Exosomes derived from differentiated human ADMSC with the Schwann cell phenotype modulate peripheral nerve-related cellular functions

Peripheral nerve regeneration remains a significant clinical challenge due to the unsatisfactory functional recovery and public health burden. Exosomes, especially those derived from mesenchymal stem cells (MSCs), are promising as potential cell-free therapeutics and gene therapy vehicles for promoting neural regeneration. In this study, we reported the differentiation of human adipose derived MSCs (hADMSCs) towards the Schwann cell (SC) phenotype (hADMSC-SCs) and then isolated exosomes from hADMSCs with and without differentiation (i.e., dExo vs uExo). We assessed and compared the effects of uExo and dExo on antioxidative, angiogenic, antiinflammatory, and axon growth promoting properties by using various peripheral nerve-related cells. Our results demonstrated that hADMSC-SCs secreted more neurotrophic factors and other growth factors, compared to hADMSCs without differentiation. The dExo isolated from hADMSC-SCs protected rat SCs from oxidative stress and enhanced HUVEC migration and angiogenesis. Compared to uExo, dExo also had improved performances in downregulating pro-inflammatory gene expressions and cytokine secretions and promoting axonal growth of sensory neurons differentiated from human induced pluripotent stem cells. Furthermore, microRNA (miRNA) sequencing analysis revealed that exosomes and their parent cells shared some similarities in their miRNA profiles and exosomes displayed a distinct miRNA signature. Many more miRNAs were identified in dExo than in uExo. Several upregulated miRNAs, like miRNA-132-3p and miRNA-199b-5p, were highly related to neuroprotection, anti-inflammation, and angiogenesis. The dExo can effectively modulate various peripheral nerverelated cellular functions and is promising for cell-free biological therapeutics to enhance neural regeneration

Municipal managers’ responsiveness to public demands: connecting attitudinal willingness, behavioral willingness, environmental and organizational factors

Public responsiveness, or bureaucratic responsiveness to citizen demands, is central in public administration theories. It has become a key concept regarding the appropriate role of bureaucracy and professional administrators in a democratic political system. In city management, responsiveness to public demands should be particularly addressed given the fact that local professionals have constant and direct contact with local residents. This dissertation builds on existing studies that identify the determinants of public responsiveness. One significant research gap of existing researches was noticed, that is, few studies have included public administrators’ willingness into the analysis framework. Current studies have identified organizational factors, environmental factors, features of policy clients and problem intensity as predictors of public responsiveness. However, examining public responsiveness without assessing individuals’ willingness would neglect their own interpretation and interaction with the environmental and institutional factors. It is at the individual level that the functioning of environmental and organizational factors is enacted. This dissertation project focuses municipal managers’ public responsiveness in the formulation of local budgets. The main research questions of this study include: (1) What is the actual level of municipal managers’ public responsiveness? (2) Given the importance of municipal managers’ attitudes, how can we foster their favorable attitude toward public responsiveness? In other words, what are the determinants of their attitudinal willingness to be responsive to public demands? (3) What are the determinants of municipal manages’ public responsiveness? How do municipal managers’ attitudinal and behavioral willingness connect environmental and organizational factors in determining their public responsiveness? The data in this dissertation was collected from New Jersey and Pennsylvania municipal managers. The seemingly unrelated regression (SUR) result indicates that the factor with the strongest impact on municipal managers’ attitudinal willingness is successful implementation and practices in other municipalities. It highlights the importance of social learning in acquiring and assimilating social knowledge. In the public responsiveness model, the structural equation modeling (SEM) result confirms that a thorough understanding of the determinants of public responsiveness cannot be separated from examining municipal managers’ attitudinal and behavioral willingness. It further suggests that environmental and organizational factors tend to enhance municipal managers’ public responsiveness (1) through institutional constraints; (2) through enhancing their perceived behavioral control.Ph. D.Includes bibliographical referencesIncludes vitaby Yuguo Lia

How does council–manager conflict affect managerial turnover intention? The role of job embeddedness and cooperative context

Turnover intention is an important yet underexamined concept in local government studies. Although the association between council–manager conflict and managerial turnover intention is well documented, the underlying mechanisms have not yet been elucidated. This study fills this research gap by analysing two variables in the relationship: organizational job embeddedness and cooperative context. Results from partial least squares structural equation modelling (PLS‐SEM) reveal that organizational job embeddedness mediates the link between task conflict and managerial turnover intention. The results also indicate that a cooperative context can moderate the negative indirect relationship between council–manager task conflict and managerial turnover intention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163796/1/padm12663_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163796/2/padm12663.pd

High Expressions of Notch and Survivin in Elderly Patients with Glioma Contribute to an Unfavorable Prognosis

