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Composite roll produced through casting methods typically remain in the as-cast state after forming. During the preparation process, extended exposure to high temperatures often results in microstructural coarsening at the interface and surface layers, restricting their mechanical performance. To overcome this limitation, we developed a novel vacuum billet forging process for the fabrication of composite rolls. By integrating numerical simulations with experimental validation, we successfully prepared a 42CrMo/Cr5 composite roll. The comprehensive characterization of the interface, including microstructure, elemental distribution, grain texture, grain type, and mechanical properties, was conducted using OM, SEM, EPMA, EBSD, Vickers hardness testing, and a universal testing machine. The relationship between the interface microstructure and mechanical performance was systematically analyzed. The results indicate that complete metallurgical bonding at the interface was achieved with an upsetting reduction ratio of 40% and a single-pass elongation reduction ratio of less than 10%. The interfacial microstructure consisted of four zones: the roll core exhibited lamellar pearlite and blocky ferrite; the diffusion layer near 42CrMo featured pearlite; the diffusion layer near Cr5 contained pearlite and Cr carbides; the Cr5 layer contained fine lamellar pearlite with a greater amount of dispersed Cr carbides. Significant diffusion of Cr and Ni elements was observed, with Cr diffusion extending to 70–90 μm. The interface grains experienced substantial deformation and recrystallization, enhancing the bonding strength. Tensile tests indicated that fracture occurred on the 42CrMo side, with yield and tensile strengths of 371 MPa and 729 MPa, respectively. The microhardness of the composite interface gradually increased from 190 HV to 305 HV without abrupt changes. A significant hardness difference was observed on both sides of the interface, while the variation within the diffusion layer was relatively smooth, indicating good bonding performance at the composite interface. [ABSTRACT FROM AUTHOR]

Precision medicine provides a holistic perspective of an individual’s health, including genetic, environmental, and lifestyle aspects to realize individualized therapy. The development of the internet of things (IoT) devices, the widespread emergence of electronic medical records (EMR), and the rapid progress of cloud computing and artificial intelligence provide an opportunity to collect healthcare big data throughout the lifespan and analyze the disease risk at all stages of life. Thus, the focus of precision medicine is shifting from treatment toward prediction and prevention, i.e., precision health. To this end, various types of data such as omics, imaging, EMR, continuous physiological monitoring, lifestyle, and environmental information, need to be collected, tracked, managed and shared. Thus, internet-of-medical things (IoMT) is crucial for assimilating the health systems, applications, services, and devices that can improve the speed and accuracy of diagnosis and treatments along with real-time monitoring and modification of patient behavior as well as health status. However, security has emerged as a growing concern owing to the proliferation of IoMT devices. The increasing interconnectivity of IoMT-enabled devices with health data reception, transmission, and processing significantly increases the number of potential vulnerabilities within a system. To address the security issues of precision health in IoMT systems, this study reviews the state-of-the-art techniques and schemes from the perspective of a hierarchical system architecture. We present an IoMT system model comprising three layers: the sensing layer, network layer, and cloud infrastructure layer. In particular, we discuss the vulnerabilities and threats to security in each layer and review the existing security techniques and schemes corresponding to the system components along with their functionalities. Owing to the unique nature of biometric features in medical and health services, we highlight the biometrics-based technologies applied in IoMT systems, which contribute toward a considerable difference between the security solutions of existing IoT systems. Furthermore, we summarize the challenges and future research directions of IoMT systems to ensure an improved and more secure future of precision health.

Pancreatic ductal adenocarcinoma (PDAC) is a rapidly progressing malignancy with a poor prognosis. Quercetin is a flavonoid compound with various biological benefits that can be extracted from Chinese herbs or daily foods. Quercetin has anticancer properties in various types of cancers. However, its therapeutic effects and potential mechanisms in PDAC have not been investigated extensively. Here, we confirmed the therapeutic effect of quercetin in PDAC using a mouse model. Based on high‐throughput RNA sequencing (RNA‐seq) and bioinformatic analysis, we propose that quercetin is involved in stromal infiltration of PDAC. Quercetin attenuates the activation of cancer‐associated fibroblasts (CAFs) via tumor‐stromal interaction. Meanwhile, we have identified two quercetin‐related prognostic models for patients with PDAC. Finally, we proposed a downstream target of quercetin, the ITGB4 gene, which could be a potential therapeutic target for PDAC. [ABSTRACT FROM AUTHOR]

