A novel stratification scheme combined with internal arteries in CT imaging for guiding postoperative adjuvant transarterial chemoembolization in hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Although postoperative adjuvant transarterial chemoembolization (PA-TACE) improves survival outcomes in a subset of patients with resected hepatocellular carcinoma (HCC), the lack of reliable biomarkers for patient selection remains a significant challenge. The present study aimed to evaluate whether computed tomography imaging can provide more value for predicting benefits from PA-TACE and to establish a new scheme for guiding PA-TACE benefits. METHODS: In this retrospective study, patients with HCC who had undergone preoperative contrast-enhanced computed tomography and curative hepatectomy were evaluated. Inverse probability of treatment weight was performed to balance the difference of baseline characteristics. Cox models were used to test the interaction among PA-TACE, imaging features, and pathological indicators. An HCC imaging and pathological classification (HIPC) scheme incorporating these imaging and pathological indicators was established. RESULTS: This study included 1488 patients [median age, 52 years (IQR, 45-61 years); 1309 male]. Microvascular invasion (MVI) positive, and diameter >5 cm tumors achieved a higher recurrence-free survival (RFS), and overall survival (OS) benefit, respectively, from PA-TACE than MVI negative, and diameter ≤5 cm tumors. Patients with internal arteries (IA) positive benefited more than those with IA-negative in terms of RFS ( P =0.016) and OS ( P =0.018). PA-TACE achieved significant RFS and OS improvements in HIPC3 (IA present and diameter >5 cm, or two or three tumors) patients but not in HIPC1 (diameter ≤5 cm, MVI negative) and HIPC2 (other single tumor) patients. Our scheme may decrease the number of patients receiving PA-TACE by ~36.5% compared to the previous suggestion. CONCLUSIONS: IA can provide more value for predicting the benefit of PA-TACE treatment. The proposed HIPC scheme can be used to stratify patients with and without survival benefits from PA-TACE.

Study on adsorption of hexavalent chromium by composite material prepared from iron-based solid wastes.

A new adsorbent with chromium removal function was synthesized by carbon thermal method using iron-containing waste Fenton sludge and carbon-containing solid waste fly ash to treat high pH scoring wastewater generated from industrial processes. The results showed that the adsorbent used T = 273.15 K, pH = 10, t = 1200 min, C0 = 100 mg/L, had a removal rate of Cr(VI) of more than 80%, and the adsorption capacity could reach 393.79 mg/g. The characterization results show that the synthesized mesoporous nitrogen-doped composite material has a large specific surface area and mesoporous structure, and the surface of the material is rich in oxygen-containing functional groups and active sites. Compared with other studies, the adsorption capacity of the material is larger, which indicates that the removal effect of Cr(VI) in this study is better. The adsorption kinetic results show that the adsorption follows a pseudo second kinetic model, and the adsorption process is a chemisorption involving electron sharing or electron exchange. This experiment designed a simple method to synthesize mesoporous nitrogen-doped composites using industrial solid waste, with raw materials from cheap and easily available industrial solid waste, and solved the dual problems of heavy metals in wastewater and solid waste, providing a new idea for the resource utilization of Fenton sludge while not producing secondary pollution.

Evaluating the efficacy and microenvironment changes of HER2 + gastric cancer during HLX02 and Endostar treatment using quantitative MRI.

BACKGROUND AND OBJECTIVES: Trastuzumab is an important targeted drug for HER2-positive gastric cancer. The treatment efficacy of a more cost-effective and accessible trastuzumab biosimilar, HLX02, was not well investigated, especially when combined with antiangiogenic treatment. In addition, the tumour microenvironment detected by functional MRI was still unclear during treatment. This study attempts to evaluate the therapeutic effect of antiangiogenic agents combined with HLX02 in a HER2-positive gastric cancer xenograft model and to detect microenvironmental changes using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). MATERIALS AND METHODS: We subcutaneously injected MKN-45 human gastric cancer cells into BALB/C nude mice to establish a tumour model. Twenty-eight mice were divided into four groups and treated with saline (Group 1), Endostar (Group 2), trastuzumab biosimilar HLX02 (Group 3), or the combination of Endostar and HLX02 (Group 4). We then performed IVIM-DWI before and at different time points after treatment. HE, HER2, TUNEL, E-cadherin staining, and α-SMA and CD31 double-staining were used to confirm the pathological changes. RESULTS: Group 4 demonstrated the smallest tumour volume at the end of treatment. The D value in Group 4 increased more dramatically, with the highest value on Day 20, compared with the other groups. Perfusion-related parameters (D* and f values) in Groups 2 and 4 increased initially and reversed after Day 10. Group 4 showed the lowest CD31 and HER2 and the highest TUNEL- and E-cadherin-positive staining rates. The D value was positively correlated with TUNEL but negatively correlated with HER2 staining. The D* and f values had positive correlations with CD31 and E-cadherin expression and the vessel maturity index. CONCLUSIONS: The trastuzumab biosimilar drug HLX02 exhibited good treatment efficacy in HER2-positive gastric cancer, especially when combined with Endostar. IVIM-DWI can noninvasively monitor the process of vascular normalization and reflect the treatment effect early at the molecular level.

