Icariside II protects from marrow adipose tissue (MAT) expansion in estrogen-deficient mice by targeting S100A16.

Icariside II, a flavonoid glycoside, is the main component found invivo after the administration of Herba epimedii and has shown some pharmacological effects, such as prevention of osteoporosis and enhancement of immunity. Increased levels of marrow adipose tissue are associated with osteoporosis. S100 calcium-binding protein A16 (S100A16) promotes the differentiation of bone marrow mesenchymal stem cells (BMSCs) into adipocytes. This study aimed to confirm the anti-lipidogenesis effect of Icariside II in the bone marrow by inhibiting S100A16 expression. We used ovariectomy (OVX) and BMSC models. The results showed that Icariside II reduced bone marrow fat content and inhibited BMSCs adipogenic differentiation and S100A16 expression, which correlated with lipogenesis. Overexpression of S100A16 eliminated the inhibitory effect of Icariside II on lipid formation. ß-catenin participated in the regulation adipogenesis mediated by Icariside II/S100A16 in the bone. In conclusion, Icariside II protects against OVX-induced bone marrow adipogenesis by downregulating S100A16, in which ß-catenin might also be involved.

Long-term survival outcomes of endoscopic therapy vs. surgical resection in patients with cardia gastrointestinal stromal tumor.

The ideal surgical approach for treating cardia gastrointestinal stromal tumor (GIST) is not clearly established. This study aimed to assess the long-term survival results among patients who received endoscopic therapy (ET) or surgical resection (SR) for cardia GIST. Cardia GIST patients from 2000 to 2019 were selected from the surveillance, epidemiology, and end result (SEER) database. Multiple imputation (MI) was applied to handle missing data, and propensity score matching (PSM) was carried out to mitigate selection bias during comparisons. Demographic and clinical characteristics' effects on overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier analyses and multivariate Cox proportional hazard models. A total of 330 patients with cardia GIST were enrolled, including 47 (14.2%) patients with ET and 283 (85.8%) patients with SR. The 5-year OS and CSS rates in the ET and SR groups were comparable [before PSM, (OS) (76.1% vs. 81.2%, P = 0.722), (CSS) (95.0% vs. 89.3%, P = 0.186); after PSM, (OS) (75.4% vs. 85.4%, P = 0.540), (CSS) (94.9% vs. 92.0%, P = 0.099)]. Moreover, there was no significant difference between ET and SR in terms of long-term OS (hazard ratio [HR] 0.735, 95% confidence interval [CI] 0.422-1.282) and CSS (HR 1.560, 95% CI 0.543-4.481). Our study found no significant disparity in long-term survival outcomes between ET and SR in cardia GIST patients, implying that ET could be a valid surgical strategy for treating cardia GIST.

Calcifying fibrous tumor and pathological analysis.

A 55-year-old male presented to our outpatient department with complaints of upper abdominal dull pain. Gastroscopy revealed a submucosal eminence at the greater curvature of the gastric body, with smooth surface mucosa, and biopsy pathology indicated inflammation. Physical examination showed no obvious abnormalities, and laboratory results were within the normal range. Computerized tomography (CT) showed thickening of the gastric body. Endoscopic submucosal dissection (ESD) was performed,and representative photomicrographs of histologic sections were shown.

Largely Enhanced Surface Flashover Voltage of Poly(ether Imide) by Scalable and Durable ZnO Coating: A Gift from In Situ Growth.

Dielectric materials with high surface electric insulation strength are in great demand in a high-power space solar cell array (SSCA). A moderately conductive surface is favorable to inhibit charge accumulation and mitigate electric field distortion, thus improving the surface flashover voltage. Although numerous modification methods have been proposed to achieve this goal, the facile, efficient, scalable, and environmentally friendly modification strategy remains a critical challenge to date. Considering the excellent charge modulation ability of ZnO and its mild preparation conditions, a facile and economical hydrothermal strategy was proposed to fabricate in situ a durable poly(ether imide)/zinc oxide (PEI/ZnO) coating with a high charge decay rate. The blooming flower-like ZnO in the coating is proved to play a key role in enhancing lateral charge dissipation on the surface of PEI, thereby suppressing surface charge accumulation. It was also shown that the shielding effect of ZnO on high-energy photons during flashover and the catalytic effect of Zn2+ on PEI molecular chains during hydrothermal treatment had a facilitating and suppressing effect on outgassing, respectively, and consequently affected the flashover. Excitingly, the synergistic effects of both accelerated charge dissipation and suppressed outgassing helped to improve the flashover voltage of PEI by up to 36.7%. The strategy selected here is efficient, scalable, and facile, and the coating is durable, which makes sense for commercial promotion.

Co-exposure of maize to polyethylene microplastics and ZnO nanoparticles: Impact on growth, fate, and interaction.