Traveling wave rotary ultrasonic motors (TRUSMs) have been applied in optical systems, robotics, biomedical and other fields. However, the disadvantages such as short working life, driving performance degradation, and low energy utilization significantly limit the long-term and stable operation of TRUSMs in advanced fields like aerospace mechanisms. To address the above issues, a novel rotary ultrasonic motor based on multiple Langevin transducers is proposed in this paper. First, the structural design, driving principle and general design criteria are described in detail. Then, the structural parameters are optimized by finite element simulation analysis. Second, a prototype is assembled controllably. Subsequently, the impedance test and vibration measurement are carried out. The results show that the traveling wave is successfully generated on the tooth-ring, and all the Langevin transducers are excited to the first-order longitudinal vibration modes, which strongly verify the correctness of design principle. Finally, the driving performance experiment is carried out. The experimental results show that the no-load speed is 62 r min−1 under the pre-pressure of 10 N. The stalling torque is 0.94 N m at the driving voltage of 500 Vp-p. The response characteristics show that the start/stop time are 4.6/5.5 ms, and the angular displacement resolution of clockwise/counterclockwise driving are 6.7/10.2 μ rad. The motor proposed in this paper not only exhibits relatively high output performance with excellent vibration characteristics, but also maintains compactness of the structure. The sandwiched structure design effectively avoids the problem that the bonded-type piezoceramic rings in conventional TRUSMs are prone to damage or fall-off when vibrating for a long time. Furthermore, the general design criteria provide a new approach to develop high performance rotary ultrasonic motors. The proposed novel ultrasonic motor is expected to meet the demand for long-term and stable operation in aerospace mechanisms. [ABSTRACT FROM AUTHOR]

In outer space’s extreme electron radiation environment, the insulating medium will experience a deep dielectric charging effect. As an excellent insulating medium, polyimide is widely used in spacecraft. In practical use, glass microspheres and glass fibers are often added to increase its mechanical strength. However, the influence of glass microspheres and glass fibers on deep dielectric charging effects has often been ignored in previous studies. Therefore, the work in this article established a 3-D deep dielectric charging model of glass microsphere and glass fiber reinforced polyimide. Using the model, the effects of glass microsphere and glass fiber volume fraction, glass microsphere spacing, glass fiber orientation, and 3-D glass fiber structure were investigated. The results show that the larger the volume fraction of glass fiber or glass microsphere, the more obvious the decrease of polyimide composite media’s average electric field strength. Under the same volume fraction, glass fibers are more favorable to reduce the average electric field strength than glass microspheres. The surface of glass microspheres will form charge accumulation, increasing local maximum electric field intensity, which is greater than the maximum electric field value of pure polyimide under electron radiation. When the spacing of glass microspheres decreases, the degree of electric field distortion increases, but the electric field value decreases when the microspheres contact each other. When the glass fiber orientation is perpendicular to the ground plane, it can better provide the electronic release channel, thereby reducing the deep dielectric charging effect. Using 3-D glass fiber structures can reduce the polyimide’s average electric field value and reduce the maximum local electric field distortion. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is among the most common cancers worldwide and an important cause of cancer-related death. Inherited genetic variation plays a vital role in the occurrence and development of CRC. The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in MMP2 with CRC risk. Patients and Methods: Three candidates, MMP2 SNPs, rs1053605, rs243849, and rs14070, were selected and genotyped using the Agena MassARRAY RS1000 system, and their association with risk of CRC was evaluated in 663 CRC cases and 663 healthy controls by calculating odds ratio (OR) with 95% confidence interval (95% CI) values. Results: The minor allele of rs243849 (T) was significantly less frequent in cases than controls (p = 0.021), and this SNP was associated with a decreased risk of CRC under co-dominant (p = 0.033), dominant (p = 0.021), and log-additive (p = 0.017) models, after adjusting for confounding factors. After stratification, rs243849 was found to be protective against CRC in patients who were non-smoking, consumed alcohol, and were ≥ 60 years old (p < 0.05). Conversely, rs1053605 was associated with disease occurrence in patients with CRC who consumed alcohol and were < 60 years old (p < 0.05). Furthermore, rs1053605 genotype was associated with an increased risk of colon cancer (p < 0.05), while that of rs243849 was associated with a decreased risk of rectal cancer (p < 0.05). The rs1053605-rs243849 CT haplotype exhibited a protective role in CRC risk, following adjustment for confounders (p = 0.014). The rs14070 SNP was not associated with CRC risk. Finally, the false discovery rate (FDR) method was used to validate the study results. Conclusion: Overall, the MMP2 gene polymorphisms, rs243849 and rs1053605, may be useful for predicting CRC progression. [ABSTRACT FROM AUTHOR]

