Hepatocellular carcinoma subtypes based on metabolic pathways reveals potential therapeutic targets.

Introduction: Hepatocellular carcinoma (HCC) is an aggressive malignancy with steadily increasing incidence rates worldwide and poor therapeutic outcomes. Studies show that metabolic reprogramming plays a key role in tumor genesis and progression. In this study, we analyzed the metabolic heterogeneity of epithelial cells in the HCC and screened for potential biomarkers. Methods: The hepatic single-cell RNA sequencing (scRNA-seq) datasets of HCC patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Based on data intergration and measurement of differences among groups, the metabolic epithelial cell subpopulations were identified. The single-cell metabolic pathway was analyzed and the myeloid subpopulations were identified. Cell-cell interaction analysis and single-cell proliferation analysis were performed. The gene expression profiles of HCC patients were obtained from the GSE14520 dataset of GEO and TCGA-LIHC cohort of the UCSC Xena website. Immune analysis was performed. The differentially expressed genes (DEGs) were identified and functionally annotated. Tumor tissues from HCC patients were probed with anti-ALDOA, anti-CD68, anti-CD163, anti-CD4 and anti-FOXP3 antibodies. Results We analyzed the scRNA-seq data from 48 HCC patients and 14 healthy controls. The epithelial cells were significantly enriched in HCC patients compared to the controls (p = 0.011). The epithelial cells from HCC patients were classified into two metabolism-related subpopulations (MRSs) - pertaining to amino acid metabolism (MRS1) and glycolysis (MRS2). Depending on the abundance of these metabolic subpopulations, the HCC patients were also classified into the MRS1 and MRS2 subtype distinct prognoses and immune infiltration. The MRS2 group had significantly worse clinical outcomes and more inflamed tumor microenvironment (TME), as well as a stronger crosstalk between MRS2 cells and immune subpopulations that resulted in an immunosuppressive TME. We also detected high expression levels of ALDOA in the MRS2 cells and HCC tissues. In the clinical cohort, HCC patients with higher ALDOA expression showed greater enrichment of immunosuppressive cells including M2 macrophages and T regulatory cells. Discussion: The glycolytic subtype of HCC cells with high ALDOA expression is associated with an immunosuppressive TME and predicts worse clinical outcomes, providing new insights into the metabolism and prognosis of HCC.

Radical-Bridged Heterometallic Single-Molecule Magnets Incorporating Four Lanthanoceniums.

The syntheses and magnetic properties of organometallic heterometallic compounds [K(THF)6 ]{CoI [(µ3 -HAN)RE2 Cp*4 ]2 } (1-RE) and [K(Crypt)]2 {CoI [(µ3 -HAN)RE2 Cp*4 ]2 } (2-RE) containing hexaazatrinaphthylene radicals (HAN⋅3- ) and four rare earth (RE) ions are reported. 1-RE shows isolable species with ligand-based mixed valency as revealed by cyclic voltammetry (CV) thus leading to the isolation of 2-RE via one-electron chemical reduction. Strong electronic communication in mixed-valency supports stronger overall ferromagnetic behaviors in 2-RE than 1-RE containing Gd and Dy ions. Ac magnetic susceptibility data reveal 1-Dy and 2-Dy both exhibit slow magnetic relaxation. Importantly, larger coercive field was observed in the hysteresis of 2-Dy at 2.0 K, indicating the enhanced SMM behavior compared with 1-Dy. Ligand-based mixed-valency strategy has been used for the first time to improve the magnetic coupling in lanthanide (Ln) SMMs, thus opening up new ways to construct strongly coupled Ln-SMMs.

Artificial Intelligence Algorithm in Classification and Recognition of Primary Hepatic Carcinoma Images under Magnetic Resonance Imaging.

This study aimed to discuss the application value of the bias field correction algorithm in magnetic resonance imaging (MRI) images of patients with primary hepatic carcinoma (PHC). In total, 52 patients with PHC were selected as the experimental group and divided into three subgroups: mild (15 cases), moderate (19 cases), and severe (18 cases) according to pathological grading. Another 52 patients with hepatic nodules in the same period were included in the control group. All the patients underwent dynamic contrast-enhanced (DCE) MRI examination, and the image qualities of MRI before and after bias field correction were compared. The DCE-MRI perfusion parameters were measured, including the transport constant Ktrans, reverse rate constant Kep, extravascular extracellular volume fraction (Ve), plasma volume (Vp), microvascular density (MVD), hepatic artery perfusion index (HPI), mean transit time of contrast agent (MTT), time to peak (TTP), blood volume (BV), hepatic arterial perfusion (HAP), full perfusion (FP), and portal venous perfusion (PVP). It was found that the sensitivity (93.63%), specificity (71.62%), positive predictive value (95.63%), negative predictive value (71.62%), and accuracy (90.01%) of MRI examination processed by the bias field correction algorithm were all significantly greater than those before processing (P < 0.05). The Ktrans, Kep, Ve, Vp, and MVD of patients in the experimental group were significantly larger than those of the control group, and severe group> moderate group> mild group (P < 0.05). HPI, MTT, TTP, BV, and HAP of patients in the experimental group were also significantly greater than those of the control group, which was shown as severe group > moderate group > mild group (P < 0.05). FP and PVP of the experimental group were significantly lower than those of the control group, and severe group < moderate group < mild group (P < 0.05). It was suggested that in MRI images of patients with PHC, the bias field correction algorithm could significantly improve the diagnosis rate. Each perfusion parameter was related to the pathological grading, which could be used to evaluate the prognosis of patients.

Novel Citral-thiazolyl Hydrazine Derivatives as Promising Antifungal Agents against Phytopathogenic Fungi.

To develop new antifungal agents against phytopathogenic fungi, a series of citral-thiazolyl hydrazine derivatives were designed, synthesized, and characterized by FT-IR, 1H NMR, 13C NMR, and HRMS. Antifungal activity results showed that most synthetic compounds exhibited broad-spectrum antifungal activities against six phytopathogenic fungi in vitro. Notably, compounds b and c15 exhibited remarkable antifungal activity against Colletotrichum gloeosprioides, Rhizoctonia solani, Phytophthora nicotianae var. nicotianae, Diplodia pinea, Colletotrichum acutatum, and Fusarium oxysporum f. sp. niveum, which were all superior to the positive control tricyclazole. Structure-activity relationship (SAR) studies demonstrated that introducing electron-withdrawing groups such as F on the benzene ring exhibited outstanding antifungal activities against all the tested fungi. Furthermore, compound b could effectively control rice sheath blight and showed higher curative activities against R. solani than validamycin·bacillus in vivo. In addition, the in vitro cytotoxicity results indicated that compound b possessed moderate cytotoxicity activity, and all citral-thiazolyl hydrazine derivatives exhibited lower or no cytotoxicity to the LO2 and HEK293 cell lines. In addition, the acute oral toxicity test showed that compound b had moderate toxicity (level II) with an LD50 value of 310 mg/kg bw (95% confidence limit: 175-550 mg/kg bw). Finally, a preliminary action mechanism study showed that causing obvious malformation of mycelium and increasing cell membrane permeability are two of the potential mechanisms by which compound b exerts antifungal activity. The present work indicates that some of these derivatives may serve as novel potential fungicides, and compound b is expected to be the leading structure for the development of new antifungal agents.