Essays on corporate debt structure, leverage puzzle, competition and trade war

The thesis examines the corporate debt structure and costs of various kinds of debt including the total debt, general bank debt and public debt as well as six types of specific debt components from the perspectives of three independent and related topics. First, I reveal the underlying sources of the leverage puzzle in terms of the unrated firms’ components of corporate debt structure. For the unrated firms, the leverage puzzle is significantly contributed by the revolving credit of bank debt as well as the bonds and notes of public debt, but unrated status weakens the puzzle since the unrated firms with high profits increase the two types of debt. For robustness, I consider another two factors that might impose effects on the relationship between profitability and debt: banks’ credit supplies and monetary policy. Second, I investigate how product market competition affects specific components of corporate debt and the costs of six types of debt. The analyses of various types of debt in fine detail reveal that product market competition generally reduces most of the debt. Nevertheless, competition usually mitigates the leverage puzzle of the negative relationship between profitability and specific types of debt. Besides, competition raises the credit spreads of all types of debt due to the bank monitoring of bank debt and the need for public debt for reducing external monitoring pressure. Third, I take the trade war between the U.S. and China intensified by Section 301 in 2018 as an exogenous shock and study a quasi-natural experiment of firms affected by the trade war. Using causal inference, I investigate the impact of the trade war on, competition, the corporate debt structure, and costs. I contribute to the debate on the benefits and losses due to the trade war by showing that although credit spreads decrease, the trade war did not alleviate competition, but rather it intensified competition and hampered debt financing

Dynamics and Performance of Decentralized Portfolios with Size-Induced Fund Flows

We examine the implications of fund sizes for portfolio dynamics and performance within a decentralized structure, where the chief investment officer optimally allocates capital to two fund managers who invest in multiple assets within their own asset classes. The managers experience fund inflows/outflows depending on not only their investment performances but also their fund sizes that are mainly driven by their optimal portfolios. We characterize these practical features through a two-layer dynamic optimization model where the managers maximize their size-dependent compensations. We solve the highly path-dependent optimization problem using a simulation-projection method with a multidimensional grid search and policy iteration. Our analysis provides new interpretations on the controversial scale effects on fund performance, along with insights into portfolio dynamics and management fees for bond funds and stock funds under different fund ages

Levothyroxine Replacement Alleviates Thyroid Destruction in Hypothyroid Patients With Autoimmune Thyroiditis: Evidence From a Thyroid MRI Study

Background: Autoimmune thyroiditis (AIT) is the most frequent cause of hypothyroidism. Our previous studies have shown that magnetic resonance T1-mapping is a new technique for quantitatively evaluating the degree of thyroid destruction in AIT patients. This study aimed to evaluate the effect of levothyroxine on thyroid destruction in hypothyroid AIT patients using thyroid T1-mapping technique.Methods: This study recruited 29 hypothyroid AIT patients and 18 age- and sex-matched healthy individuals. Thyroid T1-mapping values were measured in all participants and repeated in the AIT patients at 3 months after they achieved a euthyroid state following levothyroxine treatment.Results: Thyroid T1-mapping values were higher in the AIT patients than in the healthy controls (1167.2 ± 163.2 vs. 779.6 ± 83.8 ms, P < 0.01), and levothyroxine treatment significantly decreased the thyroid T1-mapping values of AIT patients (1006.3 ± 114.6 vs. 1167.2 ± 163.2 ms, P < 0.01). Meanwhile, the reduced levels of anti-peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) were observed in the AIT patients after levothyroxine treatment [TPOAb: 257.6 (23.9–960.6) vs. 1,287.4 (12.6–2000.0) IU/mL, P < 0.01; TgAb: 53.54 (9.58–386.2) vs. 103.9 (34.2–1,596.8) IU/mL, P < 0.05]. High-sensitivity C-reactive protein (hsCRP) levels showed a descending tendency following levothyroxine treatment, although there was no statistical difference (P > 0.05).Conclusions: In the AIT patients, thyroid T1-mapping values were significantly increased, and levothyroxine treatment significantly decreased the thyroid T1-mapping values of the AIT patients. These results might suggest that levothyroxine treatment alleviates thyroid destruction in hypothyroid AIT patients

A Neuroimaging Marker Based on Diffusion Tensor Imaging and Cognitive Impairment Due to Cerebral White Matter Lesions

Background: The peak width of skeletonized mean diffusivity (PSMD) is a new, fully automated, robust imaging marker for cerebral small vessel disease (SVD), strongly associated with processing speed. However, it has never been applied to cerebral white matter lesions (WMLs). Our study aimed to investigate the correlation between PSMD and cognition, particularly in the executive function of patients with WMLs.Methods: A total of 111 WML patients and 50 healthy controls (HCs) were enrolled, and their demographic information and cardiovascular disease risk factors were recorded. Subjects were divided into three groups: WMLs with normal cognition (WMLs-NC), WMLs with vascular cognitive impairment (WMLs-VCI), and HCs. They underwent conventional head magnetic resonance imaging and diffusion tensor imaging (DTI), followed by neuropsychological and psychological examinations, including the Montreal Cognitive Assessment (MoCA), and the executive function tests. We compared executive function and PSMD among the three groups and analyzed the correlation between PSMD and cognitive function in all subjects.Results: There were no significant differences in demographic characteristics (age, sex, education level, and cardiovascular disease risk factors) among the three groups (P > 0.05), but there were significant differences in global cognition (P < 0.0001), executive function (P < 0.0001), and PSMD (P < 0.0001). The average PSMD value (×10−4 mm2/s) was 2.40 ± 0.23, 2.68 ± 0.30, and 4.51 ± 0.39 in the HC, WMLs-NC, and WMLs-VCI groups, respectively. There was no correlation between PSMD and cognition in the HC group, but PSMD was significantly correlated with MoCA scores (r = −0.3785, P < 0.0001) and executive function (r = −0.4744, P < 0.0001) in the WMLs-NC group and in the WMLs-VCI group (r = −0.4448, P < 0.0001 and r = −0.6279, P < 0.0001, respectively).Conclusions: WML patients have higher PSMD and worse cognitive performance than HCs, and PSMD is strongly associated with global cognition and executive functions in WML patients. This result provides new insights into the pathophysiology of cognitive impairment in WML patients. PSMD could be a surrogate marker for disease progression and could thus be used in therapeutic trials involving WML patients

