Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma.

BACKGROUND: The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated. AIM: To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC. METHODS: We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen. RESULTS: The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs). CONCLUSION: The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.

Temporal variability of air-water gas exchange of carbon dioxide in clam and fish aquaculture ponds.

The growing trend of land-based aquaculture has heightened the significance of comprehensively assessing air-water carbon dioxide (CO2) gas exchange in these inland waters, given their potential impact on carbon neutral strategies. However, temporal variations of partial pressure of CO2 (pCO2) and CO2 flux in clam and fish aquaculture ponds were barely investigated. We assessed the water surface pCO2 in one to five months intervals by deploying a lab-made buoy in three clam ponds and three fishponds located in tropical and subtropical climates. Measurements were conducted over a 24 h period each time, spanning from April 2021 to June 2022, covering the stocking, middle, and harvesting stages of the culture cycle. Diurnal pCO2 variations were dominantly controlled by biologically driven changes in dissolved inorganic carbon and total alkalinity (~97 %), while temperature and salinity effects were minor (~3 %). Clam ponds acted as a sink of atmospheric CO2 during stocking stages and transitioned to a source during middle to harvesting stages. In contrast, fishponds acted as a source of atmospheric CO2 throughout culture cycles and CO2 flux strengthened when reaching harvesting stages. Overall, clam ponds acted as a weak sink for atmospheric CO2 (-2.8 ± 17.3 mmol m-2 d-1), whereas fishponds acted as a source (16.8 ± 21.7 mmol m-2 d-1). CO2 emission was stronger during daytime coinciding with higher windspeeds compared to nighttime in fishponds. We suggest incorporating high temporal resolution measurements to account for diurnal and culture-stage variations, enabling more accurate estimates of air-water CO2 flux in aquaculture ponds. Moreover, the findings of this study highlight the importance of feeding, aeration, and biological activities (photosynthesis, remineralization, and calcification) in controlling the air-water CO2 flux in aquaculture ponds and such information can be used in implementing better strategies to achieve carbon neutral goals.

Atranones from Stachybotrys chartarum and their antitumor activities in MG-63 human osteosarcoma cells.

Two new atranones T and U (1 and 2), and three known analogues atranone B (3), atranone Q (4), and stachatranone C (5) were isolated from the toxigenic fungus Stachybotrys chartarum. Their structures and absolute configurations were elucidated by spectroscopic data and calculated ECD analyses. The cytotoxicities of all the atranones (1-5) were evaluated against MG-63 human osteosarcoma cell lines. Compound 4 exhibited significant cytotoxic effect against MG-63 with IC50 value of 8.6 µM, being more active than the positive control, 5-FU (IC50 10.4 µM). Morphological features of apoptosis activities were evaluated in 4-treated MG-63 cells. Compound 4 effectively induced apoptosis of MG-63, which was associated with G0/G1-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 4 significantly induced MG-63 cell apoptosis in a dose-dependent manner.