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ABSTRACTBackgroundDaratumumab is widely used in multiple myeloma (MM) and light chain amyloidosis (AL amyloidosis). The purpose of this study was to identify adverse event (AE) signals for daratumumab through the FDA Adverse Event Reporting System (FAERS) database to assess its safety in a large sample of people.MethodsBased on data from the FAERS database, three disproportionality analysis methods were used to mine AE signals for daratumumab, including reporting odd ratio (ROR), proportional reporting ratio (PRR), and bayesian configuration promotion neural network (BCPNN).ResultsA total of 9220 AE reports with daratumumab as the primary suspect drug were collected, containing 23,946 AEs. Within these reports, 252 preferred terms (PT) levels, 73 high level term (HLT) levels and 11 system organ class (SOC) levels of AE signals were detected, along with some new AEs. Most AEs occurred within the first month after drug administration.ConclusionOur findings were consistent with the results of established studies that daratumumab has a good safety profile. The newly identified AEs are of concern and prospective clinical studies are needed to confirm whether they are causally related to daratumumab. This study provided an early warning for the safe use of daratumumab and also provided guidance for further safety studies.

Irisin is an exercise-induced myokine/adipokine in mice and humans that plays an important role in ‘browning’ of white adipose tissue and has shown great potential as a treatment for some metabolic diseases, such as obesity, insulin resistance, and inflammation. The circulating irisin level is reported to be associated with exercise, obesity, diet, diseases, and exposure to different pharmacological agents. Several studies have attempted to characterize the role of irisin in PCOS and other reproductive diseases, but contradictory results have been reported. Our previous study showed that irisin may serve further functions in folliculogenesis and fertility. In this review, we present the current knowledge on the physiology of irisin and its role in gonadal axis. Firstly, we describe irisin circulating levels and speculate on the potential mechanisms involved in irisin secretion and regulation. Then, we focus on the irisin levels in PCOS, and explore the relationships between, BMI, insulin resistance, and hyperandrogenism. Finally, we present the results from animal interventional studies and in vitro experiments to investigate the relationship between irisin and gonadal axis, indicating its novel effects on reproduction and fertility.

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivoand in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation (ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-CoA and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

Background:This study was conducted to evaluate the impact of vitrification on mitochondrial of human IVM oocytes.Methods:A total of 401 immature oocytes were obtained from ovarian stimulated cycles, which were randomly divided into fresh and vitrification groups after IVM. According to the cultured time after thawing, the vitrification groups were divided into 0 hours (0 h), 2 hours (2 h), or 4 hours (4 h) subgroups. Mitochondrial morphology and oxygen consumption were compared among the four groups. After fertilization by ICSI, normal fertilization, cleaved embryos, and blastocyst formation rate were also calculated.Results:The mean gray value of mitochondria structure was significantly decreased in 0 h and 2 h groups when compared to control group (0.48 ± 0.09, 0.50 ± 0.36 vs. 0.61 ± 0.12, respectively; P <0.05), and recovered (0.61 ± 0.24 vs. 0.61 ± 0.12, P >0.05) in 4 h group. In addition, oxygen consumption was also significantly decreased in 0 h and 2 h groups compared to fresh (2.91 ± 0.77 fmol/s, 3.26 ± 1.34 fmol/s vs. 3.96 ± 1.44 fmol/s, respectively; P <0.05), and recovered after 4 h culture (3.96 ± 1.44 fmol/s vs. 4.41 ± 1.38 fmol/s, respectively; P >0.05). The percentage of normal fertilization and cleaved embryos were no differences among the four groups, however, blastocyst development rate was significantly lower in 0 h group.Conclusion:These results indicate that during the vitrification process, the oxygen consumption and mitochondrial structure of oocytes may undergo temporary dynamic changes, but appear to recover by 4 hours.

Wind tunnel test is an important way to test the performance of Gust Load Alleviation (GLA). At present, some component-level wind tunnel tests have been carried out in big aviation countries, but there is a lack of full aircraft model GLA tests. In this study, a set of large-scale GLA test system in low-speed wind tunnel is developed, which includes a gust generator, a five-degree-of-freedom suspension system, a full elastic aircraft model with control system, and gust load measuring devices. Two control schemes based on closed-loop feedback control and open-loop feed forward control are respectively designed and verified by the full-model GLA tests in the wind tunnel. The experimental results show that the designed gust generator can generate a stable wideband, wide-area gust wind field; the suspension support system can sustain static and dynamic stability during wind tunnel test, and enables the model moving in the horizontal, vertical, pitching, rolling and yawing directions. The results show that the closed-loop feedback control can obtain good control performance of reducing the peak values of elastic vibration response induced by gust excitation, but has little effect on suppressing the rigid body motion excited by low-frequency gust, while the open-loop feed forward control presents superior performance in alleviating the high-frequency elastic vibration as well as the low-frequency rigid body motion with more than 40% overall reduction rate.