Machine learning-based decision support model for selecting intra-arterial therapies for unresectable hepatocellular carcinoma: A national real-world evidence-based study.

IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.

Circ_0001982 aggravates breast cancer development through the circ_0001982-miR-144-3p-GSE1 axis.

This study was designed to explore the role of circ_0001982 in breast cancer (BC) development. Quantitative real-time polymerase chain reaction and western blot analysis assays were used to determine circ_0001982, miR-144-3p, and gse1 coiled-coil protein (GSE1) expression. Functional assays were performed to evaluate cell proliferation, apoptosis, migration, and invasion. The glycolysis was analyzed with commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assays were conducted to analyze the relationships among circ_0001982, miR-144-3p, and GSE1. A murine xenograft model assay was performed to determine circ_0001982-induced effects on BC cell tumor properties in vivo. Circ_0001982 expression was upregulated, but miR-144-3p was reduced in BC tissues and cells in comparison with normal breast tissues and normal human mammary epithelial cells. Circ_0001982 knockdown or miR-144-3p overexpression inhibited BC cell proliferation, glycolysis, migration and invasion, and promoted apoptosis. Circ_0001982 sponged miR-144-3p and negatively regulated miR-144-3p expression in BC cells. In addition, GSE1 was identified as a target mRNA of miR-144-3p. Ectopic GSE1 expression relieved circ_0001982 depletion-induced effects on BC cell tumor properties. Furthermore, circ_0001982 absence suppressed BC cell tumor properties in vivo. Circ_0001982 contributed to the BC cell tumor properties by regulating the miR-144-3p-GSE1 axis.

Learning to detect boundary information for brain image segmentation.

MRI brain images are always of low contrast, which makes it difficult to identify to which area the information at the boundary of brain images belongs. This can make the extraction of features at the boundary more challenging, since those features can be misleading as they might mix properties of different brain regions. Hence, to alleviate such a problem, image boundary detection plays a vital role in medical image segmentation, and brain segmentation in particular, as unclear boundaries can worsen brain segmentation results. Yet, given the low quality of brain images, boundary detection in the context of brain image segmentation remains challenging. Despite the research invested to improve boundary detection and brain segmentation, these two problems were addressed independently, i.e., little attention was paid to applying boundary detection to brain segmentation tasks. Therefore, in this paper, we propose a boundary detection-based model for brain image segmentation. To this end, we first design a boundary segmentation network for detecting and segmenting images brain tissues. Then, we design a boundary information module (BIM) to distinguish boundaries from the three different brain tissues. After that, we add a boundary attention gate (BAG) to the encoder output layers of our transformer to capture more informative local details. We evaluate our proposed model on two datasets of brain tissue images, including infant and adult brains. The extensive evaluation experiments of our model show better performance (a Dice Coefficient (DC) accuracy of up to [Formula: see text] compared to the state-of-the-art models) in detecting and segmenting brain tissue images.

FAM49B promotes breast cancer proliferation, metastasis, and chemoresistance by stabilizing ELAVL1 protein and regulating downstream Rab10/TLR4 pathway.

BACKGROUND: Breast cancer (BC) is one of the most common cancers and the leading cause of death in women. Previous studies have demonstrated that FAM49B is implicated in several tumor progression, however, the role and mechanism of FAM49B in BC remain to be explored. Therefore, in this study, we aimed to systematically study the role of FAM49B in the proliferation, metastasis, apoptosis, and chemoresistance of BC, as well as the corresponding molecular mechanisms and downstream target. METHODS: The ONCOMINE databases and Kaplan-Meier plotter databases were analyzed to find FAM49B and its prognostic values in BC. FAM49B expression in BC and adjacent non-tumor tissues was detected by western blot and IHC. Kaplan-Meier analysis was used to identify the prognosis of BC patients. After FAM49B knockdown in MCF-7 and MDA-MB-231 cells, a combination of co-immunoprecipitation, MTT, migration, and apoptosis assays, nude mouse xenograft tumor model, in addition to microarray detection and data analysis was used for further mechanistic studies. RESULTS: In BC, the results showed that the expression level of FAM49B was significantly higher than that in normal breast tissue, and highly expression of FAM49B was significantly positively correlated with tumor volume, histological grade, lymph node metastasis rate, and poor prognosis. Knockdown of FAM49B inhibited the proliferation and migration of BC cells in vitro and in vivo. Microarray analysis revealed that the Toll-like receptor signaling pathway was inhibited upon FAM49B knockdown. In addition, the gene interaction network and downstream protein validation of FAM49B revealed that FAM49B positively regulates BC cell proliferation and migration by promoting the Rab10/TLR4 pathway. Furthermore, endogenous FAM49B interacted with ELAVL1 and positively regulated Rab10 and TLR4 expression by stabilizing ELAVL1. Moreover, mechanistic studies indicated that the lack of FAM49B expression in BC cells conferred more sensitivity to anthracycline and increased cell apoptosis by downregulating the ELAVL1/Rab10/TLR4/NF-κB signaling pathway. CONCLUSION: These results demonstrate that FAM49B functions as an oncogene in BC progression, and may provide a promising target for clinical diagnosis and therapy of BC.