Microplastics (MPs), especially polyethylene MPs (PE MPs), which are the primary component of mulch, have attracted increasing attention in recent years. ZnO nanoparticles (NPs), which constitute a metal-based nanomaterial commonly used in agricultural production, co-converge with PE MPs in the soil. However, studies revealing the behavior and fate of ZnO NPs in soil-plant systems in the presence of MPs are limited. In this study, a pot experiment was used to evaluate the effects of maize co-exposure to PE MPs (0.5 % and 5 % w/w) and ZnO NPs (500 mg/kg) on growth, element distribution, speciation, and adsorption mechanism. The results demonstrate that individual exposure to PE MPs posed no significant toxicity; however, it significantly decreased maize grain yield (essentially 0). ZnO NP-exposure treatments significantly increased the Zn concentration and distribution intensity in maize tissues. Among them, the Zn concentration in the maize root exceeded 200 mg/kg, compared with 40 mg/kg in the grain. Moreover, the Zn concentrations in various tissues decreased in the following order: stem, leaf, cob, bract, and grain. Reassuringly, ZnO NPs still could not be transported to the maize stem under co-exposure to PE MPs. ZnO NPs had been biotransformed (64 % of the Zn was associated with histidine, with the remainder being associated with P [phytate] and cysteine) in maize stem. This study provides new insights into the plant physiological risks of PE MP and ZnO NP co-exposure in the soil-plant system and assesses the fate of ZnO NPs.

Flagellin/Virus-like Particle Hybrid Platform with High Immunogenicity, Safety, and Versatility for Vaccine Development.

Hepatitis B core (HBc) virus-like particles (VLPs) and flagellin are highly immunogenic and widely explored vaccine delivery platforms. Yet, HBc VLPs mainly allow the insertion of relatively short antigenic epitopes into the immunodominant c/e1 loop without affecting VLP assembly, and flagellin-based vaccines carry the risk of inducing systemic adverse reactions. This study explored a hybrid flagellin/HBc VLP (FH VLP) platform to present heterologous antigens by replacing the surface-exposed D3 domain of flagellin. FH VLPs were prepared by the insertion of flagellin gene into the c/e1 loop of HBc, followed by E. coli expression, purification, and self-assembly into VLPs. Using the ectodomain of influenza matrix protein 2 (M2e) and ovalbumin (OVA) as models, we found that the D3 domain of flagellin could be replaced with four tandem copies of M2e or the cytotoxic T lymphocyte (CTL) epitope of OVA without interfering with the FH VLP assembly, while the insertion of four tandem copies of M2e into the c/e1 loop of HBc disrupted the VLP assembly. FH VLP-based M2e vaccine elicited potent anti-M2e antibody responses and conferred significant protection against multiple influenza A viral strains, while FljB- or HBc-based M2e vaccine failed to elicit significant protection. FH VLP-based OVA peptide vaccine elicited more potent CTL responses and protection against OVA-expressing lymphoma or melanoma challenges than FljB- or HBc-based OVA peptide vaccine. FH VLP-based vaccines showed a good systemic safety, while flagellin-based vaccines significantly increased serum interleukin 6 and tumor necrosis factor α levels and also rectal temperature at increased doses. We further found that the incorporation of a clinical CpG 1018 adjuvant could enhance the efficacy of FH VLP-based vaccines. Our data support FH VLPs to be a highly immunogenic, safe, and versatile platform for vaccine development to elicit potent humoral and cellular immune responses.

CALR-TLR4 Complex Inhibits Non-Small Cell Lung Cancer Progression by Regulating the Migration and Maturation of Dendritic Cells.

BACKGROUND: Lung cancer is a common malignant tumor that threatens human life and is associated with high morbidity and mortality rates. Calreticulin (CALR) is a antigen characteristic of immunogenic cell death in non-small cell lung cancer (NSCLC), which is closely related to anti-tumor immunity, but its specific mechanism in anti-tumor immunity remains unclear. METHODS: Immunohistochemical staining was performed to detect the expression of CALR and dendritic cell-lysosome-associated membrane glycoprotein (DC-LAMP) in NSCLC tissues. The cell supernatant was used to induce migration and maturation of dendritic cells (DCs). Western blot and real-time PCR were used to investigate the corresponding molecule expression in the CALR-Toll-like receptor 4 (TLR4)-MyD88 signaling pathway. In vivo experiments were conducted to evaluate the role of mCALR in lung cancer progression. RESULTS: The expression of CALR on NSCLC cell membrane (mCALR) and DC infiltration in NSCLC were positively correlated and were closely related to the prognosis of NSCLC patients. Moreover, mCALR facilitated the migration and maturation of DCs by activating CALR-TLR4-MyD88 signaling and increasing the secretion of TNFα and CCL19, which was inhibited by the loss of TLR4. In vivo experiments demonstrated that mCALR inhibited lung cancer progression by facilitating DC infiltration in lung cancer tissues. CONCLUSION: Our study explores the function and mechanism of the CALR-TLR4 complex in DC migration and maturation and investigates the inhibitory effect of the CALR-TLR4 complex on lung cancer progression, providing a theoretical basis and ideas for immunotherapy of NSCLC.