Search

Objective To explore the impact of the sialic acid binding lectin-E (Siglec-E) on the inhibitory properties of parthenolide(PTL) against lipopolysaccharide (LPS)-induced M1 polarization of microglia(BV2). Methods ① Single cell sequencing data of Siglece related mouse brain tissue was obtained from Gene Expression Omnibus (GEO) database and divided into the WT group (n=3) and the Siglece-/- group (n=4). The microglia cells were screened, and the enrichment analysis was performed to analyze related differential genes and pathways. BV2 cells were constructed by the shRNA interference technique and were divided into NC-shRNA and Siglece-shRNA to detect the expression level of Siglec-E (Siglece). ② NC-shRNA and Siglece-shRNA cells were respectively divided into the Control group, LPS group, PTL group and PTL+LPS group (n=3). The mRNA levels of markers of M1 polarization in microglia, iNOS, IL-1β and IL-6, were detected by RT-qPCR. Siglecefl/fl and Cx3cr1cre mice were mated to obtain microglia-specific Siglece deletion (Siglecefl/fl×Cx3cr1cre) mice, and LPS-induced neuroinflammation model was established. ③ Nine WT and Siglecefl/fl×Cx3cr1cre male mice were assigned to the Control group, LPS group and PTL+LPS group (n=3). RT-qPCR, immunofluorescence assay and Western blotting were used to verify the knock-out effect and polarization-related pathways, and to investigate the mechanism of Siglec-E affecting PTL inhibition of M1 polarization of microglia. Results Compared with the NC-shRNA group, the expression of Siglec-E in the Siglece-shRNA group was significantly decreased (P < 0.01), indicating that the Siglec-E knock-down cell model was successfully established. With the stimulation of LPS, mRNA levels of iNOS, IL-1β and IL-6 were significantly up-regulated compared with the Control group both in shRNA cells and Siglece -shRNA cells (P < 0.01). With the influence of PTL and LPS, the markers of M1 polarization in NC-shRNA cells mentioned before were significantly decreased (P < 0.05), while for Siglice-shRNA cells, there were no significant changes in the markers of M1 polarization. PTL inhibited the phosphorylation of JNK and IκB protein (P < 0.01) and the nuclear translocation of NF-κB in BV2 cells, down-regulated Siglec-E, and weakened the inhibitory effect. Compared with mice in the WT group, the expression of Siglec-E in microglia of Siglecefl/fl×Cx3cr1cre mice was decreased significantly (P < 0.01), and the inhibitory effect of PTL on the phosphorylation of NF-κB in microglia of Siglecefl/fl×Cx3cr1cre mice was also decreased. Conclusion The absence of Siglec-E in microglia attenuates the inhibition of M1 polarization by the MAPK/NF-κB pathway targeted by PTL.

Isolated attosecond pulses (IAPs) can be readily generated via high-order harmonic generation driven by an ultrashort laser pulse. Here, it is shown that the best way to obtain the ultrashort waveform for producing a short and intense IAP in the soft x rays is to optimize the three-color (TC) laser pulse consisting of the fundamental field and its second and third harmonic fields. To calibrate it, another way of constructing the ultrashort waveform directly in time using a truncated basis set of B-spline functions is first proposed. The calibration waveform (CW) contains more frequency components up to the eighth harmonic order. It is found that the IAP by the TC waveform has a shorter duration after macroscopic propagation in a nonlinear gas medium compared to that by the CW field. It is uncovered that the CW field is additionally modified by the higher-order frequency components during propagation, dominated by the neutral atom dispersion. The effect of phase jitter in the TC waveform and the extension of the TC scheme into higher photon energies are also discussed. Currently, precise control of TC laser waveform synthesis is already achievable in the labs, thus paving an effective way for generating a useful attosecond light source in the soft x rays. [ABSTRACT FROM AUTHOR]

