Neuroinflammation in the central nervous system (CNS) is an important subject of neuroimmunological research. Emerging evidence suggests that neuroinflammation is a key player in various neurological ...disorders, including neurodegenerative diseases and CNS injury. Neuroinflammation is a complex and well‐orchestrated process by various groups of glial cells in CNS and peripheral immune cells. The cross‐talks between various groups of glial cells in CNS neuroinflammation is an extremely complex and dynamic process which resembles a well‐orchestrated symphony. However, the understanding of how glial cells interact with each other to shape the distinctive immune responses of the CNS remains limited. In this review, we will discuss the joint actions of glial cells in three phases of neuroinflammation, including initiation, progression, and prognosis, the three movements of the symphony, as the role of each type of glial cells in neuroinflammation depends on the nature of inflammatory cues and specific course of diseases. This perspective of glial cells in neuroinflammation might provide helpful clues to the development of the early diagnosis and therapeutic intervention of the various CNS diseases.
Main Points
Neuroinflammation in the CNS is well orchestrated by different groups of glial cells and immune cells.
Neuroinflammation reflects joint actions of glial cells in three phases of neuroinflammation, including initiation, progression and prognosis.
Cryogels are a subset of hydrogels synthesized under sub‐zero temperatures: initially solvents undergo active freezing, which causes crystal formation, which is then followed by active melting to ...create interconnected supermacropores. Cryogels possess several attributes suited for their use as bioscaffolds, including physical resilience, bio‐adaptability, and a macroporous architecture. Furthermore, their structure facilitates cellular migration, tissue‐ingrowth, and diffusion of solutes, including nano‐ and micro‐particle trafficking, into its supermacropores. Currently, subsets of cryogels made from both natural biopolymers such as gelatin, collagen, laminin, chitosan, silk fibroin, and agarose and/or synthetic biopolymers such as hydroxyethyl methacrylate, poly‐vinyl alcohol, and poly(ethylene glycol) have been employed as 3D bioscaffolds. These cryogels have been used for different applications such as cartilage, bone, muscle, nerve, cardiovascular, and lung regeneration. Cryogels have also been used in wound healing, stem cell therapy, and diabetes cellular therapy. In this review, we summarize the synthesis protocol and properties of cryogels, evaluation techniques as well as current in vitro and in vivo cryogel applications. A discussion of the potential benefit of cryogels for future research and their application are also presented.
Cenozoic structures in the Bohai Bay basin province can be subdivided into eleven extensional systems and three strike-slip systems. The extensional systems consist of normal faults and transfer ...faults. The normal faults predominantly trend NNE and NE, and their attitudes vary in different tectonic settings. Paleogene rifting sub-basins were developed in the hanging walls of the normal faults that were most likely growth faults. Neogene–Quaternary sequences were deposited in both the rifting sub-basins and horsts to form a unified basin province. The extensional systems were overprinted by three NNE-trending, right-lateral strike-slip systems (fault zones). Although the principal displacement zones (PDZ) of the strike-slip fault zones are developed only in the basement and lower basin sequences in some cross sections, the structural deformation characteristics of the upper basin sequences also indicate that they are basement-involved, right-lateral strike-slip fault zones. According to the relationships between faults and sedimentary sequences, the extensional systems were mainly developed from the middle Paleocene to the late Oligocene, whereas the strike-slip systems were mainly developed from the Oligocene to the Miocene. Strike-slip deformation was intensified as extensional deformation was weakened. Extensional deformation was derived from horizontal tension induced by upwelling of hot mantle material, whereas strike-slip deformation was probably related to a regional stress field induced by plate movement.
The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel ...drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.
Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that master transcription factors (TFs) TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. ...However, functional consequence of their frequent co-localization at super-enhancers remains incompletely understood. Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter. Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. These results together identify a SCC-specific DNA/RNA/protein complex which activates TP63/SOX2-CCAT1-EGFR cascade and promotes SCC tumorigenesis, advancing our understanding of transcription dysregulation in cancer biology mediated by master TFs and super-enhancers.
