Novel therapeutic perspectives for crescentic glomerulonephritis through targeting parietal epithelial cell activation and proliferation.

INTRODUCTION: Kidney injury is clinically classified as crescentic glomerulonephritis (CrGN) when ≥50% of the glomeruli in a biopsy sample contain crescentic lesions. However, current strategies, such as systemic immunosuppressive therapy and plasmapheresis for CrGN, are partially effective, and these drugs have considerable systemic side effects. Hence, targeted therapy to prevent glomerular crescent formation and expansion remains an unmet clinical need. AREAS COVERED: Hyperproliferative parietal epithelial cells (PECs) are the main constituent cells of the glomerular crescent with cell-tracing evidence. Crescents obstruct the flow of primary urine, pressure the capillaries, and degenerate the affected nephrons. We reviewed the markers of PEC activation and proliferation, potential therapeutic effects of thrombin and thrombin receptor inhibitors, and how podocytes cross-talk with PECs. These experiments may help identify potential early specific targets for the prevention and treatment of glomerular crescentic injury. EXPERT OPINION: Inhibiting PEC activation and proliferation in CrGN can alleviate glomerular crescent progression, which has been supported by preclinical studies with evidence of genetic deletion. Clarifying the outcome of PEC transformation to the podocyte phenotype and suppressing thrombin, thrombin receptors, and PEC hyperproliferation in early therapeutic strategies will be the research goals in the next ten years.

It is clinically classified as crescentic glomerulonephritis (CrGN) when more than 50% of the glomeruli of the kidney in a biopsy sample contain crescentic lesions (crescent shaped injuries). However, current strategies, such as immunosuppressive therapy and plasmapheresis (the removal, treatment and returning of blood) for CrGN, are partially effective, and these drugs have considerable side effects. In order to seek targeted therapy for CrGN, we reviewed the current research evidences. First, the hyperproliferative parietal epithelial cells (PECs) are the main cells within the glomerular crescent seen with cell-tracing evidence. The activated PECs can express specific markers and altered biological characteristics, such as cell growth and multiplication, migration, and extracellular matrix production. CD44, CD74, CD9, and pERK-1/2 are specific markers for PEC activation, and also as the potential therapeutic targets with evidence of gene knockout and inhibitor. Second, during the formation of glomerular crescents, PECs grow and multiply also through cross-talking with podocyte cells by the AngII/SDF-1/CXCR4/ERK1/2, HB-EGF/EGFR/JAK/STAT3, and PDGF/PDGFR signaling pathways, suggesting that the intervention of key molecules in these disease processes may be promising therapeutic targets for CrGN. Third, thrombin and protease-activated receptors (PARs) participate in the excessive proliferation of PEC through activation of the coagulation cascade reaction, PAR-1 and PAR-2. Therefore, anticoagulation therapy, especially inhibition of PAR-1 and PAR-2, is expected to be an effective strategy for the early prevention and treatment of CrGN. The drug vorapaxar selectively antagonizes PAR-1 and is the most promising candidate. These findings will not only improve the outlook for CrGN treatment, but will also help in the treatment of other glomerular diseases with crescentic lesions. [Figure: see text].

Effects of Ionic Liquid Content on the Electrical Properties of PVDF Films by Fused Deposition Modeling.

In this study, polyvinylidene fluoride (PVDF) composite films were prepared by fused deposition modeling, and the effects of ionic liquid (IL) content on the printability, crystallization behavior, and electrical properties of melted PVDF were systematically investigated. The results show that the addition of IL increased the temperature sensitivity of melted PVDF and decreased its viscosity, while IL acted as a plasticizer to lower the melting point of PVDF and improve its FDM printability. The imidazole cations in IL had electrostatic interactions with the -CF2- groups in PVDF, which promoted the transformation of the nonpolar phase to the polar phase in PVDF; thus, the addition of IL was beneficial to the increase in the polar ß phase. The PVDF with 20 wt.% IL contained the highest proportion of ß phase content (32.59%). Moreover, the increase in polar ß-phase content also increased the polarization strength of PVDF and improved its ferroelectric properties. PVDF with 10 wt.% IL had the highest residual polarization strength (16.87 µC/m2).

Robust topological one-way edge states in radius-fluctuated photonic Chern topological insulators.

Recent developments in topological photonics have shown that the introduction of disorders can yield the innovative and striking transport phenomena. Here, we theoretically investigate topological one-way edge states in radius-fluctuated photonic Chern topological insulators (PCTIs), which are composed of two-dimensional gyromagnetic photonic crystals with cylinder site fixed but with cylinder radius fluctuated. We use a fluctuation index to characterize the degree of radius fluctuation, employ two empirical parameters to inspect the evolution of topological one-way edge states, and verify the stability of topological one-way edge states by calculating massive samples with various random numbers. We find that as the radius-fluctuation strength increases, there arises a competition between topological one-way edge state, Anderson localization state and trivial bulk state. We reveal that the Anderson localization state appears far more easily in the radius-fluctuation PCTI with even a weak strength compared with the position-perturbed PCTI with a strong randomness. We also demonstrate that the topological one-way edge states are protected against a strong fluctuation much larger than the fabrication errors in practical experiments. Our results show that the PCTIs consisting of gyromagnetic photonic crystals have a high-tolerance for the material and sample fabrication errors, and this would provide a deeper understanding of fundamental topology physics.

Topological Resistance-Free One-Way Transport in a Square-Hexagon Lattice Gyromagnetic Photonic Crystal.

