Nuciferine alleviates LPS-induced mastitis in mice via suppressing the TLR4-NF-κB signaling pathway

Background

Nuciferine, a major bioactive component from the lotus leaf, has been reported to have notable anti-inflammatory activities such as renal inflammation and acute lung injury in previous studies. Mastitis is one of the most prevalent diseases in the dairy cattle, which causes large economic losses for the dairy industry. However, the effects of nuciferine on lipopolysaccharide (LPS)-induced mastitis have not been reported.

Methods and results

Here, we investigated the anti-inflammatory effects of nuciferine on LPS-induced mastitis in mice and illuminated its potential mechanism on the TLR4-mediated signaling pathway in mouse mammary epithelial cells (mMECs). Histopathological changes and myeloperoxidase (MPO) activity assay showed that nuciferine treatment significantly alleviated the LPS-induced injury of mammary gland flocculus, inflammatory cells infiltration. qPCR and ELISA assays indicated that nuciferine dose-dependently reduced the levels of TNF-α and IL-1β, which indicated that nuciferine might have therapeutic effects on mastitis. Furthermore, nuciferine treatment significantly decreased the expression of TLR4 in a dose-dependent manner. Besides, nuciferine was also found to suppress LPS-induced NF-κB activation.

Conclusion

These findings indicate that nuciferine potently ameliorates LPS-induced mastitis by inhibition of the TLR4-NF-κB signaling pathway.

     

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7%?±?5.3% versus 43.4%?±?7.0%, P?=?.015) and chronic graft-versus- host disease (GVHD; 20.1%?±?5.8% versus 46.0%?±?7.9%, P?=?.003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1%?±?3.3% versus 84.4%?±?5.7%, P?=?.235), grades III to IV acute GVHD (3.4%?±?2.4% versus 12.3%?±?4.7%, P?=?.098), moderate to severe chronic GVHD (12.6%?±?4.9% versus 11.5%?±?4.9%, P?=?.905), or graft rejection (7.4%?±?3.6% versus 5.5%?±?3.1%, P?=?.852). There was also no significant difference with regard to the incidence of severe bacterial infection (P?=?.075), invasive fungal disease (P?=?.701), or cytomeglovirus viremia (P?=?.770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.     

A cooperation of catheters and guidewires-based novel remote-controlled vascular interventional robot

Remote-controlled vascular interventional robots (RVIRs) are being developed to increase the overall accuracy of surgical operations and reduce the occupational risks of intervening physicians, such as radiation exposure and chronic neck/back pain. Several RVIRs have been used to operate catheters or guidewires accurately. However, a lack of cooperation between the catheters and guidewires results in the surgeon being unable to complete complex surgery by propelling the catheter/guidewire to the target position. Furthermore, it is a significant challenge to operate the catheter/guidewire accurately and detect their proximal force without damaging their surfaces. In this study, we introduce a novel method that allows catheters and guidewires to be operated simultaneously in complex surgery. Our method accurately captures force measurements and enables precisely controlled catheter and guidewire operation. A prototype is validated through various experiments. The results demonstrate the feasibility of the proposed RVIR to operate a catheter and guidewire accurately, detect the resistance forces, and complete complex surgical operations in a cooperative manner.     

Unusual Mott transition in multiferroic PbCrO3

The Mott insulator in correlated electron systems arises from classical Coulomb repulsion between carriers to provide a powerful force for electron localization. Turning such an insulator into a metal, the so-called Mott transition, is commonly achieved by “bandwidth” control or “band filling.” However, both mechanisms deviate from the original concept of Mott, which attributes such a transition to the screening of Coulomb potential and associated lattice contraction. Here, we report a pressure-induced isostructural Mott transition in cubic perovskite PbCrO₃. At the transition pressure of ∼3 GPa, PbCrO₃ exhibits significant collapse in both lattice volume and Coulomb potential. Concurrent with the collapse, it transforms from a hybrid multiferroic insulator to a metal. For the first time to our knowledge, these findings validate the scenario conceived by Mott. Close to the Mott criticality at ∼300 K, fluctuations of the lattice and charge give rise to elastic anomalies and Laudau critical behaviors resembling the classic liquid–gas transition. The anomalously large lattice volume and Coulomb potential in the low-pressure insulating phase are largely associated with the ferroelectric distortion, which is substantially suppressed at high pressures, leading to the first-order phase transition without symmetry breaking.Early transition-metal (TM) oxides with partially filled d electrons are strongly correlated (1, 2). Such correlated systems often present exciting new physics and technologically useful electronic and magnetic properties. Mott transition, characterized by delocalization of d electrons, is an attractive phenomenon for exploring the correlated nature of electrons (2, 3). Since the early failure of band theory in the 1930s, the Coulomb repulsion (U) has been proposed to be a strong force that causes electron localization (4, 5). In such electrostatic interaction, the repulsion energy decreases with the compressed lattice because of the screening effect (5–7). Consequently, as originally predicted by Mott (5), the Mott transition is controlled by U at pressures (P).Despite several decades of intensive study, it is still challenging to experimentally validate this view of Mott transition, because U is experimentally difficult to determine, and for most correlated materials it is independent of the pressure. For the known Mott systems, they are found to be controlled by either the bandwidth [e.g., the organic compound κ-Cl (8–10) and Cr-doped V₂O₃ (11, 12)] or band filling (i.e., doping of charge carriers into the parent insulator) (2). Recently, electronic transitions have frequently been reported in late 3d TM oxides (e.g., MnO) (13–16), which are theoretically attributed to bandwidth control (15) or crystal-field splitting (17). For those oxides, a U-controlled mechanism has also been proposed by Gavriliuk et al. (14) and Gavriliuk and coworkers (18); however, the spin cross-over, instead of the screening effect, is believed to contribute to the decreased U (14, 18). Complicating matter further is that the U of (Mg_1–xFe_x)O was computed to increase with pressures (13).TM oxides with a perovskite structure (ABO₃) often exhibit intriguing structural, magnetic, and electronic properties for the study of correlated systems. Among them, PbCrO₃ is such a material that can only be synthesized at high pressures. At ambient pressure, it adopts a paramagnetic (PM), cubic structure at room temperature (T) with an anomalously large unit-cell volume and transforms to an antiferromagnetic (AFM) ground state at low temperatures (19, 20). The magnetic properties arise from unpaired 3d electrons in Cr (i.e., nominally 3d²) with a large U value of 8.28 eV (19–21). Under high pressures, an isostructural phase transition (i.e., no symmetry breaking) has recently been reported in PbCrO₃ with ∼9.8% volume reduction at ∼1.6 GPa; it is the largest volume reduction known in transition-metal oxides (22). Compared with the low-P phase, the high-P phase possesses a more “normal” unit-cell volume (see refs. 21 and 22) and a moderate U of ∼3 eV (23), suggesting a collapse of Coulomb repulsion energy at the phase transition. Because of the reduced U, the mobility of 3d electrons at high pressures is energetically more favorable, which would lead to d-electron delocalization. Apparently, this is a U-driven Mott transition in PbCrO₃ as conceived by Mott. However, to date, the electronic properties of both PbCrO₃ phases have only poorly been explored. In particular, controversial electronic states, including semiconductor (24, 25), half-metal (21), or insulator (20), have been reported for the low-P phase. Besides, the crystal structure and elastic and magnetic properties, as well as the underlying mechanism for the isostructural transition, are still unsettled issues, calling for rigorous investigation into this material.With these aims, in this work we present a comprehensive study on PbCrO₃ with a focus on the P-induced electronic transition. Our findings unveil a unique Mott transition in this perovskite and a new mechanism underlying the isostructural transition.