Fe/C materials prepared by one-step calcination of acidified municipal sludge and their excellent adsorption of Cr(VI).

Biochar derived from municipal sludge can be applied to adsorption. But it usually requires activation and pickling due to the generation of impurities such as metal oxide particles, which is uneconomical. Here, a facile strategy, acidification-one-step calcination, was developed and sludge-based Fe-C materials with good Cr(VI) removal effect were obtained by regulating the amount of hydrochloric acid. The results show that the adsorption capacity of Fe/C-5 (the best sample) for Cr(VI) was 150.84 mg g-1. According to the Langmuir isotherm and pseudo-second-order kinetic model, the removal of Cr(VI) by Fe/C-5 is spontaneous and endothermic chemisorption process. In addition, Fe/C-5 has good ability to remove Cr(VI) under the interference of coexisting ions, and has good cycle stability. The removal of Cr(VI) by Fe/C-5 is considered to be synergistic process of adsorption and reduction. The Fe atoms were highly dispersed in Fe/C-5 and tightly bonded with C atoms, which not only strengthened the Cr(VI) adsorption by electrostatic attraction, but also activated the C atoms in the biochar material, so that the C atoms can reduce Cr(VI) to Cr(III) under acidic conditions. This may be due to the fact that acid pretreatment converted the iron in municipal sludge in the form of Fe-O/OH to free Fe3+ and entered the C lattice during the calcination process. In this work, Fe-C materials with excellent Cr(VI) adsorption capacity were prepared by one-step calcination method, which has important reference significance for the resource utilization of municipal sludge.

Highly efficient adsorption of chromium on N, S-codoped porous carbon materials derived from paper sludge.

The synergistic effect of heteroatoms is a viable method to enhance the adsorption performance of heavy metal onto carbon-based materials. However, the high cost, complex operation and a lot of pollution from the synthesis process have limited its development. Herein, a facile two-step pyrolysis method is used to prepare in situ N and S doped porous biochar from paper mill sludge for the removal of Cr(VI) from aqueous environment. The NSC-450 sample prepared under the optimum conditions has a large specific surface area of 3336.7 m2 g-1, an average pore size of 2.56 nm and a total pore volume of 2.10 cm3 g-1, manifesting the excellent adsorption capacity of 356.25 mg g-1 for Cr(VI). The adsorption of Cr(VI) by NSC-450 is consistent with the Langmuir isotherm and pseudo-second-order model, suggesting a spontaneous and endothermic chemisorption process. The analysis results show that the NH, graphitic nitrogen and thiophene structures have a positive effect on converting a large amount of Cr(VI) to Cr(III) by synergistic reduction, indicating obviously facilitating Cr(VI) removal compared to other sites. Therefore, in this material, the strong adsorption mechanism is mainly reductive complexation. Moreover, the effects of real water quality, anions, cations and fulvic acid on the adsorption behavior of Cr(VI) onto the NSC-450 were further investigated. The results demonstrate that the chromium removal rate remains above 82% even in actual electroplating wastewater, suggesting NSC-450 has great practical application prospect. This work offered a feasible method for high-value utilization of sludge, but also provided a novel perspective for the future design of heteroatom-doped carbon materials for promoting to eliminate hexavalent chromium from water environment.

A DNA-Methylation-Driven Genes Based Prognostic Signature Reveals Immune Microenvironment in Pancreatic Cancer.

