Kinetically matched C-N coupling toward efficient urea electrosynthesis enabled on copper single-atom alloy.

Chemical C-N coupling from CO2 and NO3-, driven by renewable electricity, toward urea synthesis is an appealing alternative for Bosch-Meiser urea production. However, the unmatched kinetics in CO2 and NO3- reduction reactions and the complexity of C- and N-species involved in the co-reduction render the challenge of C-N coupling, leading to the low urea yield rate and Faradaic efficiency. Here, we report a single-atom copper-alloyed Pd catalyst (Pd4Cu1) that can achieve highly efficient C-N coupling toward urea electrosynthesis. The reduction kinetics of CO2 and NO3- is regulated and matched by steering Cu doping level and Pd4Cu1/FeNi(OH)2 interface. Charge-polarized Pdδ--Cuδ+ dual-sites stabilize the key *CO and *NH2 intermediates to promote C-N coupling. The synthesized Pd4Cu1-FeNi(OH)2 composite catalyst achieves a urea yield rate of 436.9 mmol gcat.-1 h-1 and Faradaic efficiency of 66.4%, as well as a long cycling stability of 1000 h. In-situ spectroscopic results and theoretical calculation reveal that atomically dispersed Cu in Pd lattice promotes the deep reduction of NO3- to *NH2, and the Pd-Cu dual-sites lower the energy barrier of the pivotal C-N coupling between *NH2 and *CO.

Curcumin improves atherosclerosis by inhibiting the epigenetic repression of lncRNA MIAT to miR-124.

Objectives: Atherosclerosis is a dominant cardiovascular disease. Curcumin has protective effect on atherosclerosis. However, the mechanisms remain to be explored. Methods: Atherosclerosis was induced by feeding mice with high-fat diet (HFD) and ox-low-density lipoprotein (LDL)-induced human umbilical vein endothelial cells (HUVECs) were structured. Oil Red O staining was used to evaluate the plaques in the artery. Quantitative real-time PCR (qRT-PCR) was conducted to detect the level of myocardial infarction associated transcript (MIAT), miR-124, and enhancer of zeste homolog 2 (EZH2). We performed western blotting and enzyme linked immunosorbent assay to examine the expression of EZH2 and cytokines including IL-1ß, TNFα, IL-6, and IL-8, respectively. RNA immunoprecipitation and chromatin immunoprecipitation (ChIP) were used to validate the interaction between myocardial infarction associated transcript and EZH2. Flow cytometry and CCK-8 assay were used to examine cell apoptosis and proliferation, respectively. Results: Curcumin suppressed inflammation in atherosclerosis mouse model and ox-LDL-induced cell model. MIAT overexpression and miR-124 inhibition relieved the anti-inflammation effect of curcumin in ox-LDL-induced cell. MIAT regulated miR-124 by interacting with EZH2. Curcumin relieved ox-LDL-induced cell inflammation via regulating MIAT/miR-124 pathway. Conclusion: MIAT/miR-124 axis mediated the effect of curcumin on atherosclerosis and altered cell apoptosis and proliferation, both in vivo and in vitro. These data further support the application of curcumin in control of atherosclerosis advancement.

Comprehensive predictive factors for CalliSpheres® microspheres (CSM) drug-eluting bead-transarterial chemoembolization and conventional transarterial chemoembolization on treatment response and survival in hepatocellular carcinoma patients.

BACKGROUND: Transarterial chemoembolization (TACE) is widely applied in hepatocellular carcinoma (HCC) patients who are not suitable for surgical treatment. We aimed to investigate the treatment outcomes and comprehensive prognostic factors of CalliSpheres® microspheres (CSM) drug-eluting bead TACE (DEB-TACE) treatment and conventional TACE (cTACE) treatment in HCC patients. METHODS: Three hundred and thirty-five HCC patients received DEB-TACE or cTACE treatment were consecutively enrolled in multi-center, retrospective cohort study. Treatment response was conducted at M1, M3 or M6 after treatment. Progression free survival (PFS) and overall survival (OS) were recorded. Thirty-seven baseline factors including demographic characteristics, clinical features, biochemical indexes and previous treatment histories were selected. RESULTS: In total patients, history of drink and largest nodule size≥7cm independently predicted worse ORR, DEB-TACE predicted better OS, while largest nodule size≥7cm, increased Child-Pugh stage, ALB abnormal, ALP abnormal or AFP abnormal predicted worse survival. For DEB-TACE group, previous cTACE and ANC abnormal independently predicted worse ORR, and hepatic vein invasion, increased Child-Pugh stage or AFP abnormal independently predicted poor survival. For cTACE group, largest nodule size≥7cm independently predicted poor ORR, and multifocal disease as well as ALB abnormal predicted poor OS. CONCLUSIONS: History of drink, largest nodule size≥7cm, DEB-TACE, increased Child-Pugh stage, abnormal ALB, ALP or AFP are potential prognostic factors in total patients, previous cTACE and ANC abnormal, hepatic vein invasion, increased Child-Pugh stage or AFP abnormal are potential prognostic factors in DEB-TA group, and largest nodule size≥7cm, multifocal disease and ALB abnormal are potential prognostic factors in cTACE group.

