1) is unexplored in cholangiocarcinoma (CCA). In this study, we provide evidence that USP1 promotes CCA progression through the stabilization of Poly (ADP-ribose) polymerase 1 (PARP1), consistent with the observation that both USP1 and PARP1 are upregulated in human CCA. Proteomics and ubiquitylome analysis of USP1-overexpressing CCA cells nominated PARP1 as a top USP1 substrate. Indeed, their direct interaction was validated by a series of immunofluorescence, co-immunoprecipitation (CO-IP), and GST pull-down assays, and their interaction regions were identified using deletion mutants. Mechanistically, USP1 removes the ubiquitin chain at K197 of PARP1 to prevent its proteasomal degradation, with the consequent PARP1 stabilization being necessary and sufficient to promote the growth and metastasis of CCA in vitro and in vivo. Additionally, we identified the acetyltransferase GCN5 as acetylating USP1 at K130, enhancing the affinity between USP1 and PARP1 and further increasing PARP1 protein stabilization. Finally, both USP1 and PARP1 are significantly associated with poor survival in CCA patients. These findings describe PARP1 as a novel deubiquitination target of USP1 and a potential therapeutic target for CCA

Displacement and Stress Characteristics of Tunnel Foundation in Collapsible Loess Ground Reinforced by Jet Grouting Columns

Collapsible loess tunnel foundation reinforcement is a new challenge in the construction process of tunnel engineering. According to the field displacement and stress monitoring of the Fujiayao loess tunnel, this paper investigates the reinforcing effect of a high-pressure jet grouting pile on a collapsible loess tunnel foundation in the deep large-span tunnel. The field monitoring method was employed to address the performance of tunnel foundation settlement, additional stress, earth pressure, rock pressure, etc. The results indicate that the stress on the pile tops and the earth pressure between piles increase gradually over time in two stages: stress increases rapidly in the first 45 days and, after this period, stress tends to gradually stabilize. Further, stress increases uniformly with the distance from the centerline of the tunnel, and the rock pressure of the tunnel sidewalls tends to be stable within two months of being constructed. Additional stress on the tunnel foundation increases linearly with time, and it is uniformly distributed in the vertical and horizontal directions of the tunnel section. Settlement of the tunnel foundation also gradually increases with time, and it tends to be stable at 50 days from the time of construction. Additionally, the settlements of different monitoring points are similar at the same depth. The research results will further improve the theoretical knowledge of tunnel bottom reinforcement in the loess tunnel, which not only can effectively guide the design and construction of the loess tunnel and reduce disease treatment cost but also can provide the necessary basic research data and scientific theoretical basis for revision of the corresponding specifications of highway tunnels and railway tunnels

Long non-coding RNA colon cancer-associated transcript 2: role and function in human cancers

Abstract. Long non-coding RNAs (lncRNAs) are a family of non-protein-coding RNAs that span a length of over 200 nucleotides. Research reports have illustrated that lncRNAs are involved in various cellular processes and that their abnormal expression leads to the occurrence and development of various tumors. Colon cancer-associated transcript 2 (CCAT2) was first reported as an oncogene in colon cancer. LncRNA CCAT2 is abnormally expressed in hepatocellular carcinoma, cholangiocarcinoma, lung cancer, breast cancer, ovarian cancer, glioma, and other tumors. In tumor tissues, abnormally overexpressed CCAT2 can affect cell proliferation, migration, epithelial-mesenchymal transition, apoptosis, and other biological behaviors through endogenous RNAs mechanisms, various signaling pathways, transcriptional regulation, and other complex mechanisms. Additionally, the overexpression of CCAT2 is also closely related to the tumor size, tumor node metastasis (TNM) stage, survival time, and other prognostic factors, suggesting that it is a potential prognostic indicator. This article reviews the biological functions of CCAT2 and its mechanisms of action in tumors from previous studies. In this review, we attempt to provide a molecular basis for future clinical applications of lncRNA CCAT2

Automatic Monitoring System in Underground Engineering Construction: Review and Prospect

Automatic monitoring system is one of the main means to ensure the safety of underground engineering construction. This paper summarizes the current international research and application status of the underground engineering monitoring system from three aspects of data acquisition, data transmission, and data processing and emphatically introduces the mainstream new technology of the monitoring system. Furthermore, this paper puts forward specific and implementable technical routes based on the current intelligent technology and the challenges faced by future monitoring, which can provide direction and reference for future research, including high-precision real-time acquisition and safe and reliable transmission of monitoring data, multisource data fusion, and the visual intelligent early warning platform

Tunnelling-Induced Settlement and Treatment Techniques for a Loess Metro in Xi’an

