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Huiyi Yang

Publications and source records attributed to Huiyi Yang.

3 recordsLinked to original sources

Bayesian Emulation of Multi-fidelity Earth System Modelling Using Hierarchical Gaussian Processes

Multi-fidelity Earth system models provide simulations at different levels of complexity and computational cost, but exhaustive exploration of the parameter space at the highest fidelity is often prohibitively expensive. Multi-fidelity emulators can reduce this burden by combining abundant lower-fidelity simulations with limited high-fidelity evaluations. We compare four Gaussian-process-based multi-fidelity approaches: the Kennedy--O'Hagan autoregressive model (K&O), hierarchical kriging (HK), Bayesian hierarchical emulation for multi-level models (BayHEm), and multi-fidelity deep Gaussian processes (MF-DGP). We evaluate the methods using two contrasting applications: a three-fidelity tsunami simulator and a two-fidelity implementation of the Joint UK Land Environment Simulator (JULES). Performance is assessed using leave-one-out predictive accuracy, uncertainty representation, design requirements, and computational characteristics. In the tsunami application, BayHEm gives the lowest normalised root mean square error (NRMSE = 0.031) and highest SCORE (3.025), while MF-DGP performs worse than the single-fidelity baseline when only 10 high-fidelity simulations are available. In the JULES application, MF-DGP gives the lowest NRMSE (0.079) and highest SCORE (3.032), with all 30 held-out high-fidelity observations lying within their nominal 95\% predictive intervals. These contrasting results show that no single multi-fidelity emulator is uniformly superior. Instead, method choice should reflect the complexity of the inter-fidelity relationship, the amount of high-fidelity information available, and the importance placed on predictive accuracy and uncertainty quantification.

stat.AP

Low-intensity pulsed ultrasound promotes mesenchymal stem cell transplantation-based articular cartilage regeneration via inhibiting the TNF signaling pathway

Background: Mesenchymal stem cell (MSC) transplantation therapy is highly investigated for the regenerative repair of cartilage defects. Low-intensity pulsed ultrasound (LIPUS) has the potential to promote chondrogenic differentiation of MSCs. However, its underlying mechanism remains unclear. Here, we investigated the promoting effects and mechanisms underlying LIPUS stimulation on the chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and further evaluated its regenerative application value in articular cartilage defects in rats. Methods: LIPUS was applied to stimulate cultured hUC-MSCs and C28/I2 cells in vitro. Immunofluorescence staining, qPCR analysis, and transcriptome sequencing were used to detect mature cartilage-related markers of gene and protein expression for a comprehensive evaluation of differentiation. Injured articular cartilage rat models were established for further hUC-MSC transplantation and LIPUS stimulation in vivo. Histopathology and H&E staining were used to evaluate the repair effects of the injured articular cartilage with LIPUS stimulation. Results: The results showed that LIPUS stimulation with specific parameters effectively promoted the expression of mature cartilage-related genes and proteins, inhibited TNF-α gene expression in hUC-MSCs, and exhibited anti-inflammation in C28/I2 cells. In addition, the articular cartilage defects of rats were significantly repaired after hUC-MSC transplantation and LIPUS stimulation. Conclusions: Taken together, LIPUS stimulation could realize articular cartilage regeneration based on hUC-MSC transplantation due to the inhibition of the TNF signaling pathway, which is of clinical value for the relief of osteoarthritis.

physics.med-ph

Unresolved excess accumulation of myelin-derived cholesterol contributes to scar formation after spinal cord injury

Background: Spinal cord injury triggers complex pathological cascades, resulting in destructive tissue damage and incomplete tissue repair. Scar formation is generally considered as a barrier for regeneration in central nervous system (CNS), while the intrinsic mechanism of scar-forming after spinal cord injury has not been completed deciphered. Methods: We assessed cholesterol hemostasis in spinal cord lesions and injured peripheral nerves using confocal reflection microscopy and real-time PCR analyses. The involvement of the proteins, which were predicted to promote cholesterol efflux in spinal cord lesions, were assessed with Liver X receptor (LXR) agonist and Apolipoprotein E (APOE) deficiency. The role of reverse cholesterol transport (RCT) in cholesterol clearance was examined in APOE KO mice injured sciatic nerves and myelin-overloaded macrophages in vitro. Finally, we determined the consequence of excess cholesterol accumulation in CNS by transplantation of myelin into neonatal spinal cord lesions. Results: We found that excess cholesterol accumulates in phagocytes and is inefficiently removed in spinal cord lesions in young-adult mice. Interestingly, we observed that excessive cholesterol also accumulates in injured peripheral nerves, but is subsequently removed by RCT. Meanwhile, preventing RCT led to macrophage accumulation and fibrosis in injured peripheral nerves. Furthermore, the neonatal mouse spinal cord lesions are devoid of myelin-derived lipids, and able to heal without excess cholesterol accumulation. We found that transplantation of myelin into neonatal lesions disrupts healing with excessive cholesterol accumulation, persistent macrophage activation and fibrosis, indicating myelin-derived cholesterol plays a critical role in impaired wound healing.

q-bio.TO