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Background Tumor migration and invasion is a complex and diverse process that involves the epithelial–mesenchymal transition (EMT) of tumor cells and degradation of the extracellular matrix by matrix metalloproteases (MMPs). Mortalin is an important oncogene. It has been reported to play an important role in tumor migration and invasion through various signaling pathways, but the underlying mechanism is not fully understood. Methods Here, we investigated the role of mortalin in the migration of the hepatocellular carcinoma (HCC) cell lines HepG2 and HCCLM3. Results The overexpression of mortalin in HepG2 cells decreased the protein level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and activated the phosphorylation and acetylation of STAT3, thereby up-regulating matrix metalloproteinase 9 (MMP9) and promoting cell migration and invasion. In contrast, in HCCLM3 cells, mortalin knockdown increased the expression of RECK, inhibited the STAT3 pathway and the activity of MMP9, and inhibited cell migration and invasion. Furthermore, we found that salvianolic acid B, a caffeic acid phenethyl ester analog, specifically bound to mortalin and increased the degradation of mortalin proteasomes through ubiquitination, thereby up-regulating RECK, inhibiting STAT3, and finally inhibiting the migration and invasion of HCC cells. Conclusion Our work suggested that mortalin is a potential therapeutic target for hepatocellular carcinoma.

The endothelial to mesenchymal transition (EndMT) plays a major role in cancer metastasis by regulating the complexity of the tumor microenvironment (TME). Here, we investigated whether 27-hydroxycholesterol (27HC) induces EndMT in endothelial cells (ECs). EndMT markers in the human microvascular endothelial cell-1 (HMEC-1) cell line and human umbilical vein endothelial cells (HUVECs) stimulated with 27HC were evaluated with Western blot. Epithelial to mesenchymal transition (EMT) markers in breast cancer (BC) cells cultured in conditioned medium were investigated with quantitative real time polymerase chain reaction (qRT-PCR). The MMP-2 and MMP-9 mRNA expression and activity were detected with qRT-PCR and gelatin zymography assays, respectively. The effect of activated STAT3 on 27HC-induced EndMT was validated by Western blot, immunofluorescence staining, and cell transfection assays. The migration ability of BC cells was evaluated with Transwell assays. We found that 27HC induced EndMT in HMEC-1 and HUVECs, and 27HC-induced EndMT facilitated EMT and BC cell migration. The 27HC-induced EMT of BC cells also promoted EndMT and HUVEC migration. Investigation of the underlying molecular mechanisms revealed that STAT3 knockdown repressed EndMT in HUVECs as well as migration in BC cells induced with 27HC. In addition, C646 and resveratrol, inhibitors of STAT3 acetylation, repressed the expression of Ac-STAT3, p-STAT3, and EndMT markers in HUVECs exposed to 27HC; these HUVECs in turn attenuated the migration ability of BC cells in 27HC-induced EndMT. Cross-talk between 27HC-induced EndMT and EMT was observed in the TME. Moreover, activation of STAT3 signaling was found to be involved in 27HC-induced EndMT.

Enhancer of zeste homolog 2 (EZH2) is frequently overexpressed in breast cancer and plays an important role in maintaining the cell proliferative capacity. However, the mechanisms underlying the transcriptional regulation of EZH2 in estrogen receptor (ER)-positive breast cancer cells remain unclear. The antitumor effects of resveratrol have been reported. However, whether EZH2 was involved in these effects needs further exploration. Here, we showed that EZH2 is required for estrogen-induced cell proliferation in ER-positive breast cancer. Exposure to 17β-estradiol (E2) upregulated EZH2 via ERα signaling, and this effect was blocked by U0126, a MEK inhibiter. Resveratrol inhibited the proliferation and colony formation in ER-positive breast cancer cells and downregulated EZH2 through inhibition of phospho-ERK1/2. These findings indicated that ERK1/2 and ER signaling–mediated EZH2 upregulation is crucial for the proliferation of ER-positive breast cancer cells. The suppression of EZH2 expression by ERK1/2 dephosphorylation is important for the antiproliferative activities of resveratrol against ER-positive breast cancer cells.

