Effects of Shenlian Extracts () on Atherosclerosis by Inhibition of the Inflammatory Response

ObjectiveInflammation plays a critical role in atherosclerosis, and this inflammatory reaction is being intensively studied. Shenlian Extracts (), an active ingredient of Chinese medicinal herbs, is believed to have multiple therapeutic and preventive effects against human vascular diseases, including atherosclerosis. Our work investigated whether Shenlian Extracts serves as an anti-inflammatory agent during atherogenesis.MethodsWe established a model of atherosclerosis in rabbits using balloon angioplasty and a high cholesterol diet. The effects of Shenlian Extracts on vessel structure and inflammation were assessed by hematoxylin-eosin staining of the femoral artery, measurement of inflammation-related factors in serum or vascular tissue, and radioimmunoassay. Enzyme linked immunosorbent assays (ELISA), flow cytometry and western blots were also performed.ResultsWe show that oral pre-treatment with Shenlian Extracts suppressed the pathological changes associated with atherosclerosis and that graded doses of Shenlian Extracts reduced total serum levels of cholesterol (90, 180 and 360 mg/kg), triglyceride (180 and 360 mg/kg), and LDL-c (90, 180 mg/kg). Various doses of Shenlian Extracts reduced serum content of TNF-a (180 and 360 mg/kg), CRP (90, 180 and 360 mg/kg) and IL-8 (360 mg/kg) (P<0.05), but led to no significant changes in IL-1β levels. Treatment with Shenlian Extracts also significantly reduced VCAM-1 levels (90 and 360 mg/kg) and IGF-1 levels (90 and 180 mg/kg) in vascular tissue but had no significant effect on ICAM-1 and MCP-1 levels. Finally, Shenlian Extracts significantly reduced the abnormal expression of CD18 in monocytes in a dose-dependent manner.ConclusionThese results suggest that Shenlian Extracts may play a direct role in preventing and treating atherogenesis by inhibiting the inflammatory reaction, providing insights into the possible mechanism underlying the anti-atherosclerotic actions of Shenlian Extracts

CD8(+) T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPR(dn) , hIAPP and PNPLA3(I148M) . Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8(+) T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs' liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.Peer reviewe

Predictors of HIV and Syphilis among Men Who Have Sex with Men in a Chinese Metropolitan City: Comparison of Risks among Students and Non-Students

Men who have sex with men (MSM) are at a substantial risk of HIV, given rising HIV prevalence in urban China. Adolescent and adult students often take HIV-related risk as part of sexual exploration. We compared the risks of HIV and syphilis infections and risky sexual behaviors between student and non-student among urban MSM.Respondent driven sampling approach was used to recruit men who were self-identified as MSM in Chongqing Metropolitan City in southwestern China in 2009. Each participant completed a computer-assisted self-interview which collected demographic and behavioral data, and provided blood specimens for HIV and syphilis testing. Multivariable logistic regression analyses identified predictors for HIV and syphilis infections while comparing student and non-student MSM.Among 503 MSM participants, 36.4% were students, of whom 84.2% were in college. The adjusted prevalence of HIV infection was 5.5% (95% confidence interval [CI]: 2.1%-10.2%) in students and 20.9% (95% CI: 13.7%-27.5%) in non-students; the adjusted prevalence of syphilis was 4.4% (95% CI: 0.7%-9.0%) in students and 7.9% (95% CI: 3.6%-12.9%) in non-students (P = 0.12). Two groups had similar risky sexual behaviors such as number of sexual partners and exchanging sex for money. Multivariate analysis showed that students had lower HIV prevalence than non-students (adjusted odds ratio [AOR]: 0.3; 95% CI: 0.1-0.8) adjusting for age, ethnicity and other variables.Student MSM have lower HIV and similar syphilis prevalence compared with non-student MSM. However, due to a shorter duration of sexual experience and high prevalence of at-risk sexual behaviors among student MSM, HIV risk might be quite high in students as in non-students

Iridium-Catalyzed α-Selective Arylation of Styrenes by Dual C-H Functionalization

An IrI -system modified with a ferrocene derived bisphosphine ligand promotes α-selective arylation of styrenes by dual C-H functionalization. These studies offer a regioisomeric alternative to the Pd-catalyzed Fujiwara-Moritani reaction

The combination of hand grip strength and modified Glasgow prognostic score predicts clinical outcomes in patients with liver cancer

PurposePrevious studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility.MethodsThis was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan–Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used.ResultsA total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidence interval [CI],1.14–1.98; p = 0.001 and HR, 1.55; 95% CI, 1.14–2.12, p = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52–3.63; p &lt; 0.001). The area under the curve of HGS-mGPS was 0.623. The calibration curve demonstrated the validity of the HGS-mGPS nomogram model for predicting the survival of patients with liver cancer.ConclusionA combination of low HGS and high mGPS is associated with poor prognosis in patients with liver cancer. The combination of HGS and mGPS can predict the prognosis of liver cancer more accurately than HGS or mGPS alone. The nomogram model developed in this study can effectively predict the survival outcomes of liver cancer

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000

Graphene-Based Nanocomposites for Energy Storage

Since the first report of using micromechanical cleavage method to produce graphene sheets in 2004, graphene/graphene-based nanocomposites have attracted wide attention both for fundamental aspects as well as applications in advanced energy storage and conversion systems. In comparison to other materials, graphene-based nanostructured materials have unique 2D structure, high electronic mobility, exceptional electronic and thermal conductivities, excellent optical transmittance, good mechanical strength, and ultrahigh surface area. Therefore, they are considered as attractive materials for hydrogen (H2) storage and high-performance electrochemical energy storage devices, such as supercapacitors, rechargeable lithium (Li)-ion batteries, Li–sulfur batteries, Li–air batteries, sodium (Na)-ion batteries, Na–air batteries, zinc (Zn)–air batteries, and vanadium redox flow batteries (VRFB), etc., as they can improve the efficiency, capacity, gravimetric energy/power densities, and cycle life of these energy storage devices. In this article, recent progress reported on the synthesis and fabrication of graphene nanocomposite materials for applications in these aforementioned various energy storage systems is reviewed. Importantly, the prospects and future challenges in both scalable manufacturing and more energy storage-related applications are discussed

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure