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Activated Wnt/β-catenin pathway is a key genetic event in liver cancer development. Solute carrier (SLC) transporters are promising drug targets. Here, we identify SLC13A3 as a drug-targetable effector downstream of β-catenin in liver cancer. SLC13A3 expression is elevated in human liver cancer samples with gain of function (GOF) mutant CTNNB1, the gene encoding β-catenin. Activation of β-catenin up-regulates SLC13A3, leading to intracellular accumulation of endogenous SLC13A3 substrates. SLC13A3 is identified as a low-affinity transporter for glutathione (GSH). Silencing of SLC13A3 downregulates the leucine transporter SLC7A5 via c-MYC signaling, leading to leucine depletion and mTOR inactivation. Furthermore, silencing of SLC13A3 depletes GSH and induces autophagic ferroptosis in β-catenin-activated liver cancer cells. Importantly, both genetic inhibition of SLC13A3 and a small molecule SLC13A3 inhibitor suppress β-catenin-driven hepatocarcinogenesis in mice. Altogether, our study suggests that SLC13A3 could be a promising therapeutic target for treating human liver cancers with GOF CTNNB1 mutations.

Fischer-Tropsch synthesis (FTS) is a structure-sensitive reaction of which performance is strongly related to the active phase, particle size, and exposed facets. Compared with the full-pledged investigation on the active phase and particle size, the facet effect has been limited to theoretical studies or single-crystal surfaces, lacking experimental reports of practical catalysts, especially for Fe-based catalysts. Herein, we demonstrate the facet sensitivity of iron carbides in FTS. As the prerequisite, {202} and {112} facets of χ-Fe5C2 are fabricated as the outer shell through the conformal reconstruction of Fe3O4 nanocubes and octahedra, as the inner cores, respectively. During FTS, the activity and stability are highly sensitive to the exposed facet of iron carbides, whereas the facet sensitivity is not prominent for the chain growth. According to mechanistic studies, {202} χ-Fe5C2 surfaces follow hydrogen-assisted CO dissociation which lowers the activation energy compared with the direct CO dissociation over {112} surfaces, affording the high FTS activity. The impact of facets on Fischer-Tropsch synthesis has primarily been explored through theoretical studies or on single-crystal surfaces, lacking experimental data on practical catalysts. Here, the authors provide experimental evidence of the facet sensitivity of iron carbides during syngas conversion by creating {202} and {112} χ-Fe5C2 facets. [ABSTRACT FROM AUTHOR]

Syngas conversion serves as a gas‐to‐liquid technology to produce liquid fuels and valuable chemicals from coal, natural gas, or biomass. During syngas conversion, sintering is known to deactivate the catalyst owing to the loss of active surface area. However, the growth of nanoparticles might induce the formation of new active sites such as grain boundaries (GBs) which perform differently from the original nanoparticles. Herein, we reported a unique Cu‐based catalyst, Cu nanoparticles with in situ generated GBs confined in zeolite Y (denoted as activated Cu/Y), which exhibited a high selectivity for C5+ hydrocarbons (65.3 C%) during syngas conversion. Such high selectivity for long‐chain products distinguished activated Cu/Y from typical copper‐based catalysts which mainly catalyze methanol synthesis. This unique performance was attributed to the GBs, while the zeolite assisted the stabilization through spatial confinement. Specifically, the GBs enabled H‐assisted dissociation of CO and subsequent hydrogenation into CHx*. CHx* species not only serve as the initiator but also directly polymerize on Cu GBs, known as the carbide mechanism. Meanwhile, the synergy of GBs and their vicinal low‐index facets led to the CO insertion where non‐dissociative adsorbed CO on low‐index facets migrated to GBs and inserted into the metal‐alkyl bond for the chain growth. [ABSTRACT FROM AUTHOR]

Background: Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with resistant hypertension (RH) have a high risk of developing primary aldosteronism (PA). This study investigated the aldosterone-renin ratio (ARR), plasma aldosterone concentration (PAC), and plasma renin activity (PRA) to determine the optimal cutoff values for PA diagnosis in patients with OSAHS combined with RH., Methods: Patients diagnosed with moderate and severe OSAHS combined with RH were recruited from the inpatient clinic of the Department of Endocrinology at Ji'an Central Hospital between October 2020 and April 2023. The included patients were divided into PA and no-PA groups. Diagnostic accuracy measures were calculated for each group, and receiver operating characteristic (ROC) curves were generated., Results: A total of 241 patients were included, of which 103 had positive ARR screening results in the diagnostic accuracy analysis and 66 were diagnosed with PA. PAC and ARR showed moderate predictive capacity for PA, with area under the curve (AUC) values of 0.66 [95% confidence interval (CI): 0.55-0.77] and 0.72 (95% CI: 0.63-0.82), respectively, while PRA exhibited a limited predictive capacity (AUC = 0.51, 95% CI: 0.40-0.63). Using 45 as the optimal cutoff value for ARR, the sensitivity was 86% and the specificity was 52%. The optimal cutoff value for PAC was 17, with a sensitivity of 78% and a specificity of 55%. Notably, in patients with severe OSAHS, ARR at screening demonstrated significant predictive value for PA, with an AUC of 0.84 (95% CI: 0.72-0.96), a sensitivity of 85%, and a specificity of 76%. Conversely, in patients with moderate OSAHS, only ARR demonstrated significant predictive value for PA diagnosis, while PAC did not demonstrate notable diagnostic value., Conclusion: ARR and PAC are initial screening tools for PA, facilitating early detection, particularly in low-resource settings. In patients with OSAHS and RH, the ARR and PAC thresholds for PA diagnosis may require more stringent adjustment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yan, Zou, Li, Zeng, He, Guo, Wang, Zheng, Fu, Wang, Peng, Zhou, Luo, Luo, Li, Liu, Hu and Shen.)