Sustainable polyesters can be furnished via ring‐opening polymerization (ROP) of O‐carboxyanhydrides (OCAs). Various catalysts, especially metal‐based catalysts, are devised to achieve controlled ROP ...of OCAs. In the following mini review, the recent progress on the organocatalytic ROP of OCAs, including the usage of thiourea‐based bifunctional single‐molecule organocatalysts for eliminating epimerization in OCAs polymerization is summarized. Moreover, the future development of the organocatalytic ROP of OCAs for the synthesis of sustainable polyesters will be discussed.
Sustainable polyesters can be furnished via ring‐opening polymerization (ROP) of O‐carboxyanhydrides (OCAs). In this mini review, the recent progress on the organocatalytic ROP of OCAs, including the usage of thiourea‐based bifunctional single‐molecule organocatalysts for eliminating epimerization in OCAs polymerization is summarized.
Circular RNAs (circRNAs), a subclass of non-coding RNAs, play essential roles in tumorigenesis and aggressiveness. Our previous study has identified that circAGO2 drives gastric cancer progression ...through activating human antigen R (HuR), a protein stabilizing AU-rich element-containing mRNAs. However, the functions and underlying mechanisms of circRNAs derived from HuR in gastric cancer progression remain elusive.
CircRNAs derived from HuR were detected by real-time quantitative RT-PCR and validated by Sanger sequencing. Biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, RNA electrophoretic mobility shift, and in vitro binding assays were applied to identify proteins interacting with circRNA. Gene expression regulation was observed by chromatin immunoprecipitation, dual-luciferase assay, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its protein partner on the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo.
Circ-HuR (hsa_circ_0049027) was predominantly detected in the nucleus, and was down-regulated in gastric cancer tissues and cell lines. Ectopic expression of circ-HuR suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. Mechanistically, circ-HuR interacted with CCHC-type zinc finger nucleic acid binding protein (CNBP), and subsequently restrained its binding to HuR promoter, resulting in down-regulation of HuR and repression of tumor progression.
Circ-HuR serves as a tumor suppressor to inhibit CNBP-facilitated HuR expression and gastric cancer progression, indicating a potential therapeutic target for gastric cancer.
Precast concrete segmental bridges (PCSBs) have been widely used in bridge engineering due to their numerous competitive advantages. The structural behavior and health status of PCSBs largely depend ...on the performance of the joint between the assembled segments. However, due to construction errors and dynamic loading conditions, some cracks and leakages have been found at the epoxy joints of PCSBs during the construction or operation stage. These defects will affect the joint quality, negatively impacting the safety and durability of the bridge. A structural health monitoring (SHM) method using active sensing with a piezoceramic-based smart aggregate (SA) to detect the crack and leakage in the epoxy joint of PCSBs was proposed and the feasibility was studied by experiment in the present work. Two concrete prisms were prefabricated with installed SAs and assembled with epoxy joint. An initial defect was simulated by leaving a 3-cm crack at the center of the joint without epoxy. With a total of 13 test cases and the different lengths of cracks without water and filled with water were simulated and tested. Time-domain analysis, frequency-domain analysis and wavelet-packet-based energy index (WPEI) analysis were conducted to evaluate the health condition of the structure. By comparing the collected voltage signals, Power Spectrum Density (PSD) energy and WPEIs under different healthy states, it is shown that the test results are closely related to the length of the crack and the leakage in the epoxy joint. It is demonstrated that the devised approach has certain application value in detecting the crack and leakage in the joint of PCSBs.
To explore the feasibility of using ultra-high performance concrete (UHPC) to strengthen reinforced concrete (RC) beams in torsion, pure torsion tests on 9 specimens have been conducted in this ...study, including one RC beam without strengthening (referred as control beam) and 8 UHPC-strengthened beams. The variables considered for investigation included the wrapping form of UHPC layer, thickness of UHPC layer, shape of steel fibers added in UHPC layer, UHPC-RC interfacial treatment, and reinforcement ratio of UHPC layer. The overall torsional behavior, torque–twist curves, torque-principal strain curves, cracking pattern and UHPC-RC interfacial slippage for all specimens were obtained based on the torsion tests. Results show that the cracking and ultimate torsional moments of all strengthened beams were higher than those of the control beam, with maximum increases of 488.5% and 593.2%, respectively. When the RC beam cannot be fully wrapped, which is the preferred strengthening scheme, 3-sided wrapping form is also an acceptable choice, but the 2-sided strengthening scheme should be avoided. The determination of the thickness of UHPC layer should comprehensively consider the strengthening effect, cost for strengthening and requirements for RC beam's dimensions after strengthening. RC beam surfaces should be fully roughened before casting UHPC to ensure that the UHPC layers and the RC beam persistently act together as a whole to resist torsional loads. The UHPC layers are recommended to be equipped with steel bars, which could substantially improve the torsional capacity and ductility of the strengthened beam on the premise of limited increase in the cost. Finally, the effectiveness of torsional strengthening using UHPC was compared with that using fiber reinforced polymer (FRP) in terms of increase in cross-sectional area, increases in cracking and ultimate torsional moments, increase in torsional stiffness, failure mode and long-term performance.
