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Objective To verify the function of exosomes from 293T cells over-expressing membrane-localized IL-3 in vitro, so as to lay a foundation for in vivo function verification in animal models of Alzheimer′s disease. Methods Using the patented structure of the group, a recombinant IL-3 lentiviral vector was constructed and virus-infected 293T cells were packaged. Stable cell strain over-expressing IL-3 was screened. The membrane localization of IL-3 was verified by flow cytometry and immuno-fluorescence. Il-3-exosomes were purified by ultra filtration centrifugation, the exosmic morphology was observed by transmission electron microscope, the size distribution and concentration of exosomes were detected by nano-flow analysis, and the expression of IL-3 and exosome related marker proteins were detected by Western blot. The effect of BV-2 on the phagocytosis of Aβ amyloid was detected by immuno-fluorescence. Results Through vector construction, virus infection, screening and verification of puromycin, 293T cell strain with stable over-expression membrane-anchored IL-3 was obtained. The purified exosomes were collected and the structures of double-layer membrane vesicles with a diameter of 50-100 nm were observed under transmission electron microscope. Western blot results proved the presence of CD63, ALIX, TSG101 and other exosome marker proteins and these molecules were rich in IL-3 as compared with the control, that suggested the successful purification of IL-3-exosomes. The results of immuno-fluorescence assay showed that IL-3-exosomes promoted the phagocytosis of Aβ amyloid by BV-2 cells in vitro. Conclusions The gene modified 293T cell exosomes membrane-anchored expression of IL-3 can play a role of both IL-3 and exosomes in vitro, which promote the phagocytosis of microglia, there for provides a new idea for the clinical treatment of Alzheimer′s disease.

ObjectiveThis study aims at establishing a teaching catalog and content for breast rare diseases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning (CBL+PBL+RBL).MethodsBy conducting bibliometrics co-occurrence analysis, we collected 6291 articles on breast rare disease published from January, 1975 to June, 2024. Additionally, we retrieved the Textbook on Rare Diseases, the Catalog of Chinese Rare Disease, and Second Batch of Rare Disease Catalog and then decided the teaching content.ResultsFrom 16, 387 keywords, 1000 (6.1%) keywords were identified through co-occurrence analysis, including 50(0.3%) candidate diseases. These were classified into three categories: rare primary breast diseases, rare genetic mutation-related diseases associated with breast cancer, and rare systemic multi-system diseases involving the breast. From the candidate list, 20(0.1%) rare primary breast diseases were further selected for their notable clinical teaching significance, and significant multi-systemic diseases affecting the breast, whether related to gene mutations or not. Teaching plans were drafted using a diversified parallel teaching approaches, taking into account the characteristics of different diseases and the focus of different teaching methods.ConclusionsThis study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

BACKGROUND: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. METHODS: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. RESULTS: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values

The numb taste profiles of green pepper samples collected from seven regions in Sichuan and Chongqing were characterized by time-intensity (TI) sensory evaluation, and the contents of the major numb-taste components of these samples were determined by high performance liquid chromatography (HPLC). Meanwhile, correlation analyses between the numb-taste components and the sensory characteristics of green pepper were carried out by partial least squares regression (PLSR). The results showed that the numbness of green pepper rapidly rose initially, followed by a slow decline, reaching its peak after around 100 s. Amide content varied greatly among different samples, from 5 505.77 to 8 639.30 mg/100 g. The results of PLSR indicated that the numb taste of green pepper was closely related to its amide composition, and the maximum intensity, total duration (Ttot) and area under the curve (AUC) were strongly positively correlated with hydroxy-α-sorcinin, and Ttot was strongly positively correlated with hydroxy-ε-sorcinin and hydroxy-β-sorcinin. The numb taste and amide composition of green pepper varied among the geographical areas. Hydroxy-α-sorcinol and pepper oleoresin were the key substances responsible for the differences in the numb taste of different green pepper samples. We hope that this study will provide basic data reference and a scientific basis for follow-up evaluation of the numb taste quality of green pepper from Sichuan and Chongqing.

