•Compound sophorae decoction is effective for the treatment of UC.•Compound sophorae decoction ameliorates symptoms in DSS-induced mice colitis.•Compound sophorae decoction regulates the balance ...between Th17 and Treg cells in the UC mouse model.
Compound sophorae decoction, a Chinese medicinal formulae composed of six Chinese herbs, is effective for the clinical treatment of ulcerative colitis (UC). Some of its effective monomers had been proven to have suppressive effect on UC models. The aim of this study is to further explore the mechanism whether compound sophorae decoction ameliorates dextran sodium sulfate (DSS)-induced mice colitis by regulating the balance between T helper (Th) 17 and regulatory T (Treg) cells.
Experimental model of UC, established by drinking water with DSS, was treated with compound sophorae decoction and mesalazine. The stool, activity, body weight of the mice, colon length and colon histopathology were observed to evaluate severity of colitis. The concentration of cytokines in colonic tissues were detected by ELISA. The expression of phosphorylated nuclear factor-kappaB (NF-κB) p65, STAT3 and phosphorylated STAT3 in colonic tissues were determined by western blotting and immunohistochemistry. The percentage of Th17 and Treg cells in spleen and mesenteric lymph nodes (MLNs) were detected by flow cytometry. The levels of transcription factor ROR-γt and FOXP3 in colon tissues were detected by qRT-PCR and immunohistochemistry.
The aqueous extract of compound sophorae decoction was able to improve the symptoms and pathological damage of mice. The body weight of mice were increased and DAI were significantly decreased; ulcers were slighter than DSS group. The administration of compound sophorae decoction reduced the level of inflammatory factors interleukin (IL)-1β, tumor necrosis factor (TNF)-α and phospho-NF-κB p65, and also decreased the proportions of Th17 cells in spleen and MLNs and the expression of ROR-γt, IL-17A, STAT3, IL-6 in colonic tissues; while the percentage of Treg cells in spleen and MLNs and the expression of FOXP3, transforming growth factor (TGF)-β1, IL-10 in colonic tissues were upregulated.
Overall, this study suggested that compound sophorae decoction significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.
N-doped carbon materials are promising electrocatalysts for oxygen reduction reaction (ORR). However, the lack of knowledge in the nature of active sites limits the rational design of this type of ...catalysts. Although pyridinic N species are proposed to be active for ORR, little experimental evidence is provided to reveal the reactive sites. Herein, we developed a surface-modification method to identify the ortho-carbon atom of the pyridinic ring as the reactive site for ORR on N-doped graphene. The pyridinic ring of N-doped graphene was selectively grafted by an acetyl group at pyridinic N and ortho-C atoms by electrophilic and radical substitution, respectively. The former remained most of ORR catalytic activity, while the latter lost its activity completely. DFT calculations confirm that O2 can get adsorbed and reduced favorably on the ortho-C atom of the pyridinic ring. This study provides new insight into the nature of active sites and the ORR mechanism for N-doped carbon materials.
As a dipolarizing flux bundle (DFB) moves earthward, it creates pressure and flow perturbations. These perturbations may play a significant role in controlling DFB motion and generating field‐aligned ...currents (FACs) which render the DFB a “wedgelet”, a traveling building block of the substorm current wedge. To investigate this hypothesis, we use DFB observations from the Time History of Events and Macroscale Interactions during Substorms mission to reconstruct the spatial profiles of the thermal and total (thermal plus magnetic) pressures and of the plasma flow near the DFB. The total pressure reaches maximum inside the dipolarization front (DF, the leading edge of the DFB). The resultant pressure gradient force pushes ambient plasma in the direction normal to the front and exerts a gradient force density of ~0.15 nPa/RE against the DFB motion. The thermal pressure in the equatorial plane is strongest immediately ahead of the DFB's leading point; it decreases with distance from that peak: toward the ambient plasma, toward the DFB interior, and toward the DFB flanks. Combining our estimate of the flux tube volume distortion with the measured equatorial thermal pressure distribution, we obtain a region‐1‐sense FAC inside the DF layer and region‐2‐sense FAC in the ~1 RE thick region immediately ahead of it. This system of FACs is indeed consistent with a wedgelet.
