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Highlights By simultaneously incorporating the magnetic filler-modified boron nitride nanosheets (M@BNNS) and the non-magnetic filler U-BNNS into the polymer matrix, a three-dimensional heat conduction pathway composites are obtained under a horizontal magnetic field. Owing to the microstructural design of the 3D-bridging architecture, with the addition of only 5 wt% U-BNNS, the λ ⊥ of composites achieved 2.88 W m −1  K −1 , representing a remarkable increase of 194.2% compared to single-oriented composites. The 3D-bridging architecture composite also demonstrates excellent flame retardancy, attributed to the synergistic mechanisms of condensed and gas phases, effectively mitigating the risks of thermal runaway in electronic devices. The microstructure design for thermal conduction pathways in polymeric electrical encapsulation materials is essential to meet the stringent requirements for efficient thermal management and thermal runaway safety in modern electronic devices. Hence, a composite with three-dimensional network (Ho/U-BNNS/WPU) is developed by simultaneously incorporating magnetically modified boron nitride nanosheets (M@BNNS) and non-magnetic organo-grafted BNNS (U-BNNS) into waterborne polyurethane (WPU) to synchronous molding under a horizontal magnetic field. The results indicate that the continuous in-plane pathways formed by M@BNNS aligned along the magnetic field direction, combined with the bridging structure established by U-BNNS, enable Ho/U-BNNS/WPU to exhibit exceptional in-plane ( λ // ) and through-plane thermal conductivities ( λ ⊥ ). In particular, with the addition of 30 wt% M@BNNS and 5 wt% U-BNNS, the λ // and λ ⊥ of composites reach 11.47 and 2.88 W m −1  K −1 , respectively, which representing a 194.2% improvement in λ ⊥ compared to the composites with a single orientation of M@BNNS. Meanwhile, Ho/U-BNNS/WPU exhibits distinguished thermal management capabilities as thermal interface materials for LED and chips. The composites also demonstrate excellent flame retardancy, with a peak heat release and total heat release reduced by 58.9% and 36.9%, respectively, compared to WPU. Thus, this work offers new insights into the thermally conductive structural design and efficient flame-retardant systems of polymer composites, presenting broad application potential in electronic packaging fields.

HighlightsBy simultaneously incorporating the magnetic filler-modified boron nitride nanosheets (M@BNNS) and the non-magnetic filler U-BNNS into the polymer matrix, a three-dimensional heat conduction pathway composites are obtained under a horizontal magnetic field.Owing to the microstructural design of the 3D-bridging architecture, with the addition of only 5 wt% U-BNNS, the λ⊥ of composites achieved 2.88 W m−1 K−1, representing a remarkable increase of 194.2% compared to single-oriented composites.The 3D-bridging architecture composite also demonstrates excellent flame retardancy, attributed to the synergistic mechanisms of condensed and gas phases, effectively mitigating the risks of thermal runaway in electronic devices.The microstructure design for thermal conduction pathways in polymeric electrical encapsulation materials is essential to meet the stringent requirements for efficient thermal management and thermal runaway safety in modern electronic devices. Hence, a composite with three-dimensional network (Ho/U-BNNS/WPU) is developed by simultaneously incorporating magnetically modified boron nitride nanosheets (M@BNNS) and non-magnetic organo-grafted BNNS (U-BNNS) into waterborne polyurethane (WPU) to synchronous molding under a horizontal magnetic field. The results indicate that the continuous in-plane pathways formed by M@BNNS aligned along the magnetic field direction, combined with the bridging structure established by U-BNNS, enable Ho/U-BNNS/WPU to exhibit exceptional in-plane (λ//) and through-plane thermal conductivities (λ⊥). In particular, with the addition of 30 wt% M@BNNS and 5 wt% U-BNNS, the λ// and λ⊥ of composites reach 11.47 and 2.88 W m−1 K−1, respectively, which representing a 194.2% improvement in λ⊥ compared to the composites with a single orientation of M@BNNS. Meanwhile, Ho/U-BNNS/WPU exhibits distinguished thermal management capabilities as thermal interface materials for LED and chips. The composites also demonstrate excellent flame retardancy, with a peak heat release and total heat release reduced by 58.9% and 36.9%, respectively, compared to WPU. Thus, this work offers new insights into the thermally conductive structural design and efficient flame-retardant systems of polymer composites, presenting broad application potential in electronic packaging fields.

Background Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been demonstrated to promote tumor progression, while TAM-derived molecules involved in HCC metastasis warrant further investigation. Methods THP-1 was treated with IL-4 (Interleukin-4) and IL-13 (Interleukin-13) for M2 polarized macrophages. Exosomes derived from M2 macrophages were characterized. Then, HCC cells or human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 macrophages or treated with M2 macrophage-secreted exosomes. Next, Transwell®, Scratch assay, tube formation, and endothelial permeability assays were performed. Moreover, RT-PCR, western blotting, immunofluorescence, and ELISA were used to assess mRNA and protein expression levels. Finally, the miRNA expression profiles of exosomes derived from M2 and M0 macrophages were analyzed. Results M2 macrophage infiltration was correlated with metastasis and a poor prognosis in HCC patients. M2-derived exosomes were absorbed by HCC and HUVEC cells and promoted the epithelial-mesenchymal transition (EMT), vascular permeability, and angiogenesis. Notably, MiR-23a-3p levels were significantly higher in M2-derived exosomes and hnRNPA1 mediated miR-23a-3p packaging into exosomes. Phosphatase and tensin homolog (PTEN) and tight junction protein 1 (TJP1) were the targets of miR-23a-3p, as confirmed by luciferase reporter assays. Lastly, HCC cells co-cultured with M2-derived exosomes secreted more GM-CSF, VEGF, G-CSF, MCP-1, and IL-4, which in turn further recruited M2 macrophages. Conclusions Our findings suggest that M2 macrophage-derived miR-23a-3p enhances HCC metastasis by promoting EMT and angiogenesis, as well as increasing vascular permeability. 7rQrRcgVqRWt5q73M2SSUa Video Abstract

Interleukin-26 (IL-26) is one of the cytokines secreted by Th17 cells whose role in human tumors remains unknown. Here, we investigated the expression and potential role of IL-26 in human gastric cancer (GC). The expression of IL-26 and related molecules such as IL-20R1, STAT1 and STAT3 was examined by real-time PCR and immunohistochemisty. The effects of IL-26 on cell proliferation and cisplatin-induced apoptosis were analyzed by BrdU cooperation assay and PI-Annexin V co-staining, respectively. Lentiviral mediated siRNA was used to explore its mechanism of action, and IL-26 related signaling was analyzed by western blotting. Human GC tissues showed increased levels of IL-26 and its related molecules and activation of STAT3 signaling, whereas STAT1 activation did not differ significantly between GC and normal gastric tissues. Moreover, IL-26 was primarily produced by Th17 and NK cells. IL-26 promoted the proliferation and survival of MKN45 and SGC-7901 gastric cancer cells in a dose-dependent manner. Furthermore, IL-20R2 and IL-10R1, which are two essential receptors for IL-26 signaling, were expressed in both cell lines. IL-26 activated STAT1 and STAT3 signaling; however, the upregulation of the expression of Bcl-2, Bcl-xl and c-myc indicated that the effect of IL-26 is mediated by STAT3 activation. Knockdown of STAT1 and STAT3 expression suggested that the proliferative and anti-apoptotic effects of IL-26 are mediated by the modulation of STAT1/STAT3 activation. In summary, elevated levels of IL-26 in human GC promote proliferation and survival by modulating STAT1/STAT3 signaling.

Aberrant activation of the WNT/β-catenin signaling pathway is implicated in various types of cancers. Inhibitors targeting the Wnt signaling pathway are intensively studied in the current cancer research field, the outcomes of which remain to be determined. In this study, we have attempted to discover novel potent WNT/β-catenin pathway inhibitors through tankyrase 1/2 structure-based virtual screening. After screening more than 13.4 million compounds through molecular docking, we experimentally verified one compound, LZZ-02, as the most potent inhibitor out of 11 structurally representative top hits. LiCl-induced HEK293 cells containing TOPFlash reporter showed that LZZ-02 inhibited the transcriptional activity of β-catenin with an IC50 of 10 ± 1.2 μM. Mechanistically, LZZ-02 degrades the expression of β-catenin by stabilizing axin 2, thereby diminishing downstream proteins levels, including c-Myc and cyclin D1. LZZ-02 also inhibits the growth of colonic carcinoma cell harboring constitutively active β-catenin. More importantly, LZZ-02 effectively shrinks tumor xenograft derived from colonic cell lines. Our study successfully identified a novel tankyrase 1/2 inhibitor and shed light on a novel strategy for developing inhibitors targeting the WNT/β-catenin signaling axis.

Background/Aims: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has the third highest mortality rate among all cancers. MicroRNAs are a class of endogenous, single-stranded short noncoding RNAs. The purpose of this study was to study the role of microRNA-873 in HCC. Methods: The expression of miRNA-873 and tumor suppressor in lung cancer 1 (TSLC1) in HCC tissues and cell lines was detected by real-time quantitative RT-PCR (RT-qPCR) or western blot. A CCK-8 assay was used to examine cell proliferation; flow cytometry was used to assess the cell cycle; the Transwell migration assay was used to test for metastasis. Luciferase assays were performed to assess whether TSLC1 was a novel target of miRNA-873. Results: We showed that miRNA-873 was upregulated in HCC tissues and cell lines compared with the normal control. Knockdown of miRNA-873 inhibited the growth and metastasis of HepG2 and accelerated G1 phase arrest, while overexpression of miRNA-873 had the opposite effect. The dual-luciferase reporter assays revealed that TSLC1 was a novel target of miRNA-873. Further study showed that TSLC1 was decreased in HCC tissues and cell lines. There was a negative correlation between the expression levels of TSLC1 and miRNA-873. The effect of miRNA-873 overexpression was neutralized by TSLC1. We also found that miRNA-873 activated the PI3K/AKT/mTOR signaling pathway and promoted HCC. Conclusions: Our data demonstrated that miRNA-873 promoted HCC progression by targeting TSLC1 and provided a new target for the therapy of HCC.

