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关键词： Biomarkers   Hepatocellular carcinoma   Immune checkpoint inhibitors   Neutrophil-to-Lymphocyte Ratio  

摘要： Purpose: Immune checkpoint inhibitors (ICIs) are the preferred treatment for advanced hepatocellular carcinoma (HCC). However, most patients do not respond to initial immunotherapy alone, even when combined with other therapies. Our study aimed to profile ICI-based therapies for HCC patients in real-world clinical practice and to identify factors associated with survival and treatment efficacy. Methods: A retrospective cohort study was conducted to describe ICI-based therapies for HCC patients at our center, including combination modalities, effectiveness, and safety. Pre- and post-treatment indicators were collected to explore factors related to progression-free survival (PFS) and treatment efficacy in these patients. Results: All 110 patients received therapy based on immune checkpoint inhibitors (ICIs) using three strategies, with the majority (60.9%) undergoing triple combination therapy. The overall progression-free survival (PFS) was 7.0 months, and the objective response rate (ORR) was 26.4%. Analysis of PFS identified several independent risk factors: a history of hepatitis B virus (HBV) infection (hazard ratio [HR] = 1.78), a platelet-to-lymphocyte ratio (PLR) greater than 276.9 (HR = 2.19), and an international normalized ratio (INR) greater than 1.2 (HR = 3.49). Conversely, the use of PD-1 inhibitors was associated with a favorable outcome (HR = 0.44). The combination of a history of HBV infection with HBeAg positivity and TNM stage (III + IV) effectively distinguished responders from non-responders. Additionally, neutrophil count and the neutrophil-to-lymphocyte ratio (NLR) were significantly elevated in non-responders and exhibited dynamic changes during treatment. Conclusion: In HCC clinical practice, ICI-based systemic therapies are both effective and safe. Patient characteristics can serve as reliable predictors of progression-free survival (PFS) and treatment efficacy. Importantly, neutrophil count and the neutrophil-to-lymphocyte ratio (NLR) may al

摘要： Following publication of the original article [1], the authors reported that, upon verification, they identified that three image panels were inadvertently mislabeled during the figure assembly process. Specifically, in Figure 3f, the panel representing the LOVO-NC group was incorrectly sourced from the HCT116-NC group in Figure 3e. Likewise, in Figure 5e, the panel for the LOVO-NC group was mistakenly used from the corresponding HCT116-NC group within the same figure. Additionally, the panel labeled as LOVO-sh-GAS5 in Figure 5e was erroneously selected from the RKO-sh-GAS5 group in the same figure. Upon identifying these errors, the authors immediately retrieved the correct raw data and have now replaced all affected panels with the accurate images in the revised versions of Figure 3 and Figure 5. They would like to emphasize that this error was unintentional and does not affect the experimental results, data interpretation, or the conclusions of the study. The incorrect and correct figures are provided below. Incorrect Figure 3: (Figure presented.) Correct Figure 3: (Figure presented.) Incorrect Figure 5: (Figure presented.) Correct Figure 5: (Figure presented.).

摘要： Correction to: Cell Death & Diseasehttps://***/10.1038/s41419-025-08123-9, published online 18 November 2025 During our recent internal self-inspection, we identified that two IP bands in Figure 5I appear highly similar. After careful reflection and thorough analysis by the research team, we determined that this band duplication was caused by an inadvertent error during figure preparation. The original data for the manuscript have been fully preserved, are authentic and reliable, and were submitted to the journal at the time of initial submission. This image misuse does not affect the scientific integrity of the study or the validity of its conclusions. The original article has been corrected.

关键词： Anti-fibrotic   M2 macrophages   Phytochemicals   Pulmonary fibrosis   Rubiadin-1-methyl ether  

摘要： To investigate the therapeutic effects of Rubiadin-1-methyl ether (RBM) on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism by which it inhibits fibrosis through the modulation of macrophage polarization. A C57BL/6 mouse model of pulmonary fibrosis was established by intratracheal injection of BLM (3 mg/kg), followed by oral administration of RBM (3, 10, 30 mg/kg). Lung injury was assessed through histopathological examinations (HE and Masson staining), lung coefficient measurements, bronchoalveolar lavage fluid (BALF) inflammatory cell counts, and cytokine detection (TGF-β1, IL-6, etc.). Flow cytometry was employed to analyze M2 macrophages (F4/80⁺CD206⁺) in lung tissue, and qRT-PCR was used to measure the expression of fibrosis markers (Fn1, Col1a1, Acta2) and M2-related genes (Mrc1, Arg1, Tgfb1, Il10). RBM at 10 mg/kg exhibited the most potent therapeutic effect: it significantly ameliorated BLM-induced weight loss, reduced the elevated lung coefficient, and attenuated lung tissue pathological damage. In BALF, RBM reduced the total number of inflammatory cells by ~ 47.2%, with significant decreases in neutrophils (~ 59.4%) and lymphocytes (~ 25.6%) compared to the BLM group. Additionally, RBM downregulated the mRNA expression of fibrosis-associated genes: Fn1 (by ~ 52.4%), Col1a1 (by ~ 30.8%), and Acta2 (by ~ 44.3%). Flow cytometry analysis showed that RBM inhibited M2 macrophage polarization, reducing the proportion of F4/80⁺CD206⁺ cells from 28.4% ± 5.7% (BLM group) to 19.8% ± 1.8%. Correspondingly, the mRNA levels of M2 marker genes were significantly downregulated: Mrc1 (by ~ 48.3%), Arg1 (by ~ 46.1%), Tgfb1 (by ~ 59%), and Il10 (by ~ 38.7%). RBM also reduced the secretion of pro-inflammatory and pro-fibrotic factors in BALF: TGF-β1 (by ~ 28.7%), IL-6 (by ~ 26.5%), IL-1β (by ~ 55%), and TNF-α (by ~ 51%). RBM significantly attenuates pulmonary inflammation and collagen deposition, likely by inhibiting macrophage M2 polarization a

摘要： The original version of this article unfortunately contained an error introduced during the production process. The author’s name, ‘Jasmin Hasanovic,’ appeared as both the first and last author. ‘Jasmin Hasanovic’ should be listed as the first author, and ‘Felix Merboth’ should be listed as the last author. The original article has been corrected.

