Human oncoprotein Musashi-2 N-terminal RNA recognition motif backbone assignment and identification of RNA-binding pocket

RNA-binding protein Musashi-2 (MSI2) is a key regulator in stem cells, it is over-expressed in a variety of cancers and its higher expression is associated with poor prognosis. Like Musashi-1, it contains two N-terminal RRMs (RNA-recognition Motifs, also called RBDs (RNA-binding Domains)), RRM1 and RRM2, which mediate the binding to their target mRNAs. Previous studies have obtained the three-dimensional structures of the RBDs of Musashi-1 and the RBD1:RNA complex. Here we show the binding of MSI2-RRM1 to a 15nt Numb RNA in Fluorescence Polarization assay and time resolved Fluorescence Resonance Energy Transfer assay. Using nuclear magnetic resonance (NMR) spectroscopy we assigned the backbone resonances of MSI2-RRM1, and characterized the direct interaction of RRM1 to Numb RNA r(GUAGU). Our NMR titration and structure modeling studies showed that MSI2-RRM1 and MSI1-RBD1 have similar RNA binding events and binding pockets. This work adds significant information to MSI2-RRM1 structure and RNA binding pocket, and contributes to the development of MSI2 specific and MSI1/MSI2 dual inhibitors

Facile preparation of antifouling nanofiltration membrane by grafting zwitterions for reuse of shale gas wastewater

Complex organic matter causes severe fouling when membranes are applied for shale gas wastewater (SGW) treatment. This study reports the grafting of a zwitterionic polymer brush consisting of poly (sulfobetaine methacrylate) (PSBMA) onto the surface of a commercial nanofiltration (NF) membrane via electron transferatom transfer radical polymerization (ARGET-ATRP) to achieve anti-fouling property, especially against organic foulants. Compared to the pristine NF membranes, the PSBMA-grafted NF membrane showed high performance when challenged by SGW as a feed stream: (1) The flux stability was significantly improved during long-term operation, with a 64.28% increase in flux normalization at 50% recovery rate of SGW, while maintaining a suitable initial flux and near constant ion removal rate; (2) Based on excitation-emission-matrix spectra integrated in the fluorescence region, the removal of protein-like organic matters and humus-like organic matters increased by 34% and 16.5%, respectively; (3) The XDLVO theory supports the hypothesis that the hydrophobic interactions between the membrane surface and organic foulants were reduced by enhancing the Lewis acid-base interaction energy. The proposed anti-fouling zwitterionic membranes has potential in industrial application for the on-site reuse of SGW

Crystal and solution structures of human oncoprotein Musashi‐2 N‐terminal RNA recognition motif 1

This work is licensed under a Creative Commons Attribution 4.0 International License.Musashi‐2 (MSI2) belongs to Musashi family of RNA binding proteins (RBP). Like Musashi‐1 (MSI1), it is overexpressed in a variety of cancers and is a promising therapeutic target. Both MSI proteins contain two N‐terminal RNA recognition motifs and play roles in posttranscriptional regulation of target mRNAs. Previously, we have identified several inhibitors of MSI1, all of which bind to MSI2 as well. In order to design MSI2‐specific inhibitors and compare the differences of binding mode of the inhibitors, we set out to solve the structure of MSI2‐RRM1, the key motif that is responsible for the binding. Here, we report the crystal structure and the first NMR solution structure of MSI2‐RRM1, and compare these to the structures of MSI1‐RBD1 and other RBPs. A high degree of structural similarity was observed between the crystal and solution NMR structures. MSI2‐RRM1 shows a highly similar overall folding topology to MSI1‐RBD1 and other RBPs. The structural information of MSI2‐RRM1 will be helpful for understanding MSI2‐RNA interaction and for guiding rational drug design of MSI2‐specific inhibitors

An Expanded Gene Catalog of Mouse Gut Metagenomes

High-quality and comprehensive reference gene catalogs are essential for metagenomic research. The rather low diversity of samples used to construct existing catalogs of the mouse gut metagenome limits the numbers of identified genes in existing catalogs. We therefore established an expanded catalog of genes in the mouse gut metagenome (EMGC) containing >5.8 million genes by integrating 88 newly sequenced samples, 86 mouse gut-related bacterial genomes, and 3 existing gene catalogs. EMGC increases the number of nonredundant genes by more than 1 million genes compared to the so-far most extensive catalog. More than 60% of the genes in EMGC were assigned to Bacteria, with 54.20% being assigned to a phylum and 35.33% to a genus, while 30.39% were annotated at the KEGG orthology level. Nine hundred two metagenomic species (MGS) assigned to 122 taxa are identified based on the EMGC. The EMGC-based analysis of samples from groups of mice originating from different animal providers, housing laboratories, and genetic strains substantiated that diet is a major contributor to differences in composition and functional potential of the gut microbiota irrespective of differences in environment and genetic background. We envisage that EMGC will serve as a valuable reference data set for future metagenomic studies in mice.publishedVersio

Design strategies of tumor-targeted delivery systems based on 2D nanomaterials

Conventional chemotherapy and radiotherapy are nonselective and nonspecific for cell killing, causing serious side effects and threatening the lives of patients. It is of great significance to develop more accurate tumor-targeting therapeutic strategies. Nanotechnology is in a leading position to provide new treatment options for cancer, and it has great potential for selective targeted therapy and controlled drug release. 2D nanomaterials (2D NMs) have broad application prospects in the field of tumor-targeted delivery systems due to their special structure-based functions and excellent optical, electrical, and thermal properties. This review emphasizes the design strategies of tumor-targeted delivery systems based on 2D NMs from three aspects: passive targeting, active targeting, and tumor-microenvironment targeting, in order to promote the rational application of 2D NMs in clinical practice.This work was supported by the Guangdong Basic and Applied Basic Research Foundation (Nos. 2021A1515110657 and 2022A1515010056), Shenzhen Science and Technology Program (Grant No. RCBS20210609104513023), National Natural Science Foundation of China (No. 81922037), and Shanghai Biomedical Science and Technology Support Project (No. 19441903600)

Optimal Design of a Combined Cooling, Heating, and Power System and Its Ability to Adapt to Uncertainty

To realize the best performances of the distributed energy system (DES), many uncertainties including demands, solar radiation, natural gas, and electricity prices must be addressed properly in the planning process. This study aims to study the optimal sizing and performances of a hybrid combined cooling, heating, and power (CCHP) system under uncertainty in consideration of the operation parameters, including the lowest electric load ratio (LELR) and the electric cooling ratio (ECR). In addition, the ability of the system to adapt to uncertainty is analyzed. The above works are implemented separately under three operation strategies with multi-objectives in energy and cost saving, as well as CO2 reducing. Results show that the system with optimized operation parameters performs better in both the deterministic and uncertain conditions. When the ECRs in the summer and in mid-season as well as the LELR are set at 50.00%, 50.00%, and 20.00% respectively, the system operating in the strategy of following the electric load has the best ability to adapt to uncertainty. In addition, among all the uncertainties, the single uncertain natural gas price and the single uncertain heating demand have the smallest and largest effects on the optimal design respectively

Strategies to offset dissatisfactory product performance: The role of post-purchase marketing

This research examines the role of post-purchase recovery initiatives in offsetting the negative effect of a dissatisfactory product experience. Experiment 1 explores the effect of counterfactual thinking, a mental simulation process of reflecting upon past events and generating alternative possible outcomes, on product evaluations after an individual experiences a negative purchase outcome. Experiment 2 builds on these findings and shows how customer surveys can be used as tactical tools to boost post-purchase product evaluations. The results indicate that post-purchase marketing efforts, such as customer surveys, can engage consumers in counterfactual thinking and positively affect their product evaluations.Customer survey Recovery initiative Product evaluation Counterfactual thinking Processing extensiveness Need for cognition