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ABSTRACTHepatocellular carcinoma (HCC) is a principal histologic type of liver cancer with high mortality. Long non-coding RNAs (LncRNAs) exert a crucial role in the pathogenesis of human tumors. To date, the functions and mechanisms of lncRNA HAGLROS in HCC are rarely reported. In the current study, HAGLROS exhibited a higher level in HCC tissues and cells. HAGLROS expression was positively correlated with tumor size, TNM stage and poor clinical prognosis. Loss-of-function experiments showed that knockdown of HAGLROS significantly lowered cell proliferation, cell cycle progression, migration, invasion and epithelial to mesenchymal transition (EMT) but induced apoptosis in vitro. Consistently, tumor growth in the nude mice was effectively slowed by the depletion of HAGLROS. Mechanistically, HAGLROS could competitively bind to miR-26b-5p to prevent the suppression of miR-26b-5p on its downstream target gene Karyopherin α2 (KPNA2). Moreover, the inhibitory effects of HAGLROS knockdown on cell malignant behaviors were reversed due to the miR-26b-5p down-regulation or KPNA2 overexpression. It was interesting to note that HAGLROS inactivated p53 signaling through targeting miR-26b-5p/KPNA2. In conclusion, our results demonstrated that HAGLROS contributed to the malignant progression of HCC via serving as a sponge for miR-26b-5p to facilitate KPNA2 expression and inactivate p53 signaling. Targeting HAGLROS/miR-26b-5p/KPNA2 axis might be an alternative therapeutic strategy for HCC patients.

Black Phosphorus The “Tao Wu” is a fierce beast in Chinese legend, which here is symbolizing tumors. When it encounters black phosphorus, it transforms into a cat. This is analogous to how black phosphorus can effectively reverse the drug resistance of tumors and be better killed by anti‐tumor medications. This work is found in article 2301324by Xianbin Zhang, Peng Gong, and co‐workers.

Black phosphorus (BP) exhibits significant potential for clinical applications. However, further research is necessary to uncover the unknown biological functions of BP and broaden its applications across various fields. This study investigates the potential of BP as a targeting PPAR‐γ agonist to overcome chemoresistance in the treatment of pancreatic adenocarcinoma (PAAD) using 2D and 3D cell lines, patient‐derived organoids (PDOs), and mouse models. RNA‐sequencing analysis shows that BP treatment enriches differentially expressed genes in the PPAR pathway, and molecular modeling predicts the potential docking site between BP and PPAR‐γ. Transcriptional activity assays are further to verify the activation of PPAR‐γ. BP‐activated PPAR‐γ inhibits cancer stem cell (CSC) properties and expression of biomarkers such as CD44 and c‐Myc, which are involved in chemoresistance. Notably, CD44 overexpression in tumor cells renders them susceptible to BP while insensitive to gemcitabine. This indicates that BP preferentially targets stem‐like cells, which exhibit heightened resistance to chemotherapeutic drugs. A combination treatment strategy involving BP and gemcitabine is developed, demonstrating enhanced treatment efficacy of PAAD in both in vitro and in vivo models. Thus, BP serves as a PPAR‐γ agonist capable of reversing chemoresistance, establishing it as a potent anti‐tumor approach for the treatment of PAAD. Black phosphorus (BP) activates PPAR‐γ in tumor cells, leading to two important functions: inducing survivin‐related cell apoptosis and reducing chemotherapy resistance associated with cancer stemness. In pancreatic adenocarcinoma, BP effectively overcomes gemcitabine resistance by reducing cancer stemness. These findings suggest the potential of BP as a therapeutic strategy to treat cancer by functioning as a PPAR‐γ agonist.

ABO-incompatible (ABO-i) living-donor liver transplantation (LDLT) is performed if an ABO-compatible graft cannot be obtained. However, a perfect desensitization protocol has not been established worldwide, especially for simultaneous ABO-i LDLT and splenectomy. We herein report two cases of ABO-i LDLT. To the best of our knowledge, this is the first case report of ABO-i LDLT in an adult patient in China. Splenectomy and T-cell-targeted immunosuppression (basiliximab) was used to overcome the blood group barrier in these recipients. The patients had good graft function without signs of antibody-mediated rejection throughout the 12-month follow-up. Thus, ABO-i LDLT with splenectomy is undoubtedly life-saving when an ABO-compatible graft cannot be obtained for patients in critical condition.

We describe a scalable method for preparing an aminopyrazole building block using copper-catalyzed amidation with acetamide as an ammonia surrogate. This procedure provides an alternative to the standard nitration/reduction sequence and avoids energetic intermediates, specialized hydrogenation equipment, and potentially genotoxic impurities that arise from nitro reduction. The chemistry has been successfully scaled to produce >50 kg of the target compound and demonstrate the viability of this alternative route.