High-resolution vessel wall imaging for quantitatively and qualitatively evaluating in-stent stenosis of intracranial aneurysms

BackgroundIt is critical to accurately and noninvasively evaluate the stented parent artery of intracranial aneurysms (IAs) with endovascular treatment.ObjectiveTo investigate high-resolution vessel wall imaging (HR-VWI) for quantitative and qualitative evaluation of in-stent stenosis (ISS) in IAs treated with stent placement (SP).MethodsFifty-five patients (58 aneurysms) underwent HR-VWI, contrast-enhanced (CE)-HR-VWI, CE-MR angiography (MRA), time-of-flight (TOF)-MRA, and digital subtraction angiography (DSA) six months after SP, and the reliability of quantitative stent lumen measurements was evaluated by intraclass correlation coefficient (ICC) analysis. Agreement and correlation of quantitative evaluation were estimated by comparing the four MR imaging modalities with DSA. The diagnostic performance for >0%, ≥25%, and ≥50% of ISS degrees and overall diagnostic accuracy for the ISS degrees of the four MR imaging modalities were calculated to qualitative evaluation.ResultsThe reliability of CE-HR-VWI and HR-VWI for ISS quantitative measurements was excellent (ICC 0.955–0.989). The agreement and correlation of CE-HR-VWI, HR-VWI versus DSA for ISS quantitative measurements were better than those of CE-MRA and TOF-MRA (p < 0.05). The diagnostic performance for distinguishing the degree of ISS >0%, ≥25%, and ≥50% by CE-HR-VWI and HR-VWI was superior to CE-MRA and TOF-MRA, and their overall diagnostic accuracy was 96.55 and 94.83%, respectively. HR-VWI and CE-HR-VWI were not statistically significant in the quantitative and qualitative evaluation of ISS performance (p > 0.05).ConclusionHR-VWI and CE-HR-VWI have similar performance and value in the quantitative and qualitative evaluation of ISS, and HR-VWI without contrast media could be used as an ideal long-term follow-up approach after SP treatment for IAs

Growth differentiation factor-15/adiponectin ratio as a potential biomarker for metabolic syndrome in Han Chinese

AimsGrowth differentiation factor-15 (GDF-15) and adiponectin are adipokines that regulate metabolism. This study aimed to evaluate the roles of GDF-15, adiponectin, and GDF-15/adiponectin ratio (G/A ratio) as biomarkers for detecting metabolic syndrome (MS).Materials and methodsThis cross-sectional study included 676 participants aged 20–70 years in Jurong, China. The participants were divided into four groups based on sex and age (<40 and ≥40 years). MS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Receiver operating characteristic curves were used to evaluate the performance of GDF-15, adiponectin, and the G/A ratio in predicting MS.ResultsThe prevalence of MS was 22.0% (149/676). Logistic regression analysis indicated that the G/A ratio and adiponectin levels, but not GDF-15 levels, were correlated with MS [odds ratio; 95% CI 1.010 (1.006–1.013) and 0.798 (0.735–0.865), respectively] after adjusting for confounding factors. The G/A ratio displayed a significant relationship with MS in each subgroup and with each MS component in both men and women; however, adiponectin concentrations were significantly associated with MS and all its components only in men (all P <0.05). The area under the curve (AUC) of the G/A ratio and the adiponectin level for MS was 0.758 and 0.748, respectively. The highest AUC was 0.757 for the adiponectin level in men and 0.724 for the G/A ratio in women.ConclusionsThis study suggests that the G/A ratio and adiponectin are potential biomarkers for detecting MS in women and men, respectively

