Browsing by Author "Li, Yang"
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Item Ballistic-diffusive phonon heat transport across grain boundaries(Elsevier, 2017-09) Chen, Xiang; Li, Weixuan; Xiong, Liming; Li, Yang; Yang, Shengfang; Zheng, Zexi; McDowell, David L.; Chen, Youping; Mechanical Engineering, School of Engineering and TechnologyThe propagation of a heat pulse in a single crystal and across grain boundaries (GBs) is simulated using a concurrent atomistic-continuum method furnished with a coherent phonon pulse model. With a heat pulse constructed based on a Bose-Einstein distribution of phonons, this work has reproduced the phenomenon of phonon focusing in single and polycrystalline materials. Simulation results provide visual evidence that the propagation of a heat pulse in crystalline solids with or without GBs is partially ballistic and partially diffusive, i.e., there is a co-existence of ballistic and diffusive thermal transport, with the long-wavelength phonons traveling ballistically while the short-wavelength phonons scatter with each other and travel diffusively. To gain a quantitative understanding of GB thermal resistance, the kinetic energy transmitted across GBs is monitored on the fly and the time-dependent energy transmission for each specimen is measured; the contributions of coherent and incoherent phonon transport to the energy transmission are estimated. Simulation results reveal that the presence of GBs modifies the nature of thermal transport, with the coherent long-wavelength phonons dominating the heat conduction in materials with GBs. In addition, it is found that phonon-GB interactions can result in reconstruction of GBs.Item Epimeric vitamin D and cardiovascular structure and function in advanced CKD and after kidney transplantation(Oxford University Press, 2024) Arroyo, Eliott; Leber, Cecilia A.; Burney, Heather N.; Li, Yang; Li, Xiaochun; Lu, Tzong-shi; Jones, Glenville; Kaufmann, Martin; Ting, Stephen M. S.; Hiemstra, Thomas F.; Zehnder, Daniel; Lim, Kenneth; Medicine, School of MedicineBackground: 25-hydroxyvitamin D can undergo C-3 epimerization to produce 3-epi-25(OH)D3. 3-epi-25(OH)D3 levels decline in chronic kidney disease (CKD), but its role in regulating the cardiovascular system is unknown. Herein, we examined the relationship between 3-epi-25(OH)D3, and cardiovascular functional and structural endpoints in patients with CKD. Methods: We examined n = 165 patients with advanced CKD from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study cohort, including those who underwent kidney transplant (KTR, n = 76) and waitlisted patients who did not (NTWC, n = 89). All patients underwent cardiopulmonary exercise testing and echocardiography at baseline, 2 months and 12 months. Serum 3-epi-25(OH)D3 was analyzed by liquid chromatography-tandem mass spectrometry. Results: Patients were stratified into quartiles of baseline 3-epi-25(OH)D3 (Q1: <0.4 ng/mL, n = 51; Q2: 0.4 ng/mL, n = 26; Q3: 0.5-0.7 ng/mL, n = 47; Q4: ≥0.8 ng/mL, n = 41). Patients in Q1 exhibited lower peak oxygen uptake [VO2Peak = 18.4 (16.2-20.8) mL/min/kg] compared with Q4 [20.8 (18.6-23.2) mL/min/kg; P = .009]. Linear mixed regression model showed that 3-epi-25(OH)D3 levels increased in KTR [from 0.47 (0.30) ng/mL to 0.90 (0.45) ng/mL] and declined in NTWC [from 0.61 (0.32) ng/mL to 0.45 (0.29) ng/mL; P < .001]. Serum 3-epi-25(OH)D3 was associated with VO2Peak longitudinally in both groups [KTR: β (standard error) = 2.53 (0.56), P < .001; NTWC: 2.73 (0.70), P < .001], but was not with left ventricular mass or arterial stiffness. Non-epimeric 25(OH)D3, 24,25(OH)2D3 and the 25(OH)D3:24,25(OH)2D3 ratio were not associated with any cardiovascular outcome (all P > .05). Conclusions: Changes in 3-epi-25(OH)D3 levels may regulate cardiovascular functional capacity in patients with advanced CKD.Item FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease(Wolters Kluwer, 2022-07-05) Halim, Arvin; Burney, Heather N.; Li, Xiaochun; Li, Yang; Tomkins, Claudia; Siedlecki, Andrew M.; Lu, Tzong-shi; Kalim, Sahir; Thadhani, Ravi; Moe, Sharon; Ting, Stephen M.S.; Zehnder, Daniel; Hiemstra, Thomas F.; Lim, Kenneth; Medicine, School of MedicineBackground: Fibroblast growth factor 23 (FGF23) is a bone-derived phosphatonin that is elevated in chronic kidney disease (CKD) and has been implicated in the development of cardiovascular disease. It is unknown whether elevated FGF23 in CKD is associated with impaired cardiovascular functional capacity, as assessed by maximum exercise oxygen consumption (VO2Max). We sought to determine whether FGF23 is associated with cardiovascular functional capacity in patients with advanced CKD and after improvement of VO2Max by kidney transplantation. Methods: We performed secondary analysis of 235 patients from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) cohort, which recruited patients with stage 5 CKD who underwent kidney transplantation or were waitlisted and hypertensive controls. All patients underwent cardiopulmonary exercise testing (CPET) and echocardiography and were followed