Waterborne polyester is a common eco‐friendly material in which ester bonds are easy to hydrolyze. Therefore, we synthesized a series of waterborne comb‐like polyesters (WCPEs) with hydrophilic side ...chains through aza‐Michael addition under green and mild conditions. The physicochemical structure of the polyesters was verified by 1H NMR, FTIR, and GPC characterizations. The pH value of dispersions dropped by less than 0.7 after storage for 2 months. The dispersions remained stable after 6 months at room temperature. In addition, the WCPEs exhibited good wetting and dispersing ability for pigment particles as Tego 740 W, which is a mature pigment dispersant product for waterborne coatings. Moreover, the cross‐linked WCPEs exhibited excellent chemical resistance, there was only 1.2% weight loss, and almost no mechanism properties decline for cross‐linked transparent films even after treatment under an alkaline environment for 20 days. Thus, the synthesized WCPE has potential application as an alkali resistance eco‐friendly material, and possesses excellent performance as pigment‐dispersion resin.
The self‐dispersible waterborne nonionic comb‐like polyesters are prepared via aza‐Michael addition. The polyester dispersions possess excellent storage stability and hydrolysis resistance, and the dispersions also exhibit excellent performance as pigment wetting and dispersing agent in waterborne coating. No additional dispersants are required in the preparation of coatings with the synthesized polyester used as resin. After cross‐linking with waterborne nonionic hexamethylene diisocyanate trimer, the polyester films showed good alkali resistance and mechanical properties.
Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) ...derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.
The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.
Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.
The high molecular weight polyacrylate self‐emulsifying emulsion with 20% hydroxyl monomer and 50% solid content was prepared. Waterborne polyester was used to modify the acrylate resin. Besides ...acrylic acid (AA) and methacrylic acid (MAA), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) was also used as functional monomer to stabilize the polymerization process and improve the properties of the emulsion. The effects of the amount of waterborne polyester (WP), ammonium persulfate (APS), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA), methacrylic acid (MAA)/acrylic acid (AA) monomer ratio, butyl acrylate (BA)/styrene (St) monomer ratio on the molecular weight, particle size, viscosity, storage stability, and cured film properties of the polyacrylate emulsion were investigated. The average molecular weight of the modified polyacrylate was up to about 2.5 × 104 g mol−1. The emulsion remained stable after 6 months at room temperature. Transmission electron microscope (TEM) images showed that the latex particles had core‐shell structure. The films cured with melamine formaldehyde (MF) resin showed excellent water resistance, adhesion, and hardness.
The polyacrylate with core‐shell structure was prepared without any emulsifier. The molecular weight of the polyacrylate modified by waterborne polyester was up to 2.5×104 g·mol‐1 under the premise of 20% hydroxyl monomer content and 50% solid content. The film cured with melamine formaldehyde resin showed excellent water resistance, adhesion, hardness and tensile property.
Asymmetric Total Synthesis of Naphthospironone A Liu, Jia‐Xuan; Zhang, Shi‐Peng; Sun, Feng‐Sen ...
Angewandte Chemie International Edition,
May 22, 2023, Letnik:
62, Številka:
22
Journal Article
Recenzirano
Naphthospironone A, a polyhydroxy cagelike bioactive natural product, was synthesised for the first time in this study. The spirobicyclo3.2.1octane‐pyran core was constructed by an acid‐promoted ...epoxide‐opening lactonisation and a base‐induced intramolecular aldol‐type cyclisation.
Naphthospironone A, a cytotoxic and antibacterial natural product, was synthesised for the first time. The key to construction of its spirobicyclo3.2.1octane‐pyran core was a two‐step sequence involving hydrogenolytic debrominative olefin migration followed by a base‐induced intramolecular aldol‐type cyclisation.
Hypopharyngeal squamous cell carcinoma (HSCC) is a rare type of head and neck cancer with poor prognosis. However, till now, there is still no model predicting the survival outcomes for HSCC ...patients. We aim to develop a novel nomogram predicting the long-term cancer-specific survival (CSS) for patients with HSCC and establish a prognostic classification system.
Data of 2021 eligible HSCC patients were retrieved from the Surveillance, Epidemiology and End Results database between 2010 and 2015. We randomly split the whole cases (ratio: 7:3) into the training and the validation cohort. Cox regression as well as the Least absolute shrinkage and selection operator (LASSO) COX were used to select significant predictors of CSS. Based on the beta-value of these predictors, a novel nomogram was built. The concordance index (C-index), the calibration curve and the decision curve analysis (DCA) were utilized for the model validation and evaluation using the validation cohort.
In total, cancer-specific death occurred in 974/2021 (48.2%) patients. LASSO COX indicated that age, race, T stage, N stage, M stage, surgery, radiotherapy and chemotherapy are significant prognosticators of CSS. A prognostic model based on these factors was constructed and visually presented as nomogram. The C-index of the model was 0.764, indicating great predictive accuracy. Additionally, DCA and calibration curves also demonstrated that the nomogram had good clinical effect and satisfactory consistency between the predictive CSS and actual observation. Furthermore, we developed a prognostic classification system that divides HSCC patients into three groups with different prognosis. The median CSS for HSCC patients in the favorable, intermediate and poor prognosis group was not reached, 39.0-Mo and 10.0-Mo, respectively (p < 0.001).
