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Abstract The electrochemical reduction of CO has drawn a large amount of attention due to its potential to produce sustainable fuels and chemicals by using renewable energy. However, the reaction’s mechanism is not yet well understood. A major debate is whether the rate-determining step for the generation of multi-carbon products is C-C coupling or CO hydrogenation. This paper conducts an experimental analysis of the rate-determining step, exploring pH dependency, kinetic isotope effects, and the impact of CO partial pressure on multi-carbon product activity. Results reveal constant multi-carbon product activity with pH or electrolyte deuteration changes, and CO partial pressure data aligns with the theoretical formula derived from *CO-*CO coupling as the rate-determining step. These findings establish the dimerization of two *CO as the rate-determining step for multi-carbon product formation. Extending the study to commercial copper nanoparticles and oxide-derived copper catalysts shows their rate-determining step also involves *CO-*CO coupling. This investigation provides vital kinetic data and a theoretical foundation for enhancing multi-carbon product production.

Abstract Background China has one of the highest hepatitis B virus (HBV) disease burdens worldwide and tracking progress toward the 2030 HBV elimination targets is essential. This study aimed to assess the impact of biomedical interventions (i.e., adult vaccination, screening and treatment) on the adult HBV epidemic, estimate the time for HBV elimination, and evaluate the cost-effectiveness of the interventions in China. Methods A deterministic compartmental model was developed to project the HBV epidemic from 2022 to 2050 and estimate the time to meet elimination targets under four intervention scenarios. Cost-effectiveness was calculated using incremental cost per quality-adjusted life year (QALY) gained, i.e., average cost-effectiveness ratio (CER). Results Under the status quo, there will be 42.09–45.42 million adults living with HBV in 2050 and 11.04–14.36 million HBV-related deaths cumulatively from 2022 to 2050. Universal vaccination would cumulatively avert 3.44–3.95 million new cases at a cost of US$1027–1261/QALY gained. The comprehensive strategy would cumulatively avert 4.67–5.24 million new chronic cases and 1.39–1.85 million deaths, expediting the realization of the elimination targets forward to 2049. This strategy was also cost-effective with an average CER of US$20,796–26,685/QALY and a saved healthcare cost of US$16.10–26.84 per person. Conclusion China is not on track to meet the elimination targets but comprehensive biomedical interventions can accelerate the realization of the targets. A comprehensive strategy is cost-effective and cost-saving, which should be promoted in primary care infrastructures. Universal adult vaccination may be appropriate in the near future considering practical feasibility.

Previous studies have revealed multiple tissue- or cell-specific or enriched miRNA profiles. However, miRNA profiles enriched in hepatic cell types and their effect on HBV replication have not been well elucidated. In this study, primary human hepatocytes (PHHs), Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs) were prepared from liver specimens of non-HBV-infected patients. Four hepatic cell type-enriched miRNA profiles were identified from purified liver cells miRNA microarray assay. The results revealed that 12 miRNAs, including miR-122-5p and miR-192-3p were PHH-enriched; 9 miRNAs, including miR-142-5p and miR-155-5p were KC-enriched; 6 miRNAs, including miR-126-3p and miR-222-3p were LSEC-enriched; and 14 miRNAs, including miR-214-3p and miR-199a-3p were HSC-enriched. By testing the effect of 11 PHH-enriched miRNAs on HBV production, we observed that miR-192-3p had the greatest pro-virus effect in hepatic cell lines. Moreover, we further found that miR-192-3p promoted HBV replication and gene expression through inhibiting Akt/mTOR signalling by direct targeting of ZNF143 in HepG2.2.15 cells. Additionally, the serum and hepatic miR-192-3p expression levels were significantly higher in chronic hepatitis B patients than in healthy controls and serum miR-192-3p positively correlated with the serum levels of HBV DNA and HBsAg. Collectively, we identified miRNA profiles enriched in four hepatic cell types and revealed that PHH-enriched miR-192-3p promoted HBV replication through inhibiting Akt/mTOR signalling by direct targeting of ZNF143 in hepatic cell lines. Our study provides a specific perspective for the role of hepatic cell type-enriched miRNA in interaction with viral replication and various liver pathogenesis.

Electroreduction of CO2 is heavily investigated but its reaction mechanism needs to be further explored. Here, the authors investigate pH dependency and kinetic isotope effect with respect to the rate expression of CO2 electroreduction to gain further insights into the rate-limiting step.

CO2 electroreduction (CO2 ER) using renewable energy is ideal for mitigating the greenhouse effect and closing the carbon cycle. Bicarbonate (HCO3−) is most commonly employed as the electrolyte anion because it is known to facilitate CO2 ER. However, its dynamics in the electric double layer remains obscure and requires more in-depth investigation. Herein, we investigate the refined reduction process of bicarbonate by employing in situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy. By comparing the product distributions in Ar-saturated KCl and KHCO3 electrolytes, we confirmed CO production from HCO3− in the absence of an external CO2 source. Notably, in contrast to an electric compulsion, negatively charged HCO3− anions were found to accumulate near the electrode surface. A reduction mechanism of HCO3− is proposed in that HCO3− is not adsorbed over a catalyst, but may be enriched near the electrode surface and converted to CO2 and react over Au and Cu electrodes. The dependence of the CO2 ER activity on the local HCO3− concentration was subsequently discovered, which was in turn dependent on the bulk HCO3− concentration and cathodic potential. In particular, the local HCO3− concentration was limited by the cathodic potential, leading to a plateau in the CO2 ER activity. The proposed mechanism provides insights into the interaction between the catalyst and the electrolyte in CO2 ER.

Hepatitis B virus (HBV) infection remains a major global threat to human health worldwide. Recently, the Chinese medicines with antiviral properties and low toxicity have been a concern. In our previous study, Eupolyphaga sinensis Walker polysaccharide (ESPS) has been isolated and characterized, while its antiviral effect on HBV remained unclear. The anti-HBV activity of ESPS and its regulatory pathway were investigated in vitro and in vivo. The results showed that ESPS significantly inhibited the production of HBsAg, HBeAg, and HBV DNA in the supernatants of HepG2.2.15 in a dose-dependent manner; HBV RNA and core protein expression were also decreased by ESPS. The in vivo studies using HBV transgenic mice further revealed that ESPS (20 and 40 mg/kg/2 days) significantly reduced the levels HBsAg, HBeAg, and HBV DNA in the serum, as well as HBV DNA and HBV RNA in mice liver. In addition, ESPS activated the Toll-like receptor 4 (TLR4) pathway; elevated levels of IFN-β, TNF-α, and IL-6 in the serum were observed, indicating that the anti-HBV effect of ESPS was achieved by potentiating innate immunity function. In conclusion, our study shows that ESPS is a potential anti-HBV ingredient and is of great value in the development of new anti-HBV drugs.

Nowadays, multi-view clustering has attracted more and more attention, which provides a way to partition multi-view data into their corresponding clusters. Previous studies assume that each data instance appears in all views. However, in real-world applications, it is common that each view may contain some missing data instances, resulting in incomplete multi-view data. To address the incomplete multi-view clustering problem, we will propose an auto-weighted incomplete multi-view clustering method in this paper, which learns a common representation of the instances and an affinity matrix of the learned representation simultaneously in a unified framework. Learning the affinity matrix of the representation guides to learn a more discriminative and compact consensus representation for clustering. Moreover, by considering the impact of the significance of different views, an adaptive weighting strategy is designed to measure the importance of each view. An efficient iterative algorithm is proposed to optimize the objective function. Experimental results on various real-world datasets show that the proposed method can improve the clustering performance in comparison with the state-of-the-art methods in most cases.

