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关键词： apigenin   colorectal cancer   inflammatory   SMOX  

摘要： Tumor microenvironments, particularly hypoxia and inflammation, heavily influence colorectal cancer (CRC) pathogenesis by altering polyamine metabolism. Identifying natural compounds targeting these vulnerabilities remains critical. Integrating untargeted metabolomics, network pharmacology, and a human endogenous metabolite library screen, we identified apigenin (API) as a potent anti-CRC candidate. API significantly inhibited the proliferation, migration, and invasion of RKO and HCT116 cells in vitro and suppressed xenograft tumor growth in vivo. Crucially, high-throughput screening revealed that polyamines rescued CRC cells from API-induced cytotoxicity. Mechanistically, API exerts its effects by dismantling a newly identified HIF-1 alpha/SMOX positive feedback loop. In CRC, HIF-1 alpha transcriptionally activates spermine oxidase (SMOX), while SMOX-driven polyamine metabolism fuels the TLR4/MyD88 inflammatory cascade to continuously stabilize HIF-1 alpha. API acts as a "circuit breaker" for this axis, significantly reducing the spermidine/spermine ratio and downregulating inflammatory signaling. Ultimately, API effectively remodels polyamine metabolism and suppresses CRC progression by disrupting the HIF-1 alpha/SMOX and TLR4/MyD88 pathways, offering a novel metabolic mechanism for API in CRC therapy.

关键词： abdominal injury   angioembolisation   laparoscopy   laparotomy   surgical training   trauma  

摘要： Background Advances in imaging, non-operative management, and endovascular techniques have reshaped abdominal trauma care, but their impact on operative trends in blunt-dominant Australian trauma systems is incompletely described. Aims To describe temporal trends in operative and minimally invasive management of abdominal trauma at an Australian Level 1 trauma centre, and to discuss their implications. Methods A retrospective study of the Alfred Health Trauma Registry (2001-2024) identified adult major trauma (MT) patients (ISS > 12) undergoing emergency laparotomy, laparoscopy, or solid-organ embolisation within 24 h of admission. Temporal trends were assessed using linear regression and offset Poisson models. Sensitivity analyses used abdominal AIS >= 2 as the denominator. Results Among 25 497 major trauma patients, 1330 (5.2%) underwent laparotomy, 107 (0.4%) laparoscopy, and 417 (1.6%) embolisation. Annual major trauma presentations increased from 643 to 1498, while the number of patients with abdominal AIS >= 2 also rose. Laparotomy rates declined significantly over time, from 10.7% to 2.7% of major trauma admissions (R-2 = 0.80;p < 0.01), with the decline persisting when abdominal AIS >= 2 was used as the denominator. Embolisation increased significantly, whereas laparoscopy volumes rose numerically but did not demonstrate a consistent statistically significant temporal increase. Conclusion Emergency trauma laparotomies have declined despite increasing trauma volume and abdominal injury burden, consistent with greater use of selective non-operative and endovascular strategies. These changes have implications for maintaining operative readiness within contemporary multidisciplinary trauma systems.

关键词： 不对称催化   配体接力   钯催化   Tsuji-Trost反应   卡宾插入  

摘要： 经历钯-卡宾中间体的不对称环化反应为构建手性环状骨架提供了高效途径,但其发展仍面临重大挑战。本研究报道了一种钯催化的不对称[4+1]环化反应,利用动态多配体接力不对称催化策略成功构建手性茚满类化合物。该配体接力体系采用双齿Pyrox配体促进氧化加成步骤,同时使用单齿Feringa型磷酰胺配体促进卡宾化/迁移插入过程及后续分子内Tsuji-Trost反应。