The calcium-permeable channel OSCA1.3 regulates plant stomatal immunity

Perception of biotic and abiotic stresses often leads to stomatal closure in plants 1,2. Rapid influx of calcium ions (Ca 2+) across the plasma membrane has an important role in this response, but the identity of the Ca 2+ channels involved has remained elusive 3,4. Here we report that the Arabidopsis thaliana Ca 2+-permeable channel OSCA1.3 controls stomatal closure during immune signalling. OSCA1.3 is rapidly phosphorylated upon perception of pathogen-associated molecular patterns (PAMPs). Biochemical and quantitative phosphoproteomics analyses reveal that the immune receptor-associated cytosolic kinase BIK1 interacts with and phosphorylates the N-terminal cytosolic loop of OSCA1.3 within minutes of treatment with the peptidic PAMP flg22, which is derived from bacterial flagellin. Genetic and electrophysiological data reveal that OSCA1.3 is permeable to Ca 2+, and that BIK1-mediated phosphorylation on its N terminus increases this channel activity. Notably, OSCA1.3 and its phosphorylation by BIK1 are critical for stomatal closure during immune signalling, and OSCA1.3 does not regulate stomatal closure upon perception of abscisic acid—a plant hormone associated with abiotic stresses. This study thus identifies a plant Ca 2+ channel and its activation mechanisms underlying stomatal closure during immune signalling, and suggests specificity in Ca 2+ influx mechanisms in response to different stresses

Functional Study of HopZ1, a Type III Secreted Effector of the Bacterial Pathogen Pseudomonas syringae

Many Gram-negative phytopathogenic bacteria inject an array of type III secreted effectors (T3SEs) into plant cells via the type III secretion system (T3SS). These effectors play an essential role in bacterial infection mainly by targeting host immunity. However, the molecular basis of their functionalities remains largely unknown.My research focuses on a T3SE produced by Pseudomonas syringae, called HopZ1, which is a member of the widely distributed YopJ effector family. Our lab identified several HopZ1 interacting proteins (ZINPs) from soybean using yeast two-hybrid screening, among which GmJAZ1 is homologous to Arabidopsis jasmonate ZIM-domain (AtJAZ) proteins. JAZs are key negative regulators of the jasmonate (JA) signaling and major components of the JA receptor complex. The main goal of my thesis is to investigate the function of HopZ1 in plant hosts by directly targeting the JAZ proteins.In Chapter one, I proved that HopZ1 interacts with both GmJAZ1 and multiple AtJAZs in vitro and in planta. Upon interaction, JAZs can be acetylated by HopZ1a through a putative acetyltransferase activity. In addition, during bacterial infection of Arabidopsis, P. syringae producing wild type, but not the catalytic mutant, of HopZ1a induces the degradation of JAZs, activates the expression of JA-responsive genes, and suppresses the salicylic acid (SA) signaling pathway. As a result, HopZ1a promotes P. syringae infection in Arabidopsis. In Chapter two, I determined that HopZ1a can acetylate AtJAZ6, AtJAZ8, AtJAZ9 and AtJAZ10 in vitro. Mass spectrometry analyses suggest that multiple serine/threonine residues within the TSYDSDSSDTTS peptide in the N-terminal region of AtJAZ8 are potentially acetylated by HopZ1a. AtJAZ8 mutants with this sequence deleted, or with all the eight serine and threonine residues within this sequence substituted with alanines, are no longer acetylated by HopZ1a, suggesting that one or more serine/threonine residues within this sequence are the acetylation sites.My research provides the first example of a bacterial effector that subverts host immunity by directly targeting the receptor complex of a defense-associated hormone in plants. This work also revealed a novel mechanism to regulate the JA signaling in plants through posttranslational modification of JAZs

Government procurement and financial statement certification: Evidence from private firms in emerging economies

In this paper, we examine the monitoring role of government customers in emerging markets, a setting where public procurement is significant but the procurement institutions are weak. In these countries, financial statement certifications could be an important mechanism for a private firm to facilitate contracting with governments. Employing a sample of private firms across 98 emerging economies, we first document in-depth private-firm audit regulations for each country. We find that firms are more likely to have financial statements certified by an external auditor when they have government contracts. We further find that the association is less pronounced when governments have weaker monitoring incentives – when suppliers are subject to monitoring from tax authorities or creditors, when government contracting officials receive bribes, and when government spending is less transparent. We corroborate our inferences using the staggered adoption of an E-Procurement system to infer changes in governments’ monitoring incentives and several other robustness checks

