Activation of Src family kinases in spinal microglia contributes to formalin-induced persistent pain state through p38 pathway

pre-printProtein tyrosine phosphorylation has been implicated in normal and pathological functions, such as cell proliferation, migration and differentiation. Recently, some studies have shown that Src family kinases (SFKs) were involved in neurological disorders and neuropathic pain states in which microglial activation plays a role. In the formalin test, we have reported that microglia undergo at least two distinct stages of activation on the basis of signaling events regarding p38 mitogen-activated protein kinases (MAPK). Here, we investigated the involvement of SFKs signaling in formalin pain animal model, and the association with p38 MAPK. Our results showed that SFKs were activated in the spinal microglia beginning 1 day after peripheral formalin injection, lasting for 7 days. Pretreatment with SFK specific inhibitor PP2 could not inhibit formalin induced spontaneous pain behaviors. However, PP2 inhibited formalin injury induced persistent mechanical hyperalgesia, and reversed microglial phospho-p38 expression as well using immunohistostaining and Western blot at day 3 and 7 after injection. Our results suggested that the activation of the Src/p38MAPK signaling cascade in spinal microglia contributed to late stage persistent mechanical hyperalgesia evoked by formalin injection into the paw

Cross-linked CoMoO4/rGO nanosheets as oxygen reduction catalyst

Development of inexpensive and robust electrocatalysts towards oxygen reduction reaction (ORR) is crucial for the cost-affordable manufacturing of metal-air batteries and fuel cells. Here we show that cross-linked CoMoO4 nanosheets and reduced graphene oxide (CoMoO4/rGO) can be integrated in a hybrid material under one-pot hydrothermal conditions, yielding a composite material with promising catalytic activity for oxygen reduction reaction (ORR). Cyclic voltammetry (CV) and linear sweep voltammetry (LSV) were used to investigate the efficiency of the fabricated CoMoO4/rGO catalyst towards ORR in alkaline conditions. The CoMoO4/rGO composite revealed the main reduction peak and onset potential centered at 0.78 and 0.89 V (vs. RHE), respectively. This study shows that the CoMoO4/rGO composite is a highly promising catalyst for the ORR under alkaline conditions, and potential noble metal replacement cathode in fuel cells and metal-air batteries

Donor CD47 controls T cell alloresponses and is required for tolerance induction following hepatocyte allotransplantation

CD47-deficient hepatocyte transplantation induces rapid innate immune cell activation and subsequent associated graft loss in syngeneic recipients. However, the role of donor CD47 in regulation of T-cell alloresponses is poorly understood. We addressed this question by assessing OVA-specific immune responses in mice following hepatocyte transplantation from CD47-competent or -deficient OVAtransgenic donors. Compared to sham-operated controls, intrasplenic transplantation of CD47-deficient OVA+ hepatocytes significantly accelerated rejection of OVA+ skin grafted 7 days after hepatocyte transplantation. In contrast, mice receiving CD47-competent OVA+ hepatocytes showed prolonged and even indefinite survival of OVA+ skin allografts. T cells from mice receiving CD47-deficient, but not CD47-competent, OVA+ hepatocytes showed significantly enhanced responses to OVA+ stimulators compared to sham-operated controls. In contrast to the production of tolerogenic cytokines (IL-4 and IL-10) in the recipients of CD47-competent hepatocytes, mice receiving CD47-deficient hepatocytes showed elevated production of IFN-γ and IL-1α. Moreover, significant expansion of myeloid-derived suppressor cells was detected in the recipients of CD47-competent hepatocytes, which was required for tolerance induction in these mice. Thus, donor CD47 plays an important role in the control of T-cell alloresponses and tolerance induction following hepatocyte transplantation. Our data also suggest that intrasplenic hepatocyte transplantation may provide a means to induce allograft tolerance

Effects of the Inductive Charging on the Electrification and Lightning Discharges in Thunderstorms

A two-dimensional cloud model with electrification and lightning processes is used to investigate the role of inductive charge separation in thunderstorm clouds. For the same dynamic and microphysical evolution, four cases that the same non-inductive charging parameterization is combined with different inductive charging process are compared. Non-inductive charge separation alone is found to be sufficient to produce a dipolar charge structure. Intracloud (IC) and positive cloud-to-ground (+CG) flashes are initiated between a main negative charge region and an upper positive charge region. The inductive charging process between graupel and cloud droplets exhibits a normal tripole charge structure, consisting of a lower positive charge region under the main negative charge region. In the simulated tripole structure, negative cloud-to-ground (-CG) flashes are initiated between the main negative and lower positive charge regions. In addition, inductive charge separation between the graupel and ice crystal is found to be capable of producing strong charge separation in a dipole charge structure. Tests with inductive graupel-ice crystals process produce more flashes than that in the other cases