Polyimide, which is widely used to insulate power equipment operating in a vacuum environment, is prone to insulation failure due to surface flashover. Using POSS to modify it is an effective solution. This paper focuses on the study of DC surface flashover characteristics in vacuum of POSS/polyimide composite film, by introducing 1%, 3%, 5% equivalent mole content of POSS into polyimide, and conducting a surface flashover characteristics test in vacuum together with pure polyimide. The physical and chemical properties of the composite films were tested utilizing Fourier transform infrared spectroscopy and ultraviolet–visible spectroscopy. Combined with resistivity, SEM, and other test techniques, the influence mechanism of POSS molecular modification on DC surface flashover characteristics of polyimide films in vacuum was initially revealed. The results showed that after the introduction of POSS, the overall functional group structure of polyimide remained unchanged, the intermolecular charge transfer complexation was inhibited, and the transmittance of the film increased. The thermal conductivity and thermogravimetric temperature of the film are improved to a certain extent, and the mechanical properties are slightly decreased. With the increase of the introduced POSS content, the dielectric strength of the composite film is also enhanced. The surface flashover voltage of the composite film with a POSS content of 5% is 17.5 kV in vacuum, which is 30.5% higher than that of the pure film. Further analysis shows that the introduction of POSS will reduce the resistivity of the composite film, accelerate the dissipation of surface charges, and increase the flashover voltage. In addition, POSS forms a uniformly distributed Si-O-Si cage-like structure through molecular modification. When the surface of the film is damaged, SiOx inorganic flocculent particles are generated, which can not only scatter electrons, but also shallow the depth of trap energy level and accelerate the dissipation rate of surface charge, thus increasing the flashover voltage. [ABSTRACT FROM AUTHOR]

The deep dielectric charging of the slip ring assembly caused by high-energy electron radiation leads to the failure of the solar array drive assembly (SADA), which accelerates the failure of the whole satellite. It is necessary to optimize the structure of the slip ring assembly according to the deep dielectric charging characteristics to reduce the risk of discharge accidents. In this article, based on the law of current conservation, a 3-D simulation model for deep charging of slip ring assembly is established by combining Geant4 with COMSOL. Under the FLUMIC3 electron radiation environment, the essential characteristics of the electric field and potential distributions in the slip ring assembly are studied. Based on these, optimization schemes for aluminum shielding structures, insulation baffles, and ground structures are proposed. The simulation results show that the simultaneous use of the three proposed optimization schemes can significantly reduce the electric field distortion caused by high-energy electron radiation, and the maximum reduction is about 70%. At the same time, the overall quality of the aluminum shield and the basic structure of the slip ring assembly can be maintained. It provides specific references for the actual design of slip ring assembly in SADA. [ABSTRACT FROM AUTHOR]

aimed to explore the prognostic patterns of ferroptosis-related genes in papillary renal cell carcinoma (PRCC) and investigate the relationship between ferroptosis-related genes and PRCC tumor immune microenvironment. Methods: We obtained the mRNA expression and corresponding clinical data of PRCC from the public tumor cancer genome atlas database (TCGA). The PRCC patients were randomly divided into two cohort, training cohort and verification cohort, respectively. Univariate Cox regression, LASSO Cox regression, multivariate Cox regression analysis were utilized to construct ferroptosis signature for PRCC patients. And then, risk prognostic model was established and verified. The correlation of ferroptosis-related signature with survival and immune microenvironment was systematically analyzed. Results: A 4-genes ferroptosis signature (CDKN1A, MIOX, PSAT1, and RRM2) was constructed. Multivariate Cox regression assay indicates that the risk score of ferroptosis signature was an independent prognostic indicator (HR=1.391, p< 0.001). The survival curve shows that the high-risk group has a poorer prognosis than the low-risk group (p< 0.001). The risk prognostic model was established based on prognostic factors of clinical-stage, hemoglobin, and risk score. The time-dependent receiver operating characteristic curve (ROC) analysis proves the predictive capacity of the ferroptosis signature, the 3 years area under the curve (AUC) is 0.890, and the 5 years AUC is 0.733. Further analysis suggested that cell cycle, pentose phosphate pathway, P53 signaling pathway were significantly enriched in the high-risk group. The significantly different fractions of dendritic cells resting, macrophage cells, and T cells follicular helper were observed in risk groups. Conclusion: This study implicates a ferroptosis signature which has a good predict capacity of the prognosis in PRCC patients. Ferroptosis-related genes may have a key role in the process of anti-tumor and serve as therapeutic targets for PRCC. [ABSTRACT FROM AUTHOR]

NIMA-related kinase 7 (NEK7) is a serine/threonine kinase involved in cell cycle progression via mitotic spindle formation and cytokinesis. It has been related to multiple cancers, including breast cancer, hepatocellular cancer, lung cancer, and colorectal cancer. Moreover, NEK7 regulated the NLRP3 inflammasome to activate Caspase-1, resulting in cell pyroptosis. In the present study, we investigated whether NEK7 is involved in cell pyroptosis of hepatocellular carcinoma (HCC). Interestingly, we found that NEK7 was significantly related to expression of pyroptosis marker GSDMD in HCC. We found that NEK7 expression was significantly correlated with GSDMD expression in bioinformatics analysis, and NEK7 expression was significantly co-expressed with GSDMD in our HCC specimens. Cell viability, migration, and invasion capacity of HCC cell lines were inhibited, and the tumor growth in the xenograft mouse model was also suppressed following knockdown of NEK7 expression. Mechanistic studies revealed that knockdown of NEK7 in HCC cells significantly upregulated the expression of pyroptosis markers such as NLRP3, Caspase-1, and GSDMD. Coculture of HCC cells stimulated hepatic stellate cell activation by increasing p-ERK1/2 and α-SMA. Knockdown of NEK7 impaired the stimulation of HCC cells. Therefore, downregulation of NEK7 inhibited cancer–stromal interaction by triggering cancer cell pyroptosis. Taken together, this study highlights the functional role of NEK7-regulated pyroptosis in tumor progression and cancer–stromal interaction of HCC, suggesting NEK7 as a potential target for a new therapeutic strategy of HCC treatment. [ABSTRACT FROM AUTHOR]

Kidney renal clear cell carcinoma (KIRC) is the most common malignant kidney tumor as its characterization of highly metastatic potential. Patients with KIRC are associated with poor clinical outcomes with limited treatment options. Up to date, the underlying molecular mechanisms of KIRC pathogenesis and progression are still poorly understood. Instead, particular features of Cancer-Associated Fibroblasts (CAFs) are highly associated with adverse outcomes of patients with KIRC, while the precise regulatory mechanisms at the epigenetic level of KIRC in governing CAFs remain poorly defined. Therefore, explore the correlations between epigenetic regulation and CAFs infiltration may help us better understand the molecular mechanisms behind KIRC progression, which may improve clinical outcomes and patients quality of life. In the present study, we identified a set of clinically relevant CAFs-related methylation-driven genes, NAT8, TINAG, and SLC17A1 in KIRC. Our comprehensive in silico analysis revealed that the expression levels of NAT8, TINAG, and SLC17A1 are highly associated with outcomes of patients with KIRC. Meanwhile, their methylation levels are highly correlates with the severity of KIRC. We suggest that the biomarkers might contribute to CAFs infiltration in KIRC. Taken together, our study provides a set of promising biomarkers which could predict the progression and prognosis of KIRC. Our findings could have potential prognosis and therapeutic significance in the progression of KIRC. [ABSTRACT FROM AUTHOR]

Pancreatic carcinoma (PC) easily invades the peripancreatic arteries, which is the main reason for the poor prognosis. This meta-analysis aimed to investigate the perioperative outcomes and long-term survival of pancreatectomy combined with arterial resection (AR) in PC patients with arterial infiltration. We searched the Medline, EMbase, and Cochrane Library and used the Review Manager 5.3. A total of 11 studies were reviewed, including 1829 patients who underwent pancreatectomy or palliative therapies, of whom 205 received AR. The results showed that AR was associated with a longer operation time (MD = 87.05, P < 0.00001), higher blood loss (MD = 422.73, P < 0.00001), and an increased risk for overall complication (OR = 2.10, P < 0.0001), postpancreatectomy hemorrhage (PPH) (OR = 3.32, P = 0.003), and reoperation (OR = 2.38, P = 0.001). The occurrence of postoperative pancreatic fistula (POPF) (OR = 1.66, P = 0.05), delayed gastric emptying (DGE) (OR = 2.15, P = 0.13), and perioperative mortality (OR = 1.94, P = 0.06) seemed higher in AR group. Pancreatectomy with AR showed a better survival at 1 year (OR = 1.55, P = 0.05), 3 years (OR = 1.78, P = 0.04), and 5 years (OR = 3.24, P = 0.03). Therefore, we concluded that pancreatectomy with AR could be conducted under the comprehensive consideration of patients' conditions, and it may be especially beneficial for those who have the probability to achieve R0 resection. [ABSTRACT FROM AUTHOR]

The prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is still dismal. Elucidation of associated genomic alteration may provide effective therapeutic strategies for PDAC treatment. NIMA-related protein kinase 7 is widely expressed in various tumors, including breast cancer, colorectal cancer and lung cancer, and promotes the proliferation of liver cancer cells in vitro and in vivo. We investigated the protein expression level of NEK7 in tumor tissues and adjacent normal tissues using immunohistochemistry of 90 patients with PADC. Meanwhile, the RNA expression level of NEK7 was examined using database-based bioinformatic analysis. Correlation and significance of NEK7 expression with patient clinicopathological features and prognosis were examined. Cell proliferation, cell adhesion, migration and invasion capabilities were measured following downregulation of NEK7 expression. 3D tumor organoids of pancreatic cancer were established and splenic xenografted into nude mice, then liver metastatic ability of NEK7 was evaluated in following 4 weeks. We observed NEK7 expression was upregulated in tumor tissues compared to normal tissues at both RNA and protein levels using bioinformatic analysis and immunohistochemistry analysis in PDAC. NEK7 expression was undetectable in normal pancreatic ducts; NEK7 was overexpressed in primary tumor of PDAC; NEK7 expression was highly correlated with advanced T stage, poorly differentiated histological grade invasive ductal carcinoma, and lymphatic invasion. Meanwhile, patients with higher NEK7 expression accompanied by worse survival outcome. Moreover, NEK7 promoted migration, invasion, adhesion, proliferation and liver metastatic ability of pancreatic cancer cells. Taken together, our data indicate that NEK7 promotes pancreatic cancer progression and it may be a potential marker for PDAC prognosis. [ABSTRACT FROM AUTHOR]

Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, and it has a high mortality rate. Despite surgical treatments, radiotherapy, and chemotherapy, the median survival of patients with advanced HCC is low. Evidence has shown that tanshinone (TA) I exhibits anti-proliferative activity against numerous cancers. However, the role of TA I and its mechanism in HCC remain unknown. Here, we determined the anti-cancer potential of TA I against HCC cell lines HepG2 and Huh7. Cell viability was analyzed using a Cell Counting Kit-8 assay. Flow cytometry was used to analyze cell cycles and apoptosis. Western blotting was used to detect protein expression and phosphorylation levels. TA I was found to inhibit cell proliferation, induce G0/G1 phase arrest, and trigger apoptosis in HepG2 and Huh7 cells. We further explored the molecular mechanism of TA I-mediated apoptosis. Our results showed that TA I induced G0/G1 phase arrest through downregulation of cyclin D1 expression and upregulation of p21 expression. TA I induced cell apoptosis via reactive oxygen species-mediated endoplasmic reticulum stress and by inhibiting p53/damage-regulated autophagy modulator (DRAM)-mediated autophagy in HepG2 and Huh7 cells. Therefore, TA I may be an anti-cancer drug candidate in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Electrically insulating yet thermally conductive polymer-based composites are highly sought after in aerospace field. In this work, for the first time, electrically insulating but thermally conductive polyimide (PI) composites are fabricated by simultaneously incorporating micro- and nano-sized aluminum nitride (AlN) particles via a simple, economic, and scalable method of ball milling and subsequent hot-pressing process. The thermal conductivity, dielectric, and mechanical properties of the PI composites depend on the ratio of micro-sized AlN (m-AlN) to nano-sized AlN (n-AlN) and the total content of AlN in the PI composites. The thermal conductivity of the PI composites with 40 wt% m-AlN and 20 wt% n-AlN is 1.5 ± 0.05 W·m−1·K−1, which is 10 times higher than that of bare PI. The PI composites hold a great potential in aerospace industries. [ABSTRACT FROM AUTHOR]

The present study aimed to determine whether HepG2 can induce epithelial-mesenchymal transition (EMT) via angiotensin II (AngII) simulation. The expression levels of EMT markers vimentin and E-cadherin in cancer tissues and adjacent tissues of patients with hepatocellular carcinoma (HCC) were detected by immunohistochemistry. In addition, HepG2 cells were stimulated with AngII, and the gene and protein expression levels of vimentin and E-cadherin were measured by reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively, whereas cell migration and invasion were assessed using Transwell assays. The AngII inhibitor Ang1-7 and the Ang1-7 inhibitor A779 were added to the system to further evaluate AngII-induced EMT. Compared with that in normal tissue, the expression level of vimentin in HCC tissue was increased, whereas that of E-cadherin was decreased. EMT occurred 48 h following AngII stimulation. The transcription level of E-cadherin in HepG2 cells was decreased, whereas that of vimentin was increased. In addition, the migration and invasion abilities of the cells were increased simultaneously. Ang1-7 partly inhibited AngII-induced EMT. When stimulated at an appropriate time, HepG2 cells have the ability to undergo EMT. [ABSTRACT FROM AUTHOR]

