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LY01005 is an investigational new drug product of goserelin acetate which is formulated as extended-release microspheres for intramuscular injection. To support the proposed clinical trials and marketing application of LY01005, pharmacodynamics, pharmacokinetics and toxicity studies were performed in rats. In the pharmacological study in rats, LY01005 induced an initial supra-physiological level increase of testosterone at 24 h post-dosing which then rapidly fell to castration level. The potency of LY01005 was comparable to the comparator Zoladex® but its effect lasted longer and more stable. A single-dose pharmacokinetics study in rats demonstrated that the Cmax and AUClast of LY01005 increased in a dose-proportional manner in the range of 0.45–1.80 mg/kg and the relative bioavailability was 101.0% between LY01005 and Zoladex®. In the toxicity study, almost all of the positive findings of LY01005 in rats including the changes in hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, progestin) and in reproductive system (uterus, ovary, vagina, cervix uteri, mammary gland, testis, epididymis and prostate) were related to the direct pharmacological effects of goserelin. Mild histopathological changes in foreign body removal reaction induced by excipient were also observed. In conclusion, LY01005 displayed a sustained-release profile of goserelin, and exerted a continuous efficacy in vivo in animal models, which had a comparable potency but with a more sustained effect than that of Zoladex®. The safety profile of LY01005 was largely the same with Zoladex®. These results strongly support the planned LY01005 clinical trials.

The cumulative probability distribution of the lightning current amplitude can reflect the lightning activity and is important for the lightning protection engineering technology. Based on the lightning location data from 2009 to 2019, the distribution characteristics of the lightning current amplitude and cumulative probability are studied. The results show that a total of 8,634,858 lightning flashes occurred in Zhejiang province in last 11 years. Negative flashes are much more common than positive ones, accounting for 87.44% of the total. The percentage of the lightning current amplitude between 2 and 100 kA is 94.3%. The average amplitude of positive flashes is significantly higher than that of negative flashes. For the current amplitude of positive flashes, the peak occurs in March and gradually decreases with the increase of the month, reaching its lowest in December. But the monthly distribution of negative flashes is relatively concentrated, especially from February to October. When lightning current amplitude is higher than 25.5 kA, the cumulative probability of positive flashes is significantly higher than that of negative flashes and vice versa. The cumulative probability distribution of negative flashes is closer to that of total flashes and is significantly different from that of positive flashes. In order to get a more suitable cumulative probability formula of lightning current amplitude and corresponding parameters in Zhejiang province, the Levenberg–Marquardt method is used. By fitting the measured data with the formulas recommended by the Institute of Electrical and Electronics Engineers (IEEE) and Electric Power Industry Standard of China (Code for design of overvoltage protection and insulation coordination for AC electrical installations GB/T 50064-2014), respectively, the correlation coefficients of different polarities are obtained. By comparing the aforementioned two fitting results, it is found that the formula recommended by the IEEE can more objectively reflect the probability distribution characteristics in Zhejiang province, and the accuracy of the derived formula is verified by using the lightning current data in 2020. It shows that the curve based on the measured values is consistent with that fitted by the IEEE formula but quite different from that fitted by the GB/T 50064-2014 formula.

To investigate the relationship between immune dynamic and graft-versus-host-disease (GVHD) risk, 111 initial diagnostic acute myeloid leukemia patients were reviewed. The flow cytometry data of 12 major lymphocyte subsets in bone marrow (BM) from 60 transplant patients at four different time points were analyzed. Additionally, 90 immune subsets in peripheral blood (PB) of 11 post-transplantation on day 100 were reviewed. Our results demonstrated that transplant patients had longer OS compared to non-transplant patients (P < 0.001). Among transplant patients, those who developed GVHD showed longer OS than those without GVHD (P < 0.05). URD donors and CMV-negative status donors were associated with improved OS in transplant patients (P < 0.05). Importantly, we observed a decreased Th/Tc ratio in BM at initial diagnostic in patients with GVHD compared to those without GVHD (P = 0.034). Receiver operating characteristic analysis indicated that a low Th/Tc ratio predicted an increased risk of GVHD with a sensitivity of 44.44% and specificity of 87.50%. Moreover, an increased T/NK ratio in BM of post-induction chemotherapy was found to be associated with GVHD, with a sensitivity of 75.76% and specificity of 65.22%. Additionally, we observed a decreased percentage of NK1 (CD56-CD16+NK) in PB on day 100 post-transplantation in the GVHD group (P < 0.05). These three indicators exhibit promising potential as specific and useful biomarkers for predicting GVHD. These findings provide valuable insights for the early identification and management of GVHD risk, thereby facilitating the possibility of improving patient outcomes. In this manuscript, the clinical data of 150 untreated acute myeloid leukemia (AML) patients were reviewed. Three immune indicators at different time-points were detected, especially the Th/Tc and T/NK ratio in pre-transplant bone marrow, and NK1 (CD56-CD16 + NK) in peripheral blood on day 100 of the post-transplantation, which may contribute to predicting the graft-versus-host-disease occurrence of AML after transplantation. [ABSTRACT FROM AUTHOR]

Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the "direct" reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0–4.0 nm. They exhibited well-separated dual emission in the visible region (500–590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from − 23.9 to − 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes. [ABSTRACT FROM AUTHOR]