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Organic acid is a crucial indicator of fruit quality traits. Citric acid, the predominant organic acid in citrus fruit, directly influences its edible quality and economic value. While the transcriptional regulatory mechanisms of citric acid metabolism have been extensively studied, the understanding about the transcriptional and epigenetic co-regulation mechanisms is limited. This study characterized a transcription factor, CitGATA7, which directly binds to and activates the expression of genes associated with the glutamine synthetase pathway regulating citric acid degradation. These genes include the aconitase encoding gene CitACO3, the isocitrate dehydrogenase encoding gene CitIDH1, and the glutamine synthetase encoding gene CitGS1. Furthermore, CitGATA7 physically interacts with the histone acetyltransferase CitHAG28 to enhance histone 3 acetylation levels near the transcription start site of CitACO3, CitIDH1, and CitGS1, thereby increasing their transcription and promoting citric acid degradation. The findings demonstrate that the CitGATA7-CitHAG28 protein complex transcriptionally regulate the expression of the GS pathway genes, i.e., CitACO3, CitIDH1, and CitGS1, via histone acetylation, thus promoting citric acid catabolism. This study establishes a direct link between transcriptional regulation and histone acetylation regarding citric acid metabolism, providing insights for strategies to manipulate organic acid accumulation in fruit. [ABSTRACT FROM AUTHOR]

Tumor immune microenvironment is strongly associated with the malignancy behavior of hepatocellular carcinoma (HCC). However, the immune function and regulatory mechanisms of B cells in HCC remain unclear. The expression differences between B cell high‐ and low‐infiltration HCC samples are explored to identify the key regulator. Pre‐mRNA processing factor 19 (PRP19) expression is increased in B cell low‐infiltrated tissues and negatively correlated with the B cell marker, CD20. Inhibition of PRP19 expression promoted B cell infiltration in tumor tissue and impeded HCC growth. Mechanically, the co‐immunoprecipitation (Co‐IP) assay revealed that PRP19 interacts with DEAD‐box helicase 5 (DDX5), leading to ubiquitination and degradation of the DDX5 protein. The attenuated DDX5 impairs CXCL12 mRNA stability to suppress B cell recruitment and plasma cell differentiation via CXCL12/CXCR4 axis. Moreover, the adoptive transfer of CXCR4+ B cells combined with CXCL12 treatment in mice models effectively inhibits HCC development by reshaping the immune response. The expression of PRP19, DDX5, and infiltrating B cells are recognized as clinical prognosis indicators for HCC patients. Overall, this study provides valuable insights into the clinical benefits of HCC immunotherapy by targeting PRP19 and modulating tumor‐infiltrating B cell immune function. [ABSTRACT FROM AUTHOR]

Skin damage is one of the most prevalent human injuries, which affects the health of human beings. However, skin damage is often accompanied by bacterial infection and wound microenvironment changes, causing damage to normal cells and inhibiting wound healing. Herein, we designed a thermal-responsive antibacterial hydrogel (GAG hydrogel) loaded with catalase (CAT)-like Au@Pt@MgSiO3 nanoparticles (APM NPs) and gentamicin (GM) to promote wound healing. The GAG hydrogel was used in a photothermal therapy (PTT)/antibiotic combination to kill bacteria, reduce the use of antibiotics, improve the wound microenvironment, promote cell proliferation, and accelerate wound healing. Under near-infrared laser irradiation, APM NPs in the hydrogel generated local hyperthermia to kill bacteria. Meanwhile, the generated heat led to a change in the hydrogel's morphology, enabling it to release GM and APM NPs to prevent the overuse of antibiotics. Subsequently, the CAT-like ability of the APM NPs decreased the oxidative stress caused by hydrogen peroxide (H2O2), thus remodeling the wound microenvironment. Then, the weakly acidic microenvironment of the wound caused the decomposition of the APM NPs and the release of magnesium ions (Mg2+), promoting the growth and migration of cells for wound healing. Therefore, the studied thermal-responsive antibacterial (GAG) hydrogel has potential in the field of wound healing. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) is a promising ultrasound (US)-triggered therapeutic modality for anticancer treatments due to its high penetration, safety, and noninvasiveness. Its therapeutic efficiency is closely related to the performance of sonosensitizers and the oxygen concentration of the tumor microenvironment (TME). Herein, inspired by the adhesion of cocklebur, a rough-surface sonosensitizer gold platinum encapsulated with magnesium silicate loaded with glucose oxidase (AuPt@MgSiO3@GOx, APMS-GOx) with an enzymatic cascade activity was designed to improve delivery capability, produce reactive oxygen species, and reduce the glucose concentration in tumor tissue. The rough surface of APMS-GOx can improve the ability of nanomaterials to deliver to tumor areas. The enzymatic cascade reaction of APMS-GOx can induce starvation therapy and improve the level of oxygen. Adequate oxygen can not only alleviate hypoxia TME but also further convert to singlet oxygen (1O2) by APMS-GOx under US activation. Moreover, the activity of GOx increases due to the involvement of US, resulting in a positive effect on starvation therapy. Furthermore, APMS-GOx exhibits near-infrared absorption properties, providing a photoacoustic imaging-guided combination breast tumor therapy strategy. [ABSTRACT FROM AUTHOR]

