Early human development remains poorly understood at the molecular level. Emerging models based on human reprogrammed cells may provide critical insights into process such as somitogenesis. Here we report that CDX2 anchors regulatory network that activate genes such as Wnt, FGF and Hox families, but repress those critical for mesenchymal-epithelial transition (MET) and TGF-β signalings in an in vitro human presomitic mesoderm model system. Mechanistically, CDX2 partners with SIN3A to activate and suppress downstream genes critical for anterior-posterior (AP) elongation and HES7 oscillation. Specifically, we demonstrate a critical downstream gene TBX15 that inhibits AP elongation, but has no impact on the oscillation of the segmentation clock, thus, separating oscillation from AP elongation. Our work may pave ways to further dissection the somitogenesis process at the molecular level.
As the major components of natural tissue microenvironments, both extracellular matrix (ECM) and cells exhibit dynamic mechanical properties. In particular, viscoelastic interactions are influenced by external stresses and strains over time. The tunability in the mechanical properties of cells and ECM contributes significantly to the development, physiology and pathophysiology of living organisms. For instance, hydrogels of various compositions were synthesized, as cell culture substrate, to mimick the properties of native ECMs. The fate of cultured cells can be regulated by adjusting viscoelasticity of hydrogels. Meanwhile, the precise measurement on the mechanical properties of cells and surrounding ECM, as well as the interactive relationship between these two counterparts have also received extensive attention from various avenues of researchers. However, due to the inconsistency of experimental methods, experimental conditions and other factors, there is a lack of systematic comparison and summary between different research results in studying ECM and cell viscoelasticity. Here, we discussed the origin of ECM and cell viscoelasticity, reviewed recently-developed methods for measuring ECM and cell viscoelasticity, and further summarized possible interactions between the viscoelasticity of cell and ECM. Latest studies have shown that ECM and cell viscoelasticity would change correspondingly throughout the pathogenesis in vivo, suggesting potential applications of customized viscoelastic ECM and cells in regenerative medicine.
Abstract This paper summarises the concepts of the Internet of things and its examples of application in libraries throughout the world. Given the existing university library digital infrastructure, a development path for our national university intelligent libraries based on the Internet of things was studied in detail from three aspects. We hope more university libraries will move towards true university intelligent libraries.
Background Obesity accelerates the development of lumbar disease and increase the risk during surgery. Unilateral biportal endoscopic discectomy (UBE) is a newly developed minimally invasive technique, which refers to the spinal surgery under unilateral double-channel endoscopic surgery. Therefore, the purpose of this study is whether UBE decompression alone can bring good clinical results to young obese patients with lumbar degenerative diseases. Methods The patients with lumbar diseases who underwent UBE and open surgery (open discectomy) in our hospital from February 2020 to February 2022 were selected as young (age ≤ 44 years old) and obesity (BMI ≥ 30 kg/m 2 ). The patients were evaluated with VAS, ODI, JOA and modified Macnab score before operation, 1 month, 6 months and 12 months after operation. Nerve root function sensation, muscle strength and tendon reflex were evaluated. The operation time, estimated blood loss, postoperative hospital stay, incidence of postoperative complications and reoperation rate were recorded. MRI quantitative lumbar multifidus muscle (LMM) comparison was performed 12 months after operation. Results 77 patients were included, and the scores of VAS, ODI and JOA were similar in the two groups during the last follow-up. There were no difference in nerve root function sensation, muscle strength or tendon reflex. However, one month after operation, the VAS back score and ODI improvement in the UBE group were significantly better than those in the open group, which were 2.44 ± 0.97, 33.10 ± 6.78 and 2.93 ± 0.79 and 36.13 ± 5.84, respectively, with a statistically significant difference ( p = 0.020 and 0.038). According to the modified Macnab criteria, UBE group, the excellent and good rate was 97.2%. The excellent and good rate of open group was 97.6%. The estimated blood loss and postoperative hospital stay in UBE group (36.81 ± 17.81, 3.92 ± 1.32) were significantly better than those in open group (104.88 ± 31.41, 6.41 ± 1.94), with a statistically significant difference ( p = 0.010). There was no significant difference in operation time between the two groups ( p = 0.070). The number of complications in UBE group was 2 (5.6%) and open group was 4 (9.8%). The fat infiltration rate of 19.3%+11.0% in UBE group was significantly lower than that of 27.0%±13.9% in open group ( p = 0.010). Conclusion UBE has the advantage of early recovery in the treatment of lumbar degenerative diseases in young obese patients, and reduces the damage to LMM, so it has a good clinical effect.