In recent years, along with the development and application of magnesium alloys, magnesium alloys have been widely used in automotive, aerospace, medicine, sports, and other fields. In the field of ...medical materials, magnesium not only has the advantage of light weight, high strength, and a density similar to that of human bone, but also has good biocompatibility and promotes the growth of human bone. However, the mechanical properties and corrosion resistance of magnesium alloys need to be further improved to meet the requirements for human biodegradable implants. In this study, three alloys (mass fractions: Mg–10Zn, Mg–20Zn, and Mg–30Zn (wt.%)) were prepared using powder metallurgy by homogeneously mixing powders of the above materials in a certain amount with magnesium as the substrate through the addition of zinc elements, which also have good biocompatibility. The effect of zinc on the microstructure, mechanical properties, wear performance, and corrosion resistance of magnesium–zinc alloys was studied when the zinc content was different. The results show that compared with the traditional magnesium alloy using powder metallurgy, prepared magnesium alloy has good resistance to compression and bending, its maximum compressive stress can reach up to 318.96 MPa, the maximum bending strength reached 189.41 MPa, and can meet the mechanical properties of the alloy as a human bone-plate requirements. On the polarization curve, the maximum positive shift of corrosion potential of the specimens was 73 mv and the maximum decrease of corrosion-current density was 53.2%. From the comparison of the above properties, it was concluded that the three prepared alloys of which Mg–20% Zn had the best overall performance. Its maximum compressive stress, maximum bending strength, and corrosion-current density reached 318.96 MPa, 189.41 MPa and 2.08 × 10
−5
A·cm
−2
respectively, which are more suitable for use as human implant bone splints in human-body fluid environment.
The mechanical properties of the sintered Mg–Zn alloys were analyzed using powder-metallurgy techniques, and their microstructure, micromotion wear properties, electrochemical corrosion properties and composition of the physical phases were analyzed and discussed.
One of the most sustainable and promising approaches for hydrogen peroxide (H2O2) production in a low‐cost and environment‐friendly way is photosynthesis, which, however, suffers from poor carrier ...utilization and low H2O2 productivity. The addition of proton donors such as isopropanol or ethanol can increase H2O2 production, which, unfortunately, will inevitably elevate the entire cost while wasting the oxidizing power of holes (h+). Herein, the tetrahydroisoquinolines (THIQs) is employed as a distinctive proton donor for the thermodynamically feasible and selective semi‐dehydrogenation reaction to highly valuable dihydroisoquinolines (DHIQs), and meanwhile, to couple with and promote H2O2 generation in one photoredox reaction under the photocatalysis by dual‐functional Zn3In2S6 photocatalyst. Surprisingly, the suitably defective Zn3In2S6 offers an excellent and near‐stoichiometric co‐production performance of H2O2 and DHIQs at unprecedentedly high rates of 66.4 and 62.1 mmol h‐1 g‐1 under visible light (λ ≥ 400 nm), respectively, which outperforms all the previously available reports even though sacrificial agents were employed in those reports. Additionally, photocatalytic redox reaction mechanism demonstrates that H2O2 can be generated through multiple pathways, highlighting the synergistic effect among ROS (·O2‐ and 1O2), h+ and proton donor, which has been ignored in previous studies.
A dual‐functional and defective Zn3In2S6 photocatalyst is developed for the simultaneous efficient photocatalytic co‐syntheses of dihydroisoquinoline and H2O2, which shows the highest rate for both reactions up to date.
Magnesium alloy, as an absorbable and implantable biomaterial, has been greatly developed in the application field of biomaterials in recent years due to its excellent biocompatibility and ...biomechanics. However, due to the poor corrosion resistance of magnesium alloy in the physiological environment, the degradation rate will be unbalanced, which seriously affects the clinical use. There are two main ways to improve the corrosion resistance of magnesium alloy: one is by adding alloying elements, the other is by surface modification technology. Compared with adding alloy elements, the surface coating modification has the following advantages: (1) The surface coating modification is carried out without changing the matrix elements of magnesium alloy, avoiding the introduction of other elements; (2) The corrosion resistance of magnesium alloy can be improved by relatively simple physical, chemical, or electrochemical improvement. From the perspective of corrosion resistance and biocompatibility of biomedical magnesium alloy materials, this paper summarizes the application and characteristics of six different surface coating modifications in the biomedical magnesium alloy field, including chemical conversion method, micro-arc oxidation method, sol-gel method, electrophoretic deposition, hydrothermal method, and thermal spraying method. In the last section, it looks forward to the development prospect of surface coating modification and points out that preparing modified coatings on the implant surface combined with various modification post-treatment technologies is the main direction to improve biocompatibility and realize clinical functionalization.
Pseudohomonyx continentalis Yang & Pathomwattananurak, new species from Malaysia and Thailand, is described and illustrated herein. Male of P. apoensis Miyake & Yamaya, 1997 is described and ...illustrated for the first time. Pseudohomonyx javanus (Burmeister, 1847) is newly recorded from Malaysia and Thailand. An annotated catalogue and a distribution map for the genus are also provided.
Brain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson's disease ...(PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown.
Cre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation.
We show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-β2 (TGF-β2)-TGF-β type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-β2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model.
These findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.
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