Public Environmental Enforcement and Private Lender Monitoring: Evidence from Environmental Covenants

In this study, we examine the interplay between public environmental enforcement and private lender monitoring and its effects on borrowers’ environmental activities. To capture lender environmental monitoring, we use environmental covenants in loan agreements that require borrowers to take environmental remedial actions, disclose adverse environmental events, or conduct environmental audits. We predict and find that, in the presence of higher regulatory enforcement intensity, loan agreements are more likely to include environmental covenants when loans are secured by real property versus non-real property and when borrowers belong to more polluting industries. We further find that after loan initiations, borrowers with environmental covenants in loan contracts have lower toxic chemical releases when they are located in states with higher regulatory enforcement intensity. Taken together, our study suggests that public environmental enforcement reinforces lenders’ environmental monitoring that has positive externalities in shaping borrowers’ environmental activities

Developing Effective Cancer Vaccines Using Rendered-Inactive Tumor Cells

Cancer is a major public health threat, and researchers are constantly looking for new ways to develop effective treatments. One approach is the use of cancer vaccines, which work by boosting the body’s immune system to fight cancer. The goal of this study was to develop an effective cancer vaccine using rendered-inactive tumor cells. A CMS5 fibrosarcoma tumor model in BALB/c mice and an E.G7 lymphoma tumor model in C57BL/6 mice were used to evaluate how mitomycin C-inactivated tumor cells mediated tumor protection. The results showed that immunization with inactivated CMS5 cells significantly improved tumor suppression after a challenge with live CMS5 tumor cells, but no effect was observed using the E.G7 tumor model. The results suggested that DC (dendritic cell) responses to tumor antigens are critical. The maturation and activation of DCs were effectively promoted by mitomycin C-treated CMS5 cells, as well as enhanced phagocytosis ability in vitro. The tumor-protective effects established by the vaccination of inactivated CMS5 cells were CD8+ T cell-dependent, as the antitumor responses disappeared after eliminating CD8+ T cells. It was found that the tumor-prevention efficacy was dramatically increased by combining inactivated CM55 tumor cells with anti-CD25 antibodies to temporarily deplete Treg cells (regulatory T cells). This strategy could also significantly induce the rejection against E.G7 tumors. In addition, vaccination with anti-CD25 antibodies plus inactivated CMS5 cells elicited antitumor responses against heterologous tumors. According to the findings of this study, combining the immunization of inactivated tumor cells with an anti-CD25 antibody may be an effective method for cancer prevention

Transient regulatory-T-cell interruption promotes skin-resident memory T cells mediated tumor protection

Abstract Most cancer immunotherapy approaches aim to stimulate cytotoxic CD8+ T lymphocytes to reject tumor cells. Due to the tumor-mediated suppressive micro-environment, of which the major contributor is regulatory T cells (Tregs), promising preclinical approaches were disappointing in clinical settings. Our recent study demonstrated that transient interruption of Tregs could induce CD8+ T cell responses to reject tumors in an animal model. The long-term tumor protective effect has yet not to be investigated. In this study, mice with Treg depletion rejected tumors and were rechallenged to study anti-tumor memory immune responses. The effects of major immune cell subsets on tumor protection were explored. Finally, we demonstrate that transient depletion of Tregs during primary tumor challenge can result in long-lasting protection against the tumor rechallenge. Skin-resident memory T cells (sTRM) were major factors in rejecting rechallenged tumors even when peripheral T cells were deficient. These findings highlight a promising strategy for empowering tissue-resident memory T cells for cancer prevention and immunotherapy in humans by interrupting Tregs