Cong Wang’s research while affiliated with Xi’an Jiaotong-Liverpool University and other places

In order to further understand the formation and development process of cathode spot crater on copper-chromium (CuCr) nanocrystalline alloy electrode in vacuum arc, a new simulation method considering the distribution of different components is proposed. And a two-dimensional axisymmetric model is established to study the effects of different components on the formation and development of cathode spot crater. The differences in physical properties are considered in the model, and the interface between the Cu component and the Cr component is effectively tracked. The distribution, flow, and heat transfer of the Cu and Cr components are simulated. To directly demonstrate the advantages of the method, the simulation results are compared with those adopting the method that linearly combines the physical property parameters according to the weight percentage of components. Simulation result shows that the presence of Cr components has an important influence on the formation and development of cathode spot crater on CuCr nanocrystalline alloy electrode. The effects of different weight percentages of Cr components on the formation and development of cathode spot crater on CuCr nanocrystalline alloys are also studied. The results indicate that with the improvement of Cr component weight percentages, the temperature on the cathode spot crater is increased, and the fluidity of liquid metal is reduced during erosion. Finally, the simulation results have been compared with experimental results of other researchers.

Background Accurate preoperative non-invasive assessment of HER2 expression in breast cancer is crucial for personalized treatment and prognostic stratification. Purpose To evaluate the effectiveness of radiomics models based on multi-parametric magnetic resonance imaging (MRI) in distinguishing HER2 expression status in invasive breast cancer. Material and Methods We conducted a retrospective analysis of baseline MRI scans and clinical data from 400 patients with breast cancer between January 2018 and December 2019. Two-dimensional regions of interest were manually segmented on the maximum tumor images obtained from turbo inversion recovery magnitude (TIRM), dynamic contrast-enhanced magnetic resonance imaging phase 2 (DCE2), dynamic contrast-enhanced magnetic resonance imaging phase 4 (DCE4), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) sequences using ITK-SNAP software. Features were extracted and screened for dimensionality reduction. Logistic regression models were developed to predict HER2 expression status. Results In distinguishing HER2-overexpression from non-HER2-overexpression, the DCE2 model outperformed other single-parameter models, with areas under the curve (AUCs) of 0.91 (training) and 0.88 (test). Combination models with DCE features showed significantly improved performance ( P ≤ 0.001). The multiparameter model achieved the highest AUCs of 0.93 (training) and 0.91 (test). In distinguishing HER2-low from HER2-zero, the TIRM model performed best among single-parameter models, with AUCs of 0.80 (training) and 0.72 (test). The multiparameter model further enhanced prediction, yielding an AUC of 0.83 (test). Conclusion Radiomics models based on multi-parametric MRI features demonstrated strong clinical utility in assessing HER2 expression status in invasive breast cancer, particularly in identifying HER2-overexpression and HER2-low expression subtypes.

BACKGROUND The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has continued to increase annually. Recent studies have indicated that inhibition of metabotropic glutamate receptor 5 (mGluR5) may alleviate hepatic steatosis. However, the precise mechanism warrants further exploration. AIM To investigate the potential mechanism by which mGluR5 attenuates hepatocyte steatosis in vitro and in vivo. METHODS Free fatty acids (FFAs)-stimulated HepG2 cells were treated with the mGluR5 antagonist MPEP and the mGluR5 agonist CHPG. Oil Red O staining and a triglyceride assay kit were used to evaluate lipid content. Western blot analysis was conducted to detect the expression of the autophagy-associated proteins p62 and LC3-II, as well as the expression of the key signaling molecules AMPK and ULK1, in the treated cells. To further elucidate the contributions of autophagy and AMPK, we used chloroquine (CQ) to inhibit autophagy and compound C (CC) to inhibit AMPK activity. In parallel, wild-type mice and mGluR5 knockout (KO) mice fed a normal chow diet or a high-fat diet (HFD) were used to evaluate the effect of mGluR5 inhibition in vivo. RESULTS mGluR5 inhibition by MPEP attenuated hepatocellular steatosis and increased LC3-II and p62 protein expression. The autophagy inhibitor CQ reversed the effects of MPEP. In addition, MPEP promoted AMPK and ULK1 expression in HepG2 cells exposed to FFAs. MPEP treatment led to the nuclear translocation of transcription factor EB, which is known to promote p62 expression. This effect was negated by the AMPK inhibitor CC. mGluR5 KO mice presented reduced body weight, improved glucose tolerance and reduced hyperlipidemia when fed a HFD. Additionally, the livers of HFD-fed mGluR5 KO mice presented increases in LC3-II and p62. CONCLUSION Our results suggest that mGluR5 inhibition promoted autophagy and reduced hepatocyte steatosis through activation of the AMPK signaling pathway. These findings reveal a new functional mechanism of mGluR5 as a target in the treatment of MASLD.