PurposeTo unravel the oncogenic role of CDCA4 in different cancers from the perspective of tumor immunity.MethodsRaw data on CDCA4 expression in tumor samples and paracancerous samples were obtained from TCGA and GTEX databases. In addition, we investigated pathological stages and the survival analysis of CDCA4 in pan-cancer across Gene Expression Profiling Interactive Analysis (GEPIA) database. Cox Proportional Hazards Model shows that high CDCA4 levels are associated with several vital indicators in oncology. On the one hand, we explored the correlation between CADA4 expression and tumor immune infiltration by the TIMER tool; On the other hand, we utilized the methods of CIBERSORT and ESTIMATE computational to evaluate the proportion of tumor infiltrating immune cells (TIIC) and the amounts of stromal and immune components based on TCGA database. The use of antineoplastic drugs and the expression of CDCA4 also showed a high correlation via linear regression. Protein–Protein Interaction analysis was performed in the GeneMANIA database, and enrichment analysis was performed and predicted signaling pathways were identified by using Gene Ontology and Kyoto Encyclopedia of Genes. The correlation between CDCA4 expression with Copy number variations (CNV) and methylation is detailed, respectively. Molecular biology experiments including Western blotting, flow cytometry, EDU staining, Transwell and Wound Healing assay to validate the cancer promoting role of CDCA4 in hepatocellular carcinoma (HCC).ResultsMost tumors highly expressed CDCA4. Elevated CDCA4 expression was associated with poor OS and DFS. There was a significant correlation between CDCA4 expression and TITCs. Moreover, markers of TIICs exhibited distinct patterns of CDCA4 associated immune infiltration. In addition, we pay attention to the association between the expression of CDCA4 and the use of the anti-tumor drugs. CDCA4 is related to biological progress (BP), cellular component (CC) and molecular function (MF). Dopaminergic Synapse, AMPK, Sphingolipid, Chagas Disease, mRNA Surveillance were significantly enriched pathways in positive and negative correlation genes with CDCA4. CNV is thought to be a positive correlation with CDCA4 expression. Conversely, methylation is negative correlation with CDCA4 expression. Molecular biology experiments confirm a cancer promoting role for CDCA4 in HCCConclusionCDCA4 may serve as a biomarker for cancer immunologic infiltration and poor prognosis, providing a new way of thinking for cancer treatment.

Drug resistance, either intrinsic or acquired, can impair treatment effects and result in increased cell motility and death. MicroRNA-21 (miR-21), a proto-oncogene, may facilitate the development or maintenance of drug resistance in cancer cells. Restoring drug sensitivity can improve therapeutic strategies, a possibility that requires functional evaluation and mechanistic exploration. For miR-21 detection, matched tissue samples from 30 head and neck squamous cell carcinoma (HNSCC) patients and 8 head and neck cancer (HNC) cell lines were obtained. Reverse transcription-PCR to detect expression, MTT and clonogenic assays to evaluate cell proliferation, apoptosis assays, resazurin cell viability assays, western blot and luciferase reporter assays to detect protein expression, and flow cytometry to analyse the cell cycle were adopted. Compared to the corresponding normal control (NC) tissues, 25 cancer tissues had miR-21 upregulation among the 30 matched pair tissues (25/30, 83.8%); furthermore, among the 8 HNC cell lines, miR-21 expression that was notably upregulated in three: UPCI-4B, UMSCC-1, and UPCI-15B. In both the UMSCC-1 and UPCI-4B cell lines, the miR-21 mimic enhanced cell proliferation with reduced apoptosis and increased viability, whereas the miR-21 inhibitor resulted in the opposite effects (all P

Background: Hepatitis B virus (HBV) infection is a major risk factor causing hepatocellular carcinoma (HCC) development, but the molecular mechanisms are not fully elucidated. It has been reported that virus infection induces ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2) expression, the latter participates in tumor progression. Therefore, the aim of the present study was to investigate whether HBV induced HCC malignancy via ENPP2.Methods: HCC patient clinical data were collected and prognosis was analyzed. Transient transfection and stable ectopic expression of the HBV genome were established in hepatoma cell lines. Immunohistochemical staining, RT-qPCR, western blot, and ELISA assays were used to detect the expression and secretion of ENPP2. Finally, CCK-8, colony formation, and migration assays as well as a subcutaneous xenograft mouse model were used to investigate the influence of HBV infection, ENPP2 expression, and activated hepatic stellate cells (aHSCs) on HCC progression in vitro and in vivo.Results: The data from cancer databases indicated that the level of ENPP2 was significant higher in HCC compared within normal liver tissues. Clinical relevance analysis using 158 HCC patients displayed that ENPP2 expression was positively correlated with poor overall survival and disease-free survival. Statistical analysis revealed that compared to HBV-negative HCC tissues, HBV-positive tissues expressed a higher level of ENPP2. In vitro, HBV upregulated ENPP2 expression and secretion in hepatoma cells and promoted hepatoma cell proliferation, colony formation, and migration via enhancement of ENPP2; downregulation of ENPP2 expression or inhibition of its function suppressed HCC progression. In addition, aHSCs strengthened hepatoma cell proliferation, migration in vitro, and promoted tumorigenesis synergistically with HBV in vivo; a loss-function assay further verified that ENPP2 is essential for HBV/aHSC-induced HCC progression.Conclusion: HBV enhanced the expression and secretion of ENPP2 in hepatoma cells, combined with aHSCs to promote HCC progression via ENPP2.

Waxy sorghum has greater economic value than wild sorghum in relation to their use in food processing and the brewing industry. Thus, the authentication of the waxy sorghum species is an important issue. Herein, a rapid and sensitive Authentication Amplification Refractory Mutation System-PCR (aARMS-PCR) method was employed to identify sorghum species via its ability to resolve single-nucleotide in genes. As a proof of concept, we chose a species of waxy sorghum containing the wxc mutation which is abundantly used in liquor brewing. The aARMS-PCR can distinguish non-wxc sorghum from wxc sorghum to guarantee identification of specific waxy sorghum species. It allowed to detect as low as 1% non-wxc sorghum in sorghum mixtures, which ar one of the most sensitive tools for food authentication. Due to its ability for resolving genes with single-nucleotide resolution and high sensitivity, aARMS-PCR may have wider applicability in monitoring food adulteration, offering a rapid food authenticity verification in the control of adulteration.

The hepatitis C virus (HCV) core protein is a multifunctional protein that can interfere with the induction of an immune response. It has been reported that the HCV core protein inhibits HBV replication in vitro. In this study, we test the effect of the HCV core gene on the priming of the immune response to hepatitis B surface antigen (HBsAg) and on the replication of HBV in vivo. Our results showed that the full-length HCV core gene inhibits the induction of an immune response to the heterogeneous antigen, HBsAg, at the site of inoculation when HCV core (pC191) and HBsAg (pHBsAg) expression plasmids are co-administered as DNA vaccines into BALB/c mice. The observed interference effect of the HCV core occurs in the priming stage and is limited to the DNA form of the HBsAg antigen, but not to the protein form. The HCV core reduces the protective effect of the HBsAg when the HBsAg and the HCV core are co-administered as vaccines in an HBV hydrodynamic mouse model because the HCV core induces immune tolerance to the heterogeneous HBsAg DNA antigen. These results suggest that HCV core may play an important role in viral persistence by the attenuation of host immune responses to different antigens. We further tested whether the HCV core interfered with the priming of the immune response in hepatocytes via the hydrodynamic co-injection of an HBV replication-competent plasmid and an HCV core plasmid. The HCV core inhibited HBV replication and antigen expression in both BALB/c (H-2d) and C57BL/6 (H-2b) mice, the mouse models of acute and chronic hepatitis B virus infections. Thus, the HCV core inhibits the induction of a specific immune response to an HBsAg DNA vaccine. However, HCV C also interferes with HBV gene expression and replication in vivo, as observed in patients with coinfection.

Hepatocellular carcinoma (HCC) is a highly lethal disease, and surgical resection is one of the major treatment methods used. However, to date, at least to the best of our knowledge, there is no effective prognostic scoring system for the overall survival (OS) and relapse-free survival (RFS) of patients following hepatectomy. The present study developed a low-cost and easy-to-use model based on the clinicopathological characteristics of patients with HCC for assessment of outcome prediction and risk stratification. A total of 690 patients with HCC undergoing surgery were included and randomly divided into two cohorts (n=345). Cox regression analysis was conducted to investigate the association between the clinicopathological and treatment features, and patient survival. Multivariate analysis revealed that ascites, vascular tumor thrombus, low tumor differentiation and extrahepatic metastasis were independent risk factors for OS. Extrahepatic metastasis and multiple tumors were independent risk factors to predict tumor recurrence. These variables were weighted to construct the ascites, vascular tumor thrombus, low tumor differentiation, extrahepatic metastasis and multiple tumors (AVLEM) score based on the cumulative incidence (CuI) of the aforementioned variables, and the patients were classified into grade 0 (CuI=0), grade 1 (CuI=1 for OS and CuI ≥1 for RFS), and grade 2 (CuI ≥2) subgroups, respectively. Kaplan-Meier analysis revealed that the OS and RFS differed significantly among the subgroups; however, the survival rate between the two cohorts did not exhibit any marked differences. On the whole, the present study demonstrates that with this AVLEM scoring system, patients with HCC with a high score had a poor OS and RFS; thus, it is suggested that such patients undergo imaging examinations following a hepatectomy more frequently. [ABSTRACT FROM AUTHOR]