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Ti3C2, one typical MXene, has great potential to be coupled with various transition metals. Herein, a novel and effective catalyst is developed by synergistically loading VCoCOx onto Ti3C2‐modified nickel foam (VCoCOx–Ti3C2@NF). Field emission scanning electron microscope and high‐resolution transmission electron microscopy are employed to characterize the morphology and structure. As expected, the catalyst optimized by response surface methodology attains overpotentials of 290 and 64 mV and Tafel slopes of 82 and 79 mV dec−1 for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively. By using the bifunctional VCoCOx–Ti3C2@NF catalyst, the water splitting current density achieves 10 mA cm−2 in 1.0 mol L−1 KOH electrolyte at cell voltage of 1.52 V, comparable with the noble metal electrolyzer Pt@C@NF||RuO2@NF (1.57 V). Furthermore, the resulting catalyst exhibits excellent cycling durability after 120 h of continuous catalysis, which retains 103.8% and 105.4% of potential (V vs reversible hydrogen electrode) for OER and HER, respectively. Density functional theory calculation reveals that the Gibbs free energy barriers for the OER and HER intermediates are reduced due to the integration of VCoCOx with Ti3C2@NF. The fabricated VCoCOx–Ti3C2@NF catalyst is a promising electrochemical material for clean energy production. [ABSTRACT FROM AUTHOR]

Activation of extracellular matrix–producing hepatic stellate cells (HSCs) is a key event in liver fibrogenesis. We showed that the expression of the heme-thiolate monooxygenase cytochrome P450 1B1 (CYP1B1) was elevated in human and mouse fibrotic livers and activated HSCs. Systemic or HSC-specific ablation and pharmacological inhibition of CYP1B1 attenuated HSC activation and protected male but not female mice from thioacetamide (TAA)–, carbon tetrachloride (CCl4)–, or bile duct ligation (BDL)–induced liver fibrosis. Metabolomic analysis revealed an increase in the disaccharide trehalose in CYP1B1-deficient HSCs resulting from intestinal suppression of the trehalose-metabolizing enzyme trehalase, whose gene we found to be a target of RARα. Trehalose or its hydrolysis-resistant derivative lactotrehalose exhibited potent antifibrotic activity in vitro and in vivo by functioning as an HSC-specific autophagy inhibitor, which may account for the antifibrotic effect of CYP1B1 inhibition. Our study thus reveals an endobiotic function of CYP1B1 in liver fibrosis in males, mediated by liver-intestine cross-talk and trehalose. At the translational level, pharmacological inhibition of CYP1B1 or the use of trehalose/lactotrehalose may represent therapeutic strategies for liver fibrosis. Editor's summary: Hepatic stellate cells (HSCs) are well-known actors in liver fibrosis, and a better understanding of the factors governing their activity could open up therapeutic opportunities. Tung et al. examined the role of the cytochrome P450 analog CYP1B1 in liver fibrosis, finding that its inhibition or depletion reduced liver pathology in multiple mouse models in a sex-dependent manner. The authors tied the observed antifibrotic effect in males to HSC accumulation of trehalose as a result of inhibition of trehalase in the intestine. As a test of therapeutic potential, male mice fed trehalose or nonhydrolyzable lactotrehalose in drinking water showed reduced liver fibrogenesis, with follow-up analysis of similarly treated HSCs demonstrating reduced autophagic degradation. This study suggests that the metabolite trehalose may play a sex-specific role in liver fibrosis. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Nanomedicine shows promise in the therapy of eradicating bladder tumors and preventing tumor recurrence caused by cancer‐related inflammation. Shell‐core structured BNN6/Z8@ALA/Z67 nanoparticles with sequential release kinetics is designed, aiming to eliminate tumors and curb inflammation, thereby ablating bladder tumors and preventing their recurrence. The shell of this nanoparticle comprises zeolitic imidazolate framework‐67 (Z67) and 5-aminolevulinic acid (ALA), while the core comprises zeolitic imidazolate framework‐8 (Z8) and N,N'‐di‐sec‐butyl‐N,N'‐dinitroso‐1,4‐phenylenediamine (BNN6). Modified with polydopamine‐methoxypolyethylene glycol amine, these nanoparticles efficiently target bladder tumors. In the acidic tumor environment, the outer‐layered Z67 breaks down rapidly, releasing ALA, which transforms into protoporphyrin IX (PpIX) in mitochondria. Additionally, the degraded Z67 triggers the conversion of hydrogen peroxide into oxygen, aiding PpIX to generate reactive oxygen species under ultrasound, facilitating tumor ablation. As Z67 decomposes, the inner‐layered Z8 releases BNN6 in the acidic environment. Ultrasound exposure prompts the release of nitric oxide, effectively reducing inflammation. Under ultrasound, BNN6/Z8@ALA/Z67 showcased outstanding staged anti‐tumor and anti‐inflammatory effects in both in vitro and murine subcutaneous tumor model tests, and effectively prevents tumor recurrence in rat bladder tumor models. These findings underscore the promising potential of the designed shell‐core nanoparticle with staged tumor ablation and inflammation suppression in preventing bladder tumor recurrence. [ABSTRACT FROM AUTHOR]

In the healthy adult liver, most hepatocytes proliferate minimally. However, upon physical or chemical injury to the liver, hepatocytes proliferate extensively in vivo under the direction of multiple extracellular cues, including Wnt and pro-inflammatory signals. Currently, liver organoids can be generated readily in vitro from bile-duct epithelial cells, but not hepatocytes. Here, we show that TNFα, an injury-induced inflammatory cytokine, promotes the expansion of hepatocytes in 3D culture and enables serial passaging and long-term culture for more than 6 months. Single-cell RNA sequencing reveals broad expression of hepatocyte markers. Strikingly, in vitro-expanded hepatocytes engrafted, and significantly repopulated, the injured livers of Fah-/- mice. We anticipate that tissue repair signals can be harnessed to promote the expansion of otherwise hard-to-culture cell-types, with broad implications.