longitudinally for 1 year after study enrollment. Results: Patients across FGF23 quartiles differed in BMI (P=0.004) and mean arterial pressure (P<0.001) but did not significantly differ in sex (P=0.5) or age (P=0.08) compared with patients with lower levels of FGF23. Patients with higher FGF23 levels had impaired VO2Max (Q1: 24.2±4.8 ml/min per kilogram; Q4: 18.6±5.2 ml/min per kilogram; P<0.001), greater left ventricular mass index (LVMI; P<0.001), reduced HR at peak exercise (P<0.001), and maximal workload (P<0.001). Kidney transplantation conferred a significant decline in FGF23 at 2 months (P<0.001) before improvement in VO2Max at 1 year (P=0.008). Multivariable regression modeling revealed that changes in FGF23 was significantly associated with VO2Max in advanced CKD (P<0.001) and after improvement after kidney transplantation (P=0.006). FGF23 was associated with LVMI before kidney transplantation (P=0.003), however this association was lost after adjustment for dialysis status (P=0.4). FGF23 was not associated with LVMI after kidney transplantation in all models. Conclusions: FGF23 levels are associated with alterations in cardiovascular functional capacity in advanced CKD and after kidney transplantation. FGF23 is only associated with structural cardiac adaptations in advanced CKD but this was modified by dialysis status, and was not associated after kidney transplantation.Item Goodness-of-fit inference for the additive hazards regression model with clustered current status data(Taylor & Francis, 2022-03-24) Feng, Yanqin; Wang, Jie; Li, Yang; Biostatistics and Health Data Science, School of MedicineClustered current status data are frequently encountered in biomedical research and other areas that require survival analysis. This paper proposes graphical and formal model assessment procedures to evaluate the goodness of fit of the additive hazards model to clustered current status data. The test statistics proposed are based on sums of martingale-based residuals. Relevant asymptotic properties are established, and empirical distributions of the test statistics can be simulated utilizing Gaussian multipliers. Extensive simulation studies confirmed that the proposed test procedures work well for practical scenarios. This proposed method applies when failure times within the same cluster are correlated, and in particular, when cluster sizes can be informative about intra-cluster correlations. The method is applied to analyze clustered current status data from a lung tumorigenicity study.Item Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats(Frontiers Media, 2020-05-01) Liu, Peifang; Li, Hui; Wang, Yueqiu; Su, Xiaolin; Li, Yang; Yan, Meiling; Ma, Lan; Che, Hui; Biochemistry and Molecular Biology, School of MedicineDiabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction.Item Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity.(AHA, 2022-07-19) Arroyo, Eliott; Umukoro, Peter E.; Burney, Heather N.; Li, Yang; Li, Xiaochun; Lane, Kathleen A.; Sher, S. Jawad; Lu, Tzong-Shi; Moe, Sharon M.; Moorthi, Ranjani; Coggan, Andrew R.; McGregor, Gordon; Hiemstra, Thomas F.; Zehnder, Daniel; Lim, Kenneth; Kinesiology, School of Health and Human SciencesBackground The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis. Methods and Results We conducted a cross-sectional study of 241 patients with chronic kidney disease stage 5 from the CAPER (Cardiopulmonary Exercise Testing in Renal Failure) study and from the intradialytic low-frequency electrical muscle stimulation pilot randomized controlled trial cohorts. Patients underwent cardiopulmonary exercise testing and echocardiography. Of the 241 patients (age, 48.9 [15.0] years; 154 [63.9%] men), 42 were predialytic (mean estimated glomerular filtration rate, 14 mL·min·1.73 m), 54 had a dialysis vintage ≤12 months, and 145 had a dialysis vintage >12 months. Dialysis vintage ≤12 months exhibited a significantly impaired cardiovascular functional capacity, as assessed by oxygen uptake at peak exercise (18.7 [5.8] mL·min·kg) compared with predialysis (22.7 [5.2] mL·min·kg; <0.001). Dialysis vintage ≤12 months also exhibited reduced peak workload, impaired peak heart rate, reduced circulatory power, and increased left ventricular mass index (<0.05 for all) compared with predialysis. After excluding those with prior kidney transplant, dialysis vintage >12 months exhibited a lower oxygen uptake at peak exercise (17.0 [4.9] mL·min·kg) compared with dialysis vintage ≤12 months (18.9 [5.9] mL·min·kg; =0.033). Conclusions Initiating dialysis is associated with a significant impairment in oxygen uptake at peak exercise and overall decrements in ventilatory and hemodynamic exercise responses that predispose patients to functional dependence. The magnitude of these changes is comparable to the differences between low-risk New York Heart Association class I and higher-risk New York Heart Association class II to IV heart failure.Item Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression(Springer Nature, 2024) Hu, Junyi; Wang, Shao-Gang; Hou, Yaxin; Chen, Zhaohui; Liu, Lilong; Li, Ruizhi; Li, Nisha; Zhou, Lijie; Yang, Yu; Wang, Liping; Wang, Liang; Yang, Xiong; Lei, Yichen; Deng, Changqi; Li, Yang; Deng, Zhiyao; Ding, Yuhong; Kuang, Yingchun; Yao, Zhipeng; Xun, Yang; Li, Fan; Li, Heng; Hu, Jia; Liu, Zheng; Wang, Tao; Hao, Yi; Jiao, Xuanmao; Guan, Wei; Tao, Zhen; Ren, Shancheng; Chen, Ke; Pathology and Laboratory Medicine, School of MedicineClear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.Item Nondirected Living Kidney Donation and Recipient Outcomes in the United States: A 20-Year Review(Elsevier, 2022-03-22) Jan, Muhammad Y.; Yaqub, Muhammad S.; Adebiyi, Oluwafisayo O.; Taber, Tim E.; Anderson, Melissa D.; Mishler, Dennis P.; Burney, Heather N.; Li, Yang; Li, Xiaochun; Sharfuddin, Asif A.; Medicine, School of MedicineIntroduction: Nondirected donation (NDD) of the kidneys is a growing practice where donors who do not have any genetic or emotional relationship are selected to donate to a wide variety of recipients with a range of selection criteria and decisions which are left up to individual transplant centers. Methods: We review all adult living kidney donor-recipient (DR) pairs and outcomes from NDDs who were recorded in United Network for Organ Sharing (UNOS) database as code 10 (anonymous) from October 1997 to September 2017 for demographics and outcomes. Results: A total of 2174 DR pairs were identified. The number of NDDs increased from 18 in 2000 to 256 in 2016. Survival analysis showed higher death-censored-graft survival (DC-GS) when recipient was 20 years or more older than donor followed by recipient-donor within 20 years of age and lowest when donor was 20 years or more older than recipient (P = 0.0114). Conclusion: Overall, the number of NDDs has increased significantly in the 20-year review period. Transplants from NDDs have excellent long-term outcomes. Better matching of controllable DR factors, such as age and body mass index (BMI), could further improve GS. Further research is needed to incorporate these DR factors into paired kidney donation programs potentially enhancing the utility and beneficence of this invaluable donation.Item Prediction of regulatory motifs from human Chip-sequencing data using a deep learning framework(Oxford University Press, 2019-09-05) Yang, Jinyu; Ma, Anjun; Hoppe, Adam D.; Wang, Cankun; Li, Yang; Zhang, Chi; Wang, Yan; Liu, Bingqiang; Ma, Qin; Medical and Molecular Genetics, School of MedicineThe identification of transcription factor binding sites and cis-regulatory motifs is a frontier whereupon the rules governing protein-DNA binding are being revealed. Here, we developed a new method (DEep Sequence and Shape mOtif or DESSO) for cis-regulatory motif prediction using deep neural networks and the binomial distribution model. DESSO outperformed existing tools, including DeepBind, in predicting motifs in 690 human ENCODE ChIP-sequencing datasets. Furthermore, the deep-learning framework of DESSO expanded motif discovery beyond the state-of-the-art by allowing the identification of known and new protein-protein-DNA tethering interactions in human transcription factors (TFs). Specifically, 61 putative tethering interactions were identified among the 100 TFs expressed in the K562 cell line. In this work, the power of DESSO was further expanded by integrating the detection of DNA shape features. We found that shape information has strong predictive power for TF-DNA binding and provides new putative shape motif information for human TFs. Thus, DESSO improves in the identification and structural analysis of TF binding sites, by integrating the complexities of DNA binding into a deep-learning framework.Item scGNN 2.0: a graph neural network tool for imputation and clustering of single-cell RNA-Seq data(Oxford University Press, 2022) Gu, Haocheng; Cheng, Hao; Ma, Anjun; Li, Yang; Wang, Juexin; Xu, Dong; Ma, Qin; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthMotivation: Gene expression imputation has been an essential step of the single-cell RNA-Seq data analysis workflow. Among several deep-learning methods, the debut of scGNN gained substantial recognition in 2021 for its superior performance and the ability to produce a cell-cell graph. However, the implementation of scGNN was relatively time-consuming and its performance could still be optimized. Results: The implementation of scGNN 2.0 is significantly faster than scGNN thanks to a simplified close-loop architecture. For all eight datasets, cell clustering performance was increased by 85.02% on average in terms of adjusted rand index, and the imputation Median L1 Error was reduced by 67.94% on average. With the built-in visualizations, users can quickly assess the imputation and cell clustering results, compare against benchmarks and interpret the cell-cell interaction. The expanded input and output formats also pave the way for custom workflows that integrate scGNN 2.0 with other scRNA-Seq toolkits on both Python and R platforms. Availability and implementation: scGNN 2.0 is implemented in Python (as of version 3.8) with the source code available at https://github.com/OSU-BMBL/scGNN2.0.