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Growing evidence for the importance of the gut-brain axis in Parkinson's disease (PD) has attracted researchers' interest in the possible application of microbiota-based treatment approaches. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, we looked into the prospect of treating PD with fucosylated chondroitin sulfate obtained from sea cucumbers

The new near-α TNW700 titanium alloy is a potential candidate material for high performance ultrasonic/hypersonic aircrafts, which is designed for short-term service at 700°C. This study systematically investigated the superplastic deformation microstructure evolution and mechanism of TNW700 alloy at different strain rates and true strains at 925°C. Results show that TNW700 alloy exhibits excellent superplastic behavior in a constant strain rate range of 0.0005 to 0.005 s−1 with elongation above 400%. The peak stress decreases with decreasing strain rate, which is related to the increase of β-phase volume fraction caused by the increase of thermal exposure time. In addition, significant strain hardening is observed in early-middle stage of superplastic deformation, and flow softening is followed in middle-late stage. To rationalize these complex flow behaviors, electron backscatter diffraction (EBSD) and high resolution transmission electron microscopy (HRTEM) were used to characterize the microstructure. Strain hardening is correlated to the synergistic effect of β grain growth, dislocation accumulation, silicide precipitate, and solid solution strengthening of α phase. Continuous dynamic recrystallization (CDRX) induced the fragmentation of primary α grains in middle-late stage of superplastic deformation, and the refinement of α grains, the increase of β phase volume fraction and dynamic dislocation recovery are main causes of high strain softening. In addition, EBSD and TEM observations confirmed texture randomization, fine equiaxed primary α grains and intragranular dislocation movement, indicating that grain boundary sliding (GBS) accommodated by dislocation sliding / climb is the dominant superplastic deformation mechanism of TNW700 alloy.

Alzheimer's disease (AD) is a type of progressive neurodegenerative disease, and amyloid β-protein 42 (Aβ42) serves an important role in the pathological process of development of AD. Paired immunoglobulin-like receptor B (PirB) is a functional receptor for myelin inhibitors of neuron regeneration in the CNS, and it has also been identified to function as a high-affinity receptor for Aβ. Here, we used a phage display to identify a specific PirB antagonist peptide 11(PAP11, PFRLQLS), which could reverse Aβ42-induced neurotoxicity and promote neurite outgrowth in vitro. Immunofluorescence analysis showed that PAP11 colocalized with PirB on the membrane of cortical neurons. Horseradish peroxidase-streptavidin-biotin assay further proved that PAP11 directly binds to PirB and the dissociation constant (Kd) was 0.128μM. PAP11 functionally antagonized the neurite outgrowth inhibitory effect induced by Aβ42 in cortical neurons, and the underlying mechanism was associated with a PirB-ROCK2/CRMP2 signaling pathway. The novel PirB antagonist peptide PAP11 may be a promising candidate therapeutic agent for the treatment of AD and other neurodegenerative diseases. KEY POINTS: • PAP11 was the first PirB antagonist peptide screened by phage display technology. • PAP11 could protect neurons by blocking the binding of Aβ42 and PirB. • PAP11 reverse inhibitory effect of neurite outgrowth through ROCK2/CRMP2 pathway.

The apolipoprotein E ε4 (APOE4) allele is a major genetic risk factor for Alzheimer’s disease (AD), and its protein product, ApoE4, exerts its deleterious effects mainly by influencing amyloid-β (Aβ) and Tau (neurofibrillary tangles, NFTs) deposition in the brain. However, the molecular mechanism dictating its expression during ageing and in AD remains incompletely clear. Here we show that C/EBPβ acts as a pivotal transcription factor for APOE and mediates its mRNA levels in an age-dependent manner. C/EBPβ binds the promoter of APOE and escalates its expression in the brain. Knockout of C/EBPβ in AD mouse models diminishes ApoE expression and Aβ pathologies, whereas overexpression of C/EBPβ accelerates AD pathologies, which can be attenuated by anti-ApoE monoclonal antibody or deletion of ApoE via its specific shRNA. Remarkably, C/EBPβ selectively promotes more ApoE4 expression versus ApoE3 in human neurons, correlating with higher activation of C/EBPβ in human AD brains with ApoE4/4 compared to ApoE3/3. Therefore, our data support that C/EBPβ is a crucial transcription factor for temporally regulating APOE gene expression, modulating ApoE4’s role in AD pathogenesis.

Relativistic electron injections are one of the mechanisms of enhancements of relativistic (≥ 0.5 MeV) electrons in the Earth’s outer radiation belt. In this study, we present the statistical observation of 600 keV electron injections in the outer radiation belt using the Van Allen Probes data. Based on the different injection characteristics, 600 keV electron injections in the outer radiation belt are divided into “pulsed electron injections” and “non-pulsed electron injections”. The 600 keV electron injections are observed at over 4.5 < L < 6.4 under the geomagnetic conditions of 450 nT < AE < 1450 nT. L ~ 4.5 is an inward limit for 600 keV electron injections. Before the electron injections, the flux negative L shell gradient for ≤ 0.6 MeV electrons or the low electron fluxes in the injected region are observed. For 600 keV electron injections at different L shells, the source populations from the Earth’s plasma sheet are different. For 600 keV electron injections at higher L shells, the source populations are higher energy electrons (~ 200 keV at X ~ –9 RE), while the source populations for 600 keV electron injections at lower L shells are lower energy electrons (~ 80 keV at X ~ –9 RE). These results are important for our further understanding of electron injections and rapid enhancements of 600 keV electrons in the Earth’s outer radiation belt.

Theoretical analysis is used to predict the dynamic response of a circular lined tunnel with an imperfect interface to plane SV-waves. The linear spring model is introduced to depict the imperfect interface between the rock mass and the lining. The expressions for the stress and displacement of the rock mass and the lining are then derived based on the wave function expansion method and the linear spring model. The dynamic stress concentration factor (DSCF) of the rock mass and lining is systematically discussed in two cases by studying its basic parameters, including the dimensionless wavenumber, the interface spring constants, and the lining thickness. The results show that the imperfect interface has a prominent effect on dynamic stress concentration. The maximum values of DSCF generated by SV-waves in the rock mass and the lining are larger than those generated by the P-waves. Additionally, the thick lining structure and tight adhesion of the lining to the rock mass are conducive to tunnel structure stability. It is suggested that the support should be strengthened at the position of the dynamic stress concentration, and the lining and the rock mass should be combined as closely as possible during the construction process.

Alzheimer's disease (AD) is a type of progressive neurodegenerative disease, and amyloid β-protein 42 (Aβ

The spatial and temporal distributions of ionospheric electromagnetic ion cyclotron (EMIC) waves during magnetic storms from 2014 to 2018 were studied using Swarm observations. Ionospheric EMIC waves preferably occurred during storms and their recovery phases at subauroral regions within an average magnetic latitude of 40–55°. There were more wave events during more intense and longer period storms. However, the correlation between event number and storm duration was not good. This might be due to the effect of heavy oxygen ions on EMIC wave generation and the loss of ring current high-energy ions by the EMIC waves. There are obvious magnetic local time (MLT) differences in the peak occurrence frequency of EMIC waves during storm phases. The enhanced solar wind dynamic pressure was favorable for duskside EMIC waves. With an increased substorm activity, the wave occurrence rate peak shifted from the morning side to the dusk-premidnight sector. During the recovery phase of a storm, EMIC waves in the 12–24 MLT sector appeared preferably in the earlier part than those in the 00–12 MLT sector. This shift in local time is related to the eastward rotation of the plasmaspheric plume toward morning during the late storm recovery phase and its overlap with the ring current. Highest occurrence frequency of the storm time EMIC waves could be found in the South Atlantic Anomaly region, which might be related to the drift shell splitting and the wave propagation effect in the weak magnetic field region.

Exposure to fenpropathrin (Fen), one of the most widely used pyrethroid pesticides, has been reported to increase the incidence of Parkinson’s disease (PD). However, the molecular mechanisms underlying Fen-induced Parkinsonism remain unknown. Here we investigated the role of the lysosomal protease asparagine endopeptidase (AEP) in Fen-induced neurodegeneration and tested the protective effect of an AEP inhibitor Compound #11 (CP11). Fen induced AEP activation, α-synuclein aggregation, and dopaminergic neuronal degeneration both in vitro and in vivo. CP11 alleviated Fen-induced cell injury in cultured SH-SY5Y cells and A53T α-synuclein transgenic mice. CP11 protected SH-SY5Y cells against Fen-induced toxicity and decreased α-synuclein aggregation in HEK293 cells stably transfected with α-synuclein. In Fen-treated mice, CP11 attenuated the degeneration of dopaminergic neurons and reduced neuroinflammation. Our findings demonstrate that neurodegeneration in Fen-treated models might be attributed to the activation of AEP. AEP might be a novel therapeutic target in PD induced by Fen and other environmental factors.

We perform a statistical study calculating electromagnetic ion cyclotron (EMIC) wave amplitudes based off in situ plasma measurements taken by the Van Allen Probes’ (1.1–5.8 Re) Helium, Oxygen, Proton, Electron (HOPE) instrument. Calculated wave amplitudes are compared to EMIC waves observed by the Electric and Magnetic Field Instrument Suite and Integrated Science on board the Van Allen Probes during the same period. The survey covers a 22-month period (1 November 2012 to 31 August 2014), a full Van Allen Probe magnetic local time (MLT) precession. The linear theory proxy was used to identify EMIC wave events with plasma conditions favorable for EMIC wave excitation. Two hundred and thirty-two EMIC wave events (103 H+-band and 129 He+-band) were selected for this comparison. Nearly all events selected are observed beyond L = 4. Results show that calculated wave amplitudes exclusively using the in situ HOPE measurements produce amplitudes too low compared to the observed EMIC wave amplitudes. Hot proton anisotropy (Ahp) distributions are asymmetric in MLT within the inner (L

Lingde Kong,* Jiangbo Bai,* Kunlun Yu, Bing Zhang, Jichun Zhang, Dehu Tian Department of Hand Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China *These authors contributed equally to this work Background: In the treatment of cubital tunnel syndrome (CuTS), in situ ulnar nerve decompression is commonly used. This study aims to investigate predictive factors for poor recovery and ulnar nerve instability following this procedure. Methods: We enrolled 235 patients who underwent in situ ulnar nerve decompression for the treatment of CuTS from January 2010 to December 2014. All patients underwent >2 years’ follow-up. The primary outcome was postoperative recovery, which was assessed by Messina’s criteria, and the secondary outcome was postoperative ulnar nerve instability. Potential risk factors were collected from demographic data and electrodiagnostic test, which included age, gender, body mass index, history of tobacco or alcohol use, history of major medical comorbidities, disease duration, preoperative severity, motor conduction velocity, and sensory conduction velocity. Results: A total of 208 patients (88.5%) had satisfactory outcomes, while the other 27 patients (11.5%) had not. There were 25 patients (10.6%) showing postoperative ulnar nerve instability during follow-up. The multivariate analysis showed that only severe preoperative symptom (odds ratio [OR], 3.06; 95% confidence interval [CI], 2.16–4.32) was associated with unsatisfactory postoperative outcomes in patients with CuTS (P

Academic research trends involving public health education may reflect a certain degree of talent construction status. This study systematically reviews the data for published literature on graduate public health education, aiming to provide evidence for the optimization of public health postgraduate training mechanisms in China. Keyword cooccurrence analysis was performed based on high-frequency keywords. From 1992 to 2008, the annual number of publications in this field was relatively low in China, averaging fewer than 5 articles. The number of publications showed a steep increase after 2009. The publications were mostly from single research institutions, including comprehensive universities and military medical universities, concentrated in Beijing and Shanghai. The high-frequency keywords were public health and preventive medicine, postgraduate training, professional degree, MPH, curriculum, and teaching reform. Hotspots consisted of practical teaching research, training, educational reform and comparative education research. Research on public health postgraduate education has not reached scale and has insufficient support. Moreover, many problems in graduate public health education still cannot be solved by existing studies: authentic and practical learning, a unified approach to cultivate graduate students, organizational change of graduate public health education, and international cooperation and public health education.

