Exploring the microRNA-mRNA regulatory network associated with solasonine in bladder cancer.

Background: Solasonine has been demonstrated to exert an inhibitory effect on bladder cancer (BC), but the potential mechanisms remain unclear. Therefore, the aim of this study is to explore the association between microRNAs (miRNAs)-mediated regulation and the anti-tumor activities of solasonine in BC. Methods: MiRNA sequencing was performed to identify the differentially expressed microRNAs (DE-miRNAs) associated with solasonine in BC cells. Functional enrichment analyses of the DE-miRNAs activated and inhibited by solasonine were then conducted. The DE-miRNAs with prognostic value for BC and those differentially expressed in the BC samples were subsequently identified as the hub DE-miRNAs. After identifying the messenger RNAs (mRNAs) that were targeted by the hub DE-miRNAs and those differentially expressed in the BC samples, a protein-protein interaction analysis was performed to identify the core downstream genes, which were then used to construct a solasonine-miRNA-mRNA regulatory network. Results: A total of 27 activated and 19 inhibited solasonine-mediated DE-miRNAs were identified that were found to be associated with several tumor-related biological functions and pathways. After integrating the results of the survival analysis and expression assessment, the following nine hub DE-miRNAs were identified: hsa-miR-127-3p, hsa-miR-450b-5p, hsa-miR-99a-5p, hsa-miR-197-3p, hsa-miR-423-3p, hsa-miR-4326, hsa-miR-625-3p, hsa-miR-625-5p, and hsa-miR-92a-3p. The DE-mRNAs targeted by the hub DE-miRNAs were predicted, and 30 core downstream genes were used to construct the solasonine-miRNA-mRNA regulatory network. miR-450b-5p was shown to be associated with the most mRNAs in this network, which suggests that it plays a crucial role in the solasonine-mediated anti-BC effect. Conclusions: A regulatory network, including solasonine, miRNAs, and mRNAs related to BC, was constructed. This network provides extensive insights into the molecular regulatory mechanisms that underlie the anti-cancer efficacy of solasonine in BC.

IP3R2-mediated Ca2+ release promotes LPS-induced cardiomyocyte pyroptosis via the activation of NLRP3/Caspase-1/GSDMD pathway.

Pyroptosis plays a crucial role in sepsis, and the abnormal handling of myocyte calcium (Ca2+) has been associated with cardiomyocyte pyroptosis. Specifically, the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is a Ca2+ release channel in the endoplasmic reticulum (ER). However, the specific role of IP3R2 in sepsis-induced cardiomyopathy (SIC) has not yet been determined. Thus, this study aimed to investigate the underlying mechanism by which IP3R2 channel-mediated Ca2+ signaling contributes to lipopolysaccharide (LPS)-induced cardiac pyroptosis. The SIC model was established in rats by intraperitoneal injection of LPS (10 mg/kg). Cardiac dysfunction was assessed using echocardiography, and the protein expression of relevant signaling pathways was analyzed using ELISA, RT-qPCR, and western blot. Small interfering RNAs (siRNA) and an inhibitor were used to explore the role of IP3R2 in neonatal rat cardiomyocytes (NRCMs) stimulated by LPS in vitro. LPS-induced NLRP3 overexpression and GSDMD-mediated pyroptosis in the rats' heart. Treatment with the NLRP3 inhibitor MCC950 alleviated LPS-induced cardiomyocyte pyroptosis. Furthermore, LPS increased ATP-induced intracellular Ca2+ release and IP3R2 expression in NRCMs. Inhibiting IP3R activity with xestospongin C (XeC) or knocking down IP3R2 reversed LPS-induced intracellular Ca2+ release. Additionally, inhibiting IP3R2 reversed LPS-induced pyroptosis by suppressing the NLRP3/Caspase-1/GSDMD pathway. We also found that ER stress and IP3R2-mediated Ca2+ release mutually regulated each other, contributing to cardiomyocyte pyroptosis. IP3R2 promotes NLRP3-mediated pyroptosis by regulating ER Ca2+ release, and the mutual regulation of IP3R2 and ER stress further promotes LPS-induced pyroptosis in cardiomyocytes.

Engineering High-Performance Hypergolic Propellant by Synergistic Contribution of Metal-Organic Framework Shell and Aluminum Core.

Hypergolicity is a highly desired characteristic for hybrid rocket engine-based fuels because it eliminates the need for a separate ignition system. Introducing hypergolic additives into conventional fuels through physical mixing is a feasible approach, but achieving highly reliable hypergolic ignition and energy release remains a major challenge. Here, the construction of core-shell Al@metal organic framework (MOF) heterostructures is reported as high-performance solid hypergolic propellants. Upon contact with the liquid oxidizer the uniformly distributed hypergolic MOF (Ag-MOF) shell can induce the ignition of hypergolic-inert fuel Al, resulting in Al combustion. Such a synthetic strategy is demonstrated to be favorable in hotspot generation and heat transfer relative to a simple physical mixture of Al/Ag-MOF, thus producing shorter ignition delay times and more efficient combustion. Thermal reactivity study indicated that the functionalization of the Ag-MOF shell changes the energy release process of the inner Al, which is accompanied by a thermite reaction. The synergistic effect of implantation of hypergolic MOF and high energy Al contributes to high specific impulses of 230-270 s over a wide range of oxidizer-to-fuel ratios.

Enzyme-Immobilized Metal-Organic Frameworks: From Preparation to Application.

As a class of widely used biocatalysts, enzymes possess advantages including high catalytic efficiency, strong specificity and mild reaction condition. However, most free enzymes have high requirements on the reaction environment and are easy to deactivate. Immobilization of enzymes on nanomaterial-based substrates is a good way to solve this problem. Metal-organic framework (MOFs), with ultra-high specific surface area and adjustable porosity, can provide a large space to carry enzymes. And the tightly surrounded protective layer of MOFs can stabilize the enzyme structure to a great extent. In addition, the unique porous network structure enables selective mass transfer of substrates and facilitates catalytic processes. Therefore, these enzyme-immobilized MOFs have been widely used in various research fields, such as molecule/biomolecule sensing and imaging, disease treatment, energy and environment protection. In this review, the preparation strategies and applications of enzyme-immobilized MOFs are illustrated and the prospects and current challenges are discussed.

Identification of autophagy-related genes as potential biomarkers for type 1 diabetes mellitus.

Background: Type 1 diabetes mellitus (T1DM) is a metabolic disease in which the autoimmune destruction of pancreatic islet ß-cells occurs. This study sought to investigate the role of autophagy-related genes and immune cells in the development of T1DM. Methods: We acquired the raw gene expression profiles of 302 T1DM and 422 normal control peripheral blood samples from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the Limma package, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The Search Tool for the Retrieval of Interacting Genes/Proteins (https://string-db.org/) and Cytoscape autophagy genes were intersected with the DEGs for the immune cell analysis and the correlation analysis. Results: A total of 568 DEGs were identified in the T1DM and normal samples, of which 301 were upregulated and 267 were downregulated. The results of the functional and pathway enrichment analyses showed that the DEGs were closely associated with autophagy and immunity. Member RAS oncogene family (RAB11A), protein tyrosine phosphatase non-receptor type 11, lamin A/C, heat shock protein70, heat shock protein family A member 4, cluster of differentiation 8A, caspase 3 (CASP3), exportin 1, proto-oncogene, non-receptor tyrosine kinase, SMAD family member 4, and sirtuin 1 (SIRT1) were located at the center of the protein-protein interaction network as the core genes. The peripheral blood T cells were more elevated in the T1DM subjects than the normal subjects. RAB11A, CASP3, and SIRT1 are autophagy-associated genes. RAB11A and CASP3 were positively correlated with most immune cells, while SIRT1 was negatively correlated with most immune cells. Conclusions: Autophagy-related genes (i.e., RAB11A, CASP3, and SIRT1) and immune cells (i.e., T and B cells) may play important regulatory roles in the development of T1DM. Our findings provide novel insights into and potential targets for T1DM prediction and treatment.

Ptosoproctus gen. nov., a new genus with two new species of Shield-back Katydid, with the first record of genus Eulithoxenus Bey-Bienko, 1951 from China (Orthoptera: Tettigoniidae: Tettigoniinae: Drymadusini).