Background/Aims: Long noncoding RNAs (lncRNAs) are key regulators of cancer initiation and progression. In this study, we investigated the clinical value and functional role of LncRNA DQ786243 (LncDQ) in the pathogenesis of hepatocellular carcinoma (HCC). Methods: To investigate the expression level of LncDQ in HCC, we performed quantitative real-time PCR using total RNA extracted from HCC tumor tissues and their matched non-neoplastic counterparts, as well as from the serum of HCC patients and healthy volunteers. The correlation of LncDQ expression with clinicopathologic features and prognosis was analyzed. The functional role of LncDQ in cell proliferation, migration, and invasion were evaluated by MTT cell viability, wound healing, and transwell assays in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays were performed to analyze the potential mechanism of LncDQ in HCC cells. Results: LncDQ was upregulated in both HCC tissue samples and serum and was correlated with low survival rate and adverse clinical pathological characteristics. Multivariate analysis demonstrated that LncDQ expression was an independent prognostic factor for HCC. The area under the receiver operating characteristic curve was 0.804 with a sensitivity of 0.72 and a specificity of 0.8. Knockdown of LncDQ induced inhibition of cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, LncDQ regulated the epithelial–mesenchymal transition pathway by interacting with EZH2, to epigenetically repress the expression of E-cadherin in HCC cells. Conclusions: Taken together, the results of our study indicate that LncDQ plays a critical role in HCC progression, and may serve as a potential diagnostic and prognostic biomarker for HCC. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that long noncoding RNAs (lncRNAs) influence the pathogenesis and progression of hepatocellular carcinoma (HCC). The authors of the present study previously reported that abnormal upregulation of lncRNA DQ786243 (lncDQ) was associated with poor prognoses for patients with HCC. However, the elucidation of underlying mechanisms which influenced these results was not completed. Thus, the current study aimed to characterize the mechanisms and functions of lncDQ that facilitate its promotion of HCC progression. lncDQ, miR-15b-5p and Wnt3A expression levels were characterized in HCC and portal vein tumor thrombus tissue samples and for liver cancer and liver cancer cell lines using reverse transcription-quantitative PCR. Bioinformatics software was used for the analysis of interactions between lncDQ and miR-15b-5p, miR-15b-5p and Wnt3A. Luciferase assays confirmed the binding relationships between miR-15b-5p and the 3′ untranslated region (UTR) of Wnt3A. Using online databases, prognostic values of miR-15b-5p and Wnt3A were also assessed. Proliferation and invasion assays were used to assess liver cancer and HCC cell functions after individually silencing lncDQ and miR-15b-5p expression in the cells. Western blotting was used for the investigation of alterations of the expression of Wnt3A/β-catenin and epithelial-mesenchymal transition (EMT) signal pathways. lncDQ and Wnt3A expression were significantly increased in HCC tissues, whereas miR-15b-5p was downregulated in HCC tissues. Low expression of miR-15b-5p was also associated with poor prognoses for patients with HCC. lncDQ was able to bind with miR-15b-5p and served as a competing endogenous RNA. As the target gene of miR-15b-5p, Wnt3A was correlated with poor prognoses for patients with HCC. Silencing of lncDQ expression significantly attenuated proliferation and invasion of liver cancer and HCC cells, however the inhibition of miR-15b-5p was able to reverse this effect. However, silencing of lncDQ and miR-15b-5p expression simultaneously resulted in the partial rescue of the inhibitory effect in the liver cancer and HCC cells. lncDQ inhibited miR-15b-5p so as to promote HCC cell invasion and proliferation through activation of the Wnt3A/β-catenin/EMT pathway. Taken together, the results of the present study suggested that the lncDQ/miR-15b-5p axis modulates the progression of HCC. [ABSTRACT FROM AUTHOR]

Background: ACYP2 gene may be involved in the process of telomere shortening which may be involved in the liver cancer. So, this research was to examine whether the ACYP2 gene polymorphism has impact on the risk of liver cancer in Chinese population. Methods: Two hundred and fifty cirrhosis patients and 248 liver cancer patients were selected. Unconditional logistic regression was to calculate the odds ratio (OR) and 95% confidence intervals (CIs). Analyze the relationship between ACYP2 gene polymorphism and tumor using meta‐analysis. Analyze the expression of ACYP2 gene in liver cancer and its influence on the prognosis of liver cancer by databases (Ualcan, GTEX and Kaplan–Meier plotter). Results: In the allele model, ACYP2 rs843720 was protection against the occurrence of cirrhosis developed into liver cancer (OR = 0.76, 95% CI: 0.58–0.99, p = 0.04). Rs1682111 and rs843720 play a protective role in the additive model (rs1682111: OR = 0.69, 95% CI: 0.52–0.93, p = 0.01; rs843720: OR = 0.73, 95% CI: 0.54–0.98, p = 0.04).While rs843645 G allele increased the risk of cirrhosis developed into liver cancer under the additive model (OR = 1.42, 95% CI: 1.02–2.00, p = 0.04).The haplotype analysis detected that "ATATCGCC" decreased the risk of cirrhosis developed into liver cancer (OR = 0.69, 95% CI: 0.51–0.92, 95% CI: p = 0.013); however, "TGAGCGTC" increased the risk of cirrhosis developed into liver cancer (OR = 1.48, 95% CI: 1.04–2.10, p = 0.027). Meta‐analysis shown that ACYP2 rs1682111 was associated with the risk of cancer (OR = 0.90, 95% CI: 0.78–1.05, p = 0.02). ACYP2 gene high expression was found to be associated with better OS for all liver patients. Conclusion: Based on this research, we surmised that ACYP2 gene may be involved in the occurrence of liver cancer in Chinese populations. [ABSTRACT FROM AUTHOR]

Objective: Significant advancements have been made in hepatocellular carcinoma (HCC) therapeutics, such as immunotherapy for treating patients with HCC. However, there is a lack of reliable biomarkers for predicting the response of patients to therapy, which continues to be challenging. Cancer stem cells (CSCs) are involved in the oncogenesis, drug resistance, and invasion, as well as metastasis of HCC cells. Therefore, in this study, we aimed to create an mRNA expression-based stemness index (mRNAsi) model to predict the response of patients with HCC to immunotherapy., Methods: We retrieved gene expression and clinical data of patients with HCC from the GSE14520 dataset and the Cancer Genome Atlas (TCGA) database. Next, we used the "one-class logistic regression (OCLR)" algorithm to obtain the mRNAsi of patients with HCC. We performed "unsupervised consensus clustering" to classify patients with HCC based on the mRNAsi scores and stemness subtypes. The relationships between the mRNAsi model, clinicopathological features, and genetic profiles of patients were compared using various bioinformatic methods. We screened for differentially expressed genes to establish a stemness-based classifier for predicting the patient's prognosis. Next, we determined the effect of risk scores on the tumor immune microenvironment (TIME) and the response of patients to immune checkpoint blockade (ICB). Finally, we used qRT-PCR to investigate gene expression in patients with HCC., Results: We screened CSC-related genes using various bioinformatics tools in patients from the TCGA-LIHC cohort. We constructed a stemness classifier based on a nine-gene ( PPARGC1A, FTCD, CFHR3, MAGEA6, CXCL8, CABYR, EPO, HMMR , and UCK2 ) signature for predicting the patient's prognosis and response to ICBs. Further, the model was validated in an independent GSE14520 dataset and performed well. Our model could predict the status of TIME, immunogenomic expressions, congenic pathway, and response to chemotherapy drugs. Furthermore, a significant increase in the proportion of infiltrating macrophages, Treg cells, and immune checkpoints was observed in patients in the high-risk group. In addition, tumor cells in patients with high mRNAsi scores could escape immune surveillance. Finally, we observed that the constructed model had a good expression in the clinical samples. The HCC tumor size and UCK2 genes expression were significantly alleviated and decreased, respectively, by treatments of anti-PD1 antibody. We also found knockdown UCK2 changed expressions of immune genes in HCC cell lines., Conclusion: The novel stemness-related model could predict the prognosis of patients and aid in creating personalized immuno- and targeted therapy for patients in HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zou, Wang, Liu, Peng, Gan, Lin and Liu.)

The ERK1/2 pathway is involved in epithelial-mesenchymal transformation and cell cycle of tumor cells in hepatocellular carcinoma (HCC). In the present study, we investigated the involvement of ERK1/2 activation on hepatic stellate cells (HSCs). We identified ERK1/2 phosphorylation in activated HSCs of HCC samples. We found that tumor cells promoted the migration and invasion capacity of HSCs by activating ERK1/2 phosphorylation. Using high throughput transcriptome sequencing analysis, we found that ERK1/2 inhibition altered genes significantly correlated to signaling pathways involved in extracellular matrix remodeling. We screened genes and demonstrated that the ERK1/2 inhibition-related gene set significantly correlated to cancer-associated fibroblast infiltration in TCGA HCC tumor samples. Moreover, inhibition of ERK1/2 suppressed tumor cell-induced enhancement of HSC migration and invasion by regulating expression of fibrosis markers FAP, FN1 and COL1A1. In a tumor cell and HSC splenic co-transplanted xenograft mouse model, inhibition of ERK1/2 suppressed liver tumor formation by downregulating fibrosis, indicating ERK1/2 inhibition suppresses tumor-stromal interactions in vivo . Taken together, our data indicate that inhibition of ERK1/2 in tumor-associated HSCs suppresses tumor-stromal interactions and progression. Furthermore, inhibition of ERK1/2 may be a potential target for HCC treatment., Competing Interests: None., (AJCR Copyright © 2024.)

