MOESM1 of Monocarboxylate transporter 1 promotes classical microglial activation and pro-inflammatory effect via 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3

Additional file 1: Figure S1. Intraperitoneal injection of LPS increased the expression of MCT1 and PFKFB3 in the hippocampus. A, Immunostaining of Iba1 (green) and MCT1 (Red) in the hippocampus in PBS- and LPS-treated groups (n = 4 per group). The white arrow represents Iba1 and MCT1-positive cells. B, Immunostaining of PFKFB3 in the hippocampus in each group (n = 4 per group). Scale bar = 50 μm. Figure S2. MCT1 and PFKFB3 have no effect on alternative microglial polarization and cell viability. A, The overexpression efficiency of Lenti-PFKFB3 in BV2 cells (n = 8 per group and errors represent S.E.M, **p < 0.01; t test). B, Quantification of the mRNA level of Arg1 and CD206 after treatment with Lenti-siMCT1 and Lenti-PFKFB3 under PBS and LPS-stimulated conditions (n = 8 per group and errors represent S.E.M). C, Knockdown of MCT1 or overexpression of PFKFB3 has no effect on BV2 cell viability (n = 5 per group and errors represent S.E.M). Figure S3. Intracerebroventricular injection of lactate reduced classical microglial polarization in the substantia nigra. A, B, Immunostaining of classical microglia markers, CD86 and Iba1, and quantification of Iba1+ cells and CD86+ cells in the hippocampus in each group (n = 5-6 per group). **p and ##p < 0.01, two-way ANOVA followed by post hoc. Scale bar = 50 μm

Supramolecular Gel Electrolyte-Based Supercapacitors with a Comparable Dependence of Electrochemical Performances on Electrode Thickness to Those Based on Bulk Electrolyte Solutions

Gel polymer electrolyte (GPE)-based quasi-solid-state supercapacitors (QSSCs) have attracted great interest in the last 10 years due to the increasing demand of wearable electronics. However, the strong dependence of electrochemical performances on the electrode thickness of the GPE-based QSSCs severely limits their applications. Herein, a low-molecular-weight supramolecular gel electrolyte (SGE) has been successfully developed to render the SGE-based QSSCs a comparable dependence of electrochemical performances on electrode thickness to those based on bulk electrolyte solutions. Two main reasons are responsible for such an observation. First, the as-prepared SGE has an ionic conductivity as high as ∼421 mS cm–1. Second, the combined advantages of small molecular size, low solution viscosity, and good wettability endow the SGE with a capability to effectively infill the thick porous activated carbon electrodes through a sol–gel transition method. Moreover, it has also been demonstrated that the SGE developed here is applicable to a wide range of QSSCs

Fabrication of Hierarchical CaCO₃ Mesoporous Spheres: Particle-Mediated Self-Organization Induced by Biphase Interfaces and SAMs

Highly ordered hierarchical calcium carbonate is an important phase involved in calcification by a wide variety of invertebrate organisms, and its formation is of technological interest in the development of functional materials. In this article, porous CaCO3 hierarchical microspheres with a hedgehoglike appearance have been fabricated on the flexible substrate under mild conditions. There are two points that play important roles in the regular organization of the terminal products: one is the biphase interfaces, which are generated by organic solvent n-hexane and an aqueous saturated solution of Ca(OH)2, and the other is hydroxyl-terminated monolayers assembled on the flexible PET (poly(ethylene terephthalate)) substrate. The SEM images show that novel CaCO3 hierarchical microspheres consist of densely stacked “shuttles” by the oriented self-organization of CaCO3 nanoparticles. The IR and XRD spectra indicate that the as-synthesized products are composed of a calcite phase obtained by an ACC (amorphous calcium carbonate)-to-calcite transformation. In view of the results, a nanoparticle-mediated self-organization process induced by biphase interfaces and SAMs template is proposed for the integration of functional materials and nanodevices

Additional file 2 of ZHX2 inhibits thyroid cancer metastasis through transcriptional inhibition of S100A14

Additional file 2: Table S2. Synthetic oligonucleotides

Additional file 1 of ZHX2 inhibits thyroid cancer metastasis through transcriptional inhibition of S100A14

Additional file 1: Table S1. The information of patients involved in this study

Additional file 3 of ZHX2 inhibits thyroid cancer metastasis through transcriptional inhibition of S100A14

Additional file 3: Table S3. The cBioPortal analysis negative correlation of ZHX2 expression with S100 family in thyroid cancer patients [Thyroid Carcinoma (TCGA, PanCancer Atlas)] listed in the table

Image_2_N-Glycosylation at Asn291 Stabilizes TIM-4 and Promotes the Metastasis of NSCLC.tif