In this paper, one new genus, Ptosoproctus gen. nov., is established with two new species: P. lanzhouensis sp. nov. and P. baishishanicus sp. nov., described and illustrated based on material collected from northern China. The genus Eulithoxenus Bey-Bienko, 1951 is recorded from China for the first time. E. emeljanovi Mishchenko, 1968 is redescribed. Supplemental description of Uvarovina chinensis Ramme, 1939 is provided. COI and ND2 genes of the three Chinese Drymadusini genera mentioned above were used to reconstruct the phylogenetic tree. Molecular result support the validation of the new genus.

Genetic polymorphisms in CDH1 are associated with endometrial carcinoma susceptibility among Chinese Han women.

The cadherin 1 (CDH1) gene plays critical roles in the epithelial-mesenchymal transition process, potentially offering us a glimpse into the development of endometrial carcinoma (EC). The present study aimed to identify whether genetic variants in CDH1 affect EC susceptibility in Chinese Han women, using a strategy combining haplotype-tagging single nucleotide polymorphisms (htSNPs) association analysis with fine-scale mapping. A total of 9 htSNPs in CDH1 were genotyped among 516 cases and 706 age-matched cancer-free controls. Logistic regression analyses revealed 3 htSNPs (rs17715799, rs6499199 and rs13689) to be associated with increased EC risk and 3 htSNPs (rs12185157, rs10431923 and rs4783689) with decreased EC risk. Furthermore, 14 newly imputed SNPs of CDH1 were identified to be associated with EC risk (P<0.05) using genotype imputation analysis. Notably, multivariate logistic analysis demonstrated that rs13689, rs10431923 and rs10431924 could affect EC susceptibility independently (P≤0.001). Subsequent Generalized Multifactor Dimensionality Reduction analysis revealed several best fitting models for predicting EC risk, including SNP-SNP interactions among rs7100190, rs12185157, rs10431923, rs7186053, rs6499199, rs4783689, rs13689, rs6499197 and rs10431924, and SNP-environment interactions between related SNPs and number of childbirth. Moreover, functional annotations suggest that the majority of these susceptible variants may carry potential biological functions that affect certain gene regulatory elements. In summary, this study suggested that the genetic polymorphisms of CDH1 were indeed associated with EC susceptibility on several levels. If further additional functional studies could verify these findings, these genetic variants may serve as future personalized markers for the early prediction of endometrial cancer in Chinese Han women.

Associations of gene­wide SNPs in SNAI1 and TWIST1 with breast cancer and ovarian cancer susceptibility among Chinese Han women.

Extensive evidence suggests that the genetic etiologies of breast cancer (BC) and ovarian cancer (OC) show a certain degree of similarity. This study aimed to find out whether the single nucleotide polymorphisms (SNPs) of genes SNAI1 and TWIST1 may affect BC and OC susceptibility. A total of 7 tagging­SNPs (tSNPs) were directly genotyped in 1,161 BC cases, 286 OC cases and 1,273 cancer­free controls among Chinese Han women. Twenty­eight variants in these 2 genes were genotyped by 'in silico' genotype imputation. Logistic regression (LR) revealed that tSNPs SNAI1 rs6125849, TWIST1 rs4721746 and TWIST1 rs4721745 were protective genetic variants for BC/OC. Allelic association tests of gene­wide SNPs demonstrated that the minor alleles of SNAI1 rs6125849, TWIST1 rs4721745 and TWIST1 rs11973396 were strongly associated with BC/OC susceptibility. Multivariate LR presented that SNAI1 rs6125849, TWIST1 rs4721745, rs4721746 and rs11973396 affected BC/OC susceptibility independently, and women harboring all four protective genoytpes had the lowest risk. Multifactor dimensionality reduction analysis further showed that SNAI1 rs6125849 and TWIST1 rs4721745 had the strongest synergistic interaction. Functional annotation predicted that the minor alleles of SNAI1 rs6125849 and TWIST1 rs4721745 altered their binding affinities with transcription factors E2F6 and TCF11­MafG respectively. These results indicate that genetic variants in SNAI1 and TWIST1, most probably SNAI1 rs6125849 and TWIST1 rs4721745, may modulate BC and OC susceptibility.