Dysregulation of amino acid metabolism is recognized to have a substantial influence on tumorigenesis and the modulation of tumor microenvironment. However, the role of amino acid metabolism-related genes in diffuse large B-cell lymphoma (DLBCL) remains undefined. Therefore, we aimed to explore the influence of amino acid metabolism-related genes in DLBCL using bioinformatics approaches. Consensus clustering demonstrated that the reprogramming of amino acid metabolism has prognostic value in DLBCL. Subsequently, we developed a risk model using LASSO-Cox regression analysis to accurately predict DLBCL prognosis and identified kynureninase (KYNU) as a potentially valuable biomarker. Analysis of immune infiltration was conducted to examine the correlation between risk scores and immune profiles. Furthermore, RT-qPCR showed that the KYNU mRNA levels were upregulated in OCI-LY1, OCI-LY3, and OCI-LY10 DLBCL cells compared with normal CD19+B lymphocytes. Cell proliferation assays and flow cytometry analysis showed that inhibition of KYNU expression reduced cell proliferation and induced apoptosis of DLBCL cells. Overall, we demonstrated the significant impact of amino acid metabolism on DLBCL. Our findings may help improve the assessment of disease prognosis and provide potential therapeutic strategies for DLBCL.

Although a fraction of functional peptides concealed within long non‐coding RNAs (lncRNAs) is identified, it remains unclear whether lncRNA‐encoded peptides are involved in the malignancy of cervical cancer (CC). Here, a 92‐amino acid peptide is discovered, which is named TUBORF, encoded by lncRNA TUBA3FP and highly expressed in CC tissues. TUBORF inhibits ferroptosis to promote the malignant proliferation of CC cells. Mechanistically, human papillomavirus (HPV) oncogenes E6 and E7 upregulate TUBORF through CREB‐binding protein (CBP)/E1A‐binding protein p300 (p300)‐mediated histone H3 lysine 27 acetylation (H3K27ac) of lncTUBA3FP enhancer. Furthermore, E6 and E7 elevate and recruit acetyltransferase establishment of sister chromatid cohesion N‐acetyltransferase 1 (ESCO1) to bind to and acetylate TUBORF, which facilitates the degradation of immunity‐related GTPase Q (IRGQ) via a ubiquitin‐proteasome pathway, resulting in the inhibition of ferroptosis and promotion of the malignant proliferation of CC cells. Importantly, silencing ESCO1 or TURORF amplifies anticancer effects by paclitaxel both in CC cells and in vivo. These novel findings reveal oncopeptide TUBORF and its acetyltransferase ESCO1 as important regulators of ferroptosis and tumorigenesis during cervical cancer pathogenesis and establish the scientific basis for targeting these molecules for treating CC.