Key Points
Pressure at the dipolarization front requires field‐aligned currents (FACs)
The pressure‐related FACs are consistent with the “wedgelet” configuration
A wedgelet (element of substorm current wedge) can support its FACs by itself
Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent ...decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be targets for the treatment of this disorder.
•LH glutamatergic neurons are involved in neuropathic pain.•The activity of the LH-LHb circuit is enhanced in neuropathic pain.•Inhibition of the LH-LHb circuit relieves neuropathic pain.•Activation of the LH-LHb circuit induces nociceptive hypersensitivity in mice without nerve injury.
The ternary Fe/N/C material is a promising non‐precious‐metal oxygen reduction electrocatalyst for proton exchange membrane cells (PEMFCs). However, its practical application is severely hampered by ...poor stability under PEMFC working conditions, especially at a cell voltage higher than 0.5 V. Herein, we report a new strategy to significantly improve the stability of the Fe/N/C catalyst in PEMFCs by covalent grafting of a trifluoromethylphenyl (Ar‐CF3) group. The hydrophobic character of Ar‐CF3 can effectively prevent water flooding of the Fe/N/C catalyst layer, and thus form robust mass‐transport channels for gas−liquid two‐phase flow. Simultaneously, both electron‐withdrawing and hydrophobic properties considerably suppress the oxidative corrosion of the carbon matrix that hosts the catalytically active sites. Therefore, fluorinated Fe/N/C could perform stably over 100 h at 0.5 V with a current density of 0.56 A cm−2 in a H2−O2 PEMFC. Even when the cell voltage increased to 0.6 V, only 15 % performance was lost after 100 h operation.
Flood prevention: A hydrophobic and electron‐withdrawing trifluoromethylphenyl (Ar‐CF3) group was grafted on Fe/N/C oxygen reduction reaction catalysts to significantly prevent water flooding and carbon oxidation corrosion. The resulting Fe/N/C−F cathode exhibits high stability at 0.5–0.6 V in H2−O2 proton exchange membrane fuel cells.
•A bi-level belief rule based model is proposed for diagnosing gastric cancer.•A clonal selection algorithm based method is proposed for optimizing the model.•A case study demonstrates the ...effectiveness of the proposed method.•Comparative studies show the better performance of the proposed method.
Lymph Node Metastasis (LNM) in gastric cancer is an important prognostic factor regarding long-term survival. As it is difficult for doctors to combine multiple factors for a comprehensive analysis, Clinical Decision Support System (CDSS) is desired to help the analysis. In this paper, a novel Bi-level Belief Rule Based (BBRB) prototype CDSS is proposed. The CDSS consists of a two-layer Belief Rule Base (BRB) system. It can be used to handle uncertainty in both clinical data and specific domain knowledge. Initial BRBs are constructed by domain specific knowledge, which may not be accurate. Traditional methods for optimizing BRB are sensitive to initialization and are limited by their weak local searching abilities. In this paper, a new Clonal Selection Algorithm (CSA) is proposed to train a BRB system. Based on CSA, efficient global search can be achieved by reproducing individuals and selecting their improved maturated progenies after the affinity maturation process. The proposed prototype CDSS is validated using a set of real patient data and performs extremely well. In particular, BBRB is capable of providing more reliable and informative diagnosis than a single-layer BRB system in the case study. Compared with conventional optimization method, the new CSA could improve the diagnostic performance further by trying to avoid immature convergence to local optima.
