1. |
- Xie, Jiaying, et al.
(author)
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STING activation in TET2-mutated hematopoietic stem/progenitor cells contributes to the increased self-renewal and neoplastic transformation
- 2023
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In: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 37:12, s. 2457-2467
-
Journal article (peer-reviewed)abstract
- Somatic loss-of-function mutations of the dioxygenase Ten-eleven translocation-2 (TET2) occur frequently in individuals with clonal hematopoiesis (CH) and acute myeloid leukemia (AML). These common hematopoietic disorders can be recapitulated in mouse models. However, the underlying mechanisms by which the deficiency in TET2 promotes these disorders remain unclear. Here we show that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is activated to mediate the effect of TET2 deficiency in dysregulated hematopoiesis in mouse models. DNA damage arising in Tet2-deficient hematopoietic stem/progenitor cells (HSPCs) leads to activation of the cGAS-STING pathway which in turn promotes the enhanced self-renewal and development of CH. Notably, both pharmacological inhibition and genetic deletion of STING suppresses Tet2 mutation-induced aberrant hematopoiesis. In patient-derived xenograft (PDX) models, STING inhibition specifically attenuates the proliferation of leukemia cells from TET2-mutated individuals. These observations suggest that the development of CH associated with TET2 mutations is powered through chronic inflammation dependent on the activated cGAS-STING pathway and that STING may represent a potential target for intervention of relevant hematopoietic diseases.
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2. |
- Shao, Linus Ruijin, 1964, et al.
(author)
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From mice to women and back again: Causalities and clues for Chlamydia-induced tubal ectopic pregnancy.
- 2012
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In: Fertility and sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 98:5, s. 1175-85
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Journal article (peer-reviewed)abstract
- To provide an overview of knockout mouse models that have pathological tubal phenotypes after Chlamydia muridarum infection, discuss factors and pathological processes that contribute to inflammation, summarize data on tubal transport and progression of tubal implantation from studies in humans and animal models, and highlight research questions in the field.
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3. |
- Wang, Hao, et al.
(author)
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In-situ growth of low-dimensional perovskite-based insular nanocrystals for highly efficient light emitting diodes
- 2023
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In: Light. - : SPRINGERNATURE. - 2095-5545 .- 2047-7538. ; 12:1
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Journal article (peer-reviewed)abstract
- Regulation of perovskite growth plays a critical role in the development of high-performance optoelectronic devices. However, judicious control of the grain growth for perovskite light emitting diodes is elusive due to its multiple requirements in terms of morphology, composition, and defect. Herein, we demonstrate a supramolecular dynamic coordination strategy to regulate perovskite crystallization. The combined use of crown ether and sodium trifluoroacetate can coordinate with A site and B site cations in ABX(3) perovskite, respectively. The formation of supramolecular structure retard perovskite nucleation, while the transformation of supramolecular intermediate structure enables the release of components for slow perovskite growth. This judicious control enables a segmented growth, inducing the growth of insular nanocrystal consist of low-dimensional structure. Light emitting diode based on this perovskite film eventually brings a peak external quantum efficiency up to 23.9%, ranking among the highest efficiency achieved. The homogeneous nano-island structure also enables high-efficiency large area (1 cm(2)) device up to 21.6%, and a record high value of 13.6% for highly semi-transparent ones.
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4. |
- Wang, Y., et al.
(author)
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The Impact of Different Degrees of Intraventricular Hemorrhage on Mortality and Neurological Outcomes in Very Preterm Infants: A Prospective Cohort Study
- 2022
-
In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
-
Journal article (peer-reviewed)abstract
- ObjectiveIntraventricular hemorrhage (IVH) is a common complication in preterm infants and is related to neurodevelopmental outcomes. Infants with severe IVH are at higher risk of adverse neurological outcomes and death, but the effect of low-grade IVH remains controversial. The purpose of this study was to evaluate the impact of different degrees of IVH on mortality and neurodevelopmental outcomes in very preterm infants. MethodsPreterm infants with a gestational age of ResultsA total of 1,079 preterm infants were included, and 380 (35.2%) infants had grade I-II IVH, 74 (6.9%) infants had grade III-IV IVH, and 625 (57.9%) infants did not have IVH. The mortality in the non-IVH, I-II IVH, and III-IV IVH groups was 20.1, 19.7, and 55.2%, respectively (p < 0.05), and the incidence of neurodevelopmental disabilities was 13.9, 16.1, and 43.3%, respectively (p < 0.05), at 18-24 months of corrected age. After adjusting for confounding factors, preterm infants with III-IV IVH had higher rates of cerebral palsy [26.7 vs. 2.4%, OR = 6.10, 95% CI (1.840-20.231), p = 0.003], disability [43.3 vs. 13.9%, OR = 2.49, 95% CI (1.059-5.873), p = 0.037], death [55.2 vs. 20.1%, OR = 3.84, 95% CI (2.090-7.067), p < 0.001], and disability + death [73.7 vs. 28.7%, OR = 4.77, 95% CI (2.518-9.021), p < 0.001] compared to those without IVH. However, the mortality and the incidence of neurodevelopmental disability in infants with I-II IVH were similar to those without IVH (p > 0.05). ConclusionsSevere IVH but not mild IVH increased the risk of mortality and neurodevelopmental disability in very preterm infants.
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5. |
- Xu, Xiaoqin, et al.
(author)
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Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes
- 2024
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In: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 40:4
-
Journal article (peer-reviewed)abstract
- Objective: Prediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes-related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors.Methods: This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow-up of 14 years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results.Results: We included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5 years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0-1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5-6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5-6 versus 0-1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively.Conclusions: Combined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.
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6. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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7. |
- Cui, Peng, et al.