Anlotinib, an anti-angiogenic agent, has demonstrated significant anti-tumor effects in non-small cell lung cancer (NSCLC). However, whether anlotinib exerts its anti-tumor activity in NSCLC through ferroptosis, and its underlying mechanisms, remain unclear. This study revealed that anlotinib effectively inhibited the proliferation of NSCLC cells in a time- and dose-dependent manner. Treatment with anlotinib resulted in increased levels of ferroptosis targets (lipid reactive oxygen species and malondialdehyde) and p53 protein expression, while decreasing glutathione levels and the protein expression of solute carrier family 7 member 11 (xCT) and glutathione peroxidase 4 (GPX4). Notably, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), or the p53 inhibitor, Pifithrin-α (PFT-α), reversed the observed effects on ferroptosis induction in NSCLC cells. Consistently, our in vivo studies showed accelerated tumor growth rates for the anlotinib/Fer-1 group and the anlotinib/PFT-α group compared with administration of anlotinib alone. However, anlotinib-induced ferroptosis was suppressed in p53-deficient cells. Collectively, these findings confirm that anlotinib exerts potent anti-tumor effects both in vitro and in vivo by inducing ferroptosis by modulating the p53/xCT/GPX4 pathway specifically within NSCLC cells.

Pancreatic cancer is characterized by occult onset, low early diagnosis rate, rapid progress, and poor prognosis. Due to the low response rate and low PD-L1 expression in pancreatic cancer, the therapeutic application of PL-L1 inhibitors in pancreatic cancer is greatly limited. In vitro studies showed that the expression of PD-L1 increased in pancreatic cancer cells stimulated by fluorouracil (5-FU). We aim to explore the combining effect of 5-FU and anti-PD-L1 antibody, and to provide a reference for the clinical application of PD-L1 antibody in pancreatic cancer. In the current study, male BALB/c mice were adopted to construct a tumor-bearing model of pancreatic cancer cells. 5-FU and anti-mouse PD-L1 antibodies were combined and administered to evaluate their synergistic effects. The enhancing immune cytotoxicity effect of 5-FU sensitizing the anti-PD-L1 antibody in vivo and in vitro was analyzed by immunohistochemistry (IHC) and western blot assays. Results showed that 5-FU and anti-PD-L1 antibody combination increased the expression of PD-L1 and IFN-γ, and infiltration of CD8+ T lymphocytes in pancreatic xenograft tumor tissues, which was proven by IHC and western analysis. Moreover, the combination with the 5-FU remarkably enhanced the immune cytotoxicity of anti-PD-L1 antibodies in mice. In vitro analysis demonstrates that 5-FU increases the expression of PD-L1 on the surface of pancreatic cancer cell lines via up-regulating NF-κB and AKT pathways. This synergistic effect could be abolished by NF-κB and AKT inhibitors.

In this paper, a three-dimensional cathode spot erosion model is proposed to study the development of cathode spot motion process on the surface of copper cathode. The formation and development process of cathode spots motion without external magnetic field is studied. In this model, energy flux density, pressure, and current value are considered as external parameters. The simulation results compared the cathode spot ablation trajectories and temperature distribution under different motion forms and motion velocities. The results indicated that during the spots expansion process, the flow of liquid metal will form a convex structure on the surface of the cathode and a hollow structure inside the cathode. Comparing different motion types, the annular motion significantly increased the roughness of the cathode surface. With the increase of the speed of spots movement, the interaction between the craters is significantly weakened, which will reduce the temperature and the roughness of the cathode surface. The simulation results are consistent with the experimental results.