Inflammation plays important roles in the initiation and progress of many diseases. Caffeic acid (CaA) is a naturally occurring hydroxycinnamic acid derivative, which shows hypotoxicity and diverse biological functions, including anti-inflammation. The molecular mechanisms involved in the CaA-inhibited inflammatory response are very complex; generally, the down-regulated phosphorylation of such important transcriptional factors, for example, nuclear factor κB (NF-κB) and signal transducers and activators of transcription-3 (STAT-3), plays an important role. Here, we found that in RAW264.7 macrophage cells, CaA blocked lipopolysaccharide (LPS)-stimulated inflammatory response by attenuating the expression of 14-3-3ζ (a phosphorylated protein regulator). Briefly, the increased expression of 14-3-3ζ was involved in the LPS-induced inflammatory response. CaA blocked the LPS-elevated 14-3-3ζ via attenuating the LPS-induced tumor necrosis factor-α (TNF-α) secretion and via enhancing the 14-3-3ζ ubiquitination. These processes inhibited the LPS-induced activation (phosphorylation) of NF-κB and STAT-3, in turn blocked the transcriptional activation of inducible NO synthase ( iNOS ), interleukin-6 ( IL-6 ), and TNF-α , and finally attenuated the productions of nitric oxide (NO), IL-6, and TNF-α. By understanding a novel mechanism whereby CaA inhibited the 14-3-3ζ, our study expanded the understanding of the molecular mechanisms involved in the anti-inflammation potential induced by CaA.

Inflammation plays important roles in the initiation and progress of many diseases. Caffeic acid (CaA) is a naturally occurring hydroxycinnamic acid derivative, which shows hypotoxicity and diverse biological functions, including anti-inflammation. The molecular mechanisms involved in the CaA-inhibited inflammatory response are very complex; generally, the down-regulated phosphorylation of such important transcriptional factors, for example, nuclear factor [kappa]B (NF-[kappa]B) and signal transducers and activators of transcription-3 (STAT-3), plays an important role. Here, we found that in RAW264.7 macrophage cells, CaA blocked lipopolysaccharide (LPS)-stimulated inflammatory response by attenuating the expression of 14-3-3[zeta] (a phosphorylated protein regulator). Briefly, the increased expression of 14-3-3[zeta] was involved in the LPS-induced inflammatory response. CaA blocked the LPS-elevated 14-3-3[zeta] via attenuating the LPS-induced tumor necrosis factor-[alpha] (TNF-[alpha]) secretion and via enhancing the 14-3-3[zeta] ubiquitination. These processes inhibited the LPS-induced activation (phosphorylation) of NF-[kappa]B and STAT-3, in turn blocked the transcriptional activation of inducible NO synthase (iNOS), interleukin-6 (IL-6), and TNF-[alpha], and finally attenuated the productions of nitric oxide (NO), IL-6, and TNF-[alpha]. By understanding a novel mechanism whereby CaA inhibited the 14-3-3[zeta], our study expanded the understanding of the molecular mechanisms involved in the anti-inflammation potential induced by CaA.

Ionospheric scintillation frequently occurs in equatorial, auroral and polar regions, posing a threat to the performance of the global navigation satellite system (GNSS). Thus, the detection of ionospheric scintillation is of great significance in regard to improving GNSS performance, especially when severe ionospheric scintillation occurs. Normal algorithms exhibit insensitivity in strong scintillation detection in that the natural phenomenon of strong scintillation appears only occasionally, and such samples account for a small proportion of the data in datasets relative to those for weak/moderate scintillation events. Aiming at improving the detection accuracy, we proposed a strategy combining an improved eXtreme Gradient Boosting (XGBoost) algorithm by using the synthetic minority, oversampling technique and edited nearest neighbor (SMOTE-ENN) resampling technique for detecting events imbalanced with respect to weak, medium and strong ionospheric scintillation. It outperformed the decision tree and random forest by 12% when using imbalanced training and validation data, for tree depths ranging from 1 to 30. For different degrees of imbalance in the training datasets, the testing accuracy of the improved XGBoost was about 4% to 5% higher than that of the decision tree and random forest. Meanwhile, the testing results for the improved method showed significant increases in evaluation indicators, while the recall value for strong scintillation events was relatively stable, above 90%, and the corresponding F1 scores were over 92%. When testing on datasets with different degrees of imbalance, there was a distinct increase of about 10% to 20% in the recall value and 6% to 11% in the F1 score for strong scintillation events, with the testing accuracy ranging from 90.42% to 96.04%.

Analyzing the magnetization reversal process is crucial for enhancing the magnetic properties of nanocomposite magnets, thereby subsequently increasing the magnetic energy product and advancing the development of next-generation rare earth permanent magnet materials. Here, the open recoil loop is systematically investigated based on micromagnetic simulations and comparing magnetization configurations, which is strongly associated with the asymmetric behavior of weak pinning at the soft/hard magnetic interface. By removing and reapplying field, the irreversible weak pinning sites exhibit asymmetric behavior, leading to the formation of open phenomena in nanocomposites. The open degree of recoil loops obtained from experimental testing was also correlated with the irreversible magnetization, which supports the simulation results. Our findings provide a novel approach for understanding the magnetization reversal mechanism in nanocomposite magnets.

Background Cancer‐associated cardiac cachexia (CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra‐abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied. Results Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin‐mediated Myh6 degradation via MuRF‐1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor‐induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer‐related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration. This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer‐related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration. These findings mechanistically link tumor‐induced cachexia to cardiac dysfunction through contractile protein remodeling.