Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion.

Microglial activation participates in white matter injury after cerebral hypoperfusion. However, the underlying mechanism is unclear. Here, we explore whether activated microglia aggravate white matter injury via complement C3-C3aR pathway after chronic cerebral hypoperfusion. Methods: Adult male Sprague-Dawley rats (n = 80) underwent bilateral common carotid artery occlusion for 7, 14, and 28 days. Cerebral vessel density and blood flow were examined by synchrotron radiation angiography and three-dimensional arterial spin labeling. Neurobehavioral assessments, CLARITY imaging, and immunohistochemistry were performed to evaluate activation of microglia and C3-C3aR pathway. Furthermore, C3aR knockout mice were used to establish the causal relationship of C3-C3aR signaling on microglia activation and white matter injury after hypoperfusion. Results: Cerebral vessel density and blood flow were reduced after hypoperfusion (p<0.05). Spatial learning and memory deficits and white matter injury were shown (p<0.05). These impairments were correlated with aberrant microglia activation and an increase in the number of reactive microglia adhering to and phagocytosed myelin in the hypoperfusion group (p<0.05), which were accompanied by the up-regulation of complement C3 and its receptors C3aR (p<0.05). Genetic deletion of C3ar1 significantly inhibited aberrant microglial activation and reversed white matter injury after hypoperfusion (p<0.05). Furthermore, the C3aR antagonist SB290157 decreased the number of microglia adhering to myelin (p<0.05), attenuated white matter injury and cognitive deficits in chronic hypoperfusion rats (p<0.05). Conclusions: Our results demonstrated that aberrant activated microglia aggravate white matter injury via C3-C3aR pathway during chronic hypoperfusion. These findings indicate C3aR plays a critical role in mediating neuroinflammation and white matter injury through aberrant microglia activation, which provides a novel therapeutic target for the small vessel disease and vascular dementia

Serum metabolites and hypercholesterolemia: insights from a two-sample Mendelian randomization study

BackgroundHypercholesterolemia, a critical contributor to cardiovascular disease, is not fully understood in terms of its relationship with serum metabolites and their role in disease pathogenesis.MethodsThis study leveraged GWAS data to explore the relationship between serum metabolites and hypercholesterolemia, pinpointing significant metabolites via Mendelian Randomization (MR) and KEGG pathway enrichment analysis. Data on metabolites were sourced from a European population, with analysis focusing on individuals diagnosed with hypercholesterolemia.ResultsOut of 486 metabolites analyzed, ten showed significant associations with hypercholesterolemia, categorized into those enhancing risk and those with protective effects. Specifically, 2-methoxyacetaminophen sulfate and 1-oleoylglycerol (1-monoolein) were identified as risk-enhancing, with odds ratios (OR) of 1.545 (95% CI: 1.230–1.939; P_FDR = 3E−04) and 1.462 (95% CI: 1.036–2.063; P_FDR = 0.037), respectively. On the protective side, 3-(cystein-S-yl)acetaminophen, hydroquinone sulfate, and 2-hydroxyacetaminophen sulfate demonstrated ORs of 0.793 (95% CI: 0.735–0.856; P_FDR = 6.18E−09), 0.641 (95% CI: 0.423–0.971; P_FDR = 0.042), and 0.607 (95% CI: 0.541–0.681; P_FDR = 5.39E−17), respectively. In addition, KEGG pathway enrichment analysis further revealed eight critical pathways, comprising “biosynthesis of valine, leucine, and isoleucine”, “phenylalanine metabolism”, and “pyruvate metabolism”, emphasizing their significant role in the pathogenesis of hypercholesterolemia.ConclusionThis study underscores the potential causal links between particular serum metabolites and hypercholesterolemia, offering innovative viewpoints on the metabolic basis of the disease. The identified metabolites and pathways offer promising targets for therapeutic intervention and warrant further investigation

Carbon dots-based dual-emission ratiometric fluorescence sensor for dopamine detection

The detection of Dopamine (DA) is significant for disease surveillance and prevention. However, the development of the precise and simple detection techniques is still at a preliminary stage due to their high tester requirements, time-consuming process, and low accuracy. In this work, we present a novel dual-emission ratiometric fluorescence sensing system based on a hybrid of carbon dots (CDs) and 7-amino-4-methylcoumarin (AMC) to quickly monitor the DA concentration. Linked via amide bonds, the CDs and AMC offered dual-emissions with peaks located at 455 and 505 nm, respectively, under a single excitation wavelength of 300 nm. Attributed to the fluorescence of the CDs and AMC in the nanohybrid system can be quenched by DA, the concentration of DA could be quantitatively detected by monitoring the ratiometric ratio change in fluorescent intensity. More importantly, the CDs-AMC-based dual-emission ratiometric fluorescence sensing system demonstrated a remarkable linear relationship in the range of 0–33.6 μM to detection of DA, and a low detection limit of 5.67 nM. Additionally, this sensor successfully applied to the detection of DA in real samples. Therefore, the ratiometric fluorescence sensing system may become promising to find potential applications in biomedical dopamine detection