Overweight with HBV infection limited the efficacy of TACE in hepatocellular carcinoma by inhibiting the upregulated HMGB1.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC. METHODS: Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population. RESULTS: Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE. CONCLUSIONS: In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1.

Circ-ZNF124 downregulation inhibits non-small cell lung cancer progression partly by inactivating the Wnt/ß-catenin signaling pathway via mediating the miR-498/YES1 axis.

Non-small cell lung cancer (NSCLC) is a major type of lung cancer, leading to a high fatality rate. The role of circular RNAs (circRNAs) in cancer has been increasingly emphasized and studied. However, the function of circ-ZNF124 in NSCLC is largely unclear, and associated regulatory mechanism is not studied. Here, we examined the expression pattern of circ-ZNF124 using quantitative real-time PCR. For functional analysis, cell proliferation, cell apoptosis/cycle and cell invasion were investigated using MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay, flow cytometry assay and transwell assay, respectively. As results, we found that the expression of circ-ZNF124 was elevated in NSCLC tissues and cells. Functionally, circ-ZNF124 downregulation inhibited NSCLC cell proliferation and invasion but induced apoptosis and cycle arrest in vitro, and blocked tumor growth in vivo by animal experiments. Mechanistically, we identified that miR-498 was a target of circ-ZNF124, and miR-498 directly bound to YES proto-oncogene 1 (YES1). Besides, rescue experiments discovered that the cellular effects caused by circ-ZNF124 downregulation could be reversed by miR-498 inhibition or YES1 overexpression. Moreover, we discovered that circ-ZNF124 downregulation inactivated the expression of ß-catenin and c-Myc by mediating the miR-498/YES axis. In conclusion, these findings supported that circ-ZNF124 regulated the expression of YES1 by acting as a sponge of miR-498, thus restraining NSCLC development by inactivating the Wnt/ß-catenin signaling pathway, which provided a novel strategy to treat NSCLC.

TUFT1 promotes metastasis and chemoresistance in triple negative breast cancer through the TUFT1/Rab5/Rac1 pathway.

BACKGROUND: Triple negative breast cancer (TNBC) is a breast cancer (BC) subtype that is characterized by its strong invasion and a high risk of metastasis. However, the specific mechanisms underlying these phenotypes are unclear. TUFT1 plays an important role in BC and impacts the proliferation and survival of BC cells. Recent studies have shown that TUFT1 mediates intracellular lysosome localization and vesicle transport by regulating Rab GTPase, but the relevance of this activity in TNBC is unknown. Therefore, our aim was to systematically study the role of TUFT1 in the metastasis and chemoresistance of TNBC. METHODS: We measured TUFT1, Rab5-GTP, and Rac1-GTP expression levels in samples of human TNBC by immunohistochemistry (IHC) and conducted univariate and multivariate analyses. shRNA-mediated knockdown and overexpression, combined with transwell assays, co-immunoprecipitation, a nude mouse xenograft tumor model, and GTP activity assays were used for further mechanistic studies. RESULTS: TUFT1 expression was positively correlated with Rab5-GTP and Rac1-GTP in the TNBC samples, and co-expression of TUFT1 and Rab5-GTP predicted poor prognosis in TNBC patients who were treated with chemotherapy. Mechanism studies showed that TUFT1 could activate Rab5 by binding to p85α, leading to activation of Rac1 through recruitment of Tiam1, and concurrent down-regulation of the NF-κB pathway and proapoptotic factors, ultimately promoting metastasis and chemoresistance in TNBC cells. CONCLUSIONS: Our findings suggest that the TUFT1/Rab5/Rac1 pathway may be a potential target for the effective treatment of TNBC.