(author)
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Lack of cyclical fluctuations of endometrial GLUT4 expression in women with polycystic ovary syndrome: Evidence for direct regulation of GLUT4 by steroid hormones
- 2015
-
In: BBA Clinical. - : Elsevier BV. - 2214-6474. ; 4, s. 85-91
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Journal article (peer-reviewed)abstract
- Background Determination of the role of steroid hormones in expression and regulation of endometrial glucose transport 4 (GLUT4) in humans is important for understanding endometrial disorders such as polycystic ovary syndrome (PCOS), a common hormone-imbalance disease. Methods Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia and from PCOS patients with or without hyperplasia. In addition, endometrial tissues from postmenopausal women were incubated with human chorionic gonadotropin (hCG, 10 IU/ml), 17β-estradiol (E2, 10 nM), progesterone (P4, 100 nM), or a combination of E2 and P4 for 24 h. The expression of GLUT4 was measured at the mRNA level using quantitative real-time polymerase chain reaction (qRT-PCR) and at the protein level using Western blot analysis and immunohistochemistry. Results A cyclical change in GLUT4 expression pattern was observed in non-PCOS patients, and a high level of GLUT4 expression was seen in the proliferative phase compared to the secretory phase. Low levels of GLUT4 expression were found in PCOS patients compared to menstrual cycle phase-matched non-PCOS patients, and there was no significant change in GLUT4 expression in PCOS patients during the menstrual cycle. GLUT4 was localized in both epithelial and stromal cells, with notable changes in epithelial cells. We postulate that decreased GLUT4 expression might be regulated by steroid hormones. In support of this, we showed that in cultured endometrial tissues hCG and E2 alone had no effect on GLUT4 expression. However, P4 alone and P4 in combination with E2 decreased GLUT4 expression. Compared with non-PCOS controls, PCOS patients with endometrial hyperplasia exhibited decreased GLUT4 expression in particular in the epithelial cells. Conclusion We conclude that P4 can induce changes in endometrial GLUT4 expression during the menstrual cycle and that abnormal hormonal conditions such as PCOS disrupt normal patterns of GLUT4 expression in endometrial cells.
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8. |
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9. |
- Ekström, Karin, 1978, et al.
(author)
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Monocyte Exosomes Stimulate the Osteogenic Gene Expression of Mesenchymal Stem Cells
- 2013
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
-
Journal article (peer-reviewed)abstract
- Inflammation and regeneration at the implant-bone interface are intimately coupled via cell-cell communication. In contrast to the prevailing view that monocytes/macrophages orchestrate mesenchymal stem cells (MSCs) and progenitor cells via the secretion of soluble factors, we examined whether communication between these different cell types also occurs via exosomes. LPS-stimulated human monocytes released exosomes, positive for CD9, CD63, CD81, Tsg101 and Hsp70, as determined by flow cytometry and Western blot. These exosomes also contained wide size distribution of RNA, including RNA in the size of microRNAs. The exosomes were shown to interact with human mesenchymal stem cells. After 24 h of culture, a considerable portion of the MSCs had internalised PKH67-labelled exosomes. Furthermore, after 72 h, the gene expression of the osteogenic markers runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein-2 (BMP-2) had increased in comparison with control medium, whereas no significant difference in osteocalcin (OC) expression was demonstrated. The present results show that, under given experimental conditions, monocytes communicate with MSCs via exosomes, resulting in the uptake of exosomes in MSCs and the stimulation of osteogenic differentiation. The present observations suggest that exosomes constitute an additional mode of cell-cell signalling with an effect on MSC differentiation during the transition from injury and inflammation to bone regeneration.
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10. |
- Jin, Binghan, et al.
(author)
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Abdominal Adiposity and Total Body Fat as Predictors of Cardiometabolic Health in Children and Adolescents With Obesity
- 2020
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In: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 11
-
Journal article (peer-reviewed)abstract
- Objective:We aimed to assess the role of adipose tissue distribution in cardiometabolic risk (in particular insulin sensitivity) in a population of children and adolescents with obesity. Methods:In this cross-sectional study, participants were 479 children and adolescents with obesity (322 boys and 157 girls) aged 3 to 18 years attending the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China). Clinical assessments included anthropometry, body composition (DXA scans), carotid artery ultrasounds, and OGTT. Insulin sensitivity was assessed using the Matsuda index. Participants were stratified into groups by sex and pubertal stage. Key predictors were DXA-derived android-to-gynoid-fat ratio (A/G) and total body fat percentage (TBF%). Results:Irrespective of sex and pubertal stage, there was a strong association between increasing A/G (i.e., greater abdominal adiposity) and lower insulin sensitivity. In multivariable models, every 0.1 increase in A/G was associated with a reduction in insulin sensitivity in prepubertal boys [-29% (95% CI -36%, -20%);p< 0.0001], pubertal boys [-13% (95% CI -21%, -6%);p= 0.001], and pubertal girls [-16% (95% CI -24%, -6%);p= 0.002]. In contrast, TBF% was not associated with insulin sensitivity when A/G was adjusted for, irrespective of pubertal stage or sex. In addition, every 0.1 increase in A/G was associated with increased likelihood of dyslipidemia in prepubertal boys [adjusted odds ratio (aOR) 1.62 (95% CI 1.05, 2.49)], impaired glucose tolerance in pubertal boys [aOR 1.64 (95% CI 1.07, 2.51)] and pubertal girls [aOR 1.81 (95% CI 1.10, 2.98)], and odds of NAFLD in both prepubertal [aOR 2.57 (95% CI 1.56, 4.21)] and pubertal [aOR 1.69 (95% CI 1.18, 2.40)] boys. In contrast, higher TBF% was only associated with higher fasting insulin and ALT in pubertal boys, being also predictive of NAFLD in this group [aOR 1.15 per percentage point (95% CI 1.06, 1.26)], but was not associated with the likelihood of other cardiometabolic outcomes assessed in any group. Conclusions:A/G is a much stronger independent predictor of cardiometabolic risk factors in children and adolescents with obesity in China, particularly glucose metabolism.
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11. |
- Lan, Yihong, et al.
(author)
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Dynamics of COVID-19 progression and the long-term influences of measures on pandemic outcomes
- 2022
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In: Emerging Themes in Epidemiology. - : BMC. - 1742-7622. ; 19
-
Journal article (peer-reviewed)abstract
- The pandemic progression is a dynamic process, in which measures yield outcomes, and outcomes in turn influence subsequent measures and outcomes. Due to the dynamics of pandemic progression, it is challenging to analyse the long-term influence of an individual measure in the sequence on pandemic outcomes. To demonstrate the problem and find solutions, in this article, we study the first wave of the pandemic—probably the most dynamic period—in the Nordic countries and analyse the influences of the Swedish measures relative to the measures adopted by its neighbouring countries on COVID-19 mortality, general mortality, COVID-19 incidence, and unemployment. The design is a longitudinal observational study. The linear regressions based on the Poisson distribution or the binomial distribution are employed for the analysis. To show that analysis can be timely conducted, we use table data available during the first wave. We found that the early Swedish measure had a long-term and significant causal effect on public health outcomes and a certain degree of long-term mitigating causal effect on unemployment during the first wave, where the effect was measured by an increase of these outcomes under the Swedish measures relative to the measures adopted by the other Nordic countries. This information from the first wave has not been provided by available analyses but could have played an important role in combating the second wave. In conclusion, analysis based on table data may provide timely information about the dynamic progression of a pandemic and the long-term influence of an individual measure in the sequence on pandemic outcomes.
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12. |
- Li, Shuo, et al.
(author)
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Economic and environmental sustainability of maize-wheat rotation production when substituting mineral fertilizers with manure in the North China Plain
- 2020
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In: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 271
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Journal article (peer-reviewed)abstract
- Substituting mineral fertilizers with manure has been promoted to enrich soil fertility and maintain field productivity in agricultural production systems. However, there is limited information regarding the effect of substituting mineral-N with manure on eco-efficiency (economic and environmental trade-offs) from a Life Cycle Assessment (LCA) perspective. This study investigated the eco-efficiency of maize-wheat rotation production under three fertilization strategies: mineral fertilizer NPK (CK), substituting 50% of mineral-N with solid manure (SM + NK), and substituting 50% of mineral-N with liquid manure (LM + NP) in the North China Plain. The economic profits were evaluated based on the prevailing market prices of inputs, outputs, and services. The potential environmental impacts were assessed by the LCA approach. The eco-efficiency was evaluated as the ratio of economic profit to individual environmental impact categories. The results from the economic analysis and the LCA showed that, compared with CK, the economic profit increased by 17.2% and 19.1%, while the environmental impacts at the endpoint level decreased by 24.6% and 37.9% under SM + NK and LM + NP, respectively. Additionally, the eco-efficiencies under SM + NK and LM + NP at the endpoint level were calculated to be 55.4% and 91.7%, respectively, higher than CK. Overall, the results suggested that substituting 50% of mineral-N with manure, especially liquid manure, had a great potential for sustainable maize-wheat rotation production in the North China Plain.
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13. |
- Nawaz, Muhammad, et al.
(author)
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The emerging role of extracellular vesicles as biomarkers for urogenital cancers.
- 2014
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In: Nature reviews. Urology. - : Springer Science and Business Media LLC. - 1759-4820 .- 1759-4812. ; 11, s. 688-701
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Journal article (peer-reviewed)abstract
- The knowledge gained from comprehensive profiling projects that aim to define the complex genomic alterations present within cancers will undoubtedly improve our ability to detect and treat those diseases, but the influence of these resources on our understanding of basic cancer biology is still to be demonstrated. Extracellular vesicles have gained considerable attention in past years, both as mediators of intercellular signalling and as potential sources for the discovery of novel cancer biomarkers. In general, research on extracellular vesicles investigates either the basic mechanism of vesicle formation and cargo incorporation, or the isolation of vesicles from available body fluids for biomarker discovery. A deeper understanding of the cargo molecules present in extracellular vesicles obtained from patients with urogenital cancers, through high-throughput proteomics or genomics approaches, will aid in the identification of novel diagnostic and prognostic biomarkers, and can potentially lead to the discovery of new therapeutic targets.
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14. |
- Paolini, Lucia, et al.
(author)
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Large-scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop
- 2022
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In: Journal of Extracellular Biology. - : Wiley. - 2768-2811. ; 1:10
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Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles from a natural source for tailor-made nanomaterials” (VES4US), organized a workshop entitled “massivEVs” to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during “massivEVs”, the most important points raised, and the points of consensus reached after discussion among academia and industry representatives. Overall, the review of the existing EV manufacturing, upscaling challenges and directions for their resolution highlighted in the workshop painted an optimistic future for the expanding EV field.
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15. |
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16. |
- Shao, Linus Ruijin, 1964, et al.
(author)
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Coordinate regulation of heterogeneous nuclear ribonucleoprotein dynamics by steroid hormones in the human Fallopian tube and endometrium in vivo and in vitro.
- 2012
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 302:10
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Journal article (peer-reviewed)abstract
- Heterogeneous nuclear ribonucleoproteins (hnRNPs), chromatin-associated RNA-binding proteins, participate in mRNA stability, transport, intracellular localization, and translation by acting as transacting factors. Several studies have shown that steroid hormones can regulate hnRNP expression. However, to date, the regulation of hnRNPs and their interactions with steroid hormone signaling in Fallopian tubes and endometrium are not fully elucidated. In the present study, we determined whether hnRNP expression is regulated during the menstrual cycle and correlates with estrogen receptor (ER) and progesterone receptor (PR) levels in human Fallopian tubes in vivo. Due to the limited availability of human tubal tissues for the research, we also explored the mechanisms of hnRNP regulation in human endometrium in vitro. Fallopian tissue was obtained from patients in early, late, and postovulatory phases and mid-secretory phase, and endometrial tissue from premenopausal and postmenopausal women undergoing hysterectomy. We measured expression of hnRNPs and assessed their intracellular localization and interactions with ERs and PRs. We also determined the effects of human chorionic gonadotropin, 17β-estradiol (E2), and progesterone (P4) on hnRNP expression. In Fallopian tubes, mRNA and protein levels of hnRNP A1, AB, D, G, H, and U changed dynamically during ovulation and in the mid-secretory phase. In coimmunolocation and coimmunoprecipitation experiments, hnRNPs interacted with each other and with ERs and PRs in Fallopian tubes. After treatment with E2 and/or P4 to activate ERs and PRs, hnRNP A1, AB, D, G, and U proteins displayed overlapping but distinct patterns of regulation in the endometrium in vitro. Our findings expand the physiological repertoire of hnRNPs in human Fallopian tubes and endometrium and suggest that steroid hormones regulate different hnRNPs directly by interacting with ERs and/or PRs or indirectly by binding other hnRNPs. Both actions may contribute to regulation of gene transcription.
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17. |
- Shao, Linus Ruijin, 1964, et al.
(author)
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Revealing the Hidden Mechanisms of Smoke-Induced Fallopian Tubal Implantation.
- 2012
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In: Biology of reproduction. - : Oxford University Press (OUP). - 1529-7268 .- 0006-3363. ; 86:4
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Journal article (peer-reviewed)abstract
- Ectopic pregnancy (EP) is an enigmatic reproductive disorder. Although tubal EP is difficult to predict, several hypotheses about its etiology have been proposed. In retrospective case-control studies, smoking is associated with an increased rate of EPs in the Fallopian tube. Studies of experimental animals in vivo and human Fallopian tubal tissues in vitro have suggested mechanisms of Fallopian tubal damage and dysfunction induced by nicotine and other smoking-related chemicals that may explain this association. However, the pathogenesis of smoking-induced modulation of implantation leading to tubal EP is largely unknown. Since cigarette/tobacco smoke adversely affects the success of intrauterine implantation, there is a great need to determine how embryo implantation occurs in the Fallopian tube in female smokers of reproductive age.
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18. |
- Vazirisani, Forugh, 1967, et al.
(author)
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Extracellular vesicles from gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis induce a strong inflammatory response and cell death in vitro
- 2016
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In: ISEV 2016, Rotherdam, Netherlands.
-
Conference paper (other academic/artistic)abstract
- The majority of biomaterial-associated infections (BAI) are caused by S.aureus and S.epidermidis. Bacterial extracellular vesicles (EVs) are involved in the delivery of toxins and bacterial components to host cells. It is therefore of relevance to investigate if the EVs from these bacterial species have a role in BAI. The aim of the present study was: i) to investigate whether clinical strains from S. aureus and S. epidermidis, isolated from osteomyelitis associated with bone-anchored amputation prosthesis, release EVs, ii) to study the biological effects of these EVs on monocytes and iii) to evaluate the effect of these EVs on the secretion of pro-inflammatory substances by monocytes. Material & Methods EVs were isolated from S. aureus 64516 and S. epidermidis 64518 cultures. The collected EVs were characterized by Western blot. Human primary monocytes were stimulated by different concentrations of EVs (0, 5, 10 and 50 µg/ml). After 24 h, cell death was evaluated using propidium iodide in a nucleocounter and further, levels of IL-8, IL-6, TNF-α, MCP-1 and MMP-9 were determined by ELISA. Results The two staphylococcal strains secreted EVs in vitro. Both types of EVs contained δ-toxin whereas protein A and SCP-A were only detected in S. aureus EVs. The monocyte viability was reduced in a dose-dependent manner after incubation with EVs. More than 50 % of monocytes died with 5 µg S. aureus EVs. The S. epidermidis EVs had relatively less toxic effects. Stimulation of monocytes with S. aureus and S. epidermidis EVs significantly increased the release of IL-8, IL-6, TNF-α, MCP-1 and MMP-9. Conclusion The results from this study show that clinical pathogens causing BAI have the ability to secrete EVs in vitro. The EVs promote pro-inflammatory cytokine release from human monocyte and subsequent cell death. It is suggested that EVs contribute to the inflammation and injury associated with biomaterials-associated infection.
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19. |
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20. |
- Wang, Shuping, 1987, et al.
(author)
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Alkali-activated slag foamed concrete with lightweight glass aggregates
- 2015
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In: Proceedings of the 14th International Congress on the Chemistry of Cement, Beijing, China.
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Conference paper (peer-reviewed)abstract
- Alkali activated slag foamed concrete (AASFC) is considered as an environmentally friendly lightweight cementitious material alternatives to similar materials based on Portland cement. However, due to the lack of understanding of important properties, the use of this type of materials is still very limited. The purpose of the study is to design alkali-activated slag foam concretes with bulk densities in the range of 300- 1100 kg m-3 and thermal conductivities ranging from 0.1 to 0.35 W m-1 K-1. Properties, such as consistency, mechanical strength, drying shrinkage and thermal conductivity, were investigated. In addition, two types of lightweight glass aggregates were used for improving the properties and to reduce the amount of paste in the material. The results shows that the wet bulk density of the AASFC is consistent with the designed value if prepared with suitable volume of foam and water/slag ratio. For these materials, the compressive strength is between 0.1 and 7 MPa and the thermal conductivity ranges from 0.09 to 0.35 W m-1K-1. However, the foam concretes display quite huge drying shrinkage. Furthermore, it is shown that the use of lightweight glass aggregates (LGA) in AASFC can reduce the amount of paste by 50% (by volume) without any negative influence on mechanical properties, although the concretes showed poorer flowability. The aggregates are also beneficial to lower the thermal conductivity and to improve the resistance of drying shrinkage. The expanded LGA showed better effect on both the consistency and the hardened properties of the material than the simply foamed LGA.
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21. |
- Wang, Shuping, 1987, et al.
(author)
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Contact-hardening behavior of calcium silicate hydrate powders
- 2018
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In: Materials. - : MDPI AG. - 1996-1944. ; 11:12
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Journal article (peer-reviewed)abstract
- Calciumsilicate hydrate (C-S-H) synthesized by a hydrothermal process fromlime and siliceous materials was oven-dried and compressed into compacts. The microstructure and compaction properties of the resulting powderswere characterized. The results showthat the powders containing an amorphous structure become hardened compacts immediately after compression. Compacts with high strength but a relatively lower bulk density were produced. Amorphous C-S-H plays a key role in the bonding formation during powder compaction. According to the Heckel plots, particle rearrangement and plastic deformation were involved in the compaction of C-S-H powders. Point contact between C-S-H particles due to particle rearrangement dominates at a low compression pressure (i.e., < 20MPa). Van derWaals forces and hydrogen bonding are the main bonding types. Plastic deformation occurs at a higher compression pressure (i.e., > 60MPa), which results in surface contact. Consequently, a solid bridge forms, and the strength of compacts increases rapidly. These findings provide novel insight into the utilization of materials containing amorphous calcium silicate hydrate.
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22. |
- Wang, Shuping, 1987, et al.
(author)
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High-strength lightweight blocks prepared from the by-product of aluminium removed from fly ash
- 2014
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In: Proceedings of International Symposium on Eco-Crete – Environmentally Friendly Concrete, 13 - 15 August 2014, Reykjavik Iceland. ; , s. 29-36
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Conference paper (peer-reviewed)abstract
- A large amount of powder by-product is generated when Al2O3 is extracted from fly ash. The purpose of this study is to investigate the properties of the powder and find an effective method to reuse it. XRF, XRD, and SEM were used to analysis its compositions and microstructures. The powder was then compressed at the pressure of from 20 to 100 MPa. Results show that the powder was disordered calcium silicate hydrate with an average Ca/Si molar ratio of 1.08. It becomes hardened blocks by compressing. The bulk density of the hardened blocks is between 500 and 800 kg m-3 corresponding to the pressure of 20 to 60 MPa. Their flexible strength is from 1.60 to 5.35 MPa, and compressive strength from 8.50 to 30.50 MPa. The blocks can be recycled by repeating the procedure of crushing blocks, grinding them into powder, and compressing the powder into hardened blocks. This powder can be sustainably reused to prepare lightweight blocks with high strength.