Using the electron phase space density (PSD) data measured by Van Allen Probe A from January 2013 to April 2015, we investigate the effects of magnetospheric processes on relativistic electron dynamics in the Earth's outer radiation belt during 50 geomagnetic storms. A statistical study shows that the maximum electron PSDs for various μ (μ = 630, 1096, 2290, and 3311 MeV/G) at L*~4.0 after the storm peak have good correlations with storm intensity (cc~0.70). This suggests that the occurrence and magnitude of geomagnetic storms are necessary for relativistic electron enhancements at the inner edge of the outer radiation belt (L* = 4.0). For moderate or weak storm events (SYM-Hmin > ~−100 nT) with weak substorm activity (AEmax 0.77). For storm events with intense substorms after the storm peak, relativistic electron enhancements at L* = 4.5 and 5.0 are observed. This shows that intense substorms during the storm recovery phase are crucial to relativistic electron enhancements in the heart of the outer radiation belt. Our statistics study suggests that magnetospheric processes during geomagnetic storms have a significant effect on relativistic electron dynamics.

Using the particle data measured by Van Allen Probe A from October 2012 to March 2016, we investigate in detail the radiation belt seed population and its association with the relativistic electron dynamics during 74 geomagnetic storms. The period of the storm recovery phase was limited to 72 h. The statistical study shows that geomagnetic storms and substorms play important roles in the radiation belt seed population (336 keV electrons) dynamics. Based on the flux changes of 1 MeV electrons before and after the storm peak, these storm events are divided into two groups of “large flux enhancement” and “small flux enhancement.” For large flux enhancement storm events, the correlation coefficients between the peak flux location of the seed population and those of relativistic electrons (592 keV, 1 MeV, 1.8 MeV, and 2.1 MeV) during the storm recovery phase decrease with electron kinetic energy, being 0.92, 0.68, 0.49, and 0.39, respectively. The correlation coefficients between the peak flux of the seed population and those of relativistic electrons are 0.92, 0.81, 0.75, and 0.73. For small flux enhancement storm events, the correlation coefficients between the peak flux location of the seed population and those of relativistic electrons are relatively smaller, while the peak flux of the seed population is well correlated with those of relativistic electrons (correlation coefficients >0.84). It is suggested that during geomagnetic storms there is a good correlation between the seed population and ≤1 MeV electrons and the seed population is important to the relativistic electron dynamics.

To date, most research on the characteristics of glacial debris flow along the Sichuan–Tibet railway has focused on numerical simulations and remote sensing, resulting in a lack of direct experimental data from debris flow samples. Therefore, in the present study, a field investigation was conducted along the Sichuan–Tibet railway, and 55 samples of glacial debris flow deposits were systematically analyzed to determine their grading and rheological properties. This is the first systematic experimental study on glacial debris flow deposits. The results showed that the proportion of coarse particles was high and the proportion of fine particles was low in the glacial debris flow along the Sichuan–Tibet railway. The average gravel and sand contents were 37.8% and 58%, respectively, and the average contents of silt and clay were 3.7% and 0.47%, respectively. The average fractal dimension was 2.1507, which is much greater than that of viscous debris flow. Under the same gravity and shear rate, the stress of typical glacial debris flow was significantly less than that of viscous debris flow, whereas the variability of the stress was more significant. These findings will contribute to revealing the movement rules and disaster risk of glacier debris flow along the Sichuan–Tibet railway and have considerable theoretical and practical significance for ensuring safety during both its construction and later operation.

In this paper, the radial distribution laws of damage factors under decoupled charge blasting are studied for the optimization design of blasting parameters. Through defining the critical radial decoupling coefficient, the damage zone around the borehole is partitioned and the characteristics are described. Based on the damage factor defined by Taylor’s effective elastic modulus, the formulas of the radial distribution laws of damage factors are derived by the attenuation law of stress wave and the theory of thick-walled cylinder, respectively, which are then superposed to obtain the formula under the combined action of explosion stress wave and quasistatic gas. Experimental verification indicates that the theoretical values, which have a good correlation with the test data and are of high accuracy, can characterize the radial distribution laws of damage factors and estimate the damage range. When a radial decoupling coefficient is less than the critical value, the attenuation rate of damage factors firstly increases and then decreases with the increase of distance, and a serious damage zone is caused. Conversely, it decreases gradually, and the serious damage zone is not caused. Therefore, on the premise of stable detonation, it is necessary to apply an appropriate radial decoupling coefficient which is larger than the critical value to smooth or presplit blasting.