Upregulation of Fibroblast Growth Factor 19 Is Associated with the Initiation of Colorectal Adenoma.

Fibroblast growth factor 19 (FGF19) promotes tumor growth in various types of cancer, but its function has not been investigated in the context of colorectal adenoma. Here, we report that FGF19 expression was greater in colorectal adenoma than in normal tissues, as measured by an enzyme-linked immunosorbent assay, quantitative reverse-transcription PCR and immunohistochemistry. FGF19 expression was also elevated in a subset of human colon cancer cell lines. Moreover, FGF receptor 4 (FGFR4), the cognate receptor for FGF19, was upregulated in colorectal adenoma tissues. Lipid levels and body mass index values strongly correlated with FGF19 and FGFR4 levels in patients with colon adenomas. These observations indicate that the FGF19/FGFR4 pathway may be involved in the development of neoplasia, and that FGF19 may be a valuable diagnostic marker for the identification of patients with colorectal adenomas.

Clinical characteristics of hepatic Arterioportal shunts associated with hepatocellular carcinoma.

BACKGROUND: Hepatic arterioportal shunt (A-P shunt) is defined as the direct blood flow established between hepatic artery and portal venous system; it is frequently observed in patients with hepatocellular carcinoma (HCC). Clinically, it is important to diagnose HCC associated A-P shunts, as it may impact the treatment strategy of the patients. In the present study, we described the imaging findings of the HCC associated A-P shunts and discussed the treatments strategy of such patients. From the findings, we also discussed the potential cause of A-P shunts. METHODS: Clinical data of HCC patients (n = 560), admitted to the hospital between April 2012 to April 2014, were reviewed. Hepatic angiography was used to examine the presence of A-P shunts. Of the 137 patients with A-P shunts, grading of the A-P shunts was performed, and statistical analysis of the different grades of A-P shunts and clinical characteristics was performed. RESULTS: The hepatic angiography confirmed that 99 patients had typical A-P shunts (Grade 1-3), and 38 patients had atypical A-P shunts. Embolization was the main strategy used to treat A-P shunts, in which liquid embolic agents appeared to provide a better treatment outcome. The correlation analysis showed that the grading of portal vein tumor thrombus was significantly associated with the grading of A-P shunt (p = < 0.001, Spearman correlation coefficient was 0.816 ± 0.043). CONCLUSIONS: We characterized A-P shunts and proposed treatment strategy for treating HCC patients with various levels of A-P shunts. The findings supported the hypothesis that the formation of HCC associated A-P shunts was caused by tumor thrombus.

Near-infrared anti-Stokes photoluminescence of PbS QDs embedded in glasses.

Near-infrared photoluminescence properties of PbS QDs embedded in glasses were investigated upon below-bandgap excitation. PbS QDs were precipitated in the glasses upon thermal treatment. Near-infrared anti-Stokes photoluminescence (ASPL) from PbS QDs was observed. Dependence of the ASPL on size and excitation power indicated that ASPL was phonon-assisted one-photon process. These near-infrared anti-Stokes photoluminescence of PbS QDs in glasses have potential applications for light conversion and laser cooling.

Low temperature photoluminescence properties of CsPbBr3 quantum dots embedded in glasses.

The photoluminescence properties of perovskite CsPbBr3 QDs embedded in glasses were investigated at cryogenic temperature in the range of 40-240 K. CsPbBr3 QDs with radii of 3.3 nm, 4.2 nm and 4.8 nm were precipitated in phosphate glasses using conventional thermal treatment. Photoluminescence (PL) integral intensities, bandgap energies and full with at half maximum of the PL bands of CsPbBr3 QDs showed a strong dependence on temperature. An exciton binding energy of ∼40 meV was derived from the temperature-dependent emission intensity. Optical phonon energy involved in the exciton-phonon interaction was found to be ∼56 meV, about three times as that of the single phonon energy. Exciton-phonon coupling strength and the lattice thermal expansion coefficient were strongly dependent on the size of CsPbBr3 QDs, and as a result, inflection temperature of the PL peak energies of CsPbBr3 QDs increased as the size increased.