We theoretically propose and experimentally realize a new configuration of a photonic Chern topological insulator (PCTI) composed of a two-dimensional square-hexagon lattice gyromagnetic photonic crystal immersed in an external magnetic field. This PCTI possesses five distinct types of edges and all of them allowed the propagation of truly one-way edge states. We proceeded to utilize this special PCTI to design topological transmission lines of various configurations with sharp turns. Although the wave impedances of the edge states on both sides of the intersections in these transmission lines were very different, definitely no back reflection occurred and no mode-mixing problems and impedance-mismatching issues at the intersections were present, leading to topological resistance-free one-way transport in the whole transmission line network. Our results enrich the geometric and physical means and infrastructure to construct one-way transport and bring about novel platforms for developing topology-driven resistance-free photonic devices.

Annexin A2: The diversity of pathological effects in tumorigenesis and immune response.

Annexin A2 (ANXA2) is widely used as a marker in a variety of tumors. By regulating multiple signal pathways, ANXA2 promotes the epithelial-mesenchymal transition, which can cause tumorigenesis and accelerate thymus degeneration. The elevated ANXA2 heterotetramer facilitates the production of plasmin, which participates in pathophysiologic processes such as tumor cell invasion and metastasis, bleeding diseases, angiogenesis, inducing the expression of inflammatory factors. In addition, the ANXA2 on the cell membrane mediates immune response via its interaction with surface proteins of pathogens, C1q, toll-like receptor 2, anti-dsDNA antibodies and immunoglobulins. Nuclear ANXA2 plays a role as part of a primer recognition protein complex that enhances DNA synthesis and cells proliferation by acting on the G1-S phase of the cell. ANXA2 reduction leads to the inhibition of invasion and metastasis in multiple tumor cells, bleeding complications in acute promyelocytic leukemia, retinal angiogenesis, autoimmunity response and tumor drug resistance. In this review, we provide an update on the pathological effects of ANXA2 in both tumorigenesis and the immune response. We highlight ANXA2 as a critical protein in numerous malignancies and the immune host response.

Efficacy and Safety of Scalp Acupuncture for Insomnia: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of scalp acupuncture in the treatment of insomnia. METHODS: CNKI, Wanfang database, CQVIP database, CBM, Web of Science, Cochrane Library, and PubMed were searched for the literature on the treatment of insomnia by scalp acupuncture from the establishment of the database to July 23, 2020. Two researchers independently screened the literatures and extracted the data, then evaluated the quality of the literatures, and used RevMan 5.3 software for statistical analysis. RESULTS: A total of 21 studies including 1606 cases were included. 21 studies were included in the analysis of effective rate. The heterogeneity test showed that there was no significant heterogeneity. The fixed effect model was used, P < 0.00001. The effective rate of scalp acupuncture in the treatment of insomnia was significantly higher than that of the control group. The analysis of PSQI score was finally included in 19 studies. The heterogeneity test showed that there was obvious heterogeneity. The random effect model was used, and the subgroup analysis was conducted according to the different intervention measures of the control group. The P values of the drug group and the blank group were both less than 0.05, indicating that the improvement of PSQI score in the scalp acupuncture treatment of insomnia was significantly better than that in the drug group and the blank group; P = 0.05 in other acupuncture groups, suggesting in scalp acupuncture treatment, there was no difference between insomnia and other acupuncture in improving the PSQI score. Six studies were included in the analysis of adverse events. The heterogeneity test showed no significant heterogeneity. The fixed effect model was used, P = 0.04 < 0.05, indicating that the adverse events of scalp acupuncture in the treatment of insomnia were better than those of the control group. No publication bias analysis was conducted due to the small number of adverse events included. Publication bias was analyzed for effective rate and PSQI score. Egger's TSTs test (effective rate P = 0.001, PSQI score P = 0.001) and funnel plot showed publication bias. CONCLUSION: Scalp acupuncture is effective and safe in the treatment of insomnia, which is worthy of clinical application. However, due to the limited number of included literature, the methodology of some studies is slightly low and the quality of literature is slightly poor. In the future, we need to design rigorous, large sample, multiple center randomized controlled study to further verify the conclusion of this study.

Ultra-high strength Al-Zn-Mg-Cu alloys with high zinc content prepared via powder hot extrusion.

In this paper, two kinds of Al-Zn-Mg-Cu alloys with high Zn content (Al-8.1Zn-2.0Mg-2.3Cu-0.12Zr-0.12Sc and Al-10.5Zn-2.5Mg-1.5Cu-0.12Zr-0.12Sc) are fabricated by powder hot extrusion. Microstructure and mechanical properties are investigated by optical microscopy (OM), scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and tensile tests. The results show that the formation of ultrafine grains and homogeneous second phases in as-extruded alloys is achieved by perfect metallurgical bonding during severe plastic deformation. After the optimal solution treatment and peak aging treatment, the strength of the two alloys reaches up to 734 MPa and 802 MPa, and the elongation is 9.8 % and 5.3 %, respectively. The excellent mechanical properties are attributed to the grain boundary strengthening, precipitation strengthening and homogenous microstructure. The element content has little effect on the grain size of the powder hot-extruded Al-Zn-Mg-Cu alloy, but high Zn and Mg contents can improve the density of strengthening phases while low Cu content can reduce the difficulty of solution treatment by inhibiting the precipitation of S(Al2CuMg) phase.

Transitional Suspensions Containing Thermosensitive Dispersant for Three-Dimensional Printing.

Tailoring the rheology of suspensions is an essential and persistent issue form many applications, especially three-dimensional (3D) printing. Colloidal suspensions of ceramic powder (Al2O3) dispersed by a special thermosensitive dispersant (poly(acrylic acid)-poly(N-isopropylacrylamide), PAA-PNIPAM) were designed, which underwent a remarkable fluid-gel transition in response to thermal stimulus due to the phase transition of the graft chains (-PNIPAM). 3D periodic structures with a fine size of 100 µm were assembled by 3D printing.