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Rhodium(III)-catalyzed C2-selective C–H activation of indoles bearing a 1,3,5-triazine directing group (DG) with conjugated addition to maleimides under an air atmosphere has been described, furnishing the corresponding products in up to 95% yield. This transformation proceeds efficiently with low catalyst loading, a broad range of substrates with excellent site selectivity, satisfactory product yields and functional group tolerance. The gram-scale reaction was successfully conducted with 0.5 or 0.1 mol% of [RhCp*Cl2]2 without a significant decrease in yield. [ABSTRACT FROM AUTHOR]

Numerous deep leaning methods for low-dose computed technology (CT) image denoising have been proposed, achieving impressive results. However, issues such as loss of structure and edge information and low denoising efficiency still exist.To improve image denoising quality, an enhanced multi-dimensional hybrid attention LDCT image denoising network based on edge detection is proposed in this paper.In our network, we employ a trainable Sobel convolution to design an edge enhancement module and fuse an enhanced triplet attention network (ETAN) after each 3 × 3 convolutional layer to extract richer features more comprehensively and suppress useless information. During the training process, we adopt a strategy that combines total variation loss (TVLoss) with mean squared error (MSE) loss to reduce high-frequency artifacts in image reconstruction and balance image denoising and detail preservation.Compared with other advanced algorithms (CT-former, REDCNN and EDCNN), our proposed model achieves the best PSNR and SSIM values in CT image of the abdomen, which are 34.8211and 0.9131, respectively.Through comparative experiments with other related algorithms, it can be seen that the algorithm proposed in this article has achieved significant improvements in both subjective vision and objective indicators. [ABSTRACT FROM AUTHOR]

Background and Purpose: As a highly heterogeneous cancer, hepatocellular carcinoma (HCC) shows different response rates to the multi-kinase inhibitor lenvatinib. Thus, it is important to explore genetic biomarkers for precision lenvatinib therapy in HCC., Experimental Approach: The effect and mechanism of AXIN1 mutation on HCC were revealed by cell proliferation assay, long-term clone formation assay, sphere formation assay and small molecule inhibitor library screening. A new therapeutic strategy targeting HCC with AXIN1 mutation was evaluated in humanized models (patient-derived xenograft [PDX] and patient-derived organoid [PDO])., Key Results: Based on The Cancer Genome Atlas (TCGA) data, we screened 6 most frequently lost tumour suppressor genes in HCC (TP53, ARID1A, AXIN1, CDKN2A, ARID2 and PTEN) and identified AXIN1 as the most crucial gene for lenvatinib sensitivity. Further study showed that AXIN1-knockout HCC cells had a more malignant phenotype and lower sensitivity to lenvatinib in vitro and in vivo. Mechanistically, the WNT pathway and its target gene c-Myc were activated when AXIN1 was missing, and the expression of tumour suppressor p15 was inhibited by transcription co-repressors c-Myc and Miz-1, resulting in the exacerbation of the resistant phenotype. Screening of a library of epigenetic-related enzyme inhibitors showed that a KDM5B inhibitor up-regulated p15 expression, leading to increased sensitivity to lenvatinib in vitro and in vivo., Conclusion and Implications: AXIN1-deficient patients have a lower response to lenvatinib, which may be associated with suppression of p15 mediated by WNT pathway activation. KDM5B inhibitors can restore p15 levels, resulting in efficient killing of resistant cells in HCC., (© 2024 British Pharmacological Society.)

To investigate the influence of early dysphagia on quality of life in patients with partial laryngectomy, and to investigate the application value of Flexible Endoscopic Evaluation of Swallowing (FEES). This study included 30 inpatients who underwent partial laryngectomy due to laryngeal cancer. In the early postoperative period, a comprehensive assessment was conducted on each patient, encompassing Videofluoroscopic Swallowing Study (VFSS), Flexible Endoscopic Evaluation of Swallowing (FEES), and MD Anderson Dysphagia Inventory (MDADI). Each patient underwent two evaluations at different time points following the surgical procedure, all conducted on the same day. The patients' first MDADI assement score after surgery was 45.4 ± 3.6 points, and the second score was 54.7 ± 13.4 points. VFSS as the gold standard, FEES showed good sensitivity (84%) and specificity (94%) for detecting aspiration, as well as good sensitivity (78%) and moderate specificity (86%) for detecting penetration. The Kappa consistency test results showed high consistency between FEES and VFSS swallowing function evaluations (Kappa value = 0.669); evaluations of thin liquid, thick liquid, and solid bolus had high consistency (Kappa value = 0.631, 0.675, and 0.678, respectively), while evaluations of semi-liquid bolus had poor consistency (Kappa value = 0.598); evaluations of four bolus sizes all had high consistency (Kappa value = 0.658, 0.647, 0.705, 0.670). The Kappa values for evaluating patients undergoing horizontal partial laryngectomy, vertical partial laryngectomy, and supraglottic laryngectomy were 0.572, 0.604, and 0.680, respectively. This study shows that dysphagia is an important problem affecting the early quality of life of patients after partial laryngectomy, and early instrumental evaluation is also extremely important. This study also emphasizes the reliability problems in the identification of false invasion and aspiration. FEES can be used to evaluate the early swallowing function of patients after partial laryngectomy, thus guiding the timing and type of eating, and evaluating the rehabilitation effect. In addition, compared with VFSS, FEES have more advantages for the identification of penetration., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Ethics Committee of the First Hospital of Shanxi Medical University (No.KYLL-2023-191). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2025. The Author(s).)

Mutant EGFR is a common driver of non-small cell lung cancer (NSCLC). Although mutant EGFR has been reported to limit the efficacy of immunotherapy, a subset of patients with EGFR-mutant NSCLC benefit from treatment with immune checkpoint inhibitors. A better understanding of how co-occurring genomic alterations in oncogenic driver genes impact immunotherapy efficacy may provide a more complete understanding of cancer heterogeneity and identify biomarkers of response. Here, we investigated the effects of frequent EGFR co-mutations in EGFR-mutant lung cancer models and identified loss-of-function mutation of CDKN2A as a potential sensitizer to anti-PD-1 treatment in vitro and in vivo. Mechanistically, CDKN2A loss impacted the composition of the tumor immune microenvironment by promoting the expression of PD-L2 through reduced ubiquitination of c-MYC, and mutant EGFR cooperating to upregulate c-MYC and PD-L2 by activating the MAPK pathway. Blocking PD-L2 induced antitumor immune responses mediated by CD8+ T cells in EGFR/CDKN2A co-mutated lung cancer. Importantly, a small-molecule PD-L2 inhibitor, zinc undecylenate, remodeled the tumor immune microenvironment of EGFR/CDKN2A co-mutant tumors and enhanced the antitumor efficacy of EGFR tyrosine kinase inhibitors. Collectively, these results identify EGFR/CDKN2A co-mutation as a distinct subtype of NSCLC that shows superior sensitivity to immune checkpoint blockade and reveals a potential combined therapeutic strategy for treating this NSCLC subtype. Significance: Upregulation of c-MYC driven by co-mutation of CDKN2A and EGFR increases PD-L2 to abrogate CD8+ T-cell activity in lung cancer, which confers sensitivity to PD-L2 blockade in combination with tyrosine kinase inhibitors., (©2024 American Association for Cancer Research.)