Robotic versus laparoscopic low anterior resection for rectal cancer: a meta-analysis.

BACKGROUND: The objective of this meta-analysis was to compare the clinical and oncologic outcomes of robotic low anterior resection (R-LAR) with conventional laparoscopic low anterior resection (L-LAR). METHODS: A search in the MEDLINE, Embase, and Ovid databases was performed for studies published before July 2014 that compared the clinical and oncologic outcomes of R-LAR and L-LAR. The methodological quality of the selected studies was assessed. Depending on statistical heterogeneity, a fixed or random effects model was used for the meta-analysis. The clinical and oncologic outcomes evaluated included operative time, estimated blood loss, length of hospital stay, rate of conversion to open surgery, post-operative complications, circumferential margin status, and number of lymph nodes collected. RESULTS: Eight studies, including 324 R-LAR cases and 268 conventional L-LAR cases, were analyzed. The meta-analysis showed that R-LAR was associated with a shorter hospital stay (mean difference (MD) = -1.03; 95% confidence interval (CI) = -1.78, -0.28; P = 0.007), lower conversion rate (odds ratio (OR) = 0.08; 95% CI = 0.02, 0.31; P = 0.0002), lower rate of circumferential margin involvement (OR = 0.5; 95% CI = 0.25, 1.01; P = 0.05), and lower overall complication rate (MD = 0.65; 95% CI = 0.43, 0.99; P = 0.04) compared with L-LAR. There was no difference in operative time (MD = 28.4; 95% CI = -3.48, 60.27; P = 0.08), the number of lymph nodes removed (MD = -0.63; 95% CI = -0.78, 2.05; P = 0.38), and days to return of bowel function (MD = -0.15; 95% CI = -0.37, 0.06; P = 0.17). CONCLUSIONS: R-LAR was shown to be associated with a shorter hospital stay, lower conversion rate, lower rate of circumferential margin involvement, and lower overall complication rate compared with L-LAR. There were no differences in operative time, the number of lymph nodes removed, and days to return of bowel function.

Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling.

OBJECTIVES: Obesity and diabetes are well-known risk factors for the development of endometrial cancer. A high rate of aerobic glycolysis represents a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. This study aimed to investigate the effect of various concentrations of glucose on cell proliferation in endometrial cancer. METHODS: ECC-1 and Ishikawa cells were treated with low glucose (1mM), normal glucose (5mM) and high glucose (25mM), and cytotoxicity, apoptosis, cell cycle, adhesion/invasion, and changes of AMPK/mTOR/S6 and MAPK pathways were evaluated. RESULTS: Our results revealed that high glucose increased cell growth and clonogenicity in two endometrial cancer cell lines in a dose dependent manner. Low glucose induced the activity of cleaved caspase 3 and caused cell cycle G1 arrest. High glucose increased the ability of adhesion and invasion by decreasing E-cadherin and increasing Snail expression. In addition, high glucose increased glucose uptake and glycolytic activity through modulating the AMPK/mTOR/S6 and MAPK pathways. CONCLUSIONS: Our findings suggest that glucose stimulated cell proliferation through multiple complex signaling pathways. Targeting glucose metabolism may be a promising therapeutic strategy in the treatment of endometrial cancer.

Transcatheter arterial chemoembolization (TACE) for lymph node metastases in patients with hepatocellular carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) with regional lymph node metastases. METHODS: Forty-eight patients with HCC and regional lymph node metastases were enrolled in this study. The patients were allocated into two groups: Group A (28 patients) underwent TACE for both intrahepatic tumors and lymph node metastasis and Group B (20 patients) received TACE for intrahepatic tumors only. RESULTS: The patients were followed-up by contrast enhanced CT scan 6-8 weeks after TACE treatment. In Group A, seven and nine patients achieved complete and partial response for lymph node metastasis, respectively, with 1-year and 2-year overall survival rates of 60.7% and 35.7%, respectively. In contrast, none of the patients in Group B achieved a complete response, whereas four patients achieved a partial response. The 1-year and 2-year survival rates for the patients in Group B were 40% and 0%, respectively. The difference in survival between the two groups was statistically significant (P = 0.001). CONCLUSIONS: TACE is an effective treatment to regional lymph node metastasis in HCC without significant side effects and could provide survival benefits to the patients with advanced HCC.