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23. |
- Wang, Shuping, 1987, et al.
(author)
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Influence of drying conditions on the contact-hardening behaviours of calcium silicate hydrate powder
- 2017
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In: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 136, s. 465-473
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Journal article (peer-reviewed)abstract
- Contact-hardening is a new type of binding property for amorphous calcium silicate hydrate (C-S-H) withwhich a hardened specimen can be prepared in a few minutes by compressing C-S-H powders directly.However, the relation between contact-hardening behaviours and the drying conditions of powders isstill poorly understood. In this study, the influence of air-drying and oven-drying on the physical propertiesand microstructure of hydrothermally synthesised C-S-H powders were investigated. The results provide further insight into the contact-hardening behaviours of these powders by measuring the bulk density, mechanical strength and water-resistant properties of the compacts. Factors affecting particleparticle contact and hardening of C-S-H powders are discussed in parallel with the mechanical properties and microstructure of the compacts. The result highlights that the moisture content, which is highly related to the drying conditions, is essential to contact hardening of C-S-H.
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24. |
- Wang, Shuping, 1987, et al.
(author)
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Influence of inorganic admixtures on the 11 angstrom-tobermorite formation prepared from steel slags: XRD and FTIR analysis
- 2014
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In: Construction and Building Materials. - : Elsevier BV. - 0950-0618 .- 1879-0526. ; 60, s. 42-47
-
Journal article (peer-reviewed)abstract
- Calcium silicate hydrate is synthesized from steel slag by adding lime and quartz by dynamic hydrothermal method at 185 degrees C. The products mainly consist of disordered calcium silicate hydrate, but more crystallized phase such as 11 angstrom-tobermorite forms for the presence of inorganic admixtures. The formation of tobermorite is affected by the types of ions according to XRD and FTIR results. Adding 2% crystallized tobermorite is beneficial to form the ordered structure; alkali cations and SO42- anions are effective accelerators; Al3+ plays a role of stabilization during the reaction. The products also vary with the initial alkalinities of steel slag.
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25. |
- Wang, Shuping, 1987, et al.
(author)
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Influence of moisture content on the contact-hardening properties of calcium silicate hydrate by direct compression
- 2021
-
In: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 278
-
Journal article (peer-reviewed)abstract
- The purpose of this study is to investigate the influence of moisture content on the contact-hardening properties of calcium silicate hydrate. The materials with moisture content ranging from 0 to 76% were directly compressed at the pressure of 40 MPa for three minutes to produce solid compacts. Bulk density, mechanical strength and water-resistant property of the compacts were measured, and temperature evolution of the powders during compaction was evaluated. An obvious increase in bulk density of compacts but a slight decrease in compressive strength was found with moisture content increased up to approximately 25%, ascribed to the lubricant effect of water films on the surface of particles that facilitates the rearrangement and spillage of particles. Moisture could reduce the temperature evolution by reducing surface energy of the particles, and separate the interparticulate bonding. Consequently, for the material with moisture content higher than 25%, the bulk density of the compacts was almost constant, but the compressive strength decreased dramatically. Different tendency was observed in the flexural strength that the value increased with moisture content increased up to 11%, attributed to the consolidation of particles and formation of hydrogen bonding, and the water- resistant property of the compacts was also improved. Subsequent decrease in flexural strength was due to the disruption of hydrogen bonding.
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26. |
- Wang, Shuping, 1987, et al.
(author)
-
Pb2+ adsorption by calcium silicate hydrate synthesized from steel slag
- 2015
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In: Nordic Concrete Research. - 0800-6377. ; 52, s. 77-92
-
Journal article (peer-reviewed)abstract
- This study aims to investigate the adsorption properties of Pb2+ by calcium silicate hydrate synthesized from steel slag. The influence of various factors on the adsorption properties was investigated. The static desorption test was conducted to investigate the leaching of Pb2+. The kinetic model and isotherm model of adsorption are then discussed. Results show that Pb2+ adsorption capacity of C-S-H depends on Ca/Si ratios. Kinetic adsorption data is in consistence with Lagegren pseudo-second-order model, and steady-state data fits to Langmuir isothermal model. Leaching result demonstrates that Pb2+ ions are stably adsorbed by C-S-H structures.
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27. |
- Wang, Shuping, 1987, et al.
(author)
-
Temperature evolution during the compaction of calcium silicate hydrate powders using a compression calorimeter
- 2020
-
In: Journal of Thermal Analysis and Calorimetry. - : Springer Science and Business Media LLC. - 1388-6150 .- 1588-2926. ; 139:2, s. 863-875
-
Journal article (peer-reviewed)abstract
- Amorphous calcium silicate hydrate (CSH) undergoes contact-hardening property, i.e. the powder can be hardened by compression. A compression calorimeter was designed to determine the temperature evolution during the compaction of the powder. A platinum sensor (Pt100) was used as the temperature sensor and was positioned in the powder as well as in the compression die. A resolution of 0.01 °C with a sampling time of every second was used to monitor the temperature. Both theoretical calculation and simulations by COMSOL multiphysics showed that the device reliably evaluated the temperature during the compaction of CSH powders. The measurement was taken under semi-adiabatic conditions. The temperature profiles obtained from the measurement revealed the compression process and bonding development during the compaction of the powders. Finally, a linear relationship was observed between the compressive strength and the maximum temperature increase. This provides insight into the contact-hardening mechanism during the compaction of CSH powders.
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28. |
- Wang Shuping,, et al.
(author)
-
Influence of Hydrothermal Synthesis Conditions on the Formation of Calcium Silicate Hydrates: from Amorphous to Crystalline Phases
- 2018
-
In: Journal Wuhan University of Technology, Materials Science Edition. - : Springer Science and Business Media LLC. - 1993-0437 .- 1000-2413. ; 33:5, s. 1150-1158
-
Journal article (peer-reviewed)abstract
- Hydrothermal treatment has been widely applied in the synthesis of well crystalline calcium silicate hydrate (CSH), such as tobermorite and xonotlite. However, both morphology and crystallinity of CSH are greatly affected by the conditions of hydrothermal treatment including siliceous materials, temperature increase rate and isothermal periods. In this study, the influence of hydrothermal conditions on the growth of nano-crystalline CSH was investigated based on XRD analysis. Results showed that siliceous materials with amorphous nature (i e, nano silica powder) are beneficial to synthesize pure amorphous CSH, while the use of more crystallized siliceous materials (i e, diatomite and quartz powder) leads to producing crystalline CSH. Results also indicate that the formation of tobermorite and xonotlite is greatly affected by the temperature rise rate during hydrothermal treatment.
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29. |
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30. |
- Wang, Xiaoqin
(author)
-
Analyticity theorems for parameter-dependent currents
- 1991
-
In: Mathematica Scandinavica. - 0025-5521 .- 1903-1807. ; 69:2, s. 179-198
-
Journal article (peer-reviewed)abstract
- Plurisubharmonic functions of two groups of complex variables (x1,...,x(n)) and (a1,...,a(m)) are considered; their partial functions are defined by f(a)(x) = f(x, a). We discuss analyticity theorems for the level sets associated to Lelong numbers of the parameter-dependent currents dd(c)f(a).
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31. |
- Wang, Xiaoqin, Docent, 1963-, et al.
(author)
-
Estimating and testing the influence of early diagnosis on cancer survival via point effects of diagnoses and treatments
- 2022
-
In: Statistical Methods in Medical Research. - : Sage. - 0962-2802 .- 1477-0334. ; 31:8, s. 1538-1548
-
Journal article (peer-reviewed)abstract
- A cancer diagnosis is part of a complex stochastic process, which involves patient's characteristics, diagnosing methods, an initial assessment of cancer progression, treatments and a certain outcome of interest. To evaluate the performance of diagnoses, one needs not only a consistent estimation of the causal effect under a specified regime of diagnoses and treatments but also reliable confidence interval, P-value and hypothesis testing of the causal effect. In this article, we identify causal effects under various regimes of diagnoses and treatments by the point effects of diagnoses and treatments and thus are able to estimate and test these causal effects by estimating and testing point effects in the familiar framework of single-point causal inference. Specifically, using data from a Swedish prognosis study of stomach cancer, we estimate and test the causal effects on cancer survival under various regimes of diagnosing and treating hospitals including the optimal regime. We also estimate and test the modification of the causal effect by age. With its simple setting, one can readily extend the example to a large variety of settings in the area of cancer diagnosis: different personal characteristics such as family history, different diagnosing procedures such as multistage screening, and different cancer outcomes such as cancer progression.
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32. |
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33. |
- Wang, Xiaoqin, et al.
(author)
-
Exosomes influence the behavior of human mesenchymal stem cells on titanium surfaces.
- 2020
-
In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 230
-
Journal article (peer-reviewed)abstract
- Mesenchymal stem cells (MSCs) have important roles during osseointegration. This study determined (i) if MSC-derived extracellular vesicles (EVs)/exosomes can be immobilized on titanium (Ti) surfaces and influence the behavior of MSCs, (ii) if the response is differentially affected by EVs from expanded vs differentiated MSCs and (iii) if the EV protein cargos predict the functional features of the exosomes. EVs secreted by human adipose-derived MSCs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis, Western blotting and relative quantitative mass spectrometry. Fluorescence microscopy, scanning electron microscopy, cell counting assay and quantitative polymerase chain reaction were used to analyze MSC adhesion, proliferation and differentiation. Exosome immobilization on Ti promoted MSC adhesion and spreading after 24h and proliferation after 3 and 6 days, irrespective of whether the exosomes were obtained from expansion or differentiation conditions. Immobilized exosomes upregulated stromal cell-derived factor (SDF-1α) gene expression. Cell adhesion molecules and signaling molecules were abundant in the exosomal proteome. The predicted functions of the equally-abundant proteins in both exosome types were in line with the observed biological effects mediated by the exosomes. Thus, exosomes derived from MSCs and immobilized on Ti surfaces interact with MSCs and rapidly promote MSC adhesion and proliferation. These findings provide a novel route for modification of titanium implant surfaces.
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34. |
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35. |
- Wang, Xiaoqin, 1963-, et al.
(author)
-
Identifying and estimating net effects of treatments in sequential casual inference
- 2015
-
In: Electronic Journal of Statistics. - 1935-7524. ; 9, s. 1608-1643
-
Journal article (peer-reviewed)abstract
- Suppose that a sequence of treatments are assigned to influence an outcome of interest that occurs after the last treatment. Between treatments, there are time-dependent covariates that may be post-treatment variables of the earlier treatments and confounders of the subsequent treatments. In this article, we study identification and estimation of the net effect of each treatment in the treatment sequence. We construct a point parametrization for the joint distribution of treatments, time-dependent covariates and the outcome, in which the point parameters of interest are the point effects of treatments considered as single-point treatments. We identify net effects of treatments by their expressions in terms of point effects of treatments and express patterns of net effects of treatments by constraints on point effects of treatments. We estimate net effects of treatments through their point effects under the constraint by maximum likelihood and reduce the number of point parameters in the estimation by the treatment assignment condition. As a result, we obtain an unbiased consistent maximum-likelihood estimate for the net effect of treatment even in a long treatment sequence. We also show by simulation that the interval estimation of the net effect of treatment achieves the nominal coverage probability.
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36. |
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37. |
- Wang, Xiaoqin, 1963-, et al.
(author)
-
Measuring and estimating the interaction between exposures on a dichotomous outcome for observational studies
- 2017
-
In: Journal of Applied Statistics. - : Informa UK Limited. - 0266-4763 .- 1360-0532. ; 44:14, s. 2483-2498
-
Journal article (peer-reviewed)abstract
- In observational studies for the interaction between exposures on a dichotomous outcome of a certain population, usually one parameter of a regression model is used to describe the interaction, leading to one measure of the interaction. In this article we use the conditional risk of an outcome given exposures and covariates to describe the interaction and obtain five different measures of the interaction, that is, difference between the marginal risk differences, ratio of the marginal risk ratios, ratio of the marginal odds ratios, ratio of the conditional risk ratios, and ratio of the conditional odds ratios. These measures reflect different aspects of the interaction. By using only one regression model for the conditional risk, we obtain the maximum-likelihood (ML)-based point and interval estimates of these measures, which are most efficient due to the nature of ML. We use the ML estimates of the model parameters to obtain the ML estimates of these measures. We use the approximate normal distribution of the ML estimates of the model parameters to obtain approximate non-normal distributions of the ML estimates of these measures and then confidence intervals of these measures. The method can be easily implemented and is presented via a medical example.