Gliomas account for 24% of all primary brain and central nervous system tumors. To date, elderly patients constitute 10-25% of patients with a diagnosis of glioblastoma multiforme, but limited attention has been put on their optimal treatment, largely due to a very poor expected survival (only 4-6 months). Unraveling the molecular mechanism of gliomas provides an opportunity to develop novel biomarkers and therapeutic targets. In this study, we collected fasting blood samples from elderly patients diagnosed with glioma and who received treatment in our hospital between May 2016 and May 2019 and determined the expression levels of Notch and Survivin proteins in different clinical stages and their relationship with patient survival. A total of 68 healthy volunteers in this hospital during the same period served as healthy controls. Compared with the healthy controls, the expressions of Notch 1, Notch 2, Notch 3, and Survivin protein in the serum of elderly glioma patients were remarkably increased (P<0.05), but the expression of caspase-3 protein declined (P<0.05). As the clinical stage of the patient advanced, the expressions of Notch 1, Notch 2, Notch 3, and Survivin increased, and this increase was statistically significant (P<0.05). It was observed that high expressions of serum Notch 1, Notch 2, Notch 3, and Survivin were associated with poor overall survival of elderly patients with glioma. We used γ-secretase inhibitor MRK-003 and specific ligand Jagged1 to alter the Notch pathway in U251 cells. It was revealed that MRK-003 incubation effectively suppressed the mRNA expression of Survivin in U251 cells, but Jagged1 stimulation significantly promoted the mRNA expression of Survivin in U251 cells. Results of MTT and transwell migration assays revealed reduced U251 cell viability and migration following MRK-003 treatment and enhanced cell viability and migration following Jagged1 stimulation. In conclusion, the finding obtained from these results supports that Notch and Survivin proteins contribute to the development of glioma in elderly patients and could serve as prognostic factors

Trimester-specific reference intervals for hemoglobin A1c in non-diabetic pregnancy in a Chinese population

Abstract Background Physiological glycated hemoglobin (HbA1c) values in each trimester are not well defined. This study aimed to determine trimester-specific reference intervals for HbA1c levels in non-diabetic pregnant women in China. Methods In this cross-sectional study, 5,042 Chinese pregnant women from 6 to 41 weeks of gestation were screened. An inclusion of 4,134 non-diabetic women was made to determine the reference intervals, they were divided into three trimesters: trimester 1 (T1), 6 weeks to 13 weeks + 6 days, trimester 2 (T2), 14 weeks to 27 weeks + 6 days, and trimester 3 (T3), 28 weeks to 41 weeks + 6 days. A total of 4,134 women (T1 n = 760, T2 n = 1,953, and T3 n = 1,421) provided blood samples which were analyzed for HbA1c concentrations. HbA1c was measured using high-performance liquid chromatography. The median and percentile (2.5th to 97.5th) for the HbA1c reference intervals were calculated for each trimester. Results In total, 8,732 HbA1c measurements were taken. Reference intervals for HbA1c expressed as median and percentile (2.5th to 97.5th) for each trimester were: T1: 4.7 (4.0–5.5%), T2: 4.5 (3.9–5.3%), and T3: 4.8 (4.1–5.7%) respectively. The HbA1c levels were significantly lower in the second trimester compared to those in the first trimester (p < 0.0001), and higher in the third trimester compared to the second trimester (p < 0.0001). Conclusions The reference intervals for HbA1c levels were 3.9–5.7% with upper limits of 5.5% in the first trimester, 5.3% in the second trimester, and 5.7% in the third trimester. These findings highlight the importance of considering trimester-specific reference intervals for HbA1c in non-diabetic pregnant women to promote maternal and fetal health

Additional file 1 of Social support and cognitive activity and their associations with incident cognitive impairment in cognitively normal older adults

Supplementary Material

microsatellites data for Bayesass

input file of bayesass (neutral loci

Data from: Are habitat fragmentation, local adaptation and isolation by distance driving population divergence in wild rice Oryza rufipogon?

Habitat fragmentation weakens the connection between populations and is accompanied with isolation by distance (IBD) and local adaptation (isolation by adaptation, IBA), both leading to genetic divergence between populations. To understand the evolutionary potential of a population and to formulate proper conservation strategies, information on the roles of IBD and IBA in driving population divergence is critical. The putative ancestor of Asian cultivated rice (Oryza sativa) is endangered in China due to habitat loss and fragmentation. We investigated the genetic variation in 11 Chinese Oryza rufipogon populations using 79 microsatellite loci to infer the effects of habitat fragmentation, IBD and IBA on genetic structure. Historical and current gene flows were found to be rare (mh = 0.0002–0.0013, mc = 0.007–0.029), indicating IBD and resulting in a high level of population divergence (FST = 0.343). High within-population genetic variation (HE = 0.377–0.515), relatively large effective population sizes (Ne = 96–158), absence of bottlenecks and limited gene flow were found, demonstrating little impact of recent habitat fragmentation on these populations. Eleven gene-linked microsatellite loci were identified as outliers, indicating local adaptation. Hierarchical AMOVA and partial Mantel tests indicated that population divergence of Chinese O. rufipogon was significantly correlated with environmental factors, especially habitat temperature. Common garden trials detected a significant adaptive population divergence associated with latitude. Collectively, these findings imply that IBD due to historical rather than recent fragmentation, followed by local adaptation, has driven population divergence in O. rufipogon