Development and Evaluation of a Composite Hydrogel for Growth Plate Repair

The growth plate is the area of cartilaginous tissue located at ends of long bones that drives skeletal growth in children. Damage to the growth plate can cause formation of bony tethers bridging the epiphysis and metaphysis, ultimately leading to growth disturbances. Surgical procedures are required to correct these deformities, particularly when lower limbs are involved. However, they are costly and often ineffective, driving a clear need for a regenerative approach for growth plate repair. The growth plate consists of populations of chondrocytes at distinct stages of differentiation. The coordinated proliferation and differentiation of the chondrocytes drive bone growth. Prior studies have attempted to restore the growth plate using tissue engineering methods. Nevertheless, no approach has succeeded in preventing bony tethers and restoring growth plate structure. In this dissertation, a composite hydrogel (PGH) was developed and evaluated for growth plate repair. It consists of Poly (ethylene glycol) diacrylate, methacrylated Gelatin (GEL-MA), and methacrylated Heparin. The PGH hydrogel was fabricated in-house and characterized for physiochemical properties including mechanical stiffness, swelling properties, and cytocompatibility. To evaluate the potential of the hydrogel to regenerate the growth plate cartilage, its effects on chondrocyte phenotype progression were analyzed and compared to a GEL-MA only hydrogel. To evaluate its ability to drive differentiation of stem cells to growth plate chondrocytes, its effects on stem cell chondrogenic and osteogenic differentiation were evaluated. Finally, the efficacy of the stem cell-laden PGH hydrogel in regenerating cartilage and preventing bony tethers was accessed in a growth plate defect model in goats. The results showed that compared to the GEL-MA hydrogel, the PGH hydrogel maintained glycosaminoglycan production by hypertrophic chondrocytes, arrested terminal differentiation, and inhibited mineralization. While supporting chondrogenesis, it did not permit osteogenesis or mineral deposition by stem cells. When implanted into a growth plate defect, the PGH hydrogel was biodegradable and supported chondrogenesis. Although unable to completely prevent bony tether formation, implantation of the PGH hydrogel reduced bone and increased fat content at the defect site. This work advanced understanding of the regenerative approach for growth plate repair. The PGH hydrogel also showed great potential in regenerating stable cartilage

Flood risk management in sponge cities:The role of integrated simulation and 3D visualization

The Sponge City concept has been promoted as a major programme of work to address increasing flood risk in urban areas, in combination with wider benefits for water resources and urban renewal. However, realization of the concept requires collaborative engagement with a wide range of professionals and with affected communities. Visualization can play an important role in this process. In this research, a sponge city flood simulation and forecasting system has been built which combines hydrological data, topographic data, GIS data and hydrodynamic models in real-time and interactive display in a three-dimensional environment. Actual and design flood events in a pilot sponge city have been simulated. The validation results show that the simulated urban water accumulation process is consistent with the actual monitoring data. Use of advanced virtual reality technology can enable simulations to be placed in the wider design context including enhanced awareness of multiple functions of urban ecosystems. This procedure can therefore reduce the information communication gap and encourage innovation regarding low impact development required for sponge city construction

T-Eval: Evaluating the Tool Utilization Capability of Large Language Models Step by Step

Large language models (LLM) have achieved remarkable performance on various NLP tasks and are augmented by tools for broader applications. Yet, how to evaluate and analyze the tool-utilization capability of LLMs is still under-explored. In contrast to previous works that evaluate models holistically, we comprehensively decompose the tool utilization into multiple sub-processes, including instruction following, planning, reasoning, retrieval, understanding, and review. Based on that, we further introduce T-Eval to evaluate the tool utilization capability step by step. T-Eval disentangles the tool utilization evaluation into several sub-domains along model capabilities, facilitating the inner understanding of both holistic and isolated competency of LLMs. We conduct extensive experiments on T-Eval and in-depth analysis of various LLMs. T-Eval not only exhibits consistency with the outcome-oriented evaluation but also provides a more fine-grained analysis of the capabilities of LLMs, providing a new perspective in LLM evaluation on tool-utilization ability. The benchmark will be available at https://github.com/open-compass/T-Eval.Comment: Project: https://open-compass.github.io/T-Eva

