Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA

PurposeIn this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.ResultsThe prepared 68Ga-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.Conclusions68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease

Status and future of the soft X-ray free-electron laser beamline at the SHINE

The Shanghai High repetition rate XFEL and Extreme light facility (SHINE) is under construction and aims at generating X-rays between 0.4 and 25 keV with three FEL beamlines at repetition rates of up to 1 MHz. The soft X-ray FEL beamline, FEL-II, will be ready for commissioning in 2025. It is designed to cover the photon energy from 0.4 to 3 keV, in which the baselines of the FEL operation modes are self-amplified spontaneous emission (SASE), self-seeding, echo-enabled harmonic generation (EEHG), and polarization control. Therefore, a high repetition-rate external seed laser, large period length modulator, soft X-ray monochromator, planar undulator, and elliptically polarized undulator have been adopted in the FEL-II beamline. Several potentials such as an ultra-short pulse mode and a multi-color mode are also foreseeable without significant equipment changes in the follow-up operation. A dual-period undulator design is suggested for the echo-enabled harmonic generation (EEHG) commissioning, and it has great potential to break through the unreachable energy of the fully coherent X-ray in the future. The FEL-II beamline will deliver SASE radiation and fully coherent radiation in all the wavelengths of interest

Active Magnetic Field Compensation System for SRF Cavities

International audienceAbstract: Superconducting Radio Frequency (SRF) cavities are becoming popular in modern particle accelerators. When the SRF cavity is transitioning from the non-conducting to the Superconducting state at the critical temperature (Tc), the ambient magnetic field can be trapped. This trapped flux may lead to an increase in the surface resistance of the cavity wall, which can reduce the Q-factor and efficiency of the cavity. In order to increase the Q-factor, it is important to lower the surface resistance by reducing the amount of magnetic flux trapped in the cavity wall to sub 10mG range during the Tc transition. In this paper, we present a 3-axis automatic active magnetic field compensation system that is capable of reducing the earth magnetic field and any local disturbance field. Design techniques are described to enhance the system stability while utilizing the flexibility of embedded electronics. This paper describes the system implementation and concludes with initial results of tests. Experimental results demonstrate that the proposed magnetic field compensation system can reduce the earth magnetic field to around 2.5 mG even without shielding

A Horizontal Distribution Model of Static Ice Cover Generated by Static and Dynamic Water Considering the Heat Transfer of Riverbanks

The thermal factor is the main reason for winter ice cover with a low Froude number flow, and the heat transfer to narrow and deep river banks accelerates ice cover formation and ice thickness change. The freezing of water flow to freezing thickening is a nonisothermal-flow phase transition process coupled with the water flow temperature, environment and riverbank. Here, the Nusselt number and viscous dissipation are used to consider the flow velocity influence on icing, and a thermodynamic model of static ice cover horizontal distribution considering riverbed heat transfer is established. The initial ice time, freezing time and static ice cover thickness formed by static and dynamic water calculated by the model were consistent with measured data. The model reflects the horizontal growth process of the static ice cover, which was significant for narrow and deep channels. The horizontal distribution of the static ice cover was thin in the center and thick on both sides. The maximum horizontal thickness difference of −20 °C indoor freezing for 24 h reached 15% of the central ice thickness. Compared with the degree-day method for calculating ice thickness, the numerical model and dimensionless formula better reflect the growth law and horizontal distribution characteristics of static ice cover and provide a theoretical basis for safe water conveyance under ice cover in winter and ice cover formation in reservoirs and lakes in cold regions

Eurothiocin A and B, Sulfur-Containing Benzofurans from a Soft Coral-Derived Fungus Eurotium rubrum SH-823

Two new sulfur-containing benzofuran derivatives, eurothiocin A and B (1 and 2), along with five known compounds, zinniol (3), butyrolactone I (4), aspernolide D (5), vermistatin (6), and methoxyvermistatin (7), were isolated from the cultures of Eurotium rubrum SH-823, a fungus obtained from a Sarcophyton sp. soft coral collected from the South China Sea. The new compounds (1 and 2) share a methyl thiolester moiety, which is quite rare among natural secondary metabolites. The structures of these metabolites were assigned on the basis of detailed spectroscopic analysis. The absolute configurations of 1 and 2 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) data. Compounds 1 and 2 exhibited more potent inhibitory effects against α-glucosidase activity than the clinical α-glucosidase inhibitor acarbose. Further mechanistic analysis showed that both of them exhibited competitive inhibition characteristics

Glycosyltransferase FvCpsA Regulates Fumonisin Biosynthesis and Virulence in Fusarium verticillioides