Objective: Thoracolumbar compression fractures resulting from high‐energy injuries are a common type of spinal fracture. Satisfying reduction of compressive vertebra body is essential for the clinical outcome. However, traditional distraction technique may lead to complications including pedicle screw loosening, pedicle screw breakage, and postoperative back pain because of excessive distraction. In this study, we reported a novel technique for reduction. Additionally, the effect and postoperative radiological parameters of this technique were compared with those of traditional distraction technique. Methods: The clinical data of 80 patients who had been treated with posterior pedicle screw fixation from January 2019 to December 2020 was retrospectively analyzed. Thirty‐six patients were performed with the leverage technique, while 22 patients were treated with the traditional distraction technique. When pedicle screw fixation was performed with either the leverage technique or the traditional distraction technique, fracture reduction was completed with monoaxial pedicle screws using either the leverage maneuver or distraction of adjacent vertebrae. Clinical evaluation, including operation time, hospital stay, blood loss volume, and postoperative complications were collected. The American Spinal Injury Association (ASIA) score for neurological condition and the visual analog scale (VAS) score for pain were used to evaluate the patients' functional outcome. The radiographic analysis included local kyphotic angle (LKA), regional kyphotic angle (RKA), anterior vertebral height (AVH), posterior vertebral height (PVH), and sagittal compression (SC). The student t‐test and the χ2‐test (or the Fisher exact test) were used to compare the outcome measures between the two groups. Results: The leverage group comprised 36 patients, while 44 patients were included in the distraction group. No statistically significant differences were found in the demographic data. The VAS score in the leverage group (3.0 ± 0.8) was significantly lower than that in the distraction group (4.2 ± 0.6) on postoperative day 1. Total correction of the LKA in the leverage group (11.5 ± 2.5°) was significantly higher than that in the distraction group (7.1 ± 1.3°) (p = 0.0004). Total correction of the RKA was higher in the leverage group (12.1 ± 4.3°) than in the distraction group (6.1 ± 0.9°) (p = 0.005). The ratio of rear pillar /front pillar correction was 0.35 ± 0.13 and 0.89 ± 0.18 in the leverage and distraction groups, respectively (p = 0.014). Total correction of the upper and lower foraminal height in the leverage group was significantly less than that in the distraction group. The leverage group had significantly higher correction of the upper and lower intervertebral space height than the distraction group. Conclusions: Our novel leverage technique provided better kyphotic reduction and restoration than compared to conventional distraction technique in the surgical treatment of thoracolumbar compression fractures. [ABSTRACT FROM AUTHOR]

Background: Regeneration of injuries occurring in the central nervous system is extremely difficult. Studies have shown that the developing cerebellum can be repopulated by a group of Nestin-expressing progenitors (NEPs) after irradiation injury, suggesting that modulating the mobilization of NEPs is beneficial to promoting nerve regeneration. To date, however, effect of exogenous pharmaceutical agonist on NEPs mobilization remains unknown. Parthenolide (PTL), a sesquiterpene lactone isolated from shoots of feverfew. Although it has been shown to possess several pharmacological activities and is considered to have potential therapeutic effects on the regeneration of peripheral nerve injury, its efficacy in promoting central nervous system (CNS) regeneration is unclear. In this study, we aimed to elucidate the role and possible mechanism of PTL on regeneration in injured CNS after irradiation using a developing cerebellum model.Methods: We investigated the radioprotective effects of PTL on the developing cerebellum by immunoblotting as well as immunofluorescence staining and ROS detection in vivo and in vitro experiments, and then determined the effects of PTL on NEPs in Nestin CFP and Nestin GFP fluorescent mice. Inducible lineage tracing analysis was used in Nestin-CreERT2×ROSA26-LSL YFP mice to label and track the fate of NEPs in the cerebellum after irradiation. Combined with cell biology and molecular biology techniques to determine changes in various cellular components in the cerebellum and possible mechanisms of PTL on NEPs mobilization in the injured developing cerebellum.Results: We found that PTL could attenuate radiation-induced acute injury of granule neuron progenitors (GNPs) in irradiated cerebellar external granule layer (EGL) by alleviating apoptosis through regulation of the cells’ redox state. Moreover, PTL increased cerebellar Shh production and secretion by inhibiting the PI3K/AKT pathway, thus promoting expansion of NEPs, which is the compensatory replenishment of granule neurons after radiation damage.Conclusion: Collectively, our results indicate that activation and expansion of NEPs are critical for regeneration of the injured cerebellum, and that PTL is a promising drug candidate to influence this process.