Manli Wu

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation.

= 188), the multivariable model, 2D SWE, and transient elastography showed comparable performance (AUC: 0.91 vs 0.86 vs 0.88, respectively). When inflammatory activity was considered, the multivariable model was highly accurate in patients with low-grade inflammation and normal levels of alanine aminotransferase (AUC: 0.97 and 0.94, respectively). Conclusion The multivariable model and two-dimensional shear-wave elastography are more accurate in predicting liver-related events than are the fibrosis stage and serum markers of liver fibrosis tests. © RSNA, 2020

Perfluorobutanoic acid (PFBA), an emerging alternative to perfluorooctanoic acid (PFOA), has become increasingly prevalent in aquatic ecosystems , yet its ecotoxicological impacts remain poorly understood. This study investigated the aquatic toxicity of PFBA using the freshwater algae Chlorella vulgaris ( C . vulgaris ) as a model organism, employing a 96h pre-exposure assay to determine the median effective concentration followed by acute toxicity experiments analyzing multiple endpoints including growth, photosynthetic parameters, oxidative stress markers, and antioxidant enzyme activities . Computer simulation techniques were utilized to illustrate the underlying molecular mechanisms of PFBA toxicity. The results showed that the 96h-EC 50 value of PFBA was 154.88 mg/L, which is comparable to conventional per- and polyfluoroalkyl substances (PFAS). Acute toxicity experiments revealed a biphasic dose-response relationship to the algal growth with the hormetic effects at the lower concentrations (30.97–92.93 mg/L) but inhibition at the higher levels (123.91–185.86 mg/L) of PFBA. High dosages of PFBA significantly decreased the maximum photosynthetic yield (Fv/Fm) and relative electron transfer rate (rETR), while inducing oxidative stress and inhibiting superoxide dismutase (SOD) and catalase (CAT) activities. Future AlphaFold2 modeling and molecular docking simulations demonstrated the potential binding of PFBA to photosystem II D1 C-terminal processing protease (PSII D1 protein), SOD, and CAT. These findings reveal a complex toxicity mechanism of PFBA on C . vulgaris involving photosynthetic disruption, oxidative stress, and antioxidant system impairment, contributing to the understanding of short-chain PFAS alternative ecotoxicity in aquatic ecosystems. • The 96h-EC 50 of PFBA on Chlorella vulgaris was determined to be 154.88 mg/L. • High PFBA levels disrupted photosynthesis and induce oxidative stress of algal. • MDA activity was the most sensitive exposed to PFBA among the toxicity endpoints. • AlphaFold2 was used to construct the 3D structure of algal SOD and CAT proteins. • Molecular docking revealed the molecular mechanism of PFBA on C. vulgaris.

An early and accurate prediction of hepatocellular carcinoma (HCC) is beneficial for individualized treatment and follow-up of chronic hepatitis B (CHB) patients. We aimed to establish a prediction model for HCC by radiomics analysis in CHB patients and compare performance with liver stiffness measurement (LSM) and other clinical prognostic scores. Initially, 1215 patients were included and finally 434 CHB patients with 5-year follow-up were enrolled, 96.3% of them underwent liver biopsy. Deep learning radiomics analysis was performed on 2170 two-dimensional shear wave elastography (2D-SWE) and corresponding B-mode ultrasound (US) images. These high-throughput imaging features were also combined with low-dimensional serological clinical data by deep learning radiomics to establish different HCC prediction models and to overcome challenges of an unbalanced sample. The best model which is simple with high accuracy was selected. Prediction performance of the selected model was compared with LSM and other clinical prognostic scores. During 5-year follow-up, 32 (7.4%) of 434 patients developed HCC. The best prediction model was HCC-R, which included 2D-SWE and B-mode US images, sex and age. This model showed a high predictive value with areas under the receiver operating characteristic curve (AUCs) of 0.981, 0.942 and 0.900 in training, validation and testing cohorts for predicting 5-year prognosis of HCC. These predictive values were significantly higher than that of LSM (AUC: 0.676~0.784, p < 0.05) and better than that of other clinical prognostic scores (AUC: 0.544~0.869). HCC-R radiomics model based on 2D-SWE and B-mode US images, sex and age comprehensively reflected biomechanical and morphological information of patients and can accurately predict HCC occurrence; thus, this model has great value for treatment and follow-up of CHB patients.

PURPOSE: To explore the usefulness of liver stiffness measurements (LSMs) by sound touch elastography (STE) and sound touch quantification (STQ) in chronic hepatitis B (CHB) patients for staging fibrosis. METHODS: This prospective multicenter study recruited normal volunteers and CHB patients between May 2018 and October 2019. The volunteers underwent LSM by STE and supersonic shear imaging (SSI) or by STQ and acoustic radiation force impulse imaging (ARFI). CHB patients underwent liver biopsy and LSM by both STE/STQ. The areas under the receiver operating characteristic curves (AUCs) for staging fibrosis were calculated. RESULTS: Overall, 97 volunteers and 524 CHB patients were finally eligible for the study. The successful STE and STQ measurement rates were both 100 % in volunteers and 99.4 % in CHB patients. The intraclass correlation coefficients (ICCs) for the intra-observer stability of STE and STQ (0.94; 0.90) were similar to those of SSI and ARFI (0.95; 0.87), respectively. STE and STQ showed better accuracy than the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) (AUC: 0.87 vs 0.86 vs 0.73 vs 0.77) in staging cirrhosis. However, both STE and STQ were not superior to APRI and FIB-4 in staging significant fibrosis (AUC: 0.76 vs 0.73 vs 0.70 vs 0.71, all P-values > 0.05). CONCLUSION: STE and STQ are convenient techniques with a reliable LSM value. They have a similar diagnostic performance and are superior to serum biomarkers in staging cirrhosis in CHB patients.