Cholangiocarcinoma (CC) is an intractable cancer, arising from biliary epithelial cells, which has a poor prognosis and is increasing in incidence. Early diagnosis of CC is essential as surgical resection remains the only effective therapy. The purpose of this study was to identify improved biomarkers to facilitate early diagnosis and prognostication in CC. A comparative expression profile of human bile samples from patients with cholangitis and CC was constructed using a classic 2D/MS/MS strategy and the expression of selected proteins was confirmed by Western blotting. Immunohistochemistry was performed to determine the expression levels of selected candidate biomarkers in CC and matched normal tissues. Finally, spermatogenesis associated 20 (SSP411; also named SPATA20) was quantified in serum samples using an ELISA. We identified 97 differentially expressed protein spots, corresponding to 49 different genes, of which 38 were upregulated in bile from CC patients. Western blotting confirmed that phosphoglycerate mutase 1 (brain) (PGAM-1), protein disulfide isomerase family A, member 3 (PDIA3), heat shock 60 kDa protein 1 (chaperonin) (HSPD1) and SSP411 were significantly upregulated in individual bile samples from CC patients. Immunohistochemistry demonstrated these proteins were also overexpressed in CC, relative to normal tissues. SSP411 displayed value as a potential serum diagnostic biomarker for CC, with a sensitivity of 90.0% and specificity of 83.3% at a cutoff value of 0.63. We successfully constructed a proteomic profile of CC bile proteins, providing a valuable pool novel of candidate biomarkers. SSP411 has potential as a biomarker for the diagnosis of CC.

Hepatitis B virus infection is one of the most common risk factors leading to the development of intrahepatic cholangiocarcinoma (ICC). This study aims to determine the impact of antiviral treatment (AVT) on the survival outcomes of ICC patients with hepatitis B virus infection. This retrospective study included ICC patients who had HBV infection and underwent hepatectomy from May 2009 to June 2023 at a single medical center. Patients' baseline characteristics were analyzed, and the 14-year follow-up data were investigated using Kaplan-Meier curves and multivariable Cox proportional hazards regression models. The propensity score matching method was performed to balance the baseline differences between the AVT group and the non-AVT group. A total of 229 patients were finally enrolled in the analysis. In the total cohort, 81 patients were classified into the AVT group and 148 patients into the non-AVT group. Kaplan-Meier curves showed that the AVT group exhibited prolonged overall survival and recurrence-free survival compared to the non-AVT group. Cox proportional hazards regression models revealed that AVT was an independent prognostic factor for both overall survival (HR 0.453, 95% CI: 0.280-0.732) and recurrence-free survival (HR 0.659, 95% CI: 0.436-0.997). A 1:1 nearest-neighbor matching algorithm was adopted, and 64 pairs of AVT and non-AVT patients were included in the propensity score matching cohort. Multivariable survival analyses confirmed AVT as a significant predictor for a favorable overall survival (HR 0.277, 95% CI: 0.147-0.519), but no statistical significance for recurrence-free survival was observed between the AVT group and the non-AVT group after propensity score matching. We analyzed the long-term follow-up data for ICC patients with hepatitis B virus infection who underwent hepatectomy. Notably, AVT exhibited a beneficial impact on overall survival for these postoperative ICC patients. However, our findings indicated no statistically significant effect of AVT on recurrence-free survival.

Whilst the benefits of applying an industrialized building system (IBS) have been well recognized globally in the construction industry, the application of IBS is particularly limited in developing countries such as China, and quality is considered one of the key issues affecting its application. This paper identifies a number of the key quality factors which present barriers to the promotion of IBS within the context of the Chinese construction industry. These include key factors such as “Inaccurate design of the connecting points between core components”, “Lack of design norms and standards for IBS components”, “Lack of quality criteria for IBS components”, “Lack of production norms and standards for IBS components”, “Lack of quality management system in production process”, and “Lack of technical guidelines for the construction of IBS projects”. The data used for analysis are derived from a comprehensive practical survey. The validity of the data is examined by using a statistical method. The findings from the study provide valuable references for formulating effective measures to mitigate the negative effects of these quality factors on IBS application in China, thereby ensuring that practice of the IBS system can be further developed within the country.