Aerobic glycolysis is a hallmark of metabolic reprogramming in tumor progression. However, the mechanisms regulating glycolytic gene expression remain elusive in neuroblastoma (NB), the most common ...extracranial malignancy in childhood. Herein, we identify that CUT‐like homeobox 1 (CUX1) and CUX1‐generated circular RNA (circ‐CUX1) contribute to aerobic glycolysis and NB progression. Mechanistically, p110 CUX1, a transcription factor generated by proteolytic processing of p200 CUX1, promotes the expression of enolase 1, glucose‐6‐phosphate isomerase, and phosphoglycerate kinase 1, while circ‐CUX1 binds to EWS RNA‐binding protein 1 (EWSR1) to facilitate its interaction with MYC‐associated zinc finger protein (MAZ), resulting in transactivation of MAZ and transcriptional alteration of CUX1 and other genes associated with tumor progression. Administration of an inhibitory peptide blocking circ‐CUX1‐EWSR1 interaction or lentivirus mediating circ‐CUX1 knockdown suppresses aerobic glycolysis, growth, and aggressiveness of NB cells. In clinical NB cases, CUX1 is an independent prognostic factor for unfavorable outcome, and patients with high circ‐CUX1 expression have lower survival probability. These results indicate circ‐CUX1/EWSR1/MAZ axis as a therapeutic target for aerobic glycolysis and NB progression.
Synopsis
Aerobic glycolysis is a hallmark of metabolic reprogramming in tumors. This study shows how CUT‐like homeobox 1 (CUX1) and its derived circular RNA (circ‐CUX1) contribute to aerobic glycolysis. The circ‐CUX1/EWSR1/MAZ axis emerges as a possible therapeutic target for neuroblastoma progression.
Transcription factor CUX1 is essential for glycolytic gene expression during tumor progression.
EWSR1 protein interacts with MAZ to facilitate its transactivation activity, resulting in transcriptional alteration of CUX1 and other genes that are associated with tumor progression.
Circ‐CUX1 binds to and facilitates the interaction of EWSR1 with MAZ.
Blocking the circ‐CUX1‐EWSR1 interaction with a small peptide might be a novel therapeutic strategy for neuroblastoma and other tumors.
Aerobic glycolysis is a hallmark of metabolic reprogramming in tumors. This study shows how CUT‐like homeobox 1 (CUX1) and its derived circular RNA (circ‐CUX1) contribute to aerobic glycolysis. The circ‐CUX1/EWSR1/MAZ axis emerges as a possible therapeutic target for neuroblastoma progression.
Metabolic reprogramming sustains tumorigenesis and aggressiveness of neuroblastoma (NB), the most common extracranial malignancy in childhood, while underlying mechanisms and therapeutic approaches ...still remain elusive.
Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation (ChIP) sequencing, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by ChIP, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA-encoded protein and its partners on the lipid metabolism, mitochondrial activity, growth, invasion, and metastasis of NB cells.
A novel 113-amino acid protein (p113) of CUT-like homeobox 1 (CUX1) was identified in NB cells treated by serum deprivation. Further validating studies revealed that nuclear p113 was encoded by circRNA of CUX1, and promoted the lipid metabolic reprogramming, mitochondrial activity, proliferation, invasion, and metastasis of NB cells. Mechanistically, p113 interacted with Zuotin-related factor 1 (ZRF1) and bromodomain protein 4 (BRD4) to form a transcriptional regulatory complex, and mediated the transactivation of ZRF1/BRD4 in upregulating ALDH3A1, NDUFA1, and NDUFAF5 essential for conversion of fatty aldehydes into fatty acids, fatty acid β-oxidation, and mitochondrial complex I activity. Administration of an inhibitory peptide blocking p113-ZRF1 interaction suppressed the tumorigenesis and aggressiveness of NB cells. In clinical NB cases, high expression of p113, ZRF1, or BRD4 was associated with poor survival of patients.
These results indicate that p113 isoform encoded by CUX1 circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation.