The evolution of fractures in mining overburden plays a pivotal role in interlayer gas migration. Therefore, a comprehensive study of crack development and distribution improve the efficiency of gas extraction. This study the west 2107 fully mechanized mining face in Weijia Mine of Gansu Province as the engineering background, Specifically, this study established numerical models of different mining heights by using the UDEC simulation software, and analyzed the relationship between the evolution of near-field fractures in the overburden of the working face and different mining based on fractal geometry theory. The optimal working face height for gas extraction was determined and validated through theoretical empirical formulas, field observations of overburden fractures, and gas extraction results. The results show that the total number of mining fractures increases with the increase of mining height, but the amplitude of increase is different at different stages, and the overburden fractures continue to develop in an "umbrella" shape around the overburden. The near-field fractures of the overburden rock at different mining heights have undergone three stages: generation, expansion and penetration, and compaction stability. Increasing mining height, smaller compaction zones. When the mining height is 4 m, the development density and range of roof fractures at 10 m and 40 m are significantly higher than those in other areas, which is consistent with the optimal position of the collaborative extraction roadway with high and low roadways.

Abstract A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L−1 (NCI-H1299), 3.16 ± 0.11 µmol L−1 (A549), and 1.83 ± 0.13 µmol L−1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L−1 (NCI-H1299), 3.86 ± 0.38 µmol L−1 (A549), and 1.69 ± 0.25 µmol L−1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Abstract Background Podoplanin (PDPN) expressed on tumour cells interacts with platelet C-type lectin-like receptor 2 (CLEC-2). This study aimed to investigate the role of the PDPN-platelet CLEC-2 interaction in melanoma pulmonary metastasis. Methods Murine melanoma B16-F0 cells, which have two populations that express podoplanin, were sorted by FACS with anti-podoplanin staining to obtain purified PDPN + and PDPN- B16-F0 cells. C57BL/6J mice transplanted with CLEC-2-deficient bone marrow cells were used for in vivo experiments. Results The in vivo data showed that the number of metastatic lung nodules in WT mice injected with PDPN + cells was significantly higher than that in WT mice injected with PDPN- cells and in WT or CLEC-2 KO mice injected with PDPN- cells. In addition, our results revealed that the platelet Syk-dependent signalling pathway contributed to platelet aggregation and melanoma metastasis. Conclusions Our study indicates that the PDPN-CLEC-2 interaction promotes experimental pulmonary metastasis in a mouse melanoma model. Tumour cell-induced platelet aggregation mediated by the interaction between PDPN and CLEC-2 is a key factor in melanoma pulmonary metastasis.

The application of collagen-based hydrogel is severely restricted due to its poor mechanical strength and functional singleness. In this paper, two-dimensional MXene nanosheets were introduced into collagen/ acrylic acid (AA) system, which was polymerized in situ to produce versatile hydrogel (GCol-MX-PAA). The tensile stress and compressive stress values of the resultant hydrogel at the MXene concentration of 5 mg/mL reached 211.5 kPa and 7.8 MPa, respectively, which were approximately 4.0 and 1.4 times higher than those of GCol-PAA. The bonding strength of the hydrogel reached 30.7 kPa in the porcine skin-adhesive model owing to the large number of free phenolic hydroxyl groups on GCol. Furthermore, GCol-MX-PAA could be applied to monitor large and subtle activities of human body due to the excellent electrical conductivity of MXene. Thanks to the outstanding photothermal conversion performance of MXene, the hydrogel could kill E. coli and S. aureus effectively under NIR irradiation. In addition, in vitro cytotoxicity test performed on L929 fibroblasts demonstrated the desirable biocompatibility of GCol-MX-PAA. The design strategy in this work gives guidance for the development of multifunctional collagen-based hydrogel in a wide range of applications. Highlights * Versatile hydrogel constructed from GA-modified collagen, PAA, and MXene. * The composite hydrogel displays improved mechanical properties. * This hydrogel possesses superior tissue adhesion and strain sensitivity. * This hydrogel shows desired photothermal antibacterial property and biocompatibility. KEYWORDS adhesion, biological applications of polymers, biomaterials, biopolymers, hydrogels, 1 | INTRODUCTION In the past decades, polymer-based hydrogels have been widely developed and applied in soft robotics, artificial skin, wearable devices, implantable biosensors, electrostimulated drug release units, and tissue [...]