T-cell immunoglobulin domain and mucin domain 4 (TIM-4) is a transmembrane protein that promotes epithelial-mesenchymal transition (EMT), migration and invasion of non-small cell lung cancer (NSCLC) cells. Most transmembrane proteins are modified by N-glycosylation and the importance of protein N-glycosylation in cancer cell metastasis has been well appreciated. However, whether TIM-4 is modified by N-glycosylation and the role of TIM-4 N-glycosylation in NSCLC remains largely unknown. In the current study, we reported that TIM-4 was extensively N-glycosylated at Asn291. After the removal of N-glycosylation, the stability of TIM-4 protein was decreased and TIM-4 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated ERAD. Thus, the expression of TIM-4 on the cell surface was decreased, which suppressed TIM-4-mediated metastasis in NSCLC. In summary, the present study identifies TIM-4 N-glycosylation and its role in NSCLS migration, which would provide a valuable biomarker for developing drugs targeting N-glycosylation at Asn291 on TIM-4.</p

Image_1_N-Glycosylation at Asn291 Stabilizes TIM-4 and Promotes the Metastasis of NSCLC.tif

T-cell immunoglobulin domain and mucin domain 4 (TIM-4) is a transmembrane protein that promotes epithelial-mesenchymal transition (EMT), migration and invasion of non-small cell lung cancer (NSCLC) cells. Most transmembrane proteins are modified by N-glycosylation and the importance of protein N-glycosylation in cancer cell metastasis has been well appreciated. However, whether TIM-4 is modified by N-glycosylation and the role of TIM-4 N-glycosylation in NSCLC remains largely unknown. In the current study, we reported that TIM-4 was extensively N-glycosylated at Asn291. After the removal of N-glycosylation, the stability of TIM-4 protein was decreased and TIM-4 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated ERAD. Thus, the expression of TIM-4 on the cell surface was decreased, which suppressed TIM-4-mediated metastasis in NSCLC. In summary, the present study identifies TIM-4 N-glycosylation and its role in NSCLS migration, which would provide a valuable biomarker for developing drugs targeting N-glycosylation at Asn291 on TIM-4.</p

Image_1_Decreased Siglec-9 Expression on Natural Killer Cell Subset Associated With Persistent HBV Replication.TIF

<p>Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56^dim NK cells. Its role in infection diseases has not been investigated yet. Here, we studied the potential regulatory roles of NK Siglec-9 in the pathogenesis of chronic hepatitis B (CHB) infection. Flow cytometry evaluated the expression of Siglec-9 and other receptors on peripheral NK cells. Immunofluorescence staining was used to detect Siglec-9 ligands on liver biopsy tissues and cultured hepatocyte cell lines. Siglec-9 blocking assay was carried out and cytokine synthesis and CD107a degranulation was detected by flow cytometry. Compared to healthy donors, CHB patients had decreased Siglec-9⁺ NK cells, which reversely correlated with serum hepatitis B e antigen and HBV DNA titer. Siglec-9 expression on NK cells from patients achieving sustained virological response recovered to the level of normal donors. Neutralization of Siglec-9 restored cytokine synthesis and degranulation of NK cells from CHB patients. Immunofluorescence staining showed increased expression of Siglec-9 ligands in liver biopsy tissues from CHB patients and in hepatocyte cell lines infected with HBV or stimulated with inflammatory cytokines (IL-6 or TGF-β). These findings identify Siglec-9 as a negative regulator for NK cells contributing to HBV persistence and the intervention of Siglec-9 signaling might be of potentially translational significance.</p

Image_2_Decreased Siglec-9 Expression on Natural Killer Cell Subset Associated With Persistent HBV Replication.TIF

<p>Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56^dim NK cells. Its role in infection diseases has not been investigated yet. Here, we studied the potential regulatory roles of NK Siglec-9 in the pathogenesis of chronic hepatitis B (CHB) infection. Flow cytometry evaluated the expression of Siglec-9 and other receptors on peripheral NK cells. Immunofluorescence staining was used to detect Siglec-9 ligands on liver biopsy tissues and cultured hepatocyte cell lines. Siglec-9 blocking assay was carried out and cytokine synthesis and CD107a degranulation was detected by flow cytometry. Compared to healthy donors, CHB patients had decreased Siglec-9⁺ NK cells, which reversely correlated with serum hepatitis B e antigen and HBV DNA titer. Siglec-9 expression on NK cells from patients achieving sustained virological response recovered to the level of normal donors. Neutralization of Siglec-9 restored cytokine synthesis and degranulation of NK cells from CHB patients. Immunofluorescence staining showed increased expression of Siglec-9 ligands in liver biopsy tissues from CHB patients and in hepatocyte cell lines infected with HBV or stimulated with inflammatory cytokines (IL-6 or TGF-β). These findings identify Siglec-9 as a negative regulator for NK cells contributing to HBV persistence and the intervention of Siglec-9 signaling might be of potentially translational significance.</p