LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling

While the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xenograft tissues (NEPC-PDX). Results from cell lines and human clinical sample surveys also revealed that lncRNA-p21 expression is up-regulated in NEPC and Enz treatment could increase the lncRNA-p21 to induce the NED. Mechanism dissection revealed that Enz could promote the lncRNA-p21 transcription via altering the androgen receptor (AR) binding to different androgen-response-elements, which switch the EZH2 function from histone-methyltransferase to non-histone methyltransferase, consequently methylating the STAT3 to promote the NED. Preclinical studies using the PDX mouse model proved that EZH2 inhibitor could block the Enz-induced NED. Together, these results suggest targeting the Enz/AR/lncRNA-p21/EZH2/STAT3 signaling may help urologists to develop a treatment for better suppression of the human CRPC progression

Archaeal lipid-inferred paleohydrology and paleotemperature of Lake Chenghai during the Pleistocene-Holocene transition

Over the past decades, paleoenvironmental studies in the Indian summer monsoon region have mainly focused on precipitation change, with few published terrestrial temperature records from the region. We analysed the distribution of isoprenoid glycerol dialkyl glycerol tetraethers (isoGDGTs) in the sediments of Lake Chenghai in southwest China across the Pleistocene-Holocene transition, to extract both regional hydrological and temperature signals for this important transition period. The lake level was reconstructed from the relative abundance of crenarchaeol in isoGDGTs (%cren) and the crenarchaeol'/crenarchaeol ratio. The %cren-inferred lake level identified a single lowstand (15.4-14.4 ka cal BP), while the crenarchaeol'/crenarchaeol ratio suggests a relatively lower lake level between 15.4-14.4 and 12.5-11.7 ka cal BP, corresponding to periods of weakened ISM during the Heinrich 1 and Younger Dryas cold event. A filtered TetraEther indeX consisting of 86 carbon atoms (TEX86 index) revealed that lake surface temperature was similar to present-day values during the last deglacial period and suggests a substantial warming of similar to 4 degrees C from the early Holocene to the mid-Holocene. Our paleotemperature record is generally consistent with other records in southwest China, suggesting that the distribution of isoGDGTs in Lake Cheng-hai sediments has potential for quantitative paleotemperature reconstruction

Observation of strong coupling between a mechanical oscillator and a cavity-magnon polariton

Cavity magnomechanics (CMM) is an emerging field and has received much attention in the past decade. It deals with coherent couplings among microwave cavity photons, magnons and vibration phonons. So far, all previous CMM experiments have been operated in the weak-coupling regime. This considerably limits prospective various applications of the system. Here, we demonstrate the CMM system in the strong-coupling regime and observe the associated normal-mode splitting. In this regime, the mechanical oscillator is strongly coupled to a cavity-magnon polariton that is formed by strongly coupled cavity photons and magnons, and the polariton-mechanics cooperativity reaches $4\times10^3$, which is improved by three orders of magnitude than previous CMM experiments. The system is then in the triple-strong-coupling regime and the normal modes of the system are the hybridization of microwave photons, magnons and phonons. This is achieved by significantly reducing the linewidth of the polariton mode using coherent perfect absorption and the linewidth is reduced by four orders of magnitude. The work paves the way towards full quantum control of phonons, photons and magnons, and provides a new platform for the study of rich strong-coupling effects in multipartite hybrid systems

Perspective of key healthcare professionals on antimicrobial resistance and stewardship programs: A multicenter cross-sectional study from Pakistan

Copyright © 2020 Hayat, Rosenthal, Gillani, Chang, Ji, Yang, Jiang, Zhao and Fang. Background: Antimicrobial resistance (AMR) is an increasing global threat, and hospital-based antimicrobial stewardship programs (ASPs) are one of the effective approaches to tackle AMR globally. This study was intended to determine the attitude of key healthcare professionals (HCPs), including physicians, nurses, and hospital pharmacists, towards AMR and hospital ASPs. Methods: A cross-sectional study design was used to collect data from HCPs employed in public teaching hospitals of Punjab, Pakistan, from January 2019 to March 2019. A cluster-stratified sampling method was applied. Descriptive statistics, Mann Whitney and Kruskal Wallis tests were used for analysis. Results: A response rate of 81.3% (881/1083) for the surveys was obtained. The majority of the physicians (247/410, 60.2%) perceived AMR to be a serious problem in Pakistani hospitals (p \u3c 0.001). Most of the HCPs considered improving antimicrobial prescribing (580/881, 65.8%; p \u3c 0.001) accompanied by the introduction of prospective audit with feedback (301/881, 75.8%; p \u3c 0.001), formulary restriction (227/881, 57.2%; p = 0.004) and regular educational activities (300/881, 75.6%; p = 0.015) as effective ASP methods to implement hospital ASPs in Pakistan. A significant association was found between median AMR and ASP scores with age, years of experience, and types of HCPs (p \u3c 0.05). Conclusions: The attitude of most of the HCPs was observed to be positive towards hospital-based ASPs regardless of their poor awareness about ASPs. The important strategies, including prospective audit with feedback and regular educational sessions proposed by HCPs, will support the initiation and development of local ASPs for Pakistani hospitals

Diaqua­bis(2,2′-biimidazole)zinc(II) 4,4′-di­carboxybiphenyl-3,3′-di­carboxyl­ate

In the title compound, [Zn(C6H6N4)2(H2O)2](C16H8O8), the ZnII atom, located on an inversion centre, is coordinated by two aqua and two bidentate biimidizole ligands, resulting in a slightly distorted octa­hedral ZnO2N4 geometry. The four N atoms from the two biimidizole ligands lie in the equatorial plane and the two aqua O atoms lie in the axial sites. The biphenyl­tetra­carboxyl­ate anion also lies on an inversion centre. The ZnII complex cation and the anion are held together by N—H⋯O hydrogen bonds, forming a zigzag chain along [21]. The chains are further connected by water mol­ecules via O—H⋯O hydrogen bonds

Diaqua­bis(2,2′-biimidazole)cobalt(II) 4,4′-dicarboxy­biphenyl-3,3′-di­car­boxylate

In the title compound, [Co(C6H6N4)2(H2O)2](C16H8O8), the CoII cation and the organic anion occupy different crystallographic inversion centres and, as a consequence, the asymmetric unit comprises two half-mol­ecules. The benzene groups are coplanar. The four coordinating N atoms of the two bidentate biimidazole ligands define the equatorial plane of a slightly distorted octa­hedral CoO2N4 geometry, and the water O atoms lie in the axial coordination sites. Translational (a,) and inversion-related symmetry operations link the Co complex mol­ecules and the negatively charged carboxyl­ate anions via inter­molecular N—H⋯O and O—H⋯O hydrogen bonds into sheets parallel to (01). The coordinated water mol­ecules connect the sheets through O—H⋯O hydrogen bonds, forming a three-dimensional framework. In addition, two intra­molecular O—H⋯O hydrogen bonds are observed between the carboxyl and carboxyl­ate groups

Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others. By contrast, the majority of truncal and clonal driver mutations occurred in tumor-suppressor genes, including TP53, KMT2D and ZNF750, among others. Interestingly, phyloepigenetic trees robustly recapitulated the topological structures of the phylogenetic trees, indicating a possible relationship between genetic and epigenetic alterations. Our integrated investigations of spatial ITH and clonal evolution provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ESCC