Sialylation is a terminal modification of cell glycosylation, including α-2,3-, α-2,6-, and α-2,8-forms, which exert a dominant role in cell recognition and immune regulation. Among them, α-2,6-sialylation and α-2,6-sialyltransferases have shown promising potential in the study of tumor mechanisms and treatment, but their function remains unknown in diffuse large B-cell lymphoma (DLBCL). This study aims to explore the function and underlying mechanism of α-2,6-sialylation in DLBCL. We first detected the expression of α-2,6-sialylation in lymph node tissues from DLBCL patients and reactive hyperplasia cases with informed consent. DLBCL tissues exhibited higher levels of α-2,6-sialylation compared to the control cases. Survival analysis revealed that DLBCL patients with elevated α-2,6-sialylation levels showed poorer clinical outcomes (P=0.0003). Within the sialyltransferase family, elevated expression of the α-2,6-sialyltransferase ST6GALNAC4 was found to be associated with a poor prognosis in DLBCL patients (P<0.05). The above findings prompted us to investigate the biological function of ST6GALNAC4 in DLBCL. Knockdown of ST6GALNAC4 declined cell proliferation and induced cell cycle arrest in the G0/G1 phase. Conversely, overexpression of the gene facilitatedcell proliferation. Moreover, the oncogenic role of ST6GALNAC4 was confirmed in DLBCL xenograft models. Both ST6GALNAC4 deficiency and sialyltransferase inhibitor-treated groups exhibited significantly delayed tumor growth compared to the control group. To explore the underlying mechanism of ST6GALNAC4 in DLBCL tumorigenesis, we performed mass spectrometry to identify interacting proteins of ST6GALNAC4. Since sialic acids are typically found at glycan termini on the cell surface, we primarily focused on cell membrane proteins as potential targets of ST6GALNAC4. Among them, BMPR-1B showed a significant positive correlation with ST6GALNAC4 (P<0.001). The correlation was also validated in DLBCL tissues. BMPR-1B, a member of the TGF-β superfamily, is implicated in tumorigenesis and progression. Co-immunoprecipitation confirmed the interaction between ST6GALNAC4 and BMPR-1B, and ST6GALNAC4 knockdown significantly reduced the protein expression of BMPR-1B in DLBCL cell lines. Notably, knockdown of ST6GALNAC4 led to an enrichment of the SMAD signaling pathway, as indicated by KEGG analysis. Furthermore, in vitro and in vivo experiments verified that inhibition of BMPR-1B could inhibit cell growth. Therefore, BMPR-1B was identified as a downstream target of ST6GALNAC4. We further elucidated the molecular mechanism by which ST6GALNAC4 regulates the expression of BMPR-1B through sialylation. Lectin immunoprecipitation demonstrated that ST6GALNAC4 mediated the sialylation of BMPR-1B. A followed cycloheximide chase experiment was carried out to show that ST6GALNAC4 knockdown decreased the half-life of BMPR-1B protein. We then used site mutations to determine the important modification sites on BMPR-1B. The potential site of BMPR-1B sialylation was predicted by the NetOGlyc web, where Thr24, Thr109, and Ser20 displayed potent potential to be sialylated. We mutated these sites respectively and examined the sialylation level, and found that both Thr109 and Thr24 mutations dramatically reduced the sialylation level of BMPR-1B. Importantly, ST6GALNAC4 significantly enhanced the sialylation levels of wild-type and Thr109-mutant BMPR-1B, but not Thr24-mutant BMPR-1B. This suggested that ST6GALNAC4 specifically mediated sialylation at Thr24. We then confirmed that the Thr24 mutation affected BMPR-1B half-life compared to wild-type BMPR-1B. Furthermore, we validated that ST6GALNAC4 knockdown decreased levels of pSMAD1/5/8, while overexpression of ST6GALNAC4 had the opposite effect. Importantly, overexpression of BMPR-1B could partially reverse the effects of ST6GALNAC4, showing that the oncogenic effects of ST6GALNAC4 were mediated by BMPR-1B. Taken together, these findings suggest that ST6GALNAC4 mediates BMPR-1B sialylation at Thr24, affecting its protein stability and ultimately regulating the SMAD signaling pathway in DLBCL. In conclusion, our results revealed that ST6GALNAC4 induced α-2,6-sialylation of BMPR-1B, which promoted malignant progression of DLBCL. This underscores the potential of ST6GALNAC4 as a novel prognostic biomarker and therapeutic target for DLBCL.