To address the constrains imposed by insufficient hydrogen peroxide (H2O2) and high glutathione (GSH) expression in tumor cells on the efficacy of chemodynamic therapy (CDT), zeolitic imidazolate framework-8 (ZIF-8) loaded with disulfiram (DSF) and 3-amino-1,2,4-triazole (3-AT) was synthesized via a one-pot approach. Subsequently, hyaluronic acid (HA)-modified cupric peroxide (CuO2) was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH (3-AT/DSF@ZIF-8@CuO2-HA). This nanoplatform disrupts the intratumoral H2O2 homeostasis, depletes GSH, and synchronously delivers DSF and Cu2+ via cascade catalysis, thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy. The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility. Its particle size and Zeta potential were 196.5 nm and −19.5 mV, respectively. It possessed a microporous structure with a specific surface area of 81.8600 m2/g, and demonstrated efficient loading capacity for DSF and 3-AT, achieving drug loading efficiencies of 5.91% and 45.07%, respectively. Moreover, ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions. In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration- and incubation time-dependent manner. Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells. Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells. DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species (ROS) generation, thereby enhancing CDT efficacy. Live/dead staining experiments showed that ADZCH efficiently induced apoptosis, with the proportion of dead cells reaching 94.74%, demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.

Objective:To establish a risk prediction model based on least absolute shrinkage and selection operator (LASSO) regression for procalcitonin (PCT), milk fat globule-epidermal growth factor 8 (MFG-E8) and CXC chemokine ligand 9 (CXCL9) in elderly patients with liver cancer after transcatheter arterial chemoembolization (TACE) .Methods:A total of 150 elderly patients with liver cancer who underwent TACE treatment in Shishi City Hospital, Fujian Province and 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force from August 2020 to August 2023 were selected as the study subjects. Patients with infection after TACE were included in the infected group and those without infection were included in the non-infected group according to whether the patients had infection during the postoperative hospitalization. The baseline data of patients were collected and compared. LASSO regression was used to screen the factors that may affect the infection after TACE in elderly patients with liver cancer and binary logistic regression analysis was performed. According to the results of regression analysis, a nomogram model was constructed based on the regression analysis results and the nomogram was internally validated using Bootstrap and receiver operator characteristic (ROC) curves.Results:There were 18 cases of infection in 150 elderly patients with liver cancer after TACE, with an incidence of 12.00%. There were statistically significant differences in focal rupture and bleeding ( χ2=5.92, P=0.015), ascites ( χ2=6.70, P=0.010), skin or mucosal damage ( χ2=6.67, P=0.010) between the infected group ( n=18) and the non-infected group ( n=132). The levels of serum PCT [ (1.17±0.32 ) μg/L vs. (0.91±0.14) μg/L], MFG-E8 [ (194.29±45.85) pg/ml vs. (158.76±28.63) pg/ml] and CXCL9 [ (948.49±52.38) pg/ml vs. (886.05±50.07) pg/ml] were higher than those in the non-infected group, with statistically significant differences ( t=4.13, P<0.001; t=4.55, P<0.001; t=4.94, P<0.001). Four factors related to infection after TACE intervention in patients with liver cancer were finally selected by LASSO regression model, skin or mucosal damage, PCT, MFG-E8, CXCL9 levels. Binary logistic regression analysis showed that skin or mucosal damage ( OR=13.48, 95% CI: 1.29-140.47, P=0.030), high levels of serum PCT ( OR=1.13, 95% CI: 1.05-1.22, P=0.001), MFG-E8 ( OR=1.04, 95% CI: 1.01-1.07, P=0.003), CXCL9 ( OR=1.05, 95% CI: 1.02-1.08, P=0.001) were risk factors for infection after TACE in elderly patients with liver cancer. Based on skin or mucosa damage, PCT, MFG-E8 and CXCL9, a nomogram prediction model for postoperative infection in elderly patients with liver cancer after TACE intervention was established. Calibration curve showed that the C-index of postoperative infection predicted by the nomogram model in elderly patients with liver cancer after TACE intervention was 0.939, indicating the model had good discrimination. ROC curve analysis showed that the area under the curve (AUC) predicted by the nomogram model for infection after TACE intervention in elderly patients with liver cancer was 0.960 (95% CI: 0.926-0.995, P<0.001), which had certain predictive value. The specificity, sensitivity and Youden index were 0.864, 0.944 and 0.808, respectively. Conclusions:Skin or mucosal damage, high levels of serum PCT, CXCL9 and MFG-E8 are closely related to postoperative infection in elderly patients with liver cancer after TACE, and the prediction model constructed based on this has better predictive performance for postoperative infection.

Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Objective:To explore the spatial correlation between gray matter volume (GMV) changes and neurotransmitter receptors/transporters in patients with first-episode schizophrenia (FES) .Methods:Fifty-four FES patients(FES group) and fifty-nine healthy controls (HC group) were selected from June 2014 to May 2020 in the Psychiatry Department of Renmin Hospital of Wuhan University. Structural magnetic resonance imaging (sMRI) was conducted on all subjects. Differences of GMV were compared across 400 cortical regions and 32 subcortical regions. Based on the positron emission tomography(PET) data from Neuromaps, which provides the density of 19 different neurotransmitter receptors and transporters, Spearman correlation analysis was performed to evaluate the spatial correlation between GMV changes and neurotransmitter systems.Results:Compared to the HC group, FES group exhibited significant GMV reductions in widespread cortical (90/400) and subcortical (6/32) regions (all FDR-corrected P<0.05). The effect size of GMV reduction (Cohen’s d) showed significant positive correlations with the density of 5-hydroxytryptamine 1a(5HT1a) ( r=0.400, Pspin=0.002), γ-aminobutyric acid type A receptor(GABA A)( r=0.307, Pspin=0.002), and metabotropic glutamate receptor 5(mGluR5) ( r=0.275, Pspin=0.020) receptors (all FDR-corrected P<0.05). Conclusion:GMV reductions in a wide range of brain regions existed in patients with FES. There are significant correlations between 5HT1a, GABA A and mGluR5 receptors and gray matter reduction in patients with FES. The disorder of these neurotransmitter receptors may be the potential neurobiological mechanism of gray matter structural abnormalities in the early stage of schizophrenia.

Objective To compare the radiotherapy treatment accuracy between 4D-CT and DIBH follow-ing liver SBRT,and to illustrate the relevant factors.Methods A retrospective analysis was conducted on the clinical data of 28 liver cancer patients who underwent SBRT from November 2020 to July 2024,all of whom exhib-ited and localizedmorphological changes on magnetic resonance imaging(MRI).Among them,8 patients used DIBH,and 17 patients used 4D-CT.The areas of localized MRI-morphologic alterations(MMA)were delineated on post-therapeutic MRI.Different isodose structures were generated on the planning CT,and after performing de-formation registration based on the liver's region of interest(ROI),the most suitable isodose structure and MMA contours were compared to obtain quantitative accuracy indices.Correlations between factors such as GTV,PTV,liver volume,and volume changes,and the accuracy indices were analyzed.Results The DSC accuracy for the DIBH group was(0.66±0.17),range 0.32～0.90,while the DSC accuracy for the 4D CT group was(0.69±0.10),range 0.49～0.80.T-test analysis showed no significant statistical differences in accuracy indices between the DIBH and 4D CT groups(P<0.05).Correlation analysis revealed that,in both groups,distance-based indices(HD,MDA,3D-CoMD)were more strongly correlated with accuracy indices than conformality indices(DSC,CIMI).Conclusion There was no significant difference in treatment accuracy between the DIBH and 4D-CT groups,although the maximum accuracy in the DIBH group was higher than that in the 4D-CT group.This method can serve as an bench-markingtool for evaluating the accuracy of liver SBRT.It is recommended to prioritize the use of conformality indices,DSC and CIMI,when assessing the treatment accuracy of liver cancer SBRT using this approach.