MiR-27a modulates radiosensitivity of triple-negative breast cancer (TNBC) cells by targeting CDC27.

BACKGROUND: MiR-27a is significantly overexpressed in triple-negative breast cancer (TNBC). However, the exact biological function of MiR-27a in TNBC is not fully understood. In this study, we verified miR-27a expression in TNBC cells and explored how its overexpression modulates radiosensitivity of the cells. MATERIAL/METHODS: qRT-PCR analysis was performed to study miR-27a expression in TNBC lines MDA-MB-435 and MDA-MB-231 and in normal human breast epithelial cell line MCF10A. Dual luciferase assay was performed to verify a putative downstream target of miR-27a, CDC27. CCK-8 assay was used to assess the influence of miR-27a-CDC27 axis on cell proliferation under irradiation (IR) treatment. RESULTS: We confirmed significantly higher miR-27a expression in 2 TNBC cell lines--MDA-MB-435 and MDA-MB-231--than in human breast epithelial cell line MCF10A. miR-27a could modulate proliferation and radiosensitivity of TNBC cells. CDC-27 is a direct target of miR-27a and its downregulation conferred increased radioresistance of the cells. CONCLUSIONS: The miR-27a-CDC27 axis might play an important role in modulating response to radiotherapy in TNBC cells. Testing miR-27a expression might be a useful way to identify a subgroup of patients who will benefit from an IR-based therapeutic approach.

[Silencing HMGB1 expression by lentivirus-mediated small interfering RNA (siRNA) inhibits the proliferation and invasion of colorectal cancer LoVo cells in vitro and in vivo].

OBJECTIVE: To inquire into the influence of silencing HMGB1 expression by small interfering RNA (siRNA) on cell growth, proliferation, invasion and metastasis of colorectal cancer LoVo cells both in vitro and in vivo. METHODS: Lentivirus-mediated HMGB1 siRNA was transfected into LoVo cells to silence the HMGB1 expression. The HMGB1 mRNA and protein expression after siRNA transfection was detected by RT-PCR and Western blot. MTT assay was used to observe the cell proliferation and to draw a growth curve. Cell cycle was measured by flow cytometry. The ability of invasion and speed of cell migration were evaluated by transwell chamber invasion and cell scratch assay. The influence of HMGB1 silencing on the proliferation of LoVo cells in vivo was observed in LoVo tumor-bearing nude mice. RESULTS: Lentivirus-mediated siRNA was successfully transfected into colorectal cancer cell line LoVo. The expression of HMGB1 mRNA and protein in the HMGB1-siRNA group were 0.24±0.04 and 0.21±0.03, respectively. Compared with the HMGB1-siRNA-Neg group (0.82±0.13, 1.15±0.18) and control group (0.93±0.15, 1.21±0.20), the difference was significant (P<0.05). MTT assay showed that the cell proliferation in the HMGB1-siRNA group was significantly inhibited when compared with that in the HMGB1-siRNA-Neg group and control group (P<0.05). Flow cytometry showed that the proliferation index (PI) of HMGB1-siRNA group was 38.27±1.32, significantly lower than 54.66±1.74 in the HMGB1-siRNA-Neg group and 57.43±1.29 in the control group (P<0.05). The transwell assay showed that the number of penetrated cells in the HMGB1-siRNA group was 14.0±3.5, significantly lower than 51.0±6.7 in the HMGB1-siRNA-Neg group and 68.0±5.3 in the control group (P<0.05). Similarly, the scrape wound recovered significantly slower in the HMGB1-siRNA group (83.61±23.21) µm than that in the other two groups (202.86±46.46) µm and (214.58±57.38) µm(P<0.05). The nude mouse xenograft tumor experiment showed that the final tumor volume was (521±34) mm3 in the HMGB1-siRNA group, significantly smaller than that in the HMGB1-siRNA-Neg group of (763±46) mm3 and control group of (802±51) mm3 (P<0.05). CONCLUSIONS: Lentivirus-mediated HMGBl-siRNA can effectively inhibit the HMGB1 expression in colorectal cancer LoVo cells both in vitro and in vivo. HMGB1 gene silencing can slow the growth of colorectal cancer cells, extend the cell proliferation cycle, decrease their invasion and migration, and significantly inhibit the growth of xenograft tumor in nude mice.