Case Report: Mosaicism of a novel nonsense variant in the neurofibromin gene underlies a mosaic generalized NF1 phenotype [version 1; peer review: 2 approved]

Neurofibromatosis 1 (NF1) is a neurocutaneous syndrome characterized by multiple café-au-lait macules, cutaneous neurofibromas or plexiform neurofibromas, iris Lisch nodules, axillary and inguinal freckling. Mosaicism in NF1 can either present as a generalized disease, or in a localized (segmental) manner. Mosaic generalized NF1 may have presentations that are similar to generalized NF1 or have a milder phenotype and hence may be under-recognised in clinical practice. We report a nonsense mutation in the NF1 gene in a 55-year old Chinese male with the mosaic generalized phenotype. He reported noticing increasing numbers of skin-colored papules over his face, neck, back and abdomen when he was about 40 years old. From both next-generation and Sanger sequencing data, the variant appeared to be mosaic and present at about 24%. It is in exon 39 and has not been reported in any database or published literature

Validated method to measure yakuchinone A in plasma by LC-MS/MS and its application to a pharmacokinetic study in rats

BACKGROUND: Yakuchinone A has a plethora of beneficial biological effects. However, the pharmacokinetic (PK) data of yakuchinone A still remain unknown so far. Furthermore, the quantification of yakuchinone A in biological samples has not been reported in the literature. Therefore, in the present study we aimed to develop a new method for the fast, efficient and accurate assessment of yakuchinone A concentration in plasma, as a means for facilitating the PK evaluation of yakuchinone A. RESULTS: A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of yakuchinone A in rat plasma. Mass spectrometric and chromatographic conditions were optimized. Plasma samples were pretreated by protein precipitation with methanol. LC separation was performed on a Phenomenex Luna C18 column with gradient elution using a mobile phase consisting of methanol–water containing 0.5 mM formic acid (HCOOH) at a flow rate of 0.28 mL/min. ESI-MS spectra were acquired in positive ion multiple reaction monitoring mode (MRM). The precursor-to-product ion pairs used for MRM of yakuchinone A and yakuchinone B were m/z 313.1 → 137.0 and 311.2 → 117.1, respectively. Low concentration of HCOOH reduced the ion suppression caused by matrix components and clearly improved the analytical sensitivity. Yakuchinone A showed good linearity over a wide concentration range (r > 0.99). The accuracy, precision, stability and linearity were found to be within the acceptable criteria. This new method was successfully applied to analyze the rat plasma concentration of parent yakuchinone A after a single oral administration of SuoQuan capsules. Low systemic exposure to parent yakuchinone A was observed. CONCLUSION: The proposed method is sensitive and reliable. It is hoped that this new method will prove useful for the future PK studies

Full velocities and propagation directions of coronal mass ejections inferred from simultaneous full-disk imaging and Sun-as-a-star spectroscopic observations

Coronal mass ejections (CMEs) are violent ejections of magnetized plasma from the Sun, which can trigger geomagnetic storms, endanger satellite operations and destroy electrical infrastructures on the Earth. After systematically searching Sun-as-a-star spectra observed by the Extreme-ultraviolet Variability Experiment (EVE) onboard the Solar Dynamics Observatory (SDO) from May 2010 to May 2022, we identified eight CMEs associated with flares and filament eruptions by analyzing the blue-wing asymmetry of the O III 52.58 nm line profiles. Combined with images simultaneously taken by the 30.4 nm channel of the Atmospheric Imaging Assembly onboard SDO, the full velocity and propagation direction for each of the eight CMEs are derived. We find a strong correlation between geomagnetic indices (Kp and Dst) and the angle between the CME propagation direction and the Sun-Earth line, suggesting that Sun-as-a-star spectroscopic observations at EUV wavelengths can potentially help to improve the prediction accuracy of the geoeffectiveness of CMEs. Moreover, an analysis of synthesized long-exposure Sun-as-a-star spectra implies that it is possible to detect CMEs from other stars through blue-wing asymmetries or blueshifts of spectral lines.Comment: Accepted by Ap

Evolution and conservation of polycomb repressive complex 1 core components and putative associated factors in the green lineage

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