Hydrodynamic modelling of flow impact on structures under extreme flow conditions

Apart from the direct threat to human lives, the flood waves as a result of the rapid catchment response to intense rainfall, breaches of flood defences, tsunamis or storm surges may induce huge impact forces on structures, causing structural damage or even failures. Most existing design codes do not properly account for these impact forces due to the limited understanding of the underlying physical processes and the lack of reliable empirical formulae or numerical approaches to quantifying them. This paper presents laboratory experiments to better understand the interaction between the extreme flow hydrodynamics and the hydraulic structures and uses the measured data to validate a numerical model. The model solves the two-dimensional shallow water equations using a finite volume Godunov-type scheme for the reliable simulation of complex flow hydrodynamics. New model components are developed for estimating the hydrostatic and hydrodynamic pressure to quantify the flow impact on structures. The model is applied to reproduce two selected experiment tests with different settings and satisfactory numerical results are obtained, which confirms its predictive capability. The model will therefore provide a potential tool for wider and more flexible field-scale applications

A Signal Processing Approach with a Smooth Empirical Mode Decomposition to Reveal Hidden Trace of Corrosion in Highly Contaminated Guided Wave Signals for Concrete-Covered Pipes

Ultrasonic guided waves have been extensively applied for non-destructive testing of plate-like structures particularly pipes in past two decades. In this regard, if a structure has a simple geometry, obtained guided waves’ signals are easy to explain. However, any small degree of complexity in the geometry such as contacting with other materials may cause an extra amount of complication in the interpretation of guided wave signals. The problem deepens if defects have irregular shapes such as natural corrosion. Signal processing techniques that have been proposed for guided wave signals’ analysis are generally good for simple signals obtained in a highly controlled experimental environment. In fact, guided wave signals in a real situation such as the existence of natural corrosion in wall-covered pipes are much more complicated. Considering pipes in residential buildings that pass through concrete walls, in this paper we introduced Smooth Empirical Mode Decomposition (SEMD) to efficiently separate overlapped guided waves. As empirical mode decomposition (EMD) which is a good candidate for analyzing non-stationary signals, suffers from some shortcomings, wavelet transform was adopted in the sifting stage of EMD to improve its outcome in SEMD. However, selection of mother wavelet that suits best for our purpose plays an important role. Since in guided wave inspection, the incident waves are well known and are usually tone-burst signals, we tailored a complex tone-burst signal to be used as our mother wavelet. In the sifting stage of EMD, wavelet de-noising was applied to eliminate unwanted frequency components from each IMF. SEMD greatly enhances the performance of EMD in guided wave analysis for highly contaminated signals. In our experiment on concrete covered pipes with natural corrosion, this method not only separates the concrete wall indication clearly in time domain signal, a natural corrosion with complex geometry that was hidden and located inside the concrete section was successfully exposed

Disrupting the Indian hedgehog signaling pathway in vivo attenuates surgically induced osteoarthritis progression in Col2a1-CreERT2; Ihhfl/fl mice

Introduction: Previous observations implicate Indian hedgehog (Ihh) signaling in osteoarthritis (OA) development because it regulates chondrocyte hypertrophy and matrix metallopeptidase 13 (MMP-13) expression. However, there is no direct genetic evidence for the role of Ihh in OA, because mice with cartilage or other tissue-specific deletion of the Ihh gene die shortly after birth. We evaluated the role of Ihh in vivo via a Cre-loxP-mediated approach to circumvent the early death caused by Ihh deficiency. Methods: To evaluate the role of Ihh in OA development, Ihh was specifically deleted in murine cartilage using an Ihh conditional deletion construct (Col2a1-CreERT2; Ihhfl/fl). The extent of cartilage degradation and OA progression after Ihh deletion was assessed by histological analysis, immunohistochemistry, real-time PCR and in vivo fluorescence molecular tomography (FMT) 2 months after OA was induced by partial medial meniscectomy. The effect of Ihh signaling on cartilage was compared between Ihh-deleted mice and their control littermates. Results: Only mild OA changes were observed in Ihh-deleted mice, while control mice displayed significantly more cartilage damage. Typical OA markers such as type X collagen and MMP-13 were decreased in Ihh-deleted mice. In vivo FMT demonstrated decreased cathepsins and MMP activity in knee joints of animals with deletion of Ihh. Conclusions: These findings support the protective role of Ihh deletion in surgically induced OA. Thus, our findings suggest the potential to develop new therapeutic strategies that can prevent and treat OA by inhibiting Ihh signaling in chondrocytes

Transcranial direct current stimulation regulates phenotypic transformation of microglia to relieve neuropathic pain induced by spinal cord injury

ObjectiveNeuropathic pain is a common complication after spinal cord injury (SCI). Transcranial direct current stimulation (tDCS) has been confirmed to be effective in relieving neuropathic pain in patients with SCI. The aim of this study is to investigate the effect of tDCS on neuropathic pain induced by SCI and its underlying mechanism.Materials and methodsThe SCI model was induced by a clip-compression injury and tDCS stimulation was performed for two courses (5 days/each). The motor function was evaluated by Basso-Beattie-Bresnahan (BBB) score, and the thermal withdrawal threshold was evaluated by the thermal radiation method. The effects of tDCS on the cerebral cortex, thalamus, midbrain, and medulla were detected by the enzyme-linked immunosorbent assay (ELISA) and immunofluorescence.ResultsThe results showed that SCI reduced the thermal withdrawal threshold and increased the concentration of inflammatory cytokines in the cortex, thalamus, midbrain, and medulla, including the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In addition, the activation of microglia and the proportion of M1 phenotypic polarization increased significantly in the ventral posterolateral (VPL), ventral tegmental (VTA), and periaqueductal gray (PAG) regions after SCI. After tDCS treatment, the thermal withdrawal threshold and motor function of SCI rats were significantly improved compared to the vehicle group. Meanwhile, tDCS effectively reduced the concentration of pro-inflammatory cytokines in the cortex, thalamus, midbrain, and medulla and increased the concentration of anti-inflammatory cytokines interleukin-10 (IL-10) in the thalamus. In addition, tDCS reduced the proportion of the M1 phenotype of microglia in VPL, VTA, and PAG regions and increase the proportion of the M2 phenotype.ConclusionThe results suggest that tDCS can effectively relieve SCI-induced neuropathic pain. Its mechanism may be related to regulating the inflammatory and anti-inflammatory cytokines in corresponding brain regions via promoting the phenotypic transformation of microglia

Changes in the Flavor Quality of Flower and Fruit Scented Black Tea Stored at Room Temperature

To explore the effect of room temperature storage on the flavor quality and biochemical composition of flower and fruit scented black tea, this study compared the sensory flavor quality of flower and fruit scented black tea produced in the years 2019, 2020, 2021 and 2022 and stored at room temperature, and it detected volatile and non-volatile compounds in the tea by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and ultra-performance liquid chromatography coupled to orbitrap high resolution mass spectrometry (UPLC-Orbitrap-MS). The results showed that the sensory quality of flower and fruit scented black tea was significantly affected by storage at room temperature, and the tea lost its floral and fruity aroma characteristics after three years of storage at room temperature; its quality characteristic was mature sour taste. The tea samples were divided into four groups of age by principal component analysis (PCA) and hierarchical cluster analysis (HCA). Totally 15 volatile differential compounds such as linalool, cis-β-ocimene, and hexanoic acid (VIP > 1 and P 2 and P < 0.05) were selected by partial least squares discriminant analysis (PLS-DA) and one-way analysis of variance (ANOVA). The content of volatile compounds such as linalool, hexanal, cis-β-ocimene, and 2-pentylfuran decreased with increasing storage time, while the contents of hexanoic acid, dihydroactinidolide 1-ethyl-2-formyl-1H-pyrrole, and β-ionone increased. The contents of non-volatile compounds such as most amino acids, nucleotides, sugars, tea polyphenols tended to decrease with increasing storage time, while the contents of organic acids and lipids showed an increasing trend. The results obtained from this study can provide a scientific basis for elucidating the quality changes of flower and fruit scented black tea during storage and help guide its rational storage and scientific consumption