Abnormal metabolism in hepatic stellate cells: Pandora's box of MAFLD related hepatocellular carcinoma.

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.

CircVIRMA enhances cell malignant behavior by governing the miR-452-5p/CREBRF pathway in cervical cancer.

Our current study aimed to investigate the role and mechanism of circVIRMA in cervical cancer (CC) progression. CircVIRMA, microRNA-452-5p (miR-452-5p) and CREB3 regulatory factor (CREBRF) mRNA levels were examined in CC via quantitative real-time PCR (qRT-PCR). The protein level of CREBRF in CC was checked by Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, cell cycle, flow cytometry and transwell assays were conducted to estimate the effects of circVIRMA on malignant phenotypes of CC tumors. Western blot was used to measure related marker protein levels. The interaction between miR-452-5p and circVIRMA or CREBRF was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circVIRMA on tumor growth in vivo. Immunohistochemistry (IHC) assay was performed to detect Ki-67 expression in tissues of mice. CircVIRMA and CREBRF levels were upregulated, while miR-452-5p was downregulated in CC tissues and cells. CircVIRMA silencing restrained CC cell proliferation, migration and invasion whereas induced apoptosis in vitro. In addition circVIRMA knockdown markedly attenuated xenograft tumor growth in vivo. circVIRMA was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. circVIRMA regulated CREBRF expression to modulate CC progression via miR-452-5p. MiR-452-5p downregulation reversed the effects of circVIRMA knockdown on CC progression. MiR-452-5p directly targeted CREBRF, and CREBRF overexpression partly restored the impact of miR-452-5p mimics on CC progression. circVIRMA mediated CC progression via regulating miR-452-5p/CREBRF axis, providing a novel therapeutic target for CC treatment.

Large rectangular cross-section tunnel undercrossing urban road by micro pipe jacking and joint assembly structure (MPJ & JAS) method in soft soils.

With the continuous construction of urban traffic roads, more and more new roads are cut off by existing roads to form "dead end roads". There is an urgent need for a trenchless method suitable for urban ultra-shallow overburden to build the undercrossing tunnel. To solve this problem, this paper proposed the micro pipe jacking and joint assembly structure (MPJ & JAS) method, which has the characteristics of shallow burial depth, low cost, short construction time, flexible cross-section setting and high space utilization. The MPJ & JAS method construct a large cross-section tunnel through assembling small cross-section elements, quite different from traditional methods. Therefore, this paper designed a CT-shaped integrated joint, the mechanical performance of which was verified and clarified by tensile test. The bending test and finite element (FE) analysis proved the reliability of MPJ & JAS tunnel structure, and confirmed the structure performances such as the failure models, crack behaviors, load-deflection response and stress-strain distribution. Moreover, the influences of the steel plate thickness, concrete strength and shear connector spacing were determined by the FE analysis. On the basis of test results and reasonable assumptions, a theoretical design method considering the influence of the CT-shaped integrated joint was proposed, which can effectively predict the bending strength of the MPJ & JAS tunnel structure with an error of less than 10%. Finally, in view of the characteristics of the MPJ & JAS method, the suitable micro pipe jacking machine, soil reinforcement measure, hydraulic traction construction technology, high-precision guidance system and concrete construction quality detection method based on the phased array ultrasonic imaging technology were developed, supporting the accurate and efficient construction of the MPJ & JAS tunnel.

Correction: Identification of serum prognostic marker miRNAs and construction of microRNA-mRNA networks of esophageal cancer.

[This corrects the article DOI: 10.1371/journal.pone.0255479.].