Evidences indicate that inflammatory process plays pivotal role in tumor disease. Soluble epoxide hydrolase inhibitors (sEHIs) have been shown to participate in anti-inflammation and tumorigenesis by protecting epoxyeicosatrienoic acids (EETs). Although we have previously revealed some effects of t-AUCB on glioma in vitro, further investigations are needed to demonstrate its effects on glioblastoma growth in vivo and how to strengthen its antitumor effect. CCK-8 kit was used to test cell growth. Cell migration capacity was performed by wound healing assays. Transwell assay was used to test cell invasion potency. Cell-cycle analysis and cell apoptosis was performed by flow cytometry. The activity of caspase-3 in cells was measured using caspase-3 activity assay kits. Total RNA was extracted from cells lysated by TRIzol reagent. qRT-PCR was performed by ABI 7500 fast RT- PCR system. Lipofectamine RNAiMAX Transfection Reagent (Invitrogen) was used for siRNA transfection. Western blootting was used to test protein expression. Tumor cell xenograft mouse models were used for in vivo study. The SPSS version 17.0 software was applied for statistical analysis. Our data shown that t-AUCB inhibits cell proliferation, migration and invasion and induces cell cycle G1 phase arrest in vitro but induces no cell apoptosis; increased Hsp27 activation and following COX-2 overexpression confer resistance to t-AUCB treatment in glioblastoma both in vitro and in vivo; quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo. These results indicate that combination of t-AUCB and quercetin may be a potential approach to treating glioblastoma.
Bullous keratopathy, a condition severely impacting vision and potentially leading to corneal blindness, necessitates corneal transplantation. However, the shortage of donor corneas and complex surgical procedures drive the exploration of tissue-engineered corneal endothelial layers. This study develops a transparent, amphiphilic, and cell-free membrane for corneal endothelial replacement. The membrane, securely attached to the posterior surface of the cornea, is created by mixing hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethylacrylate (EGDMA) in a 10:1 ratio. A 50 µL volume is used to obtain a 60 µm hydrophobic membrane on both sides, with one side treated with a polyvinylpyrrolidone (PVP) solution. The resulting membrane is transparent, foldable, biocompatible, amphiphilic, and easily handled. When exposed to 20% sulfur hexafluoride (SF
Acetylcholinesterase (AChE) is commonly used for the detection of organophosphate (OP) and carbamate (CB) insecticides. However, the cost of this commercially available enzyme is high, making high-throughput insecticide detection improbable. In this study we constructed a new AChE yeast expression system in Saccharomyces cerevisiae for the expression of a highly reactive recombinant AChE originating from Drosophila melanogaster (DmAChE). Specifically, the coding sequence of DmAChE was fused with the 3′-terminal half of an α-agglutinin anchor region, along with an antigen tag for the detection of the recombinant protein. The target sequence was cloned into the yeast expression vector pYes-DEST52, and the signal peptide sequence was replaced with a glucoamylase secretion region for induced expression. The resultant engineered vector was transformed into S. cerevisiae. DmAChE was expressed and displayed on the cell surface after galactose induction. Our results showed that the recombinant protein displayed activity comparable to the commercial enzyme. We also detected different types of OP and CB insecticides through enzyme inhibition assays, with the expressed DmAChE showing high sensitivity. These results show the construction of a new yeast expression system for DmAChE, which can subsequently be used for detecting OP and CB insecticides with reduced economic costs.
Arbutin, a natural polyphenol isolated from the bearberry plant Arctostaphylos uvaursi, possesses whitening and anticancer properties. The effects of arbutin on melanogenesis and its pro-apoptotic effect on B16 murine melanoma cells have not yet been reported. In the present study, acetylated arbutin was prepared in order to improve the biological effects of arbutin, and it was found to significantly inhibit the biosynthesis of melanin and tyrosinase activity compared with parent arbutin in B16 murine melanoma cells. Interestingly, only acetylated arbutin strongly inhibited B16 murine melanoma cell migration in a dose-dependent manner. Both arbutin and acetylated arbutin significantly reduced cell viability, promoted cell apoptosis, caused G1 cell cycle arrest and induced mitochondrial disruption in B16 murine melanoma cells. Furthermore, reduced expression of B-cell lymphoma‑extra large (Bcl-xL) and Bcl-2 were observed in arbutin- and acetylated arbutin-treated cells. Therefore, arbutin and acetylated arbutin were found to exert pro-apoptotic effects on B16 murine melanoma cells, mediated through the mitochondrial pathway. The findings of the present study also support the use of acetylated arbutin as a new potential candidate agent for skin whitening and melanoma treatment.
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