In the health state assessment of the complex equipment, there are some issues such as high-dimensional data or correlation variables. Therefore, a statistic-based feature fusion method for equipment ...health state assessment is proposed, which contains advantages in indicator decorrelation and multi-source information fusion. Specifically, principal component analysis (PCA) is introduced to extract uncorrelated principal component features. Considering that the principal components have no definite physical meaning, a statistic-based feature transformation method is developed to achieve conversion from the principal component feature to the evidence belief degree. Furthermore, the evidence weight for feature fusion can be calculated from the principal component contribution rate. Finally, the equipment health state can be assessed based on the evidential reasoning (ER) rule. Numerical simulations are performed to show that the proposed method can reduce the fusion uncertainty. The practical application is validated with case studies of the turbofan engine (TE) and the inertial measurement unit (IMU), which demonstrates the implementation process and assessment results.
With only 1.3−4.3% in total hepatic CYP content, human CYP2D6 can metabolize more than 160 drugs. It is a highly polymorphic enzyme and subject to marked inhibition by a number of drugs, causing a ...large interindividual variability in drug clearance and drug response and drug-drug interactions. The expression and activity of CYP2D6 are regulated by a number of physiological, pathological and environmental factors at transcriptional, post-transcriptional, translational and epigenetic levels. DNA hypermethylation and histone modifications can repress the expression of CYP2D6. Hepatocyte nuclear factor-4α binds to a directly repeated element in the promoter of CYP2D6 and thus regulates the expression of CYP2D6. Small heterodimer partner represses hepatocyte nuclear factor-4α-mediated transactivation of CYP2D6. GW4064, a farnesoid X receptor agonist, decreases hepatic CYP2D6 expression and activity while increasing small heterodimer partner expression and its recruitment to the CYP2D6 promoter. The genotypes are key determinants of interindividual variability in CYP2D6 expression and activity. Recent genome-wide association studies have identified a large number of genes that can regulate CYP2D6. Pregnancy induces CYP2D6 via unknown mechanisms. Renal or liver diseases, smoking and alcohol use have minor to moderate effects only on CYP2D6 activity. Unlike CYP1 and 3 and other CYP2 members, CYP2D6 is resistant to typical inducers such as rifampin, phenobarbital and dexamethasone. Post-translational modifications such as phosphorylation of CYP2D6 Ser135 have been observed, but the functional impact is unknown. Further functional and validation studies are needed to clarify the role of nuclear receptors, epigenetic factors and other factors in the regulation of CYP2D6.
•Multiphysics modeling of fluid flow, heat and mass transport, and electrochemistry.•Simulation gives in-depth information about plasmonic heated electrochemical system.•Electrochemistry experiments ...confirmed quantitative relations found by simulation.•Rotating disk electrode shows linear response under the effect of plasmonic heating.
Plasmon-mediated chemical reaction (PMCR) is an emerging research field recently, with potential applications in solar energy conversion such as water splitting and CO2 reduction. However, the exact mechanism of PMCR is still not fully understood mainly because the plasmonic heating effect and generation of energized charge carriers can both accelerate chemical reactions. It remains a challenge to quantitatively distinguish the plasmonic heating's contribution from overall plasmonic catalysis effect. To solve this problem, in this paper we utilized a strategy of combined multiphysics numerical simulation and photoelectrochemical experiment to qualitatively characterize the plasmonic heating-induced change of electrochemical response, as well as explain the mechanism behind such change, especially on the rotating disk electrode system which is commonly used in electrocatalysis research. Finite element method was used to solve the numerical model while ferricyanide oxidation was used as a probe reaction. Heat transfer, fluid flow, mass transfer, and electrode kinetics were modeled into the theoretical framework, showing convective flow near plasmonic heated electrode plays a crucial role both in terms of heat dissipation and electroactive species transportation. Simulated intermittent light chronoamperometry shows an exponential current onset process caused by plasmonic heating. For the rotating disk electrode system, a linear relationship of illuminating light power-limiting current was discovered, explained by simulation results, and confirmed by photoelectrochemical experiments. This comprehensive investigation is beneficial for future research on the mechanism of PMCR and photoelectrochemical catalysis.
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