Pancreatic cancer (PACA), which is characterized by an immunosuppressive nature, remains one of the deadliest malignancies worldwide. Aberrant DNA methylation (DNAm) reportedly influences tumor immune microenvironment. Here, we evaluated the role of DNA methylation driven genes (MDGs) in PACA through integrative analyses of epigenomic, transcriptomic, genomic and clinicopathological data obtained from TCGA, ICGC, ArrayExpress and GEO databases. Thereafter, we established a four-MDG signature, comprising GPRC5A, SOWAHC, S100A14, and ARNTL2. High signature risk-scores were associated with poor histologic grades and late TNM stages. Survival analyses showed the signature had a significant predictive effect on OS. WGCNA revealed that the signature may be associated with immune system, while high risk-scores might reflect immune dysregulation. Furthermore, GSEA and GSVA revealed significant enrichment of p53 pathway and mismatch repair pathways in high risk-score subgroups. Immune infiltration analysis showed that CD8+ T cells were more abundant in low score subgroups, while M0 macrophages exhibited an opposite trend. Moreover, negative regulatory genes of cancer-immunity cycle (CIC) illustrated that immunosuppressors TGFB1, VEGFA, and CD274 (PDL1) were all positively correlated with risk-scores. Furthermore, the four signature genes were negatively correlated with CD8+ lymphocytes, but positively associated with myeloid derived suppressor cells (MDSC). Conversely, specimens with high risk-scores exhibited heavier tumor mutation burdens (TMB) and might show better responses to some chemotherapy and targeted drugs, which would benefit stratification of PACA patients. On the other hand, we investigated the corresponding proteins of the four MDGs using paraffin-embedded PACA samples collected from patients who underwent radical surgery in our center and found that all these four proteins were elevated in cancerous tissues and might serve as prognostic markers for PACA patients, high expression levels indicated poor prognosis. In conclusion, we successfully established a four-MDG-based prognostic signature for PACA patients. We envisage that this signature will help in evaluation of intratumoral immune texture and enable identification of novel stratification biomarkers for precision therapies.

Modification of sludge-based biochar using air roasting-oxidation and its performance in adsorption of uranium(VI) from aqueous solutions.

Modification methods for sludge-based biochar are often complex and generally ineffective. In this study, sludge-based biochars were prepared at low cost using a simple air roasting-oxidation modification method and the adsorption performance on U(VI) was investigated. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) results together indicated that more carbon-oxygen functional groups were formed on the surface of oxidized biochar (OBC) compared to unoxidized biochar (BC). The adsorption performance of 550-OBC (biochar oxidized at 550 °C) on U(VI) was explored in batch experiments. The maximum adsorption capacity was up to 490.2 mg/g at 25 °C and pH 6, exceeding most of the reported biochars. 550-OBC also showed good adsorption performance at low U(VI) concentration, with 96% removal at pH 6 and an initial U(VI) concentration of 1 mg/L. Density functional theory (DFT) calculations indicated that the H-bond length between the solvated U(VI) and functional groups on the OBC was about 1.7 Å, which forms stronger H-bonds between them compared to that between U(VI) and BC (4.21 Å), and the adsorption energy value for this complex was highly negative -31.82 kcal/mol. In addition, 550-OBC exhibited high selectivity for U(VI) adsorption and excellent regeneration performance, making it a cost-effective and high-performance adsorbent.

Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340.

BACKGROUND: Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown. METHODS: qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells. RESULTS: Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1. CONCLUSIONS: Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.

Engagement of Robo1 by Slit2 induces formation of a trimeric complex consisting of Src-Robo1-E-cadherin for E-cadherin phosphorylation and epithelial-mesenchymal transition.

Loss of E-cadherin elicits epithelial-mesenchymal transition (EMT). While both the Src family of membrane-associated non-receptor tyrosine kinases (SFKs) and Slit2 binding to Roundabout 1 (Robo1) have been shown to induce E-cadherin repression and EMT, whether these two signaling pathways are mechanistically coupled remains unknown in epithelial cells. Here we found that Slit2 and Robo1 overexpression activated Src kinases for tyrosine phosphorylation, degradation of E-cadherin and induction of EMT. Specific blockade of Slit2 binding to Robo1 inactivated Src, prevented E-cadherin phosphorylation and EMT induction. Biochemically, the cytoplasmic CC3 motif of Robo1 (CC3) bound directly to the SH2 and 3 domains of c-Src and the cytoplasmic domains of E-cadherin. Slit2 induced Robo1 association with endogenous c-Src and E-cadherin, whereas ectopic expression of CC3 dissociated this protein complex in colorectal epithelial cells. These results indicate that Slit2 not only induces Robo1 binding to Src, but also recruits Src to E-cadherin for tyrosine phosphorylation of E-cadherin, leading to E-cadherin degradation and EMT induction in colorectal epithelial cells.

LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis.

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.