Techniques including pre-grouting, long pipe roof, and parameter optimization were employed to ensure the safety of loess metro tunnelling under an existing glass building. Their effects were proved through monitoring the settlement of building and surface during tunnelling. Besides, division of settlement monitoring according to processes, a new method, was conducted to control settlement in time. The highest surface settlement after construction was 16 mm only, meeting the requirement. The result indicates that it is practicable to control the tunnelling settlement strictly in extremely difficult geological areas. The settlement regularities were also studied through numerical simulation; their deformation is larger compared with in situ results while their change trends coincide during most processes. Soil excavations cause settlement primarily, accounting for more than 60%. It is suggested that dual slurry pre-grouting and process-based measurement should be employed before each excavation in water-rich loess areas

HSDL2 knockdown promotes the progression of cholangiocarcinoma by inhibiting ferroptosis through the P53/SLC7A11 axis

Abstract Background Human hydroxysteroid dehydrogenase-like 2 (HSDL2), which regulates cancer progression, is involved in lipid metabolism. However, the role of HSDL2 in cholangiocarcinoma (CCA) and the mechanism by which it regulates CCA progression by modulating ferroptosis are unclear. Methods HSDL2 expression levels in CCA cells and tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The overall survival and disease-free survival of patients with high vs. low HSDL2 expression were evaluated using Kaplan-Meier curves. The proliferation, migration, and invasion of CCA cells were assessed using Cell Counting Kit-8, colony formation, 5-ethynyl-2′-deoxyuridine DNA synthesis, and transwell assays. The effect of p53 on tumor growth was explored using a xenograft mouse model. The expression of SLC7A11 in patients with CCA was analyzed using immunofluorescence. Ferroptosis levels were measured by flow cytometry, malondialdehyde assay, and glutathione assay. HSDL2-regulated signaling pathways were analyzed by transcriptome sequencing. The correlation between p53 and SLC7A11 was assessed using bioinformatics and luciferase reporter assays. Results HSDL2 expression was lower in primary human CCA tissues than in matched adjacent non-tumorous bile duct tissues. HSDL2 downregulation was a significant risk factor for shorter overall survival and disease-free survival in patients with CCA. In addition, HSDL2 knockdown enhanced the proliferation, migration, and invasion of CCA cells. The transcriptome analysis of HSDL2 knockdown cells showed that differentially expressed genes were significantly enriched in the p53 signaling pathway, and HSDL2 downregulation increased SLC7A11 levels. These findings were consistent with the qRT-PCR and western blotting results. Other experiments showed that p53 expression modulated the effect of HSDL2 on CCA proliferation in vivo and in vitro and that p53 bound to the SLC7A11 promoter to inhibit ferroptosis. Conclusions HSDL2 knockdown promotes CCA progression by inhibiting ferroptosis through the p53/SLC7A11 axis. Thus, HSDL2 is a potential prognostic marker and therapeutic target for CCA

MiR-186-5p prevents hepatocellular carcinoma progression by targeting methyltransferase-like 3 that regulates m6A-mediated stabilization of follistatin-like 5

Background: Hepatocellular carcinoma (HCC) is a multistep process involving sophisticated genetic, epigenetic, and transcriptional changes. However, studies on microRNA (miRNA)'s regulatory effects of N6-methyladenosine (m6A) modifications on HCC progression are limited. Methods: Cell Counting Kit-8 (CCK-8), clone formation, and Transwell assays were used to investigate changes in cancer cell proliferation, invasion, and migration. RNA m6A levels were verified using methylated RNA immunoprecipitation. Luciferase reporter assay was used to study the potential binding between miRNAs and mRNA. A mouse tumor transplant model was established to study the changes in tumor progression. Results: Follistatin-like 5 (FSTL5) was significantly downregulated in HCC and inhibited its further progression. Additionally, methyltransferase-like 3 (METTL3) reduced FSTL5 mRNA stability in an m6A-YTH domain family 2(YTHDF2)-dependent manner. Functional experiments revealed that METTL3 downregulation inhibited HCC progression by upregulating FSTL5 in vitro and in vivo. Luciferase reporter assay verified that miR-186-5p directly targets METTL3. Additionally, miR-186-5p inhibits the proliferation, migration, and invasion of HCC cells by downregulating METTL3 expression. Conclusions: The miR-186-5p/METTL3/YTHDF2/FSTL5 axis may offer new directions for targeted HCC therapy

Additional file 2 of MRI-assessed diaphragmatic function can predict frequent acute exacerbation of COPD: a prospective observational study based on telehealth-based monitoring system

Additional file 2. Correlation between diaphragm function and clinical parameters in the COPD grou