Nitrogen‐containing heterocycles are found in a vast number of natural products and biologically active compounds, and have attracted a lot of attention. Among all the reported methods, ...cycloisomerization transformations involving the activation of alkynes with the aid of transition metals are a very active area in synthetic organic chemistry. This review covers the most important recent advances in the use of metal‐catalyzed or metal‐free cycloisomerizations for the preparation of indolizines and indolizinones from starting substrates consisting of pyridine‐containing propargylic esters or alcohols. Cycloisomerization transformations to heterocycles are very efficient and atom‐economic, and we hope that this review will result in further focused research to widen the application of indolizines and indolizinones.
Cycloisomerization transformations affording heterocycles are very efficient and atom‐economic. This review covers the most important recent advances in metal‐catalyzed or metal‐free cycloisomerizations to prepare indolizines and indolizinones from starting substrates consisting of pyridine‐containing propargylic esters or alcohols.
Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological ...studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients.
All 940 COPD patients were finally recruited in this study. Demographic characteristics and clinical information were extracted. Fasting serum was collected. Serum cadmium was detected through graphite furnace atomic absorption spectrophotometry. Serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay.
All patients were classified into three groups according to the tertile division of serum cadmium concentration: low (<0.77 μg/L, L), medium (0.77-1.01 μg/L, M), and high (1.01 μg/L, H). Logistic regression analysis found that serum cadmium was inversely correlated with pulmonary function before and after adjusted confounding variables. When stratified by gender, serum cadmium was still negatively correlated with pulmonary function in COPD patients. Moreover, higher serum cadmium elevated CAT (COPD Assessment Test) score before and after adjusted confounding variables. Though a non-linear association between serum cadmium and inflammatory cytokines, serum cadmium was positively associated with inflammatory cytokines (TNF-α and MCP-1). TNF-α and MCP-1 exerted a partial mediator in the association between cadmium exposure and pulmonary function decline in COPD patients.
Serum cadmium concentration is inversely correlated with pulmonary function among COPD patients. Inflammatory cytokines may be important mediators for cadmium-induced pulmonary function decline in COPD patients.
Abstract
Tumorigenic functions due to the formation of fusion genes have been targeted for cancer therapeutics (i.e. kinase inhibitors). However, many fusion proteins involved in various cellular ...processes have not been studied for targeted therapeutics. This is because the lack of complete fusion protein sequences and their whole 3D structures has made it challenging to develop new therapeutic strategies. To fill these critical gaps, we developed a computational pipeline and a resource of human fusion proteins named FusionPDB, available at https://compbio.uth.edu/FusionPDB. FusionPDB is organized into four levels: 43K fusion protein sequences (14.7K in-frame fusion genes, Level 1), over 2300 + 1267 fusion protein 3D structures (from 2300 recurrent and 266 manually curated in-frame fusion genes, Level 2), pLDDT score analysis for the 1267 fusion proteins from 266 manually curated fusion genes (Level 3), and virtual screening outcomes for 68 selected fusion proteins from 266 manually curated fusion genes (Level 4). FusionPDB is the only resource providing whole 3D structures of fusion proteins and comprehensive knowledge of human fusion proteins. It will be regularly updated until it covers all human fusion proteins in the future.
Graphical Abstract
Graphical Abstract
Zn deficiency is the most common micronutrient deficit in rice but Zn is also a widespread industrial pollutant. Zn deficiency responses in rice are well documented, but comparative responses to Zn ...deficiency and excess have not been reported. Therefore, we compared the physiological, transcriptional and biochemical properties of rice subjected to Zn starvation or excess at early and later treatment stages. Both forms of Zn stress inhibited root and shoot growth. Gene ontology analysis of differentially expressed genes highlighted the overrepresentation of Zn transport and antioxidative defense for both Zn stresses, whereas diterpene biosynthesis was solely induced by excess Zn. Divalent cations (Fe, Cu, Ca, Mn and Mg) accumulated in Zn‐deficient shoots but Mg and Mn were depleted in the Zn excess shoots, mirroring the gene expression of non‐specific Zn transporters and chelators. Ascorbate peroxidase activity was induced after 14 days of Zn starvation, scavenging H2O2 more effectively to prevent leaf chlorosis via the Fe‐dependent Fenton reaction. Conversely, excess Zn triggered the expression of genes encoding Mg/Mn‐binding proteins (OsCPS2/4 and OsKSL4/7) required for antimicrobial diterpenoid biosynthesis. Our study reveals the potential role of divalent cations in the shoot, driving the unique responses of rice to each form of Zn stress.
Comprehensive responses to Zn deficiency and excess were compared in rice. We showed the differential expression of non‐specific Zn transporter and chelator genes alters the concentrations of divalent cations in shoots that potentially drives the unique responses of rice to each form of Zn stress.
Plants are known for their capacity to regenerate the whole body through de novo formation of apical meristems from a mass of proliferating cells named callus. Exogenous cytokinin and auxin determine ...cell fate for the establishment of the stem cell niche, which is the vital step of shoot regeneration, but the underlying mechanisms remain unclear. Here, we show that type-B ARABIDOPSIS RESPONSE REGULATORs (ARRs), critical components of cytokinin signaling, activate the transcription of WUSCHEL (WUS), which encodes a key regulator for maintaining stem cells. In parallel, type-B ARRs inhibit auxin accumulation by repressing the expression of YUCCAs, which encode a key enzyme for auxin biosynthesis, indirectly promoting WUS induction. Both pathways are essential for de novo regeneration of the shoot stem cell niche. In addition, the dual regulation of type-B ARRs on WUS transcription is required for the maintenance of the shoot apical meristem in planta. Thus, our results reveal a long-standing missing link between cytokinin signaling and WUS regulator, and the findings provide critical information for understanding cell fate specification.
Background
Glucose metabolism disorder is a common feature in cancer. Cancer cells generate much energy through anaerobic glycolysis, which promote the development of tumors. However, long non‐coding ...RNA may play an important role in this process. Our aim is to explore a prognostic risk model based on the glucose metabolism‐related lncRNAs which provides clues that lncRNAs predict a clinical outcome through glucose metabolism in breast cancer.
Methods
1222 RNA‐seq were extracted from the TCGA database, and 74 glucose metabolism‐related genes were loaded from the GSEA website. Then, 7 glucose metabolism‐related lncRNAs risk score model was developed by univariate, Lasso, and multivariate regression analysis. The lncRNA risk model showed that high‐risk patients predict a poor clinical outcome with high reliability (P=2.838×10‐6). Univariate and multivariate independent prognostic analysis and ROC curve analysis proved that the risk score was an independent prognostic factor in breast cancer with an AUC value of 0.652. Finally, Gene set enrichment analysis showed that cell cycle‐related pathways were significantly enriched in a high‐risk group.
Results
Our results showed that glucose metabolism‐related lncRNAs can affect breast cancer progression. 7 glucose metabolism‐related lncRNAs prognostic signature was established to evaluate the OS of patients with breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors and expressed highly in the high‐risk group. A Nomogram was made based on this signature to judge patients' living conditions and prognosis.
Conclusion
7 glucose metabolism‐related lncRNAs risk score model had a high prognostic value in breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors. AP001505.1 expression was increased in most triple‐negative breast cancer cells treated with high glucose, which may also take part in breast cancer progression and potential therapeutic targets
A copper‐catalyzed approach for the synthesis of 2‐aryl‐quinazolinones through a domino reaction involving C–C bond cleavage is described. This protocol involves intramolecular C–C bond cleavage to ...construct 2‐aryl‐quinazolinones, which may offer an alternative method to prepare medically important quinazolinone derivatives and a new strategy for C–C bond cleavage. Besides C–C bond cleavage, this domino reaction includes N‐arylation and benzylic C–H amidation.
A copper‐catalyzed approach for the synthesis of 2‐aryl‐quinazolinones through a domino reaction involving C–C bond cleavage is described. This transformation offers an alternative method to prepare medically important quinazolinone derivatives and a new strategy for C–C bond cleavage.
The G-quadruplex ligands database (G4LDB, http://www.g4ldb.org) provides a unique collection of reported G-quadruplex ligands to streamline ligand/drug discovery targeting G-quadruplexes. ...G-quadruplexes are guanine-rich nucleic acid sequences in human telomeres and gene promoter regions. There is a growing recognition for their profound roles in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease. Ligands that affect the structure and activity of G-quadruplexes can shed light on the search for G-quadruplex-targeting drugs. Therefore, we built the G4LDB to (i) compile a data set covering various physical properties and 3D structure of G-quadruplex ligands; (ii) provide Web-based tools for G-quadruplex ligand design; and (iii) to facilitate the discovery of novel therapeutic and diagnostic agents targeting G-quadruplexes. G4LDB currently contains >800 G-quadruplex ligands with ∼4000 activity records, which, to our knowledge, is the most extensive collection of its kind. It offers a user friendly interface that can meet a variety of data inquiries from researchers. For example, ligands can be searched for by name, molecular properties, structures, ligand activities and so on. Building on the reported data, the database also provides an online ligand design module that can predict ligand binding affinity in real time.
Due to the impact of the COVID-19 pandemic, many enterprises are looking to use electronic services to avoid human-to-human contact. During this transition period, enterprises are embracing new ...business models and digital transformation to overcome the crisis. Similarly, the government is also in need of digital transformation in response to these significant changes. However, there is a lack of empirical research on the motivations behind government digital transformation. Consequently, this study aims to fill this gap in the existing literature. The push-pull-mooring model is suitable for explaining the process of transferring from an inherent way to a new way, such as migration and changes in switching behavior. Therefore, it is an apt framework for elucidating the process of adopting digital transformation within government agencies. In total, data were collected from 268 government employees to examine the proposed hypotheses. The results show that the motivations of digital transformation are indeed affected by the push-pull-mooring model. These motivations encompass service process inconvenience, avoid face-to-face contact, strengthen information security, top management support, fear of learning new IT, and the cost of digitalization. Interestingly, service process inconvenience and fear of learning new IT exhibit interaction effects in relation to age-related inertia. This finding suggests that government agencies can provide varied encouragement and incentives based on employees' age groups.
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