Di-μ-sulfato-bis­{[bis­(3,5-dimethyl­pyrazol-1-yl)methane]copper(II)}

The mol­ecule of the title compound, [Cu2(SO4)2(C11H16N4)2], sits on a center of symmetry. The CuII atom has a distorted trigonal–bipyramidal coordination geometry comprising three O atoms of the two symmetry-related SO4 2− anions and two N atoms from one bis­(3,5-dimethyl­pyrazol-1-yl)methane ligand

(meso-5,7,7,12,14,14-Hexamethyl-1,4,8,11-tetra­aza­cyclo­tetra­deca-4,11-diene)nickel(II) dibromide dihydrate

The asymmetric unit of the title compound, [Ni(C16H32N4)]Br2·2H2O, consists of one half [Ni(C16H32N4)]2+ cation, one Br− anion and one water mol­ecule of crystallization. The NiII ion lies on an inversion centre in a square-planar environment formed by the four macrocyclic ligand N atoms. In the crystal structure, the cations, anions and water mol­ecules are linked via inter­molecular N—H⋯Br and O—H⋯Br hydrogen bonds, forming discrete chains with set-graph motif D(2)D 2 2(7)D 2 1(3)D 3 2(8). The water mol­ecules and Br− ions are linked with set-graph motif R 4 2(8)

A novel intelligent adaptive control of laser-based ground thermal test

AbstractLaser heating technology is a type of potential and attractive space heat flux simulation technology, which is characterized by high heating rate, controlled spatial intensity distribution and rapid response. However, the controlled plant is nonlinear, time-varying and uncertainty when implementing the laser-based heat flux simulation. In this paper, a novel intelligent adaptive controller based on proportion–integration–differentiation (PID) type fuzzy logic is proposed to improve the performance of laser-based ground thermal test. The temperature range of thermal cycles is more than 200K in many instances. In order to improve the adaptability of controller, output scaling factors are real time adjusted while the thermal test is underway. The initial values of scaling factors are optimized using a stochastic hybrid particle swarm optimization (H-PSO) algorithm. A validating system has been established in the laboratory. The performance of the proposed controller is evaluated through extensive experiments under different operating conditions (reference and load disturbance). The results show that the proposed adaptive controller performs remarkably better compared to the conventional PID (PID) controller and the conventional PID type fuzzy (F-PID) controller considering performance indicators of overshoot, settling time and steady state error for laser-based ground thermal test. It is a reliable tool for effective temperature control of laser-based ground thermal test

TWIST Represses Estrogen Receptor-alpha Expression by Recruiting the NuRD Protein Complex in Breast Cancer Cells

Loss of estrogen receptor α (ERα) expression and gain of TWIST (TWIST1) expression in breast tumors correlate with increased disease recurrence and metastasis and poor disease-free survival. However, the molecular and functional regulatory relationship between TWIST and ERα are unclear. In this study, we found TWIST was associated with a chromatin region in intron 7 of the human ESR1 gene coding for ERα. This association of TWIST efficiently recruited the nucleosome remodeling and deacetylase (NuRD) repressor complex to this region, which subsequently decreased histone H3K9 acetylation, increased histone H3K9 methylation and repressed ESR1 expression in breast cancer cells. In agreement with these molecular events, TWIST expression was inversely correlated with ERα expression in both breast cancer cell lines and human breast ductal carcinomas. Forced expression of TWIST in TWIST-negative and ERα-positive breast cancer cells such as T47D and MCF-7 cells reduced ERα expression, while knockdown of TWIST in TWIST-positive and ERα-negative breast cancer cells such as MDA-MB-435 and 4T1 cells increased ERα expression. Furthermore, inhibition of histone deacetylase (HDAC) activity including the one in NuRD complex significantly increased ERα expression in MDA-MB-435 and 4T1 cells. HDAC inhibition together with TWIST knockdown did not further increase ERα expression in 4T1 and MDA-MB-435 cells. These results demonstrate that TWIST/NuRD represses ERα expression in breast cancer cells. Therefore, TWIST may serve as a potential molecular target for converting ERα-negative breast cancers to ERα-positive breast cancers, allowing these cancers to restore their sensitivity to endocrine therapy with selective ERα antagonists such as tamoxifen and raloxifene

Microbiome-derived bile acids contribute to elevated antigenic response and bone erosion in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, disabling and incurable autoimmune disease. It has been widely recognized that gut microbial dysbiosis is an important contributor to the pathogenesis of RA, although distinct alterations in microbiota have been associated with this disease. Yet, the metabolites that mediate the impacts of the gut microbiome on RA are less well understood. Here, with microbial profiling and non-targeted metabolomics, we revealed profound yet diverse perturbation of the gut microbiome and metabolome in RA patients in a discovery set. In the Bacteroides-dominated RA patients, differentiation of gut microbiome resulted in distinct bile acid profiles compared to healthy subjects. Predominated Bacteroides species expressing BSH and 7a-HSDH increased, leading to elevated secondary bile acid production in this subgroup of RA patients. Reduced serum fibroblast growth factor-19 and dysregulated bile acids were evidence of impaired farnesoid X receptor-mediated signaling in the patients. This gut microbiota-bile acid axis was correlated to ACPA. The patients from the validation sets demonstrated that ACPA-positive patients have more abundant bacteria expressing BSH and 7a-HSDH but less Clostridium scindens expressing 7a-dehydroxylation enzymes, together with dysregulated microbial bile acid metabolism and more severe bone erosion than ACPA-negative ones. Mediation analyses revealed putative causal relationships between the gut microbiome, bile acids, and ACPA-positive RA, supporting a potential causal effect of Bacteroides species in increasing levels of ACPA and bone erosion mediated via disturbing bile acid metabolism. These results provide insights into the role of gut dysbiosis in RA in a manifestation-specific manner, as well as the functions of bile acids in this gut-joint axis, which may be a potential intervention target for precisely controlling RA conditions.Comment: 38 pages, 6 figure

Integrated single-cell RNA-seq analysis reveals the vital cell types and dynamic development signature of atherosclerosis

Introduction: In the development of atherosclerosis, the remodeling of blood vessels is a key process involving plaque formation and rupture. So far, most reports mainly believe that macrophages, smooth muscle cells, and endothelial cells located at the intima and media of artery play the key role in this process. Few studies had focused on whether fibroblasts located at adventitia are involved in regulating disease process.Methods and results: In this study, we conducted in-depth analysis of single-cell RNA-seq data of the total of 18 samples from healthy and atherosclerotic arteries. This study combines several analysis methods including transcription regulator network, cell-cell communication network, pseudotime trajectory, gene set enrichment analysis, and differential expression analysis. We found that SERPINF1 is highly expressed in fibroblasts and is involved in the regulation of various signaling pathways.Conclusion: Our research reveals a potential mechanism of atherosclerosis, SERPINF1 regulates the formation and rupture of plaques through the Jak-STAT signaling pathway, which may provide new insights into the pathological study of disease. Moreover, we suggest that SRGN and IGKC as potential biomarkers for unstable arterial plaques