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Potassium ion transport across myocardial cell membrane is essential for type 2 long QT syndrome (LQT2). However, the dysfunction of potassium ion transport due to genetic mutations limits the therapeutic effect in treating LQT2. Biomimetic ion channels that selectively and efficiently transport potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based ion channels with different side chains, and found a biomimetic ion channel of K+ (BIC K) with the highest transport activity among them. The selected BIC K can restore potassium ion transport and increase transmembrane potassium ion current, thus shortening phase 3 of action potential (AP) repolarization and QT interval in LQT2. Moreover, BIC K does not affect heart rate and cardiac rhythm in treating LQT2 model induced by E4031 in isolated heart as well as in guinea pigs. By restoring ion transmembrane transport tactic, biomimetic ion channels, such as BIC K , will show great potential in treating diseases related to ion transport blockade. Type 2 long QT syndrome (LQT2) is a disease caused by K+ transport disorder, which can cause malignant arrhythmia and even death. There is currently no radical cure, so it is critical to explore ways to improve K+ transmembrane transport. In this study, we report that a small-molecule biomimetic ion channel BIC K can efficiently simulate natural K+ channel proteins on the cardiomyocyte and cure E4031-induced LQT2 in guinea pig by restoring K+ transport function for the first time. This study found that the potassium transmembrane transport by BIC K significantly reduced the QT interval, which provides a conceptually new strategy for the treatment of LQT2 disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Platelets are increasingly being recognized for promoting tumor growth and metastasis. Many cells derived from solid tumors have the ability to aggregate platelets, and this ability correlates with their metastatic potential. Over the past half century, our understanding of tumor cell-induced platelet aggregation (TCIPA) has grown beyond the simple concept that tumor cell-containing microthrombi mechanically embolize the microvasculature. Tumor cell-activated platelets secrete a multitude of factors that reciprocally act on tumor cells, as well as other cells within the tumor microenvironment; thus, affecting both parenychma and tumor-associated stroma. In this review, we summarize the current knowledge of tumor cell–platelet interactions and their influence on the tumor microenvironment, including how these interactions impact neoplastic epithelial cells, endothelial cells, pericytes, fibroblasts, immune cells, and early metastatic niches. In addition, we review the current knowledge of platelet–cancer cell interactions within hematological malignancies and speculate on how platelets may influence the leukemic microenvironment. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. [ABSTRACT FROM AUTHOR]

Abstract: Non-toxic K4[Fe(CN)6] was demonstrated to be effective as a green cyanating agent for the cyanation of alkyl halides using PPh3/Pd(OAc)2 as a catalyst system. The presented method allowed a series of benzyl chlorides to be smoothly cyanated in up to 88% yield. In order to avoid or suppress the deactivation of the catalyst, the reaction was required to be performed in a stringent inert ambiance. [Copyright &y& Elsevier]

Cu Fe alloys with high iron content (Fe > 10 wt%) are a class of promising copper alloys with high strength and high conductivity. However, the strength and conductivity trade-off dilemma is a longstanding problem in the high iron content Cu Fe alloys owing to macro-segregation of iron particles and incomplete precipitation of solid solution iron atoms in the traditional casting process. We adopted a comprehensive strategy of designing the ultra-fine dual structures with fine copper grains and micro-nano iron particles, and adding phosphorus element to induce solid solution iron atoms precipitation to break through the above bottleneck. In this study, Cu 20Fe alloys with 0.05–1.0 wt% P were prepared through powder metallurgy process. The results showed that the addition of P promoted the precipitation of soluble Fe atoms, reduced oxygen content, and activated sintering. Ultimately, the strength and conductivity of cost-effective Cu 20Fe alloys were significantly improved. The annealed Cu 20Fe 0.1P alloys possess unprecedented comprehensive properties with 608 MPa tensile strength and 65.2% IACS electrical conductivity, which were 7.8% and 19.8% higher than the Cu 20Fe alloys, respectively. The annealed Cu 20Fe 1.0P alloys achieved 59.7% IACS electrical conductivity, increased by 10% compared to Cu 20Fe alloys. The results broke the conventional understanding that increasing P content deteriorated material properties. The influence of P on the microstructure and properties of powder metallurgy Cu 20Fe alloys was investigated in detail. These findings provide new insight into overcoming the dilemma of the inverted relationship between the strength and conductivity of copper alloys. • Simultaneous enhancement of the mechanical and electrical properties of Cu 20Fe alloys by introducing phosphorus. • The Cu 20Fe 0.1P alloys possess unprecedented comprehensive properties and property-costs. • The influence of P on the microstructure and properties of powder metallurgy Cu 20Fe alloys was investigated in detail. [ABSTRACT FROM AUTHOR]

• Xinjiang Brown cattle had 9.88% Kazakh cattle and 90.12% Swiss Brown cattle inheritance. • Kazakh cattle contribute to the environmental adaptation in Xinjiang Brown cattle. • Swiss Brown cattle contribute to the production performance in Xinjiang Brown cattle. Xinjiang Brown cattle is characterized by wide environmental adaptation from its female parent (Kazakh cattle) and good production performance from its male parent (Swiss Brown cattle). However, the genetic basis underlying these characteristics has not been explored. Here we compared 50 genomes of Xinjiang Brown cattle to the genomes of other eight breeds worldwide to analyze patterns of genetic variation in the Xinjiang Brown cattle. We found canonical genomic characteristics of cross breed with the lowest linkage disequilibrium and the highest effective population size. At the global level, Xinjiang Brown cattle had 9.88% Kazakh cattle and 90.12% Swiss Brown cattle inheritance. Our local ancestry inference revealed the segments with the excess of Kazakh cattle blood enriched in genes or pathways involved in digestion, absorption, metabolism and disease. More importantly, we also observed the completely fixed haplotypes inherited from Swiss Brown cattle harboring genes (LCORL , GHR , MEF2D , PCSK1 and MSRB3), KEGG pathways, cattle QTLs or human NHGRI GWAS catalog related to body measurement and growth traits. Our findings will not only help understand the process of cross breeding but can provide basic materials for further QTL mapping and improvement of important traits in Xinjiang Brown cattle. [ABSTRACT FROM AUTHOR]