SEPTIN2 suppresses an IFN-γ-independent, proinflammatory macrophage activation pathway

Interferon-gamma (IFN-γ) signaling is necessary for the proinflammatory activation of macrophages but IFN-γ-independent pathways, for which the initiating stimuli and downstream mechanisms are lesser known, also contribute. Here we identify, by high-content screening, SEPTIN2 (SEPT2) as a negative regulation of IFN-γ-independent macrophage autoactivation. Mechanistically, endoplasmic reticulum (ER) stress induces the expression of SEPT2, which balances the competition between acetylation and ubiquitination of heat shock protein 5 at position Lysine 327, thereby alleviating ER stress and constraining M1-like polarization and proinflammatory cytokine release. Disruption of this negative feedback regulation leads to the accumulation of unfolded proteins, resulting in accelerated M1-like polarization, excessive inflammation and tissue damage. Our study thus uncovers an IFN-γ-independent macrophage proinflammatory autoactivation pathway and suggests that SEPT2 may play a role in the prevention or resolution of inflammation during infection

Angle dependent field-driven reorientation transitions in uniaxial antiferromagnet MnBi2_2Te4_4 single crystal

MnBi$_2$Te$_4$, a two-dimensional magnetic topological insulator with a uniaxial antiferromagnetic structure, is an ideal platform to realize quantum anomalous Hall effect. However, the strength of magnetic interactions is not clear yet. We performed systematic studies on the magnetization and angle dependent magnetotransport of MnBi$_2$Te$_4$ single crystal. The results show that the direction of the magnetic field has significant effects on the critical field values and magnetic structure of this compound, which leads to different magnetotransport behaviors. The field-driven reorientation transitions can be utilized to estimate the AFM interlayer exchange interaction coupling and uniaxial magnetic anisotropy D. The obtained Hamiltonian can well explain the experimental data by Monte Carlo simulations. Our comprehensive studies on the field-driven magnetic transitions phenomenon in MnBi$_2$Te$_4$ provide a general approach for other topological systems with antiferromagnetism.Comment: 6 figure

Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection

Coronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS-CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. Conventionally secreted ORF8 is glycosylated and loses the ability to recognize interleukin 17 receptor A of macrophages, possibly due to the steric hindrance imposed by N-glycosylation at Asn78. However, unconventionally secreted ORF8 does not undergo glycosylation without experiencing the ER-Golgi trafficking, thereby activating the downstream NF-κB signaling pathway and facilitating a burst of cytokine release. Furthermore, we show that ORF8 deletion in SARS-CoV-2 attenuates inflammation and yields less lung lesions in hamsters. Our data collectively highlights a role of ORF8 protein in the development of cytokine storms during SARS-CoV-2 infection

Electrophoretic deposition and laser cladding of bioglass coating on Ti

Bioglass coatings derived from electrophoretic deposition method were fused on Ti surface by laser cladding process using a continuous CO laser. The specimens were studied by field-emission scanning electron microscopy, X-ray diffraction and bonding tests. Titanium oxide layer with hierarchical structures consisting of submicron rows of leaf-like embossments and nano-pores was obtained by combining acid etching and anodization processes, which increased the surface roughness of Ti. When heat-treatment temperature was 700 °C and high, CaSiO phase began to crystallize from the bioglass matrix and the crystallinity reached its maximum at 700 °C. During the electrophoretic deposition process, porous bioglass coatings composed of bioglass particles and fibers were deposited on Ti surface. Bioglass coatings with similar hierarchical structure containing submillimeter bioglass beads and microfibers were synthesized on Ti surface by laser fusion. There are no obvious microcracks at the interface of the Ti-coating, which revealed the good bonding between Ti-porcelain. With the laser scanning distance decreased, the bond strength increased accordingly. After only one day immersion in SBF, calcium phosphate began to precipitate on the bioglass coating's surfaces. The thickness of the calcium phosphate precipitation and the amount of microparticles increased with immersion time

Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway

The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-κB pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR-overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10 expression by inflammatory macrophages. Adoptive transfer of AhR-expressing macrophages protected mice against LPS-induced peritonitis associated with high IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling pathway as a critical pathway in the immune regulation of inflammatory macrophages, It suggests that AhR may be a potential therapeutic target in immune response

Gadolinium embedded iron oxide nanoclusters as T-1-T-2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery

Major State Basic Research Development Program of China (973 Program) [2013CB733802]; National Science Foundation of China (NSFC) [81101101, 51273165, 81201086, 81201190]; Key Project of Chinese Ministry of Education [212149]; Fundamental Research Funds for the Central Universities [2013121039]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)This report illustrates a new strategy of designing a T-1-T-2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T-1-T-2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T-1-T-2 dual-modal MRI monitoring capability

Parametric Analysis of the Toothed Electromagnetic Spring Based on the Finite Element Model

Active vibration control shows excellent performance in vibration isolation. In this work, the finite element model of a toothed electromagnetic spring (TES) is established using ANSYS Maxwell software. Subsequently, a static characteristic experiment of the TES is carried out, and the validity of the model is verified. Based on the established finite element model, the influence of key structural parameters on the static characteristics of the electromagnetic spring is analyzed. The results show that the parameters of the magnetic teeth have a significant impact on the performance of the electromagnetic spring. As the number of teeth increases, the electromagnetic force first increases and then decreases. With the increase in the tooth height or width, the maximum electromagnetic force gradually increases to the maximum value and then stabilizes. It should be noted that the tooth width simultaneously affects the maximum electromagnetic force, stiffness characteristics, and effective working range of the TES. This work provides a basis for further exploring the application of electromagnetic springs within the field of active vibration control

Optimizing Web Search Using Social Annotations

This paper explores the use of social annotations to improve web search. Nowadays, many services, e.g. del.icio.us, have been developed for web users to organize and share their favorite web pages on line by using social annotations. We observe that the social annotations can benefit web search in two aspects: 1) the annotations are usually good summaries of corresponding web pages; 2) the count of annotations indicates the popularity of web pages. Two novel algorithms are proposed to incorporate the above information into page ranking: 1) SocialSimRank (SSR) calculates the similarity between social annotations and web queries; 2) SocialPageRank (SPR) captures the popularity of web pages. Preliminary experimental results show that SSR can find the latent semantic association between queries and annotations, while SPR successfully measures the quality (popularity) of a web page from the web users ’ perspective. We further evaluate the proposed methods empirically with 50 manually constructed queries and 3000 auto-generated queries on a dataset crawled from del.icio.us. Experiments show that both SSR and SPR benefit web search significantly