Comparison of chemoembolization with CalliSpheres® microspheres and conventional chemoembolization in the treatment of hepatocellular carcinoma: a multicenter retrospective study.

PURPOSE: This study aimed to compare the efficacy and safety between transarterial chemoembolization (TACE) with CalliSpheres® microspheres (CSM-TACE) and conventional TACE (cTACE) in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Three hundred and thirty-five HCC patients receiving CSM-TACE or cTACE were consecutively enrolled in this multi-center, retrospective cohort study, and then divided into CSM-TACE group and cTACE group accordingly. Complete response (CR), objective response (ORR) and disease control response (DCR) was assessed according to mRECIST criteria at 1 month (M1), 3 months(M3) and 6 months(M6) after treatment. Progression-free survival (PFS) and overall survival (OS) were assessed. Liver function indexes and adverse events (AEs) were also evaluated. RESULTS: CR at M3 (P=0.020) and ORR at M1 (P<0.001), M3 (P<0.001) and M6 (P=0.017) after treatment were significantly higher in the CSM-TACE compared with cTACE group. DCRs, PFS (25.3 months vs 24.2 months, P=0.503) and OS (27.8 months vs 25.3 months, P=0.203) were similar between the two groups. CSM-TACE was independently correlated with higher ORR at M1 (P=0.002) and longer OS (P=0.023). Abnormal alkaline phosphatase (ALP) (P=0.049) was independently associated with lower ORR at M3, and history of alcohol intake (P=0.019) and largest nodule size ≥7 cm (P=0.015) independently correlated with lower ORR at M6 (P=0.015). Largest nodule size ≥7 cm (P=0.029) and abnormal albumin (ALB) (P=0.046) were independently associated with shorter PFS. Child-Pugh stage B/C (P=0.023), abnormal ALB (P=0.001), ALP (P=0.008) and alpha-fetoprotein (AFP) (P=0.005) were independently associated with shorter OS. Most liver function indexes and AEs were similar between the two groups (P>0.05), except that ALP (P=0.005), total bilirubin (P=0.031), pain during procedure (P=0.034) and occurrence of fever post(treatment (P=0.017) were significantly elevated in the CSM-TACE compared with cTACE group. CONCLUSION: CSM-TACE presents with a better treatment response and similar survival profile compared with cTACE in HCC patients.

CalliSpheres Drug-Eluting Bead Transcatheter Arterial Chemoembolization Presents With Better Efficacy and Equal Safety Compared to Conventional TACE in Treating Patients With Hepatocellular Carcinoma.

The aim of this study was to compare the treatment response, survival, liver function, and adverse event incidence of drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres with conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Seventy-three patients with hepatocellular carcinoma who received drug-eluting bead transcatheter arterial chemoembolization (using CalliSpheres microspheres) or conventional transcatheter arterial chemoembolization treatment were consecutively enrolled. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors at month 1/month 3/month 6; posttreatment, liver function indexes, and adverse events were recorded. Progression-free survival and overall survival were also calculated. Objective response rate of patients at months 1, 3, and 6, disease control rate of patients and objective response rate of nodules at month 3 were increased in drug-eluting bead transcatheter arterial chemoembolization group compared with conventional transcatheter arterial chemoembolization group. In addition, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was an independent factor for predicting better objective response rate at month 1. Patients in drug-eluting bead transcatheter arterial chemoembolization group achieved longer progression-free survival and similar overall survival compared to those in conventional transcatheter arterial chemoembolization group; Cox proportional hazards regression model analyses revealed that drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was associated with better progression-free survival while it did not affect overall survival. Meanwhile, most of the occurrences of abnormal liver function indexes were similar between 2 groups, whereas drug-eluting bead transcatheter arterial chemoembolization group had a higher percentage of patients with total bile acid ≥2 upper limit of normal compared to conventional transcatheter arterial chemoembolization group at month 1. Moreover, the adverse event incidences between 2 groups were similar. In conclusion, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres achieves better treatment response and progression-free survival while equal safety compared to conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