Background: This study aimed to evaluate the relationship between LINC00665 expression levels and the risk of hepatocellular carcinoma (HCC) in Chinese Han nationality patients and to explore the influence of LINC00665 dysregulation on the proliferation and migration potential of HCC cells., Patients and Methods: We investigated the expression of LINC00665 in The Cancer Genome Atlas (TCGA) database. Then, we confirmed the expression of LINC00665 in 54 pairs of surgical tissues from HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction. Furthermore, we manipulated the expression level of LINC00665 and examined the cell proliferation and migration abilities of HCC cells., Results: In the TCGA cohort, a high level of LINC00665 in patients with HCC was significantly associated with tumor stage, tumor differentiation grade, and overall survival. In our HCC patient cohort, overexpression of LINC00665 in patients showed positive correlations with alpha-fetoprotein level, Barcelona Clinic Liver Cancer stage, and tumor differentiation grade. In addition, LINC00665 was upregulated in HCC cells, especially in cells with rapid growth rates and high migration abilities. A new LINC00665 isoform with a length of 1,371 nucleotides was identified in MHCC-97H cells. Interfering with LINC00665 expression weakened the proliferation and migration abilities of HCC cells. In contrast, LINC00665 overexpression enhanced proliferation and migration abilities., Conclusion: LINC00665 was upregulated in HCC tissues and cells and might be used to predict a poor prognosis of HCC patients. In addition, LINC00665 may promote the malignant progression of HCC by enhancing proliferation and migration capacities., Competing Interests: None., (IJCEP Copyright © 2023.)

Background: Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1-protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1-protein interaction mediated tumor metastasis., Methods: CCAT1-proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1-Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells., Results: RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and participated in the tumor metastasis pathway. Knocked down vimetin ( VIM ) and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein., Conclusion: CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Tumor oncogenesis, cancer metastasis, and immune evasion were substantially impacted by the mammalian target of the rapamycin complex 1 (mTORC1) pathway. However, in hepatocellular carcinoma (HCC), no mTORC1 signaling-based gene signature has ever been published. mTORC1 scores were computed employing a single sample gene set enrichment analysis based on databases including the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). The PAG1, LHFPL2, and FABP5 expression levels were obtained to construct a mTORC1 pathway-related model. In two databases, the overall survival (OS) rate was shorter for high-mTORC1 score patients compared to those with low scores. The activation of TFs in the group with high risk was enhanced, such as the HIF-1 pathway. Additionally, it was discovered that a high mTORC1 score was linked to an immune exclusion phenotype and enhanced immunosuppressive cell infiltration. Notably, it was discovered that high-mTORC1 scores patients had poorer immunotherapeutic results and might not gain benefit from immunotherapy. When compared to the low HCC metastatic cell lines, the high HCC metastatic cell lines have overexpressed levels of PAG1, LHFPL2, and FABP5 expression. The expression of PAG1, LHFPL2, and FABP5 was inhibited by the MAPK and mTORC1 pathway inhibitors. Our study identified mTORC1 score signature can aid in the development of individualized immunotherapy protocols and predict the HCC patients' prognoses.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant and lethal human cancers in the world due to its high metastatic potential, and patients with PDAC have a poor prognosis, yet quite little is understood regarding the underlying biological mechanisms of its high metastatic capacity. Baicalein has a dramatic anti-tumor function in the treatment of different types of cancer. However, the therapeutic effects of baicalein on human PDAC and its mechanisms of action have not been extensively understood. In order to explore the biological characteristic, molecular mechanisms, and potential clinical value of baicalein in inhibiting the metastatic capacity of PDAC. We performed several in vitro , in vivo , and in silico studies. We first examined the potential regulation of baicalein in the metastatic capacity of PDAC cells. We showed that baicalein could dramatically suppress liver metastasis of PDAC cells with highly metastatic potential in mice model. The high-throughput sequencing analysis was employed to explore the biological roles of baicalein in PDAC cells. We found that baicalein might be involved in the infiltration of Cancer-Associated Fibroblasts (CAF) in PDAC. Moreover, a baicalein-related risk model and a lncRNA-related model were built by Cox analysis according to the data set of PDAC from TCGA database which suggested a clinical value of baicalein. Finally, we revealed a potential downstream target of baicalein in PDAC, we proposed that baicalein might contribute to the infiltration of CAF via FGFBP1. Thus, we uncovered a novel role for baicalein in regulation of PDAC liver metastasis that may contribute to its anti-cancer effect. We proposed that baicalein might suppress PDAC liver metastasis via regulation of FGFBP1-mediated CAF infiltration. Our results provide a new perspective on clinical utility of baicalein and open new avenues for the inhibition of liver-metastasis of PDAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Lei, Zhou, Zhong, Li, Ai, Zheng, Liu, Piao, Yan and Lai.)