关键词： CD8 + T cell   CXCL10-CXCR3 axis   Mutant p53   Prostate cancer   Single-cell RNA sequencing  

摘要： Background: TP53 mutations are frequently linked to an immunosuppressive tumor microenvironment and resistance to immune checkpoint blockade (ICB). However, their mechanistic role in shaping antitumor immunity in advanced prostate cancer remains unclear. Methods: We generated CRISPR-Cas9-engineered murine prostate cancer models harboring the Trp53 p.R245Q knock-in mutation (orthologous to human TP53 p.R248Q). Tumor growth and response to anti-PD-1 therapy were evaluated in vivo. Single-cell RNA sequencing and integrated immune profiling were performed to characterize stromal and immune remodeling. Chromatin immunoprecipitation assays were used to assess mutant p53 binding and histone modifications at the Cxcl10 promoter. Statistical significance was assessed using Student’s t-test, Wilcoxon rank-sum test, and one-/two-way ANOVA, as appropriate. Results: Mutant p53 accelerated tumor progression yet unexpectedly enhanced responsiveness to anti-PD-1 therapy within an otherwise suppressive microenvironment. Single-cell transcriptomics revealed epithelial lineage and metabolic rewiring, accompanied by depletion of cancer-associated fibroblasts and a shift toward immune-permissive stromal states. Immune profiling demonstrated increased infiltration of cytotoxic CD8⁺ granzyme B⁺ T cells and augmented lymphoid and vascular features. Mechanistically, mutant p53 occupied the Cxcl10 promoter, remodeled local chromatin by enriching H3K4me3 while reducing repressive histone marks, and transcriptionally upregulated Cxcl10. This established a CXCL10–CXCR3 chemotactic axis that promoted recruitment of cytotoxic CD8⁺ T cells and sensitized tumors to PD-1 blockade. Consistently, cohort analysis further supported that high CXCL10 expression correlated with immune activation and clinical benefit from ICB. Conclusions: These findings indicate that mutant p53 can reprogram immune-cold prostate tumors into immune-hot ecosystems through coordinated epigenetic, metabolic, and stromal-immune

摘要： Achieving precise stereocontrol when forging two vicinal C(sp³)–C bonds on unsymmetrical internal alkenes remains a formidable challenge. The comparable reactivity of alkyl radicals often compromises chemo- and regioselectivity, while the concurrent induction of diastereo- and enantioselectivity has proven elusive. Here, we show a unified metallaphotoredox strategy that addresses these challenges through two complementary multicomponent difunctionalization protocols. First, a Ni/terpyridine catalyst system enables anti-selective 1,2-dialkylation of both cyclic and acyclic internal alkenes, delivering vicinal C(sp³)–C(sp³) linkages with high levels of chemo-, regio-, and diastereoselectivity. A switch to a chiral biimidazole ligand and replacement of the alkyl halide with a (hetero)aryl bromide unlocks enantioselective 1,2-alkylarylation of cyclic internal alkenes. This transformation affords β-aryl-α-alkylated lactones and related scaffolds bearing two contiguous stereocenters with excellent diastereo- and enantioselective control. This dual strategy offers a rapid and efficient access to drug-like molecular architectures.

关键词： Global Increlex® growth forum database   Growth dynamics   Height response   Hypoglycemia   Laron syndrome   Pubertal timing   Recombinant human (rh) insulin-like growth factor (IGF)-1   Severe primary IGF-I deficiency  

摘要： The Growth Hormone – Insulin-like Growh Factor - axis promotes linear growth in children and adolescents and accounts for approximately 1/3 of adult height. In Primary IGF-I deficiency (PIGFD) insensitivity to the actions of GH results in short stature. The most severe phenotype in children with genetic defects in the GH receptor gene is known as Laron Syndrome with height SDS of −6 to −12 in childhood and an adult height of 120–130 cm. Treatment with recombinant human (rh) IGF-1 is approved to promote linear growth in children with severe PIGFD and the EMA approval required that data on children on therapy and up to 5 years post-treatment is collected in the Global Increlex Growth Forum Database (IGFD) registry.

摘要： Correction to: Cell Death Discoveryhttps://***/10.1038/s41420-024-01856-0, published online 17 February 2024 In this article, we incidentally mis-placed pictures from a different file due to a careless overlook during our figure ppt slide preparation. Incorrect figure (Figure presented.) Correct figure (Figure presented.) Incorrect figure (Figure presented.) Correct figure (Figure presented.) The original article has been corrected.

摘要： Following publication of the original article [1], the authors identified an error in the competing interests section. Below is the correct information. Incorrect competing interests section: AG is currently an employee of the Canadian Agency for Drugs and Technologies in Health (CADTH). The current work was unrelated to her employment and CADTH had no role in the funding, design, or oversight of the work. The remaining authors declare that they have no competing interests. Correct competing interests section: AG is currently an employee of the Canada's Drug Agency (CDA). The current work was unrelated to her employment and CDA had no role in the funding, design, or oversight of the work. The remaining authors declare that they have no competing interests. The original article has been corrected.