A novel Pt@In2O3 catalyst assembled from ultrafine Pt nanoparticles confined on In2O3 nanotubes is fabricated from in situ topological transformation of H2PtCl6-soaked In-MIL-68 in an air atmosphere, which exhibits high performance for methanol production by CO2 hydrogenation. The Pt@In2O3 catalyst is revealed to exhibit a strong confinement effect to stabilize the interaction between Pt and In2O3, affording improvements in methanol production, selectivity, and stability, compared with bare In2O3 nanotubes and the Pt/In2O3 catalyst made by directly loading Pt species on In2O3 nanotubes. The optimal Pt@In2O3 catalyst shows a high methanol yield of 29.0 mmol g−1 h−1 and a selectivity of 73% at 260 °C, together with a catalytic turnover number (TON) of 4128 based on the Pt species. Such a methanol production activity is about 2 times that of the commercial Cu/ZnO/Al2O3 catalyst and surpasses that of state-of-the-art In2O3-supported catalysts. Diverse techniques including aberration-corrected scanning transmission electron microscopy (AC-STEM), temperature-programmed desorption (TPD) of H2 and CO2, and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) are used to demonstrate the crucial confinement effect of the In2O3 substrate on the Pt species for promoting the CO2-to-methanol conversion. This work may motivate the employment of MOFs to pre-anchor metal precursors for the on site construction of supported catalysts with intimate contact and tailorable compositions for high-efficiency CO2 conversion reactions. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) has the advantages of high penetration, non‐invasiveness, and controllability, and it is suitable for deep‐seated tumors. However, there is still a lack of effective sonosensitizers with high sensitivity, safety, and penetration. Now, ultrasound (US) and glutathione (GSH) dual responsive vesicles of Janus Au‐MnO nanoparticles (JNPs) were coated with PEG and a ROS‐sensitive polymer. Upon US irradiation, the vesicles were disassembled into small Janus Au‐MnO nanoparticles (NPs) with promoted penetration ability. Subsequently, GSH‐triggered MnO degradation simultaneously released smaller Au NPs as numerous cavitation nucleation sites and Mn2+ for chemodynamic therapy (CDT), resulting in enhanced reactive oxygen species (ROS) generation. This also allowed dual‐modality photoacoustic imaging in the second near‐infrared (NIR) window and T1‐MR imaging due to the released Mn2+, and inhibited orthotopic liver tumor growth via synergistic SDT/CDT. [ABSTRACT FROM AUTHOR]

The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway in hepatocellular carcinoma (HCC) is limited. NOD-like receptors (NLRs) comprise a highly evolutionarily conserved family of cytosolic bacterial sensors, yet their impact on antitumor immunity against HCC remains unclear. In this study, we uncovered that NOD1, a well-studied member of NLR family, exhibits predominant expression in tumor-associated macrophages (TAMs) and correlates positively with improved prognosis and responses to anti-PD-1 treatments in patients with HCC. Activation of NOD1 in vivo augments antitumor immunity and enhances the effectiveness of anti-PD-1 therapy. Mechanistically, NOD1 activation resulted in diminished expression of perilipin 5, thereby hindering fatty acid oxidation and inducing free fatty acid accumulation in TAMs. This metabolic alteration promoted membrane localization of the costimulatory molecule OX40L in a lipid modification-dependent manner, thereby activating CD8 + T cells. These findings unveil a previously unrecognized role for NOD1 in fortifying antitumor T cell immunity in HCC, potentially advancing cancer immunotherapy.

Background: Hepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy., Methods: Intratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy., Results: Single-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7 high macrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models., Conclusions: Macrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Exploring affordable cocatalysts with high performance for boosting charge separation and CO 2 activation is an effective strategy to reinforce CO 2 photoreduction efficiency. Herein, well-defined Co 9 S 8 cages are exploited as a nonprecious promoter for visible-light CO 2 reduction. The Co 9 S 8 cages are prepared via a multistep strategy with ZIF-67 particles as the precursor and fully characterized by physicochemical techniques. The hollow Co 9 S 8 cocatalyst with a high surface area and profuse catalytically active centers is discovered to accelerate separation and transfer of light-induced charges, and strengthen concentration and activation of CO 2 molecules. In a hybrid photosensitized system, these Co 9 S 8 cages efficiently promote the deoxygenative reduction of CO 2 to generate CO, with a high yield rate of 35 μmol h -1 ( i.e. , 35 mmol h -1 g -1 ). Besides, this cocatalyst is also of high stability for the CO 2 photoreduction reaction. Density functional theory (DFT) calculations reveal that the Ru(bpy) 3 2+ photosensitizer is strongly absorbed on the Co 9 S 8 (311) surface through forming four Co-C bonds, which can serve as the "bridges" to ensure quick electron transfer from the excited photosensitiser to the active Co 9 S 8 cocatalyst, thus promoting the separation of photoexcited charges for ehannced CO 2 reduction performance.