Dichlorido(dipyrido[3,2-a:2′,3′-c]phenazine)manganese(II)

The complete mol­ecule of the title compound, [MnCl2(C18H10N4)2], is generated by crystallographic twofold symmetry with the Mn atom lying on the rotation axis. The Mn coordination geometry is a distorted cis-MnCl2N4 octa­hedron, arising from two N,N′-bidentate dipyrido[3,2-a:2′,3′-c]phenazine (DPPZ) ligands and two chloride ions. In the crystal structure, neighbouring mononuclear units pack together through π–π contacts between the DPPZ rings [shortest centroid–centroid distance = 3.480 (2) Å], leading to a chain-like structure along [001]. C—H⋯Cl hydrogen bonds complete the structure

FFT-LB modeling of thermal liquid-vapor systems

We further develop a thermal LB model for multiphase flows. In the improved model, we propose to use the FFT scheme to calculate both the convection term and external force term. The usage of FFT scheme is detailed and analyzed. By using the FFT algorithm spatiotemporal discretization errors are decreased dramatically and the conservation of total energy is much better preserved. A direct consequence of the improvement is that the unphysical spurious velocities at the interfacial regions can be damped to neglectable scale. Together with the better conservation of total energy, the more accurate flow velocities lead to the more accurate temperature field which determines the dynamical and final states of the system. With the new model, the phase diagram of the liquid-vapor system obtained from simulation is more consistent with that from theoretical calculation. Very sharp interfaces can be achieved. The accuracy of simulation results are also verified by the Laplace law. The FFT scheme can be easily applied to other models for multiphase flows.Comment: 34 pages, 21 figure

Identifying hub genes in response to ustekinumab and the impact of ustekinumab treatment on fibrosis in Crohn’s disease

IntroductionCrohn’s disease (CD) is a chronic inflammatory disease. Approximately 50% of patients with CD progressed from inflammation to fibrosis. Currently, there are no effective drugs for treating intestinal fibrosis. Biologic therapies for CD such as ustekinumab have benefited patients; however, up to 30% of patients with CD have no response to initial treatment, and the effect of ustekinumab on intestinal fibrosis is still uncertain. Therefore, it is of great significance to explore the predictive factors of ustekinumab treatment response and the effect of ustekinumab on intestinal fibrosis.Materials and methodsPublic datasets—GSE207465 (blood samples) and GSE112366 and GSE207022 (intestinal samples)—were downloaded and analyzed individually (unmerged) based on the treatment response. Differentially expressed genes (DEGs) were identified by the “limma” R package and changes in immune cell infiltration were determined by the “CIBERSORT” R package in both blood and intestinal samples at week 0 (before treatment). To find predictive factors of ustekinumab treatment response, the weighted gene co-expression network analysis (WGCNA) R package was used to identify hub genes in GSE112366. Hub genes were then verified in GSE207022, and a prediction model was built by random forest algorithm. Furthermore, fibrosis-related gene changes were analyzed in ileal samples before and after treatment with ustekinumab.Results(1) Our analysis found that MUC1, DUOX2, LCN2, and PDZK1IP1 were hub genes in GSE112366. GSE207022 revealed that MUC1 (AUC:0.761), LCN2 (AUC:0.79), and PDZK1IP1 (AUC:0.731) were also lower in the response group. Moreover, the random forest model was shown to have strong predictive capabilities in identifying responders (AUC = 0.875). To explore the relationship between intestinal tissue and blood, we found that ITGA4 had lower expression in the intestinal and blood samples of responders. The expression of IL18R1 is also lower in responders’ intestines. IL18, the ligand of IL18R1, was also found to have lower expression in the blood samples from responders vs. non-responders. (2) GSE112366 revealed a significant decrease in fibrosis-related module genes (COL4A1, TUBB6, IFITM2, SERPING1, DRAM1, NAMPT, MMP1, ZEB2, ICAM1, PFKFB3, and ACTA2) and fibrosis-related pathways (ECM–receptor interaction and PI3K-AKT pathways) after ustekinumab treatment.ConclusionMUC1, LCN2, and PDZK1IP1 were identified as hub genes in intestinal samples, with lower expression indicating a positive prediction of ustekinumab treatment response. Moreover, ITGA4 and IL18/IL18R1 may be involved in the treatment response in blood and intestinal samples. Finally, ustekinumab treatment was shown to significantly alter fibrotic genes and pathways

A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait.

In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes

Exploring the Performance Benefits of End-to-End Path Switching

This paper explores the feasibility of improving the performance of end-to-end data transfers between different sites through path switching. Our study is focused on both the logic that controls path switching decisions and the configurations required to achieve sufficient path diversity. Specifically, we investigate two common approaches offering path diversity – multi-homing and overlay networks – and investigate their characteristics in the context of a representative wide-area testbed. We explore the end-to-end delay and loss characteristics of different paths and find that substantial improvements can potentially be achived by path switching, especially in lowering end-to-end losses. Based on this assessment, we develop a simple path-switching mechanism capable of realizing those performance improvements. Our experimental study demonstrates that substantial performance improvements are indeed achievable using this approach

Electroacupuncture Inhibition of Hyperalgesia in Rats with Adjuvant Arthritis: Involvement of Cannabinoid Receptor 1 and Dopamine Receptor Subtypes in Striatum

Electroacupuncture (EA) has been regarded as an alternative treatment for inflammatory pain for several decades. However, the molecular mechanisms underlying the antinociceptive effect of EA have not been thoroughly clarified. Previous studies have shown that cannabinoid CB1 receptors are related to pain relief. Accumulating evidence has shown that the CB1 and dopamine systems sometimes interact and may operate synergistically in rat striatum. To our knowledge, dopamine D1/D2 receptors are involved in EA analgesia. In this study, we found that repeated EA at Zusanli (ST36) and Kunlun (BL60) acupoints resulted in marked improvements in thermal hyperalgesia. Both western blot assays and FQ-PCR analysis results showed that the levels of CB1 expression in the repeated-EA group were much higher than those in any other group (P=0.001). The CB1-selective antagonist AM251 inhibited the effects of repeated EA by attenuating the increases in CB1 expression. The two kinds of dopamine receptors imparted different actions on the EA-induced CB1 upregulation in AA rat model. These results suggested that the strong activation of the CB1 receptor after repeated EA resulted in the concomitant phenomenon of the upregulation of D1 and D2 levels of gene expression