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Purpose: Stereotactic body radiotherapy (SBRT) may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors. This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab (an anti-PD1 monoclonal antibody) in patients with unresectable hepatocellular carcinoma (uHCC). Methods: Patients with uHCC, Child–Pugh A/B liver function, and at least one measurable lesion were enrolled between April 2020 and August 2022. Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks. Palliative SBRT was delivered daily over five fractions per week, with a dose range of 30–50 Gy. The primary endpoints were objective response rate (ORR) and safety. This trial was registered at ClinicalTrials.gov (NCT04193696). Results: Twenty-one patients were enrolled; the median radiation dose was 40 Gy, and the median number of cycles of camrelizumab was five. The ORR was 52.4%. After a median follow-up of 19.7 months, the median progression-free and overall survival were 5.8 and 14.2 months, respectively. The overall survival probability was 85.7% at 6 months, 76.2% at 9 months, and 59.9% at 12 months. All grade 3 treatment-related adverse events (TRAEs) occurred in five patients (23.8%) and were manageable. No grade 4/5 TRAEs were observed. Conclusion: Palliative SBRT plus camrelizumab showed promising antitumor activity against uHCC. Toxicities were manageable with no unexpected safety issues. This study provides evidence of a new therapeutic method for the treatment of uHCC. [ABSTRACT FROM AUTHOR]

We isolated a 2-alkenal reductase (AaAER) gene from Artemisia annua L. cDNA library through homologous cloning strategy. Enzymatic properties of AaAER, including substrate selectivity, enzyme kinetics, and key factors affecting enzyme activity, were characterized in vitro. We found that AaAER mainly functions in catalyzing the reduction of adjacent straight chain 'C = C' double bond in the carbonyl group. This suggests the possibility of its participation in downstream events of the HPL (hydroperoxide lyase) pathway and contribution to cell detoxification in plants. Although, AaAER shares some substrates with AaDbr 1 and AaDbr 2, which are involved in artemisinin biosynthesis, AaAER was unable to reduce the adjacent double bond of carbonyl group in artemisinic aldehyde. We also analyzed the possible causes for highly homologous reductases with different types of substrates and non-homologous enzymes sharing the same substrate. The identification of a novel double bond reductase in A. annua provides an opportunity to explore the mechanism underlying the detoxification of aldehyde ketone molecules, which are generated by HPL downstream pathway and the redox process in the metabolic pathway of artemisinin synthesis. [ABSTRACT FROM AUTHOR]