Explore the vast range of titles available.

Background The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. Methods In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. Results Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. Conclusions These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.

Background Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted similar efficacy and have many advantages over MSCs. The aim of this study was to examine the efficacy of MSC-derived exosomes in YACMJD84.2 mice. Methods Rotarod performance was evaluated every 2 weeks after a presymptomatic administration of intravenous MSC-derived exosomes twice in YACMJD84.2 mice. Loss of Purkinje cells, relative expression level of Bcl-2/Bax, cerebellar myelin loss, and neuroinflammation were assessed 8 weeks following treatment. Results MSC-derived exosomes were isolated and purified through anion exchange chromatography. Better coordination in rotarod performance was maintained for 6 weeks in YACMJD84.2 mice with exosomal treatment, compared with those without exosomal treatment. Neuropathological changes including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation were also attenuated 8 weeks after exosomal treatment. The higher relative ratio of Bcl-2/Bax was consistent with the attenuation of loss of Purkinje cells. Conclusions MSC-derived exosomes could promote rotarod performance and attenuate neuropathology, including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation. Therefore, MSC-derived exosomes have a great potential in the treatment of Machado-Joseph disease.

The corrosion resistance of 316L cladding layers was addressed via the electrochemical test, to illustrate the coupling effect of the disconnected pores and grain morphology on the corrosion tolerance of 316L cladding layers. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and electrochemical testing were employed to characterize the microstructure, elemental distribution, phase composition, and corrosion resistance of the cladding layers. The results indicate that the disconnected porosity in the surface of the cladding layer decreased from 0.79% to 0.48% and the grain morphology underwent a transformation from equiaxed crystals to columnar and lath crystals, with the increasing scanning speed. The primary phase in the cladding layer was γ-Fe. Under the dual effect of a low disconnected porosity and grain morphology, the corrosion potential of the cladding layer became more electropositive from −568 mVSCE to −307 mVSCE, and the corrosion current density reduced from 4.664 μA∙cm−2 to 1.645 μA∙cm−2. The pitting potential improved from 0.005 VSCE to 0.575 VSCE as the scanning speed increased. Thus, the non-connected pores in the 316L cladding layer also affected the corrosion resistance, especially the pitting resistance. The corrosion resistance of the cladding layer can be significantly enhanced via the control of the disconnected pores and grain morphology.

Response spectrum curve is the base of seismic design of structures, and mode-superposition response spectrum method is a practical design method of structures. Damping adjustment factors and shape parameters have been adjusted in the new Chinese code (2010) for damping rate is not equal to 0.05. Then, a new mode superposition response spectrum method combined with continuum method is introduced in this paper. Finally, the earthquake shear of a shear-wall structure’s bottom is calculated, and the results of the new method are compared with that of traditional method implemented in PM-SATWE software which is widely used in architectural design institute. The contrast results show that the new method is available and has a good accuracy.

Real-time frequency readout of time-dependent pulsed signals with a high sensitivity are key elements in many applications using atomic devices, such as FID atomic magnetometers. In this paper, we propose a frequency measurement algorithm based on the Hilbert transform and implement such a scheme in a FPGA-based frequency counter. By testing pulsed exponential-decay oscillation signals in the frequency range of 10 to 500 kHz, this frequency counter shows a frequency sensitivity better than 0.1 mHz/Hz^(1/2) at 10 Hz, with an output rate of 200 Hz. When the output rate is increased to 1000 Hz, the sensitivity remains better than 0.4 mHz/Hz^(1/2) at 10 Hz. The performance on frequency sensitivity is comparable with results obtained by off-line nonlinear fitting processes. In addition, this frequency counter does not require the pre-knowledge of the analytic expression of the input signals. The realization of such a device paves the way for practical applications of highly-sensitive FID atomic magnetometers.

We study an atomic comagnetometer design based on the spin precessions of \\(^{129}\\)Xe and \\(^{131}\\)Xe atoms in glass cells. The quadrupole splittings in the precession spectrum of \\(^{131}\\)Xe are fully resolved, allowing a precise determination of the magnetic-dipole precession frequency. The transverse asymmetry of quadrupole interactions, due to both the geometry and surface properties of the cell, characterized by a non-zero asymmetry parameter \\(\\eta\\), modifies the dependence of the quadrupole splittings on the relative orientation between the cell axes and the bias magnetic field, and lead to additional corrections in the precession frequencies of \\(^{131}\\)Xe atoms. We examine these effects both theoretically and experimentally, and develop methods to quantify and control such shifts.

Background The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. Methods In this study, live Pg were orally administrated to animals, three times a week for one month. Pg-derived lipopolysaccharide (LPS) was used to stimulate peripheral blood mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. Results Dopaminergic neurons in the substantia nigra were reduced and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) were detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. Conclusions These findings suggest that LRRK2 causes gut leakage and further mediates peripheral IL-17A response in Pg-treated animals. We, thus, put forward the hypothesis that IL-17A in the serum may result in activation of the IL-17A-IL-17RA axis that aggravates dysfunction of dopaminergic neurons and provokes microglial activation in LRRK2 R1441G mice.

Gastric cancer is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. To date, there is a lack of efficient therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem cells （CSCs） are responsible for tumor initiation, invasion, metastasis, and resistance to anticancer therapies. Thus, therapies that target gastric CSCs are attractive. However, CSCs in human gastric adenocarcinoma （GAC） have not been described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC patients. CSCs of human GAC （GCSCs） that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers, generated tumors that highly resemble the original human tumors when injected into immuno- deficient mice, differentiated into gastric epithelial cells in vitro, and self-renewed in vivo and in vitro. Our findings suggest that effective therapeutic protocols must target GCSCs. The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor me- tastasis, and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a “shield” in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.

The coherent light source is one of the most important foundations in both optical physics studies and applied photonic devices. However, the whispering gallery microcavity, as a prime platform for novel light sources, has the intrinsically chiral symmetry and severely rules out access to directional light output, all-optical flip-flops, efficient light extraction, etc. Here, we demonstrate a reconfigurable symmetry-broken microlaser in an ultrahigh-Q whispering gallery microcavity with the symmetric structure, in which a chirality of lasing field is empowered spontaneously by the optical nonlinear effect. Experimentally, the ratio of counter-propagating lasing intensities is found to exceed 160:1, and the chirality can be controlled dynamically and all-optically by the bias in the pump direction. This work not only presents a distinct recipe for coherent light sources with robust and reconfigurable performance, but also opens up an unexplored avenue to symmetry-broken physics in optical micro-structures. The directional lasing emission in whispering gallery microcavities typically resorts to breaking the structure symmetry. Here the authors demonstrate a reconfigurable symmetry-broken microlaser in a symmetric ultrahigh-Q whispering gallery microcavity, in which a chirality of lasing fields is empowered spontaneously by nonlinear effects.