Fusarium verticillioides is the major maize pathogen associated with ear rot and stalk rot worldwide. Fumonisin B1 (FB1) produced by F. verticillioides, poses a serious threat to human and animal health. However, our understanding of FB1 synthesis and virulence mechanism in this fungus is still very limited. Glycosylation catalyzed by glycosyltransferases (GTs) has been identified as contributing to fungal infection and secondary metabolism synthesis. In this study, a family 2 glycosyltransferase, FvCpsA, was identified and characterized in F. verticillioides. ΔFvcpsA exhibited significant defects in vegetative growth. Moreover, ΔFvcpsA also increased resistance to osmotic and cell wall stress agents. In addition, expression levels of FUM genes involved in FB1 production were greatly up-regulated in ΔFvcpsA. HPLC (high performance liquid chromatography) analysis revealed that ΔFvcpsA significantly increased FB1 production. Interestingly, we found that the deletion of FvCPSA showed penetration defects on cellophane membrane, and thus led to obvious defects in pathogenicity. Characterization of FvCpsA domain experiments showed that conserved DXD and QXXRW domains were vital for the biological functions of FvCpsA. Taken together, our results indicate that FvCpsA is critical for fungal growth, FB1 biosynthesis and virulence in F. verticillioides

Repairing Damaged Screen Pipes with Tube Hydroforming: Experiments and Feasibility Analysis

During oil-well production, there are often cracks, breaks, and perforation corrosion on the screen pipe that can significantly deteriorate sand control and pipe strength. To repair damaged screen pipes, we developed a technique originating from the tube hydroforming, and the feasibility of the technique was systematically investigated. First, the elastoplastic mechanics of patch tubes during the hydroforming process was analyzed to investigate the forming mechanism. Second, tensile experiments showed that AISI 321 after cold drawn and solution had good mechanical properties. A numerical simulation model of a hydroforming patch composed of AISI 321 steel was built to investigate the effect of structural parameters such as the length, initial outer diameter, and thickness of a patch tube on hydroforming patch performance. Forming pressure did not significantly change with length, but it decreased with initial outer diameter and increased with thickness. In addition to the simulation, a hydroforming test bench was constructed to experimentally test the patch method. Test results showed that the patch tube could fit closely with the screen base pipe, and residual contact stress could be more than 139.78 kN/m2. Deformation strengthening due to the deformed martensite was conducive to improving the strength of the patch tube after hydroforming. The combination of the simulation and experiment indicates that the application of hydroforming patch technology can effectively repair damaged screen pipes

Association between Abortion History and Perinatal and Neonatal Outcomes of Singleton Pregnancies after Assisted Reproductive Technology

Importance: At present, few people have studied the associations between abortion history before pregnancy on the outcomes of women and their infants after assisted reproductive technology (ART). Objective: To explore the association between the history of abortion and the outcomes of singleton pregnancies after ART. Design: This was a retrospective study in a hospital from 2015 to 2020 in Shanghai, China. Pregnant women with live singleton births through ART were included (n = 3043). Abortion was classified into spontaneous abortion (SAB) and induced abortion. We compared the maternal and fetal outcomes of singleton pregnancies obtained through ART with different abortion histories. Logistic regression analysis was used to evaluate the associations between the history of pre-pregnancy abortion with perinatal complications and neonatal outcomes. Results: We observed that compared with those who had no abortion history and obtained singleton pregnancies through ART, women who had an abortion history before pregnancy (including SAB or induced abortion history) and only SAB history were more likely to have gestational diabetes mellitus (GDM), thyroid-related diseases, and placenta-related diseases. After adjusting the potential confounding factors, these differences still existed. The adjusted odds ratios (ORs) and 95% confidence interval (CI) of GDM, thyroid-related diseases, and placenta-related diseases in women with a history of abortion and only a history of SAB were 1.239 (1.030–1.492) and 1.240 (1.010–1.522), 1.589 (1.261–2.002) and 1.724 (1.344–2.213), 1.465 (1.183–1.815) and 1.433 (1.132–1.814), respectively. However, we did not observe the association between the history of induced abortion and GDM and thyroid-related diseases. Conclusions and Relevance: Our research showed that pregnant women with singleton pregnancies through ART who had a history of abortion or only a history of SAB were more likely to have GDM, thyroid-related diseases, and placenta-related diseases. Pregnant women who had both SAB and induced abortion before pregnancy had a higher risk of thyroid-related diseases and placenta-related diseases, while women who had only a history of induced abortion had a higher risk of placenta-related diseases. Further research is needed to explore the biological mechanism of different types of abortion related to subsequent pregnancy

Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats

Summary: Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model and collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I improved phenotypes associated with ICP through the bile acid/farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment