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Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis, and novel treatment strategies are urgently needed. Mitochondria are key regulators of cellular homeostasis and potential targets for tumor therapy. Here, the role of mitochondrial translocator protein (TSPO) in the regulation of ferroptosis and antitumor immunity is investigated and the potential therapeutic implications for HCC are assessed. TSPO is highly expressed in HCC and associated with poor prognosis. Gain‐ and loss‐of‐function experiments present that TSPO promotes HCC cell growth, migration, and invasion in vitro and in vivo. In addition, TSPO inhibits ferroptosis in HCC cells via enhancing the Nrf2‐dependent antioxidant defense system. Mechanistically, TSPO directly interacts with P62 and interferes with autophagy, leading to the accumulation of P62. The P62 accumulation competes with KEAP1, preventing it from targeting Nrf2 for proteasomal degradation. Furthermore, TSPO promotes HCC immune escape by upregulating PD‐L1 expression through Nrf2‐mediated transcription. Notably, TSPO inhibitor PK11195 combines with anti‐PD‐1 antibody showing a synergistic anti‐tumor effect in a mouse model. Overall, the results demonstrated that mitochondrial TSPO promotes HCC progression by inhibiting ferroptosis and antitumor immunity. Targeting TSPO can be a promising new strategy for HCC treatment. [ABSTRACT FROM AUTHOR]

SUMMARY: Rosa roxburghii and Rosa sterilis, two species belonging to the Rosaceae family, are widespread in the southwest of China. These species have gained recognition for their remarkable abundance of ascorbate in their fresh fruits, making them an ideal vitamin C resource. In this study, we generated two high‐quality chromosome‐scale genome assemblies for R. roxburghii and R. sterilis, with genome sizes of 504 and 981.2 Mb, respectively. Notably, we present a haplotype‐resolved, chromosome‐scale assembly for diploid R. sterilis. Our results indicated that R. sterilis originated from the hybridization of R. roxburghii and R. longicuspis. Genome analysis revealed the absence of recent whole‐genome duplications in both species and identified a series of duplicated genes that possibly contributing to the accumulation of flavonoids. We identified two genes in the ascorbate synthesis pathway, GGP and GalLDH, that show signs of positive selection, along with high expression levels of GDP‐d‐mannose 3′, 5′‐epimerase (GME) and GDP‐l‐galactose phosphorylase (GGP) during fruit development. Furthermore, through co‐expression network analysis, we identified key hub genes (MYB5 and bZIP) that likely regulate genes in the ascorbate synthesis pathway, promoting ascorbate biosynthesis. Additionally, we observed the expansion of terpene synthase genes in these two species and tissue expression patterns, suggesting their involvement in terpenoid biosynthesis. Our research provides valuable insights into genome evolution and the molecular basis of the high concentration of ascorbate in these two Rosa species. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play a significant role in the initiation and progression of various cancers, including hepatocellular carcinoma (HCC). Circular syntaxin 6 (circSTX6, also known as hsa_circ_0007905) has been identified as a microRNA (miRNA) sponge in pancreatic adenocarcinoma. However, its full range of functions in terms of protein scaffold and translation remain largely unexplored in the context of HCC. Methods: The expression of circSTX6 and its encoded protein was examined in HCC tumour tissues. N6‐methyladenosine (m6A) on circSTX6 was verified and quantified by methylated RNA immunoprecipitation (Me‐RIP), RIP and dual luciferase reporter assays. The biological functions of circSTX6 and its encoded protein in HCC were clarified by in vitro and in vivo experiments. Mechanistically, the interaction between circSTX6 and heterogeneous nuclear ribonucleoprotein D (HNRNPD) was investigated by RNA pull‐down, RIP and fluorescence in situ hybridization (FISH)/IF. The regulatory effects of circSTX6 and HNRNPD on activating transcription factor 3 (ATF3) mRNA were determined by mRNA stability and RIP assays. Furthermore, the presence of circSTX6‐encoded protein was verified by mass spectrometry. Results: CircSTX6 and its encoded 144 amino acid polypeptide, circSTX6‐144aa, were highly expressed in HCC tumour tissues and served as independent risk factors for overall survival in HCC patients. The expression of circSTX6 was regulated by METTL14 in an m6A‐dependent manner. Functionally, circSTX6 accelerated HCC proliferation and tumourigenicity and reinforced tumour metastasis in vitro and in vivo. Mechanistically, circSTX6 acted as a sponge for HNRNPD protein, facilitating its binding to ATF3 mRNA, consequently promoting ATF3 mRNA decay. Meanwhile, circSTX6‐144aa promoted HCC proliferation, migration and invasion independent of circSTX6 itself. Conclusion: Collectively, our study reveals that m6A‐modified circSTX6 drives malignancy in HCC through the HNRNPD/ATF3 axis, while its encoded circSTX6‐144aa contributes to HCC progression independent of circSTX6. CirSTX6 and its encoded protein hold promise as potential biomarkers and therapeutic targets in HCC. [ABSTRACT FROM AUTHOR]

The potential interactions between aeolian and fluvial systems are critical in understanding environmental change. Whether aeolian products originated from the river depends on the river characteristics and wind regimes. In southern Tibet, aeolian sand dunes are widespread along the Yarlung River, and thus provide an ideal example to explore the relationships between large fluvial systems and aeolian products. Although previous studies postulated that those aeolian products were originated from the Yarlung River, few empirical data actually exist to support this idea. We analysed the spatial pattern, sand transportation directions, and granulometric characteristics of the sand dunes to evaluate the potential influence of the Yarlung River on the aeolian processes. Comparison of the dune field distribution against channel width and longitudinal profile of the Yarlung River shows that sand dunes are clustered at the wide and flat segments of the river. Analyses of >4,600 sand dune orientations using Google Earth imagery show that the dunes located at the southern and northern sides of the Yarlung River demonstrate opposite sand transportation directions that generally point against the river. This suggests that the sand grains probably originated from the river. Grain size distributions from dune samples show unimodal or unimodal‐like patterns. This means that each sand dune field was dominantly fed by a simple transportation process rather than by compound processes from smaller‐level fluvial systems, which in turn implies that the Yarlung River was the most possible candidate for the provenance of these aeolian deposits. This study provides new constraints to demonstrate that the Yarlung River provides both accommodation space and sorted fluvial sand for the aeolian sand dunes along the river. [ABSTRACT FROM AUTHOR]