Comparison of liver function and safety in hepatocellular cancer patients treated with DEB-TACE and cTACE: a multi-center, retrospective cohort study.

BACKGROUND: This study aimed to compare the live function change and adverse events (AEs) between drug-eluting beads (DEB) transarterial chemoembolization (TACE) with CalliSpheres® microspheres (CSM) and conventional TACE (cTACE) in treating hepatocellular carcinoma (HCC) patients. METHODS: Three hundred and thirty-five HCC patients underwent DEB-TACE with CSM (n=171, DEB-TACE group) or cTACE (n=164, cTACE group) were consecutively enrolled in this multi-center, retrospective cohort study. Liver function indexes were reviewed before treatment (W0), at 1 week (W1) and 1 month (M1) post treatment. Moreover, AEs during operation and hospitalization were retrieved as well. RESULTS: The changes of albumin (ALB) [-3.55 (-6.25 to -0.43) vs. -2.20 (-4.63-0.00), P=0.043] and total protein (TP) [-4.62 (-10.18-0.43) vs. -2.50 (-7.08-1.08), P=0.013] from W1 to W0 were lower in DEB-TACE group compared to cTACE group, while no difference was observed referring to the change of alanine aminotransferase (ALT) (P=0.494), aspartate aminotransferase (AST) (P=0.747), alkaline phosphatase (ALP) (P=0.895), total bilirubin (TBIL) (P=0.059), total bile acid (TBA) (P=0.491) from W1 to W0. And the changes of these seven indexes from M1 to W0 were all similar between DEB-TACE group and cTACE group (all P>0.05). Besides, the occurrence of pain during treatment (19.3% vs. 11.0%, P=0.034) and the occurrence of fever during hospitalization (18.1% vs. 9.1%, P=0.017) were both increased in DEB-TACE group compared to cTACE group. CONCLUSIONS: DEB-TACE with CSM is non-inferior to cTACE in terms of liver function change, while DEB-TACE with CSM leads to higher incidences of pain and fever.

Comparison of treatment efficacy and safety between drug-eluting bead transarterial chemoembolization with CalliSpheres® microspheres and conventional transarterial chemoembolization as first-line treatment in hepatocellular carcinoma patients.

We aimed to compare the treatment response, survivals and safety of drug-eluting bead (DEB) transarterial chemoembolization (TACE) with CalliSpheres® microspheres (CSM) and conventional TACE (cTACE) as first-line treatment in Chinese HCC patients. 192 HCC patients from multiple centers received DEB-TACE with CSM or cTACE treatment as first-line treatment were included and assigned to DEB-TACE group (N=94) or cTACE group (N=98) accordingly. Treatment response was assessed at 1 month (M1), M3 and M6 after treatment. Progression-free survival (PFS) and overall survival (OS) was evaluated. Liver function indexes and adverse events were recorded. Complete response (CR) and objective response rate (ORR) were higher, while disease control rate (DCR) rate was similar in DEB-TACE group compared with cTACE group, and further multivariate logistic regression analysis validated that DEB-TACE vs cTACE independently predicted higher ORR. For survivals, no difference in PFS or OS was observed between DEB-TACE and cTACE groups, and multivariate Cox's proportional hazards regression revealed that DEB-TACE vs cTACE was not correlated with PFS or OS either. Additionally, no difference in liver function indexes at M1 or changes of liver function indexes from M0 to M1 between DEB-TACE and cTACE groups after treatment was observed, whereas DEB-TACE resulted in higher incidence of pain and fever during treatment or hospitalization. DEB-TACE with CSM discloses better treatment response, similar survival profiles and equal liver function injury but increased incidence of short-term adverse events than cTACE as the first-line therapy in treating HCC patients.