Transport pathway of the Ag+ following artificial precipitation enhancement activities.

Artificial precipitation enhancement (APE) activities have been applied extensively around the world to enhance water resources. However, the transport way of the silver iodide catalyst utilized remains completely unknown. To address this issue, in this study, we monitored the content of silver ions (Ag+) in a water body under the influence of APE for a period of 16 years (2004-2019). Additionally, we monitored the content of silver ions in the multi-period rainfall and soil. Our findings indicate that after the APE operation, the detected silver content in the precipitation initially demonstrated an upward trend and then decreased to 0. Furthermore, we observed that some of the silver ions remained in the air for a period extending from the time of artificial rain till the next rain. The silver ion content in the soil during the flood season was elevated by 44 % in comparison to the non-operation period; the concentration of silver ions in the water body during the operation period was 42.86 % higher than that in the non-operation period. During the long-term study, spanning 16 years, the water body played a leading role in regulating the content of silver ions released by the APE, resulting in an increase in silver ion content by 3.3 %. Our results revealed the presence of silver in the precipitation after the APE operation, indicating that silver iodide initially entered the precipitation after catalysis. Furthermore, upon the comparison of the soil and surface water during the operation period and non-operation period, the silver content during the operation period was observed to be higher than that in the non-operation period, indicating that silver iodide was incorporated into the underlying surface from the precipitation. Therefore, we have concluded that the transport pathway of silver involves its initial entry into precipitation after sowing, subsequently descending with the precipitation to reach the soil and surface water. The findings of this study establish a scale ruler for the impact of increasing global APE activities on the environment, as well as first-hand data for preventing possible future environmental risks.

Causal relationship between immune cell phenotypes and risk of biliary tract cancer: evidence from Mendelian randomization analysis.

Background: Biliary tract cancer stands as a prevalent illness, posing significant risks to human health, where immune cells are pivotal in both its development and recovery processes. Due to the diverse functionalities exhibited by different immune cell phenotypes within the organism, and the relatively limited research on their relationship with biliary tract cancer, this study employed Mendelian randomization (MR) to explore their potential association, thereby aiding in a better understanding of the causal link between immune cell phenotypes and biliary tract cancer. Methods: In this study, the causative association of 731 immunophenotype with biliary tract cancer was established using publicly accessible genome-wide association study (GWAS) genetic data through two-sample MR analysis. Sensitivity analyses assess horizontal pleiotropy and heterogeneity of the study findings. Results: Among the 731 immunophenotypes examined, a total of 26 immune cell phenotypes were found to exhibit positive results, indicating a significant association with the risk of biliary tract cancer. We confirmed that among these 26 types of immune cells, there are primarily 13 types of B cells; three types of classical dendritic cells (CDCs), including CD80 on myeloid DC, HLA DR on myeloid DC, and Myeloid DC %DC; one type of mature stage T cell,CD4RA on TD CD4+; six types of regulatory T cells; and three types of myeloid cells.

HER2-targeting antibody drug conjugate FS-1502 in HER2-expressing metastatic breast cancer: a phase 1a/1b trial.

Currently approved HER2-targeting antibody-drug conjugates (ADCs) for HER2-positive breast cancer (BC) are associated with safety concerns. In this multicenter, single-arm, dose-escalation (phase 1a) and dose-expansion (phase 1b) phase 1 trial (NCT03944499), patients with HER2-expressing advanced solid tumors received FS-1502 (an anti-HER2 ADC) with a 3 + 3 design in phase 1a; patients with metastatic HER2-positive BC received FS-1502 at the recommended phase 2 dose (RP2D) in phase 1b. The primary end points were dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D for phase 1a and objective response rate (ORR) for phase 1b. A total of 150 patients with HER2-expressing solid tumors (n = 5) and BC (n = 145) were enrolled (female, n = 146, 97.3%). One DLT each was reported at 3.0 and 3.5 mg/kg; the MTD was not reached. The RP2D was 2.3 mg/kg once every 3 weeks. Five (3.3%) patients experienced pneumonitis; four (2.7%) had grade 3 reversible ocular events. Of 67 HER2-positive BC patients receiving the RP2D, the best ORR was 53.7% (95% CI, 41.1-66.0%), including PRs confirmed (confirmed ORR, 37.5%) and pending for confirmation. FS-1502 was well tolerated with limited ocular and pulmonary findings and demonstrated promising antitumor activity in HER2-positive BC patients.

Technical Note: Induced radioactivity in stereotactic body radiation therapy with a flattening-filter-free 10 MV beam model.

PURPOSE: The induced radioactivity in stereotactic body radiation therapy with a flattening-filter-free 10 MV beam model (10 FFF SBRT) was investigated for the risk to therapists. METHODS: This study was performed on a Varian TrueBeam linac. The induced radioisotopes were identified by γ spectroscopy. The dose rate from the induced activity was measured for 12 treatment cycles in 4 h continuously. The impacts of the characteristic factors of 10 FFF SBRT on the dose rate were investigated, including monitor units (MU), beam rate, field size, and flattening filter. The dose rate was compared between the SBRT plans and conventional fractionation plans. A mathematical model was used to analyze the results and estimate the annual dose to therapists. RESULTS: (a) The induced radioisotopes included 24 Na, 28 Al, 38 Cl, 56 Mn, 66 Cu, 187 W, and 196 Au. (b) In 4 h, the total dose contribution ratios were more than 70% for 28 Al, about 20% for 56 Mn, and 10% for all other long-lived radioisotopes, combining doses at the isocenter and end of the treatment couch. (c) The dose rate showed a nonlinear growth with increasing MU and beam rate. The variation of the dose rate was complicated with the jaw field and not sensitive to the MLC field. The removal of the flattening filter reduced the dose rate by about 40%. The dose level of SBRT was two to three times that of conventional fractionation. (d) The estimated annual dose to therapists was up to 0.20 mSv/y. CONCLUSIONS: The induced radioactivity in 10 FFF SBRT was higher compared with that in 10 MV conventional fractionation. More MU and higher beam rate were the primary factors that caused the increase. The therapists should wait longer after beam-off to reduce the occupational dose. In addition, aluminum and manganese should be less used in the treatment room.

lncRNA LINC00152 knockdown had effects to suppress biological activity of lung cancer via EGFR/PI3K/AKT pathway.

Accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression and are involved in various pathological processes. In our present study, we firstly evaluated lncRNA LINC00152 and EGFR expressions by ISH or IHC methods, and analyzed the correlation between LINC00152 and EGFR with RT-PCR. lncRNA LINC00152 of NSCLC tissues were significantly up-regulation compared with adjacent normal tissues and positively correlated with EGPR. The further cell experiments demonstrated that Linc00152 knockdown had effects of suppression cell proliferation, invasion and migration abilities and improving cell apoptosis and G1 phase rates in both A549 and H1299 cell lines. In the mechanism study, the results were shown that EGFR, PI3K, AKT, Fibronectin and Vimentin proteins expressions were significantly reduced and P21 protein expression was significantly increased in Linc00152 knockdown groups. Our results suggested lncRNA LINC00152 knock-down had anti-tumor effects via EGFR/PI3K/AKT pathway.