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38. |
- Wang, Xiaoqin, 1963-, et al.
(author)
-
Measuring and estimating treatment effect on dichotomous outcome of a population
- 2016
-
In: Statistical Methods in Medical Research. - : SAGE Publications. - 0962-2802 .- 1477-0334. ; 25:5, s. 1779-1790
-
Journal article (peer-reviewed)abstract
- In different studies for treatment effect on dichotomous outcome of a certain population, one uses different regression models, leading to different measures of the treatment effect. In observational studies, the common measures of the treatment effect are the conditional risk ratio based on a log-linear model and the conditional odds ratio based on a logistic model; in randomized trials, the common measures are the marginal risk difference based on a linear model, the marginal risk ratio based on a log-linear model, and the marginal odds ratio based on a logistic model. In this paper we express these measures in terms of the risk of a dichotomous outcome conditional on covariates and treatment, where the risk is described by a regression model. Therefore these measures do not explicitly depend on the regression model. As a result, we are able to use one regression model in one study to estimate all these measures by their maximum likelihood estimates. We show that these measures have causal interpretations and reflect different aspects of the same underlying treatment effect under the assumption of no unmeasured confounding covariate given observed covariates. We construct approximate distributions of the maximum likelihood estimates of these measures and then by using the approximate distributions we get confidence intervals for these measures. As an illustration, we estimate these measures for the effect of a triple therapy on eradication of Helicobacter pylori among Vietnamese children and are able to compare the treatment effect in this study with those in other studies.
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39. |
- Wang, Xiaoqin, et al.
(author)
-
Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation
- 2018
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:2
-
Journal article (peer-reviewed)abstract
- Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative effects, but their role in osteogenesis and the underlying mechanism are yet to be determined. In this study, we examined the time-course secretion of exosomes by hMSCs during the entire process of osteogenic differentiation. Exosomes derived from hMSCs in various stages of osteogenic differentiation committed homotypic cells to differentiate towards osteogenic lineage, but only exosomes from late stages of osteogenic differentiation induced extracellular matrix mineralisation. Exosomes from expansion and early and late stages of osteogenic differentiation were internalised by a subpopulation of hMSCs. MicroRNA profiling revealed a set of differentially expressed exosomal microRNAs from the late stage of osteogenic differentiation, which were osteogenesis related. Target prediction demonstrated that these microRNAs enriched pathways involved in regulation of osteogenic differentiation and general mechanisms how exosomes exert their functions, such as "Wnt signalling pathway" and "endocytosis". Taken together, the results show that MSCs secrete exosomes with different biological properties depending on differentiation stage of their parent cells. The exosomal cargo transferred from MSCs in the late stage of differentiation induces osteogenic differentiation and mineralisation. Moreover, it is suggested that the regulatory effect on osteogenesis by exosomes is at least partly exerted by exosomal microRNA.
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40. |
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41. |
- Wang, Xiaoqin, et al.
(author)
-
Mesenchymal stem cell-derived small extracellular vesicles and bone regeneration
- 2021
-
In: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 128:1, s. 18-36
-
Journal article (peer-reviewed)abstract
- Mesenchymal stem cells (MSCs) and MSC-derived small extracellular vesicles (sEVs) are promising candidates for cell-based and cell-free regenerative medicine, respectively. By virtue of their multiple lineage differentiation capacity, MSCs have been implicated as an ideal tool for bone and cartilage regeneration. However, later observations attributed such regenerative effects to MSC-secreted paracrine factors. Exosomes, endosomal originated sEVs carrying lipid, protein and nucleic acid cargoes, were identified as components of the MSC secretome and propagated the key regenerative and immunoregulatory characteristics of parental MSCs. Here, exosome biogenesis, the molecular composition of exosomes, sEV-cell interactions and the effects on key bone homeostasis cells are reviewed. MSC-derived sEVs show to promote neovascularization and bone and cartilage regeneration in preclinical disease models. The mechanisms include the transfer of molecules, including microRNAs, mRNAs and proteins, to other key cells. MSC-derived sEVs are interesting candidates as biopharmaceuticals for drug delivery and for the engineering of biologically functionalized materials. Although major exploratory efforts have been made for therapeutic development, the secretion, distribution and biological effects of MSC-derived sEVs in bone and cartilage regeneration are not fully understood. Moreover, techniques for high-yield production, purity and storage need to be optimized before effective and safe MSC-derived sEVs therapies are realized.
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42. |
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43. |
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44. |
- Wang, Xiaoqin, Docent, 1963-, et al.
(author)
-
New g-formula for the sequential causal effect and blip effect of treatment in sequential causal inference
- 2020
-
In: Annals of Statistics. - 0090-5364 .- 2168-8966. ; 48:1, s. 138-160
-
Journal article (peer-reviewed)abstract
- In sequential causal inference, two types of causal effects are of practical interest, namely, the causal effect of the treatment regime (called the sequential causal effect) and the blip effect of treatmenton on the potential outcome after the last treatment. The well-known G-formula expresses these causal effects in terms of the standard paramaters. In this article, we obtain a new G-formula that expresses these causal effects in terms of the point observable effects of treatments similar to treatment in the framework of single-point causal inference. Based on the new G-formula, we estimate these causal effects by maximum likelihood via point observable effects with methods extended from single-point causal inference. We are able to increase precision of the estimation without introducing biases by an unsaturated model imposing constraints on the point observable effects. We are also able to reduce the number of point observable effects in the estimation by treatment assignment conditions.
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45. |
- Wang, Xiaobao, et al.
(author)
-
Numerical evaluation and optimization of volatiles distributors with different configurations for biomass chemical looping combustion
- 2024
-
In: Chemical Engineering Journal. - 1385-8947. ; 495
-
Journal article (peer-reviewed)abstract
- The rapid devolatilization of biomass in chemical looping combustion could form a local plume of volatiles, reducing contact between volatiles and oxygen carriers and thus lowering gas conversion. Hence, a novel concept called volatiles distributor (VD) has been recently proposed to enhance the mixing between the volatiles and oxygen carriers. However, the configurations of VD have significant effects on its performance. To optimize the configurations of VD, the impact of VD with different configurations has been investigated with respect to the mixing behaviors and the pathways of volatiles in this work using computational fluid dynamics (CFD) modeling with an Eulerian-Eulerian two-fluid model coupled with a two-step EMMS/bubbling drag model. Comparison to experimental results from a cold-flow fluidized bed demonstrates that the CFD model can provide quantitative predictions for the vertical pressure profiles and reasonable trends of horizontal gas distributions of the fluidized bed under various conditions. Conditions varied were the superficial gas velocity, the percentage of the simulated volatiles, primary air distributor, and configurations of VD. The CFD simulations of both original and new designs reveal that the performance of the VD can be improved by reducing the open area of the distribution holes of the VD near the injection port and increasing it further away from the injection port. An optimal configuration is proposed to achieve an even distribution of volatiles and avoid the leakage of volatiles from the bottom of the VD.
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46. |
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47. |
- Wang, Xiaoqin, 1963-, et al.
(author)
-
Point and interval estimation of baseline risk and treatment effect based on logistic model for observational studies
- 2015
-
In: Biometrical Journal. - : Wiley. - 0323-3847 .- 1521-4036. ; 57:3, s. 441-452
-
Journal article (peer-reviewed)abstract
- In observational studies with dichotomous outcome of a population, researchers usually report treatment effect alone, although both baseline risk and treatment effect are needed to evaluate the significance of the treatment effect to the population. In this article, we study point and interval estimates including confidence region of baseline risk and treatment effect based on logistic model, where baseline risk is the risk of outcome of the population under control treatment while treatment effect is measured by the risk difference between outcomes of the population under active versus control treatments. Using approximate normal distribution of the maximum-likelihood (ML) estimate of the model parameters, we obtain an approximate joint distribution of the ML estimate of the baseline risk and the treatment effect. Using the approximate joint distribution, we obtain point estimate and confidence region of the baseline risk and the treatment effect as well as point estimate and confidence interval of the treatment effect when the ML estimate of the baseline risk falls into specified range. These interval estimates reflect nonnormality of the joint distribution of the ML estimate of the baseline risk and the treatment effect. The method can be easily implemented by using any software that generates normal distribution. The method can also be used to obtain point and interval estimates of baseline risk and any other measure of treatment effect such as risk ratio and the number needed to treat. The method can also be extended from logistic model to other models such as log-linear model.
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48. |
- Wang, Xiaoqin, 1963-, et al.
(author)
-
Point and interval estimations of marginal risk difference by logistic model
- 2015
-
In: Communications in Statistics - Theory and Methods. - : Informa UK Limited. - 0361-0926 .- 1532-415X. ; 44:17, s. 3703-3722
-
Journal article (peer-reviewed)abstract
- We use logistic model to get point and interval estimates of the marginal risk difference in observational studies and randomized trials with dichotomous outcome. We prove that the maximum likelihood estimate of the marginal risk difference is unbiased for finite sample and highly robust to the effects of dispersing covariates. We use approximate normal distribution of the maximum likelihood estimates of the logistic model parameters to get approximate distribution of the maximum likelihood estimate of the marginal risk difference and then the interval estimate of the marginal risk difference. We illustrate application of the method by a real medical example.
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49. |
- Wang, Xiaoqin
(author)
-
Regenerative effects of mesenchymal stem cell-derived exosomes
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Mesenchymal stem cells (MSCs) play pivotal roles for bone regeneration by virtue of their osteogenic differentiation ability and immunomodulatory capacity. Recently, secretion of exosomes/extracellular vesicles (EVs) has been suggested as a new mechanism of MSC-based therapy. MSC-derived EVs/exosomes have shown promising effects in tissue regeneration and immunomodulation, which are attributed to their regulatory effects in various processes. The overall objective of this thesis was to explore the cell-to-cell communication and cell-to-material surface interaction mediated by MSC-derived EVs/exosomes. The emphasis was placed on their functions in the regeneration capacity of MSCs and the determination of the microRNA and protein contents of these EVs/exosomes in order to obtain an insight into the underlying mechanisms of the EV-/exosome-mediated biological effects. The results demonstrated that exosomes secreted from MSCs in the mid and late stage of osteogenic differentiation induced osteogenic lineage commitment, but only exosomes from the late differentiation induced the mineralisation of the extracellular matrix. MSC-derived exosomes were internalised by a subpopulation of homotypic cells. The differentially expressed microRNAs were osteogenesis related and predicted to enrich pathways involved in the regulation of osteogenic differentiation and general mechanisms by which exosomes exert their functions. In vitro ageing increased the secretion of EVs and in some contexts altered the protein profiles of EVs. The top abundant proteins in high passage (HP, “aged”) and low passage (LP, “young”) EVs shared similar but not identical functional features with an overlap of the enriched pathways related to endocytosis and regulation of cell proliferation and survival. The differentially expressed proteins in HP EVs were predicted to enrich GO biological process related to transport and secretion. Both HP and LP EVs promoted MSC proliferation in autocrine and paracrine manners and in a dose-dependent fashion. In contrast to MSC-derived exosomes in suspension, exosomes which were immobilised on titanium (Ti) surfaces accelerated and increased MSC adhesion, influenced the early morphology and promoted the growth of MSCs on titanium. Proteomic analysis of the exosomal protein revealed identified proteins with predicted GO molecular function related to adhesion, structure and morphology, and growth factor and growth factor receptor activity. In conclusion, MSC-derived EVs/exosomes possess regenerative effects, in terms of the stimulation of the proliferation and osteogenic differentiation of MSCs, and influence the behaviour of MSCs on titanium surfaces. The expression of exosomal cargoes is altered during osteogenic differentiation and in vitro ageing and their predicted functions partially correspond to the observed effects. It is suggested that the MSC-derived EV-/exosome-mediated effects on the regeneration capacity of MSCs are at least partially attributed to the transfer of functional exosomal cargoes.
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50. |
- Wang, Xiaoqin
(author)
-
The finite part of singular integrals in several complex variables
- 1993
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In: Transactions of the American Mathematical Society. - 0002-9947 .- 1088-6850. ; 337:2, s. 771-793
-
Journal article (peer-reviewed)abstract
- A divergent integral can sometimes be handled by assigning to it as its value the finite part in the sense of Hadamard. This is done by expanding the integral over the complement of a symmetric neighborhood of a singularity in powers of the radius, and throwing away the negative powers. In this paper the finite part of a singular integral of Cauchy type is defined, and this is then used to describe the boundary behavior of derivatives of a Cauchy-type integral. The finite part of a singular integral of Bochner-Martinelli type is studied, and an extension of the Plemelj jump formulas is shown to hold.
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