Assisted reproductive technology and interactions between serum basal FSH/LH and ovarian sensitivity index

ObjectivesThis study aimed to investigate whether the FSH (follicle-stimulating hormone)/LH (Luteinizing hormone) ratio correlates with ovarian response in a cross-sectional retrospective study of a population with normal levels of anti-Müllerian hormone (AMH).MethodsThis was a retrospective cross‐sectional study with data obtained from medical records from March 2019 to December 2019 at the reproductive center in the Affiliated Hospital of Southwest Medical University. The Spearmans correlation test evaluated correlations between Ovarian sensitivity index (OSI) and other parameters. The relationship between basal FSH/LH and ovarian response was analyzed using smoothed curve fitting to find the threshold or saturation point for the population with mean AMH level (1.1<AMH<6μg/L). The enrolled cases were divided into two groups according to AMH threshold. Cycle characteristics, cycle information and cycle outcomes were compared. The Mann-Whitney U test was used to compare different parameters between two groups separated by basal FSH/LH in the AMH normal group. Univariate logistic regression analysis and multivariate logistic regression analysis were performed to find the risk factor for OSI.ResultsA total of 428 patients were included in the study. A significant negative correlation was observed between OSI and age, FSH, basal FSH/LH, Gn total dose, and Gn total days, while a positive correlation was found with AMH, AFC, retrieved oocytes, and MII egg. In patients with AMH <1.1 ug/L, OSI values decreased as basal FSH/LH levels increased, while in patients with 1.1<AMH<6 ug/L, OSI values remained stable with increasing basal FSH/LH levels. Logistic regression analysis identified age, AMH, AFC, and basal FSH/LH as significant independent risk factors for OSI.ConclusionsWe conclude that increased basal FSH/LH in the AMH normal group reduces the ovarian response to exogenous Gn. Meanwhile, basal FSH/LH of 3.5 was found to be a useful diagnostic threshold for assessing ovarian response in people with normal AMH levels. OSI can be used as an indicator of ovarian response in ART treatment

The role of the SGK3/TOPK signaling pathway in the transition from acute kidney injury to chronic kidney disease

Introduction: Profibrotic phenotype of renal tubular epithelial cells (TECs) featured with epithelial to mesenchymal transition (EMT) and profibrotic factors secretion, and aberrant accumulation of CD206+ M2 macrophages are the key points in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Nevertheless, the underlying mechanisms involved remain incompletely understood. Serum and glucocorticoid-inducible kinase (SGK) is a serine/threonine protein kinase, required for intestinal nutrient transport and ion channels modulation. T-LAK-cell-originated protein kinase (TOPK) is a member of the mitogen activated protein kinase family, linked to cell cycle regulation. However, little is known about their roles in AKI-CKD transition.Methods: In this study, three models were constructed in C57BL/6 mice: low dose and multiple intraperitoneal injection of cisplatin, 5/6 nephrectomy and unilateral ureteral obstruction model. Rat renal tubular epithelial cells (NRK-52E) were dealt with cisplatin to induce profibrotic phenotype, while a mouse monocytic cell line (RAW264.7) were cultured with cisplatin or TGF-β1 to induce M1 or M2 macrophage polarization respectively. And co-cultured NRK-52E and RAW264.7 through transwell plate to explore the interaction between them. The expression of SGK3 and TOPK phosphorylation were detected by immunohistochemistry, immunofluorescence and western blot analysis.Results:In vivo, the expression of SGK3 and p-TOPK were gradually inhibited in TECs, but enhanced in CD206+ M2 macrophages. In vitro, SGK3 inhibition aggravated epithelial to mesenchymal transition through reducing the phosphorylation state of TOPK, and controlling TGF-β1 synthesis and secretion in TECs. However, SGK3/TOPK axis activation promoted CD206+ M2 macrophage polarization, which caused kidney fibrosis by mediating macrophage to myofibroblast transition (MMT). When co-cultured, the TGF-β1 from profibrotic TECs evoked CD206+ M2 macrophage polarization and MMT, which could be attenuated by SGK3/TOPK axis inhibition in macrophages. Conversely, SGK3/TOPK signaling pathway activation in TECs could reverse CD206+ M2 macrophages aggravated EMT.Discussion: We revealed for the first time that SGK3 regulated TOPK phosphorylation to mediate TECs profibrotic phenotype, macrophage plasticity and the crosstalk between TECs and macrophages during AKI-CKD transition. Our results demonstrated the inverse effect of SGK3/TOPK signaling pathway in profibrotic TECs and CD206+ M2 macrophages polarization during the AKI-CKD transition

Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

Background/Aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis. Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis. Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis