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Electrochemical reduction of CO 2 (CO 2 ER) has received significant attention due to its potential to sustainably produce valuable fuels and chemicals. However, the reaction mechanism is still not well understood. One vital debate is whether the rate-limiting step (RLS) is dominated by the availability of protons, the conversion of water molecules, or the adsorption of CO 2 . This paper describes insights into the RLS by investigating pH dependency and kinetic isotope effect with respect to the rate expression of CO 2 ER. Focusing on electrocatalysts geared towards two-electron transfer reactions, we find the generation rates of CO and formate to be invariant with either pH or deuteration of the electrolyte over Au, Ag, Sn, and In. We elucidate the RLS of two-electron transfer CO 2 ER to be the adsorption of CO 2 onto the surface of electrocatalysts. We expect this finding to provide guidance for improving CO 2 ER activity through the enhancement of the CO 2 adsorption processes by strategies such as surface modification of catalysts as well as careful control of pressure and interfacial electric field within reactors. Electroreduction of CO 2 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 CO 2 electroreduction to gain further insights into the rate-limiting step.

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. The electrochemical reduction of CO for sustainable fuel production has gained attention, but the reaction mechanism needs further clarification. Here the authors delve into the discussion regarding whether the rate-determining step for the generation of multi-carbon products is the C-C coupling or the hydrogenation of CO, and provide evidence for dimerization of two *CO as the pivotal step in this process.

Transforming waste carbon into valuable fuels and chemicals is a key step toward sustainable manufacturing. One promising approach is the electrochemical conversion of carbon monoxide (CO), a product of CO 2 recycling, into energy-rich multicarbon (C 2+ ) compounds. However, current CO electrolyzers rely on anion exchange membranes (AEMs) that degrade over time when exposed to organic intermediates, limiting their practical use. Here we show that low-cost diaphragm materials, such as Zirfon, can serve as robust alternatives to AEMs in alkaline CO electrolysis. We evaluate a range of diaphragms and identify candidates that match or exceed the performance of commercial AEMs across a wide range of operating conditions (50 to 400 mA cm −2 ). At 60 °C, Zirfon-based cells maintain 45% Faradaic efficiencies for acetate over 250 hours, while state-of-the-art AEMs fail within 150 hours. Moreover, a 100 cm 2 Zirfon cell operates stably for 700 hours at 200 mA cm −2 . These findings demonstrate that diaphragms offer a scalable and durable pathway for CO electrolysis, helping reduce system costs and enhance compatibility with renewable energy inputs. Current CO electrolyzers using anion exchange membranes suffer from poor stability in the presence of organic intermediates. Here, the authors demonstrate that low-cost Zirfon diaphragms enable durable and scalable CO electrolysis toward multicarbon products.

Acetic acid is an essential chemical with industrial and consumer relevance, and global demand is expected to reach 24.5 million tonnes by 2025. Electrochemical CO reduction reaction (CORR) over Cu offers a sustainable route to acetate from waste carbon, but identifying catalysts with high CO-to-acetate selectivity remains challenging due to limited mechanistic understanding. Here, we establish an artificial intelligence (AI)-driven multi-scale simulation framework integrating grand-canonical density functional theory (GC-DFT), microkinetic modeling (MKM), and active learning to elucidate the CORR mechanism and guide catalyst discovery. The DFT-based MKM reveals that acetate forms via CO-CH coupling, with CH* binding energy identified as the key descriptor governing selectivity of acetate production from CORR. Active learning optimization predicts Cu/Pd (2:1) and Cu/Ag (3:1) as the most selective catalysts. Zero-gap electrolyzer experiments confirm their effective performance, achieving acetate Faradaic efficiencies of 50% and 47%, respectively, compared to 21% for pure Cu. This study demonstrates a data-driven catalyst design strategy for advancing selective electrocatalysis. CO electroreduction offers a sustainable route to acetate production but remains mechanistically unclear. Here, the authors develop an active learning multiscale framework revealing CH* binding strength as the key descriptor, predicting Cu/Pd and Cu/Ag as optimal catalysts.

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 <0.001); additionally, miR-21 directly targeted the tumour suppressor phosphatase and tensin homologue (PTEN) and inhibited PTEN expression. Furthermore, the miR-21 mimic induced cisplatin resistance, while the miR-21 inhibitor restored cisplatin sensitivity. Overexpression of miR-21 can enhance cell proliferation, reduce apoptosis, and induce drug resistance by inhibiting PTEN expression. Targeting miR-21 may facilitate cancer diagnosis, restore drug sensitivity, and improve therapeutic effects.

To unravel the oncogenic role of CDCA4 in different cancers from the perspective of tumor immunity. Raw 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 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). Most 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 HCC. CDCA4 may serve as a biomarker for cancer immunologic infiltration and poor prognosis, providing a new way of thinking for cancer treatment.

Chronic hepatitis B virus (HBV) infection continues to pose a significant global health burden, and current therapies rarely target the viral covalently closed circular DNA reservoir. Kaempferol (KP), a major flavonoid found in various herbs and plants, exhibits diverse bioactivities, but its potential anti-HBV activity remains unclear. This study aims to investigate the anti-HBV potential of KP and to elucidate its underlying mechanisms. The HBV-infected Huh7D cell, viral stable transfection cell HepG2.2.15, as well as a hydrodynamic injection-based chronic HBV infection mouse model, were established to evaluate the antiviral effects of KP. The levels of HBV RNAs, DNA and proteins were detected using ELISA, western blot, qPCR, immunofluorescence and immunohistochemistry. To investigate the mechanisms, viral promoter activities were assessed dual-luciferase reporter assays, and relevant transcription factors were validated through qPCR and western blot analysis. KP dose- and time-dependently reduced the levels of viral antigens, RNA, and DNA , and also significantly lowered viral markers and attenuated HBV-induced hepatic pro-inflammatory cytokines expression . Furthermore, KP acted in combination with the nucleoside analog entecavir to suppress HBV replication. Mechanistically, KP strongly inhibited the transcriptional activity of the HBV core promoter (Cp), and enhanced the phosphorylation of both extracellular signal-regulated kinase (ERK) and its downstream target forkhead box protein O1 (FOXO1). Importantly, the ERK-specific inhibitor U0126 completely abolished the antiviral effects of KP, confirming that its antiviral activity depended on the ERK/FOXO1 pathway. Collectively, our results indicate that KP activates ERK-dependent FOXO1 phosphorylation, leading to transcriptional repression of the HBV Cp and thereby suppression of viral replication. These findings identify KP as a potential candidate for developing novel therapeutics against chronic HBV infection.

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.

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.

Background The abnormal expression and overactivation of the epidermal growth factor receptor (EGFR), a typical cancer marker for non-small cell lung cancer (NSCLC), are closely related to the tumorigenesis and progression of NSCLC. However, the endocytosis mechanism of EGFR in lung cancer is not yet known. Epsin3 (EPN3), a member of the endocytic adaptor protein family, is essential for the endocytosis of multiple receptors. In this study, we aimed to investigate the role of EPN3 in modulating EGFR function, its effects on NSCLC progression, and its potential involvement in tyrosine kinase inhibitor (TKI) resistance, which remains a significant hurdle in NSCLC treatment. Results Our findings revealed that the expression of EPN3 is significantly up-regulated in NSCLC patients. Elevated EPN3 expression was proportional to shorter overall survival in patients with NSCLC. Functional analyses revealed that EPN3 directly interacts with EGFR, enhancing its recycling to the plasma membrane and preventing its degradation via the lysosomal pathway. This stabilization of EGFR led to sustained downstream signalling, promoting NSCLC cell proliferation and migration. Notably, mutations in the EGFR tyrosine kinase domain, which typically confer resistance to TKIs, did not alter the regulatory effect of EPN3. Conclusions EPN3 enhances EGFR signalling by promoting its recycling and stability, contributing to NSCLC progression and TKI resistance. Targeting EPN3 could offer a novel therapeutic strategy to overcome drug resistance in EGFR-driven NSCLC.