Metabolic cooperation between conspecific genotypic groups contributes to bacterial fitness

Abstract Microbial interactions are important for the survival of species and the stability of the microbial ecosystem. Although bacteria have diverse conspecific genotypes in the natural microbial ecosystem, little is known about whether wild-type strains within species would interact with each other and how the intraspecific interaction influences the growth of the species. In this work, using Lactobacillus acetotolerans, a dominant species with diverse conspecific genotypes in natural food fermentation ecosystems as a case, we studied the interactions between different genotypic groups of this species. In interspecific and intraspecific pairwise cocultures, the growth of L. acetotolerans decreased, but the increase of the phylogenetic similarity would reduce this negative effect, indicating a potential intraspecific interaction of this species. Meanwhile, the strain classification method affected the analysis of intraspecific interactions, which can be efficiently demonstrated using 99.5% average nucleotide identity (ANI) as the strain-level classification method. Using this ANI classification method, we revealed the population fitness significantly increased in cocultures of different genotypic groups. Facilitation involving 11 amino acids was identified between different ANI genotypic groups, which was beneficial for increasing population fitness. This work revealed that wild-type conspecific strains could interact with each other via cooperative metabolic changes and benefit each other to increase fitness. It shed new light on the survival and stability of species in natural microbial ecosystems

Study on Transmission Characteristics and Bandgap Types of Plasma Photonic Crystal

A plasma photonic crystal (PPC) was formed using an array of discharge plasma tubes. The transmission spectra and bandstructure of PPCs with different lattice types under different polarization modes were studied through simulation and measurement. To study the types of bandgap in PPCs, the bandstructure of the PPC is calculated using symplectic finite difference time domain (SFDTD), a modified plane wave expansion (PWE) method, and a finite element method (FEM) based on weak form equations. The bandstructure of the PPC is compared with the transmission curve results. The results show that the bandgap is stable in the PPC, and the experimental and numerical results of the transmission spectra agree well. There are different types of bandgap in the PPC; the bandgap under TE-like polarization is caused by localized surface plasmon (LSP) and Bragg scattering. The bandgap under TM-like polarization is caused by the cutoff effect of plasma on the electromagnetic wave and Bragg scattering. The lattice type also affects the position and number of the bandgap. The three methods have their advantages and disadvantages when calculating bandstructure. Therefore, it is necessary to combine the results of three methods and experimental results to accurately determine the bandgap type of the PPC

Influence factors and mechanism of backscattering characteristics of electromagnetic waves in a single layer plasma tube array

A single-row plasma tube array (PTA) experimental system is established to improve the backscattering attenuation of a metal plate covered by a plasma tube array. The backscattering test system is utilized in a microwave anechoic chamber to examine the effects of gas composition, pressure, tube diameter, and discharge power on the backscattering attenuation of a metal plate using a plasma tube array. The electron density is obtained via microwave diagnosis. The backscattering attenuation mechanism in different frequency bands is revealed via numerical simulation. The results show that the reasonable selection of PTA parameters achieves strong attenuation in different frequency bands. The strong attenuation frequency bands of Ar–Hg PTA are in low frequency (1.5–3.5 GHz) and high frequency (13–17 GHz), while that of Ne–Hg discharge is in medium frequency (6.4–11.7 GHz). When the pressure is 0.5 and 1 Torr, the PTA shows a low, medium, and high multi-band distribution for the backscattering strong attenuation region. The backscattering strong attenuation region shows a low and high dual-band distribution, while the pressure is 2–4 Torr. As the tube diameter increases, the strong attenuation region maintains the dual-band, but it changes from low and high frequency bands to medium frequency (6-12 GHz), where the backscattering attenuation mechanism is collisional absorption when the frequency of plasma electron oscillation is close to that of electro-magnetic waves. The backscattering attenuation mechanism in the low frequency band involves the periodic structure of PTA generating local surface plasmon to absorb electromagnetic waves

Failure Behaviour of Jointed Rock Masses with 3D Nonpenetrating Joints under Uniaxial Compression: Insights from Discrete Element Method Modelling