In this study, we constructed the first nomogram as well as a relevant prognostic classification system that predicts CSS for HSCC patients. We believe these tools would be helpful for clinical practice in patients' consultation and risk group stratification.
Chimeric antigen receptor-modified T cells (CAR-T cells) have emerged as a promising cancer immunotherapy for solid tumors. Epithelial cell adhesion molecule (EpCAM) is overexpressed in a variety of ...tumors and is recognized as a biomarker for circulating tumor cells and cancer stem cells, representing an attractive target for adoptive T-cell immunotherapy. This study generated third-generation CAR-T cells with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector. The study demonstrated that EpCAM CAR-T cells can elicit lytic cytotoxicity to target cells in an EpCAM-dependent manner and secrete cytotoxic cytokines, including interferon gamma and tumor necrosis factor alpha. Furthermore, adoptive transfer of EpCAM CAR-T cells significantly delayed tumor growth and formation in xenograft models. In addition, the safety evaluation showed that CAR-T cells have no systemic toxicity in mice. The data confirmed the antitumor ability and safety of CAR-T cells targeting EpCAM and may provide a new target for CAR-T cell therapies in treating solid tumors.
Background Tumor mutation burden (TMB) is an emerging prognostic biomarker of immunotherapy for bladder cancer (BLCA). We aim at investigating radiomic features' value in predicting the TMB status of ...BLCA patients. Methods Totally, 75 patients with BLCA were enrolled. Radiomic features extracted from the volume of interest of preoperative pelvic contrast-enhanced computed tomography (CECT) were obtained for each case. Unsupervised hierarchical clustering analysis was performed based on radiomic features. Sequential univariate Logistic regression, the least absolute shrinkage and selection operator (LASSO) regression and the backward stepwise regression were used to develop a TMB-predicting model using radiomic features. Results The unsupervised clustering analysis divided the total cohort into two groups, i.e., group A (32.0%) and B (68.0%). Patients in group A had a significantly larger proportion of having high TMB against those in group B (66.7% vs. 41.2%, p = 0.039), indicating the intrinsic ability of radiomic features in TMB-predicting. In univariate analysis, 27 radiomic features could predict TMB. Based on six radiomic features selected by logistic and LASSO regression, a TMB-predicting model was built and visualized by nomogram. The area under the ROC curve of the model reached 0.853. Besides, the calibration curve and the decision curve also revealed the good performance of the model. Conclusions Our work firstly proved the feasibility of using radiomics to predict TMB for patients with BLCA. The predictive model based on radiomic features from pelvic CECT has a promising ability to predict TMB. Future study with a larger cohort is needed to verify our findings. Keywords: Bladder cancer, Radiomics, Tumor mutation burden, Driver mutations, Predictive model
Systematic genetic access to GABAergic cell types will facilitate studying the function and development of inhibitory circuitry. However, single gene-driven recombinase lines mark relatively broad ...and heterogeneous cell populations. Although intersectional approaches improve precision, it remains unclear whether they can capture cell types defined by multiple features. Here we demonstrate that combinatorial genetic and viral approaches target restricted GABAergic subpopulations and cell types characterized by distinct laminar location, morphology, axonal projection, and electrophysiological properties. Intersectional embryonic transcription factor drivers allow finer fate mapping of progenitor pools that give rise to distinct GABAergic populations, including laminar cohorts. Conversion of progenitor fate restriction signals to constitutive recombinase expression enables viral targeting of cell types based on their lineage and birth time. Properly designed intersection, subtraction, conversion, and multi-color reporters enhance the precision and versatility of drivers and viral vectors. These strategies and tools will facilitate studying GABAergic neurons throughout the mouse brain.
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•Designed strategies for combinatorial targeting of GABAergic neurons and progenitors•Generated new drivers, reporters, and viral vectors that improve targeting specificity•Reported intersectional fate mapping of GABAergic progenitors and laminar cohorts•Combined genetic and viral method to target cells based on lineage and birth time
He et al. present strategies and tools for the combinatorial targeting of GABAergic neurons in the mouse brain. Specific cell-type targeting can be achieved by combining two to three driver-reporter alleles with viral vectors that engage multiple cell-defining features.
Benzobicyclo3.2.1octane is a cage‐like unique motif containing a bicyclo3.2.1octane structure fused with at least one benzene ring. It is found in various natural products that exhibit structural ...complexities and important biological activities. The total synthesis of natural products possessing this challenging structure has received considerable attention, and great advances have been made in this field during the past 15 years. This review summarizes thus far achieved chemical syntheses and synthetic studies of natural compounds featuring the benzobicyclo3.2.1octane core. It focuses on strategic approaches constructing the bridged structure, aiming to provide a useful reference for inspiring further advancements in strategies and total syntheses of natural products with such a framework.
The total synthetic strategies for 11 complicated natural products containing (di)benzobicyclo3.2.1octane motif are reviewed as well as the synthetic studies on model compounds and analogs. The reaction types for the key cyclization step include Friedel–Crafts, aldol, and cascaded combination of similar processes.