Weilin Wang

Aurora B is essential for mitotic progression, yet whether its activity is regulated by tumour metabolism remains unclear. Here we show that Aurora B functions as a sensor of glycolytic activity and is activated through lactate-dependent signalling. Mechanistically, increased lactate production during aerobic glycolysis promotes KAT2A-mediated lactylation of phosphoglycerate kinase 1 (PGK1) at K131. Lactylated PGK1 phosphorylates Aurora B at T232, leading to cell cycle progression. Disruption of this pathway, either by expressing a PGK1 K131R mutant or a PGK1 variant defective in Aurora B binding, leads to mitotic defects and cGAS-STING activation. These effects suppress tumour cell proliferation and inhibit tumour growth in mice. Furthermore, combining a peptide that disrupts the PGK1-Aurora B interaction with anti-PD-1 therapy enhances CD8⁺ T-cell infiltration and produces synergistic anti-tumour effects. Collectively, these findings uncover a critical role of glycolysis in governing tumour cell division.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with chemotherapy response evaluation currently relying on the Response Evaluation Criteria in Solid Tumors (RECIST). However, RECIST inadequately captures the unique biology of PDAC, particularly stromal fibrosis–induced radiographic pseudoprogression. We developed and externally validated a multivariable prognostic prediction model, the chemotherapy Progression Decision (cPD) score, integrating biological markers and imaging metrics to guide therapeutic decision‐making after the first RECIST assessment. This multicenter retrospective study enrolled 616 PDAC patients across three cohorts: the Training Cohort ( n = 155), Validation Cohort 1 ( n = 263), and Validation Cohort 2 ( n = 198). Multivariable Cox regression identified four independent prognostic predictors: neutrophil‐to‐lymphocyte ratio, baseline carbohydrate antigen 19‐9, tumor maximum cross‐sectional rate change ratio, and emergence of new lesions. These were integrated into an integer‐based score (8–13 points) stratifying patients into good prognosis (GP), poor prognosis (PP), and critical prognosis (CP) groups. The cPD model demonstrated robust discrimination and calibration, with significant survival differences across groups in all cohorts. Notably, the cPD score identified a subset of patients (GP and PP groups) for whom continuing the original chemotherapy yielded significantly better survival than switching regimens, even when RECIST classified the disease as progressive.

Early detection of focal liver lesions is critical for patient outcomes, but current imaging techniques have limitations. This study developed MULLET, an AI system using contrast-enhanced CT, and assessed its performance in assisting radiologists with FLL detection and characterization. A retrospective multicenter, multi-reader, multi-case trial was conducted, in which 10 radiologists independently interpreted 375 patients’ clinical images with and without MULLET assistance. This trial was registered on ClinicalTrials.gov (ID: NCT06068413) with the registration name “A Retrospective, Multicenter, Multiple-viewer-multiple-case (MRMC) Clinical Trial to Evaluate the Safety and Efficacy of CT Image-assisted Detection Software for Focal Liver Lesions” in April 2023. Diagnostic performance was compared using area under the receiver operating characteristic curve (AUC) analysis. Without MULLET, the average AUC was 0.8188 (sensitivity: 74.45%, specificity: 87.77%). With MULLET, the average AUC significantly improved to 0.9268 (p < 0.0001), sensitivity increased to 89.95% (p = 0.0003), and specificity rose to 93.57% (p = 0.0063). MULLET also showed improved performance across different FLL sizes and subtypes. Moreover, the average reading time for radiologists was reduced by 21.8% (p < 0.0001). In conclusion, MULLET demonstrated promising performance in significantly improving radiologists’ sensitivity, accuracy, and efficiency in FLL detection and diagnosis.

Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor prognoses and the current first-line standard treatments remain unsatisfactory. Our study aimed to evaluate gemcitabine-based chemotherapy plus PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) for untreated unresectable iCCA. The propensity score matching (PSM) method was utilized to reduce potential confounders. Overall, 392 patients were included from 12 hospitals, with data from January 2016 to December 2024. In the full cohort analysis, the combination of GEMCIS/GEMOX with PD‑1/PD‑L1 inhibitors and TKIs significantly prolonged median OS compared to GEMCIS/GEMOX alone (26.7 vs. 15.3 months; hazard ratio [HR] 0.47, 95% CI: 0.35-0.63, P < 0.001). In the primary analysis, the combination strategy was associated with a median OS of 24.8 months (95% CI: 20.8-28.8), with corresponding HRs of 0.56 (95% CI: 0.38-0.83, P = 0.004) after PSM. Furthermore, in the combination cohort, the incidence of grade 3-4 hematological adverse events was 30%, compared with 27% in the chemotherapy cohort (P = 0.604). Importantly, our treatment strategy increased the rate of conversion surgery to 42% for locally advanced disease, ultimately resulting in improved overall outcomes (HR for OS: 0.17 [95% CI: 0.05-0.61]). Thus, combining gemcitabine-based chemotherapy with PD-1/PD-L1 inhibitors and TKIs may provide a promising treatment option for patients with unresectable iCCA.

Acute liver injury (ALI), driven by diverse insults such as drug toxicity and ischemia‐reperfusion, poses a high mortality risk and lacks targeted therapies. While reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and a coordinated cell death pathway PANoptosis have been implicated, their interplay as a unified pathogenic axis remains elusive. Here, by integrating multi‐omics analyses of clinical databases and patient samples, we systematically identified and validated the ROS/NETs/PANoptosis axis as a central driver of hepatocyte damage across multiple ALI etiologies. To therapeutically target this axis, we engineered a liver‐targeted gallium‐quercetin nanocomposite (Ga@Que) via coordination‐driven self‐assembly. Ga@Que effectively overcomes the poor bioavailability of natural quercetin. In murine models of acetaminophen‐induced and ischemia‐reperfusion liver injury, Ga@Que exhibited significant liver accumulation, potently scavenged ROS, suppressed neutrophil infiltration and NETs formation, and attenuated PANoptosis. Consequently, Ga@Que treatment markedly mitigated liver damage and inflammation, outperforming its individual components. Our study not only delineates a novel pathogenic paradigm in ALI but also introduces Ga@Que as a promising precision nanotherapeutic, offering a synergistic and translatable strategy to disrupt this deleterious cascade.

The association of natural environmental exposure and air pollution with depression incidence among cancer survivors, as well as the potential role of plasma metabolomics, remains unclear. Here, we analyze 21,507 cancer survivors from the UK Biobank over a median follow-up of 12.39 years and find that individuals exposed to higher levels of green space and natural environment (tertile 3 vs. tertile 1) within a 1000-m buffer have 15.8% (95% CI: 4.0%-26.1%) and 18.2% (95% CI: 7.0%-28.1%) lower risks of depression, respectively. The strongest protective association is observed among breast cancer survivors. In contrast, higher exposures to nitrogen dioxide and nitrogen oxides are associated with an increased risk of depression. Meanwhile, plasma metabolic signatures associated with green space and natural environment may partially mediate these associations. These findings highlight that residential green space, natural environment, and lower air pollution levels may reduce depression risk among cancer survivors, possibly via metabolic pathways.

Background: Liver transplantation (LT) is a life‐saving treatment for pediatric patients suffering end‐stage liver disease, with the potential to yield positive long‐term outcomes. Recently, remarkable progress has been achieved in mainland China. The purpose of this research is to describe the status in our center. Method: 116 recipients from July 2019 to July 2023 were included in our study. The characteristics of recipients and donors, preoperative assessments, intraoperative details and posttransplant complications were described. The Kaplan–Meier method was applied to analyze the overall survival curves and was examined with the log‐rank test. Result: A total of 116 pediatric LTs were performed, including 57 (49.1%) living donor liver transplantation (LDLT), 57 (49.1%) split liver transplantation (SLT) and 2 (1.8%) whole liver transplantation (WLT). The 1‐ and 3‐year overall survival rates were 93.1% and 92.2%. The survival of DDLT was comparable to that of LDLT in our center (89.4% vs. 96.3% for 3‐year survival rate). After LT, 7 (6.03%) vascular complications and 3 (2.59%) biliary complications were observed. The primary causes of mortality were drug‐resistant bacteria infection and post‐transplant lymphoproliferative disorder (PTLD). Conclusion: Pediatric LT has achieved tremendous progress in mainland China. The survival rate of our center was comparable to the published results worldwide. The survival rate of SLT from DBD donors was comparable to LDLT. Further research on the postoperative management and attempts of ISW will be required to improve survival.

The global landscape of liver cirrhosis has undergone a significant transformation with the widespread implementation of viral vaccines, and metabolic dysfunction‐associated steatotic liver disease (MASLD) cirrhosis has emerged as a predominant etiology. Given the differences in the pathogenic mechanisms between viral and MASLD cirrhosis, conventional diagnostic and therapeutic strategies for viral cirrhosis have demonstrated limited applicability in MASLD cirrhosis. The pathogenesis of MASLD cirrhosis involves multifaceted interactions between metabolic dysregulation, inflammatory responses, immune dysregulation, and gut–liver axis disruption, presenting substantial challenges in clinical management. Although liver biopsy remains the gold standard for diagnosis, complications, including hemorrhage, infection, pain, and pneumothorax, lead to suboptimal patient compliance, thereby prompting the development of various noninvasive diagnostic tools. Current therapeutic approaches primarily target key pathological mechanisms through metabolic regulation of glucose and lipid homeostasis, inflammation control, and microbial balance restoration. This review summarized the epidemiological transition from viral to MASLD cirrhosis and aimed to provide a conceptual framework for optimizing diagnostic and therapeutic strategies in the MASLD era.

First reported post-transplant lymphoproliferative disorder after combined heart-liver transplantation