It is well known that joints or fissures have an important effect on the failure mechanism of natural rocks. Previously, many numerical and experimental papers have been carried out to study the strength anisotropy and failure characteristics of jointed rocks. However, few studies have been carried out on the failure mechanism of nonpersistent jointed rock masses with different persistence, especially for nonpersistent joints in three dimensions. In the present study, the failure characteristics of a 3D nonpersistent jointed rock mass with different inclinations (θ) and persistence (K) are studied by numerical simulation. For the 3D digital elevation model (DEM), the linear parallel bond model (LPBM) and smooth-joint model (S-J) were used to model the rock-like material and joint interface, respectively. The connections between the geometric parameters of joints and peak strength are revealed. For the peak strength, the joint persistence only plays a minor role in specimens with inclinations of 0° and 90°, and its influence on strength is mainly reflected in the specimens with shear failure (θ = 45°, 60°, and 75°). Based on microcrack accumulation and evolution, four typical failure processes (shear failure, split failure, mixed failure, and intact failure) are analysed from the micro perspective. The shear stress evolution process on the 3D nonpersistent joint of the specimen with different inclinations under K1 = 0.42 was monitored by the measurement circle, and it was found that the distribution of shear stress inside the rock bridge is related to the failure mode of the specimen. For the specimens with θ = 0° and 90°, the shear stress had little change, indicating that there is slight shear slip behaviour on the joint surface. When the inclination is 45°, 60°, and 75°, the shear stress changes obviously during loading, indicating that the shear action is strong in this failure mode

Failure Behaviour of Jointed Rock Masses with 3D Nonpenetrating Joints under Uniaxial Compression: Insights from Discrete Element Method Modelling

It is well known that joints or fissures have an important effect on the failure mechanism of natural rocks. Previously, many numerical and experimental papers have been carried out to study the strength anisotropy and failure characteristics of jointed rocks. However, few studies have been carried out on the failure mechanism of nonpersistent jointed rock masses with different persistence, especially for nonpersistent joints in three dimensions. In the present study, the failure characteristics of a 3D nonpersistent jointed rock mass with different inclinations (&theta;) and persistence (K) are studied by numerical simulation. For the 3D digital elevation model (DEM), the linear parallel bond model (LPBM) and smooth-joint model (S-J) were used to model the rock-like material and joint interface, respectively. The connections between the geometric parameters of joints and peak strength are revealed. For the peak strength, the joint persistence only plays a minor role in specimens with inclinations of 0&deg; and 90&deg;, and its influence on strength is mainly reflected in the specimens with shear failure (&theta; = 45&deg;, 60&deg;, and 75&deg;). Based on microcrack accumulation and evolution, four typical failure processes (shear failure, split failure, mixed failure, and intact failure) are analysed from the micro perspective. The shear stress evolution process on the 3D nonpersistent joint of the specimen with different inclinations under K1 = 0.42 was monitored by the measurement circle, and it was found that the distribution of shear stress inside the rock bridge is related to the failure mode of the specimen. For the specimens with &theta; = 0&deg; and 90&deg;, the shear stress had little change, indicating that there is slight shear slip behaviour on the joint surface. When the inclination is 45&deg;, 60&deg;, and 75&deg;, the shear stress changes obviously during loading, indicating that the shear action is strong in this failure mode

Characterization of the Tellurite-Resistance Properties and Identification of the Core Function Genes for Tellurite Resistance in <i>Pseudomonas citronellolis</i> SJTE-3

Tellurite is highly toxic to bacteria and commonly used in the clinical screening for pathogens; it is speculated that there is a potential relationship between tellurite resistance and bacterial pathogenicity. Until now, the core function genes of tellurite resistance and their characteristics are still obscure. Pseudomonas citronellolis SJTE-3 was found able to resist high concentrations of tellurite (250 μg/mL) and formed vacuole-like tellurium nanostructures. The terZABCDE gene cluster located in the large plasmid pRBL16 endowed strain SJTE-3 with the tellurite resistance of high levels. Although the terC and terD genes were identified as the core function genes for tellurite reduction and resistance, the inhibition of cell growth was observed when they were used solely. Interestingly, co-expression of the terA gene or terZ gene could relieve the burden caused by the expression of the terCD genes and recover normal cell growth. TerC and TerD proteins commonly shared the conserved sequences and are widely distributed in many pathogenic bacteria, highly associated with the pathogenicity factors

Study on time-varying wires structure in wire-driven parallel manipulators

Conference Name:2011 International Conference on Mechanical Engineering, Materials and Energy, ICMEME 2011. Conference Address: Dalian, China. Time:October 19, 2011 - October 21, 2011.Trans Tech Publications Inc.; BOSI Education and Consultancy Co., LtdIn the paper, the concept of time-varying wires structure is proposed to avoid interference between wires and a mobile platform in a wire-driven parallel suspension system. A mathematical model, a kinematic notation model and a calculation model for interference between wires and the mobile platform have been built for it. When the mobile platform moves at a single degree of freedom pitch rotation, the motion equations of relevant hinge are deduced. The simulation results demonstrate that interference can be avoided in the wire-driven parallel manipulators with time-varying wires structure, and the workspace of the mobile platform may be enlarged. But different motions chosen for the hinge correspond to distinguishable sizes of workspace of the wire-driven parallel manipulators with time-varying wires structure. Therefore, according to the requirements to avoid interference, the motion of the hinge can be designed. 漏 (2012) Trans Tech Publications, Switzerland