Waste glass is promising to be recycled and reused in construction for sustainability. Silicon dioxide is the main component of glass, however, its pozzolanic activity is latent mainly due to its ...stable silica tetrahedron structure. To excite the activation of waste glass, chemical activation and mechanical grinding of waste glass powder (WGP) were investigated. As the supplementary, hydrothermal and combined (mechanical-chemical-hydrothermal) treatments were conducted on part of the WGP samples. The unconfined compression strength (UCS), expansion caused by alkali–silica reaction (ASR), and the microstructural morphology of WGP were investigated. The results showed the dosage threshold (around 2%) of the chemical activators (alkali and sodium sulfate) and the combined activation were optimal. Besides, a firefly algorithm (FA) based multi-objective optimisation model (MOFA) was applied to seek the Pareto fronts based on three objectives: UCS, ASR expansion, and Cost of mixture proportion. The objective functions of UCS and expansion were established through training the machine learning (ML) models where FA was used to tune the hyperparameters. The cost was calculated by a polynomial function. The ultimate values of root mean square error (RMSE) and correlation coefficient (R) showed the robustness of the ML models. Moreover, the Pareto fronts for mortars containing 300 μm and 75 μm WGPs were successfully obtained, which contributed to the practical application of waste glass in mortar production. In addition, the sensitivity analysis was conducted to rank the importance of input variables. The results showed that curing time, activator's content, and WGP particle size were three essential parameters.
Cell survival or death is one of the key scientific issues of inflammatory response. To regulate cell death during the occurrence and development of periodontitis, various forms of programmed cell ...death, such as pyroptosis, ferroptosis, necroptosis, and apoptosis, have been proposed. It has been found that ferroptosis characterized by iron-dependent lipid peroxidation is involved in cancer, degenerative brain diseases and inflammatory diseases. Furthermore, NCOA4 is considered one of ferroptosis-related genes (FRGs) contributing to butyrate-induced cell death in the periodontitis. This research aims to analyze the expression of FRGs in periodontitis tissues and to explore the relationship between ferroptosis and periodontitis. Genes associated with periodontitis were retrieved from two Gene Expression Omnibus datasets. Then, we normalized microarray data and removed the batch effect using the R software. We used R to convert the mRNA expression data and collected the expression of FRGs. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), transcription factor (TF) and protein-protein interaction (PPI) network analyses were used. In addition, we constructed a receiver operating characteristic curve and obtained relative mRNA expression verified by quantitative reverse-transcription polymerase chain reaction (PCR). Eight and 10 FRGs related to periodontitis were upregulated and downregulated, respectively. GO analysis showed that FRGs were enriched in the regulation of glutathione biosynthetic, glutamate homeostasis, and endoplasmic reticulum-nucleus signaling pathway. The top TFs included CEBPB, JUND, ATF2. Based on the PPI network analysis, FRGs were mainly linked to the negative regulation of IRE1-mediated unfolded protein response, regulation of type IIa hypersensitivity, and regulation of apoptotic cell clearance. The expression levels of NCOA4, SLC1A5 and HSPB1 using PCR were significantly different between normal gingival samples and periodontitis samples. Furthermore, the diagnostic value of FRGs for periodontitis were "Good". We found significant associations between FRGs and periodontitis. The present study not only provides a new possible pathomechanism for the occurrence of periodontitis but also offers a new direction for the diagnosis and treatment of periodontitis.
Tongue squamous cell carcinoma (TSCC) is the most common oral cavity cancer, and p16 immunohistochemistry is an exact and available tool in the prognostic and predictive characterization of squamous ...cell cancers in the head and neck. Microorganisms have a close relationship with the development of TSCC. However, the association between oral bacteria and p16 status has not been well defined in the case of TSCC. Compared with traditional clinical microbial collection methods, formalin-fixed paraffin-embedded (FFPE) tissue samples have several advantages.
To compare the microbiota compositions between p16-positive and p16-negative patients with TSCC, we performed a small pilot study of microbiological studies of TSCC by paraffin tissue. DNA from FFPE tissue blocks were extracted and microbiomes were profiled by sequencing the 16 S-rRNA-encoding gene (V1-V2/V3-V4/V4 regions). Alterations in the functional potential of the microbiome were predicted using PICRUSt, Tax4Fun, and BugBase.
A total of 60 patients with TSCC were enrolled in the study, however, some challenges associated with DNA damage in FFPE tissues existed, and only 27 (15 p16-positive and 12 p16-negative) passed DNA quality control. Nevertheless, we have tentatively found some meaningful results. The p16 status is associated with microbiota diversity, which is significantly increased in p16-positive patients compared with p16-negative patients. Desulfobacteria, Limnochordia, Phycisphaerae, Anaerolineae, Saccharimonadia and Kapabacteria had higher abundances among participants with p16-positive. Moreover, functional prediction revealed that the increase of these bacteria may enhance viral carcinogenesis in p16-positive TSCC.
Bacterial profiles showed a significant difference between p16-positive TSCC and p16-negative TSCC. These findings may provide insights into the relationship between p16 status and the microbial taxa in TSCC, and these bacteria may provide new clues for developing therapeutic targets for TSCC.