Mechanistic aspects of the gas-phase coupling of thioanisole and chlorobenzene to dibenzothiophene catalyzed by atomic Ho+

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Mechanistic aspects of the novel gas-phase generation of dibenzothiophene via coupling of thioanisole and chlorobenzene, employing atomic Ho+ as a catalyst, have been investigated using Fourier-transform ion cyclotron resonance mass spectrometry in conjunction with density functional theory (DFT) calculations.DFG, EXC 314, Unifying Concepts in Catalysi

The model of rat lipid metabolism disorder induced by chronic stress accompanying high-fat-diet

<p>Abstract Objective</p> <p>To develop an animal model of Lipid Metabolism Disorder, which conforms to human clinical characteristic. Methods: There were 24 male Wistar rats that were randomly divided into 3 groups with 8 rats in each. They were group A (normal diet), group B (high-fat-diet), group C (chronic stress+ high-fat-diet). Group A was fed with normal diet, while group B and C were fed with high-fat-diet, going on for 55 days. From the 35th day, group B and C received one time of daily chronic stress, going on for 21 days. After that, the activities of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the levels of the serum triglyceride (TG), Cholesterol (Ch), high-density lipoprotein-Cholesterol (HDL-C) and liver TG were evaluated. Results: Compared with group A, the activities of the serum ALT and AST, and the levels of the serum CH, TG, HDL-C and liver TG were found to be markedly increased, when the level of HDL-C was markedly decreased in group B and C, and the results of group C was more obviously. Conclusion: Chronic stress and high-fat-diet have the synergistic action in rat's Lipid Metabolism Disorder. They lead to a model of Lipid Metabolism Disorder, which conforms to human clinical characteristic much better.</p

Research of influence and mechanism of combining exercise with diet control on a model of lipid metabolism rat induced by high fat diet

OBJECTIVE: To investigate the influence and mechanism of combining exercise with diet control on a model of lipid metabolism rat induced by high fat diet. METHODS: Twenty-four male Wistar rats were randomly divided into 3 groups of 8: normal, model and intervention. The model group and intervention group were fed with high fat diet, while the normal group received basal feed. From day 1, the intervention group was randomly given interventions such as swimming exercise and dietary restriction. The interventions duration were 28 days. At the end of the experiment, the levels of rats’ body weight and liver weight were detected, the serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and hepatic triglyceride content (TG) were detected by using biochemical assay, serum level of gastrin (GAS), motilin (MTL) were assayed by the enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the level of body weight and liver weight in the normal rats, body weight and liver weight in the rat of the model group were significantly increase (P<0.05 or P<0.01). Plasma concentrations of TC, LDL-C and hepatic TG in the model group were significantly increased compared with those in the normal group (P<0.05 or P<0.01). The contents of GAS, MTL, HDL-C in the model rats’plasma were significantly reduced compared with those of the normal group (P<0.05 or P<0.01). Compared with those in the model group, rats’ body weight, liver weight, serum TC, LDL-C, and TG content of liver in the intervention group decreased significantly (P<0.05 or P<0.01). Meanwhile, serum content of GAS, MTL, HDL-C were significantly improved in the intervention rats compared to the model group. CONCLUSION: The action of combining exercise with diet control for lipid metabolism disorder might be related to regulation of GAS, MTL and other gastrointestinal hormones

Nonparaxiality-triggered Landau-Zener transition in topological photonic waveguides

Photonic lattices have been widely used for simulating quantum physics, owing to the similar evolutions of paraxial waves and quantum particles. However, nonparaxial wave propagations in photonic lattices break the paradigm of the quantum-optical analogy. Here, we reveal that nonparaxiality exerts stretched and compressed forces on the energy spectrum in the celebrated Aubry-Andre-Harper model. By exploring the mini-gaps induced by the finite size of the different effects of nonparaxiality, we experimentally present that the expansion of one band gap supports the adiabatic transfer of boundary states while Landau-Zener transition occurs at the narrowing of the other gap, whereas identical transport behaviors are expected for the two gaps under paraxial approximation. Our results not only serve as a foundation of future studies of dynamic state transfer but also inspire applications leveraging nonparaxial transitions as a new degree of freedom.Comment: 17 pages, 4 figure

COSTA: A Multi-center Multi-vendor TOF-MRA Dataset and A Novel Cerebrovascular Segmentation Network

Time-of-flight magnetic resonance angiography(TOF-MRA) is the least invasive and ionizing radiation free approach for cerebrovascular imaging, but variations in imaging artifacts across different clinical centers andimaging vendors result in inter-site and inter-vendor heterogeneity, making its accurate and robust cerebrovascular segmentation challenging. Moreover, the limited availabilityand quality of annotated data pose further challenges for segmentation methods to generalize well to unseen datasets. In this paper, we construct the largest and mostdiverse TOF-MRA dataset (COSTA) from 8 individual imaging centers, with all the volumes manually annotated. Then we propose a novel network for cerebrovascular segmentation,namely CESAR, with the ability to tackle featuregranularity and image style heterogeneity issues. Specifically, a coarse-to-fine architecture is implemented to refine cerebrovascular segmentation in an iterative manner.An automatic feature selection module is proposed to selectively fuse global long-range dependencies and local contextual information of cerebrovascular structures. A style self-consistency loss is then introduced to explicitlyalign diverse styles of TOF-MRA images to a standardized one. Extensive experimental results on the COSTA dataset demonstrate the effectiveness of our CESAR network against state-of-the-art methods. We have made 6subsets of COSTA with the source code online available, in order to promote relevant research in the community

FABP4-mediated lipid droplet formation in Streptococcus uberis-infected macrophages supports host defence

Foamy macrophages containing prominent cytoplasmic lipid droplets (LDs) are found in a variety of infectious diseases. However, their role in Streptococcus uberis-induced mastitis is unknown. Herein, we report that S. uberis infection enhances the fatty acid synthesis pathway in macrophages, resulting in a sharp increase in LD levels, accompanied by a significantly enhanced inflammatory response. This process is mediated by the involvement of fatty acid binding protein 4 (FABP4), a subtype of the fatty acid-binding protein family that plays critical roles in metabolism and inflammation. In addition, FABP4 siRNA inhibitor cell models showed that the deposition of LDs decreased, and the mRNA expression of Tnf, Il1b and Il6 was significantly downregulated after gene silencing. As a result, the bacterial load in macrophages increased. Taken together, these data demonstrate that macrophage LD formation is a host-driven component of the immune response to S. uberis. FABP4 contributes to promoting inflammation via LDs, which should be considered a new target for drug development to treat infections

Taurine reprograms mammary-gland metabolism and alleviates inflammation induced by Streptococcus uberis in mice

Streptococcus uberis (S. uberis) is an important pathogen causing mastitis, which causes continuous inflammation and dysfunction of mammary glands and leads to enormous economic losses. Most research on infection continues to be microbial metabolism-centric, and many overlook the fact that pathogens require energy from host. Mouse is a common animal model for studying bovine mastitis. In this perspective, we uncover metabolic reprogramming during host immune responses is associated with infection-driven inflammation, particularly when caused by intracellular bacteria. Taurine, a metabolic regulator, has been shown to effectively ameliorate metabolic diseases. We evaluated the role of taurine in the metabolic regulation of S. uberis-induced mastitis. Metabolic profiling indicates that S. uberis exposure triggers inflammation and metabolic dysfunction of mammary glands and mammary epithelial cells (the main functional cells in mammary glands). Challenge with S. uberis upregulates glycolysis and oxidative phosphorylation in MECs. Pretreatment with taurine restores metabolic homeostasis, reverses metabolic dysfunction by decrease of lipid, amino acid and especially energy disturbance in the infectious context, and alleviates excessive inflammatory responses. These outcomes depend on taurine-mediated activation of the AMPK–mTOR pathway, which inhibits the over activation of inflammatory responses and alleviates cellular damage. Thus, metabolic homeostasis is essential for reducing inflammation. Metabolic modulation can be used as a prophylactic strategy against mastitis

Association of hepatitis B virus infection status with outcomes of non-small cell lung cancer patients undergoing anti-PD-1/PD-L1 therapy

Background: The aim of this study was to evaluate the safety and survival outcomes of anti-programmed cell death (PD)-1/programmed cell death-ligand 1 (PD-L1) monotherapy in patients with advanced nonsmall cell lung cancer (NSCLC) and different hepatitis B virus (HBV) infection status. Methods: Patients with advanced NSCLC and both chronic and/or resolved HBV infection who were treated with anti-PD-(L)1 monotherapy were retrospectively enrolled. The primary endpoint was the safety of PD-1/PD-L1 monotherapy, while the secondary endpoints included the survival outcomes. Results: Of the 62 eligible patients, 10 (16.1%) were hepatitis B surface antigen (HBsAg) positive [chronic hepatitis B (CHB) infection] and 52 (83.9%) were HBsAg negative and HBcAb positive [resolved hepatitis B (RHB) infection]; 42 (67.7%) patients had at least 1 treatment-related adverse event (AE), with 4 patients (6.5%) developing grade 3 AEs and 6 (9.7%) developing hepatic AEs. One CHB patient experienced HBV reactivation during anti-PD-1 immunotherapy due to the interruption of antiviral prophylaxis. The objective response rate and durable clinical benefit (DCB) rate were 17.7% and 29.0%, respectively. Median overall survival (OS) and progression-free survival (PFS) were 23.6 months [95% confidence interval (CI): 14.432.8] and 2.1 months (95% CI: 1.2-3.0), respectively. The DCB rate was significantly higher in the CHB group than in the RHB group (60% vs. 23.1%; P=0.048). Patients with CHB experienced a longer PFS (8.3 vs. 2.0 months; P=0.103) and OS (35.0 vs. 18.2 months, P=0.119) than did RHB patients. Conclusions: Anti-PD-(L)1 monotherapy was safe and effective in patients with NSCLC and HBV infection. This population should not be excluded from receiving immunotherapy in routine clinical practice or within clinical trials if HBV biomarkers are monitored and antiviral prophylaxis is properly used

Solenoid-free current drive via ECRH in EXL-50 spherical torus plasmas

As a new spherical tokamak (ST) designed to simplify engineering requirements of a possible future fusion power source, the EXL-50 experiment features a low aspect ratio (A) vacuum vessel (VV), encircling a central post assembly containing the toroidal field coil conductors without a central solenoid. Multiple electron cyclotron resonance heating (ECRH) resonances are located within the VV to improve current drive effectiveness. Copious energetic electrons are produced and measured with hard X-ray detectors, carry the bulk of the plasma current ranging from 50kA to 150kA, which is maintained for more than 1s duration. It is observed that over one Ampere current can be maintained per Watt of ECRH power issued from the 28-GHz gyrotrons. The plasma current reaches Ip>80kA for high density (>5e18me-2) discharge with 150kW ECHR heating. An analysis was carried out combining reconstructed multi-fluid equilibrium, guiding-center orbits of energetic electrons, and resonant heating mechanisms. It is verified that in EXL-50 a broadly distributed current of energetic electrons creates smaller closed magnetic-flux surfaces of low aspect ratio that in turn confine the thermal plasma electrons and ions and participate in maintaining the equilibrium force-balance

APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor

SUMMARY Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways