A Red-Emission Fluorescent Probe for Intracellular Biothiols and Hydrogen Sulfide Imaging in Living Cells.

This research centers on the development and synthesis of a longwave fluorescence probe, labeled as 60T, designed for the simultaneous detection of hydrogen sulfide, cysteine/homocysteine, and glutathione. The probe showcases a swift response, good linearity range, and heightened sensitivity, boasting that the detection limits of the probe for Cys, Hcy, GSH and H2S were 0.140, 0.202, 0.259 and 0.396 µM, respectively. Notably, its efficacy in monitoring thiol status changes in live MCF-7 cells is underscored by a substantial decrease in fluorescence intensity upon exposure to the thiol trapping reagent, N-ethyl maleimide (NEM). With an impressive red emission signal at 630 nm and a substantial Stokes shift of 80 nm, this probe exhibits remarkable sensitivity and selectivity for biothiols and H2S, indicating promising applications in the diagnosis and surgical navigation of relevant cancers.

Optimising total knee replacement imaging: a novel 3D printed PET/CT anthropomorphic phantom for metal artefact simulation.

PURPOSE: Arthroplasty phantoms, including total knee replacement (TKR) phantoms, have been frequently used to test metal artefact reduction methods applied to positron emission tomography/computed tomography (PET/CT) images. These phantoms generally simulate either simple anatomical features or simple activity distribution around the metal inserts in the PET/CT scans. 3D printing has been used recently to fabricate fillable anthropomorphic phantoms that accurately simulate volume and geometry. This study aims to describe the process of image segmentation, phantom modelling, 3D printing and validation of a population-based fillable TKR phantom that simulates human TKR PET/CT metal artefacts. METHODS: 10 participants (5 male and 5 female) were scanned using 3T MRI and the images were segmented to create average male and average female 3D knee models, inversely with void cortical and porous trabecular compartments for 3D printing and contrast media. Virtual total knee replacement (TKR) surgery was implemented on these models to prepare the insertion locations for knee prosthetic implants. Subsequently, TKR models were printed using a 3D photopolymer resin printer and then injected with normal saline to test the phantoms for any leaks. Subsequently, diluted iodinated contrast media was injected into the cortical compartment and saline with 18F-FDG was injected into the trabecular compartment and the phantom was scanned with PET/CT. The images were then evaluated and compared to the human knee radiographic features reported in the literature. RESULTS: Phantoms were shown to be fluid-tight with distinct compartments. They showed comparable volume and geometry to the segmented human MRI knees. The phantoms demonstrated similar values for x-ray attenuation and Hounsfield units (HU) to the literature for both cortical and trabecular compartments. The phantoms displayed a uniform distribution for the radioactive tracer, resembling that seen in human trabecular bone PET. TKR phantom PET/CT images with metal inserts replicated the clinical metal artefacts seen clinically in the periprosthetic area. CONCLUSION: This novel, 3D-printed, and customisable phantom effectively mimics the geometric, radiographic and radiotracer distribution features of real TKRs. Importantly, it simulates TKR image metal artefacts, making it suitable for repeatable and comprehensive evaluation of various metal artefact reduction methods in future research.

Gas induced formation of inactive Li in rechargeable lithium metal batteries.

The formation of inactive lithium by side reactions with liquid electrolyte contributes to cell failure of lithium metal batteries. To inhibit the formation and growth of inactive lithium, further understanding of the formation mechanisms and composition of inactive lithium are needed. Here we study the impact of gas producing reactions on the formation of inactive lithium using ethylene carbonate as a case study. Ethylene carbonate is a common electrolyte component used with graphite-based anodes but is incompatible with Li metal anodes. Using mass spectrometry titrations combined with 13C and 2H isotopic labeling, we reveal that ethylene carbonate decomposition continuously releases ethylene gas, which further reacts with lithium metal to form the electrochemically inactive species LiH and Li2C2. In addition, phase-field simulations suggest the non-ionically conducting gaseous species could result in an uneven distribution of lithium ions, detrimentally enhancing the formation of dendrites and dead Li. By optimizing the electrolyte composition, we selectively suppress the formation of ethylene gas to limit the formation of LiH and Li2C2 for both Li metal and graphite-based anodes.

The biomechanics of metaphyseal cone augmentation in revision knee replacement.

The demand for revision knee replacement (RKR) has increased dramatically with rising patient life expectancy and younger recipients for primary TKR. However, significant challenges to RKR arise from osseous defects, reduced bone quality, potential bone volume loss from implant removal and the need to achieve implant stability. This study utilizes the outcomes of an ongoing RKR clinical trial using porous metaphyseal cones 3D-printed of titanium, to investigate 1) bone mineral density (BMD) changes in three fixation zones (epiphysis, metaphysis, and diaphysis) over a year and 2) the biomechanical effects of the cones at 6 months post-surgery. It combines dual-energy x-ray absorptiometry (DXA), computed tomography (CT) with patient-specific based finite element (FE) modelling. Bone loss (-0.086 ± 0.05 g/cm2) was found in most patients over the first year. The biomechanical assessment considered four different loading scenarios from standing, walking on a flat surface, and walking downstairs, to a simulated impact of the knee. The patient-specific FE models showed that the cones marginally improved the strain distribution in the bone and shared the induced load but played a limited role in reducing the risks of bone fracture or cement debonding. This technique of obtaining real live data from a randomized clinical trial and inserting it into an in-silico FE model is unique and innovative in RKR research. The tibia RKR biomechanics examined open up further possibilities, allowing the in-silico testing of prototypes and implant combinations without putting patients at risk as per the recommended IDEAL framework standards. This process with further improvements could allow rapid innovation, optimization of implant design, and improve surgical planning.

Bone remodeling following mandibular reconstruction using fibula free flap.

To investigate bone remodelling responses to mandibulectomy, a joint external and internal remodelling algorithm is developed here by incorporating patient-specific longitudinal data. The primary aim of this study is to simulate bone remodelling activity in the conjunction region with a fibula free flap (FFF) reconstruction by correlating with a 28-month clinical follow-up. The secondary goal of this study is to compare the long-term outcomes of different designs of fixation plate with specific screw positioning. The results indicated that the overall bone density decreased over time, except for the Docking Site (namely DS1, a region of interest in mandibular symphysis with the conjunction of the bone union), in which the decrease of bone density ceased later and was followed by bone apposition. A negligible influence on bone remodeling outcome was found for different screw positioning. This study is believed to be the first of its kind for computationally simulating the bone turn-over process after FFF maxillofacial reconstruction by correlating with patient-specific follow-up.

Correlation of the quantitative methods for the measurement of bone uptake and plasma clearance of 18F-NaF using positron emission tomography. Systematic review and meta-analysis.

PURPOSE: 18F-NaF PET is valuable for detecting bone metabolism through osteoblastic activity in the assessment of bone disease. Hawkins, Patlak, and standardised uptake value (SUV) are the most common quantitative measurements used to evaluate bone metabolism. This systematic review evaluates the correlation between quantitative positron emission tomography (PET) methods and to compare their precision. METHODS: A systematic search in Medline, PubMed, SCOPUS, and Web of Science was undertaken to find relevant papers published from 2000. All studies with human adults undergoing 18F-NaF PET, PET/CT, or PET/MRI were included except for subjects diagnosed with non-diffuse metabolic bone disease or malignancy. Quality Assessment Tool for Studies of Diverse Designs (QATSDD) was used to assess risk of bias. A qualitative review and meta-analysis using Hedges random-effect model was used producing summary size effects of the correlation between methods in healthy and unhealthy bone sites and assessing study heterogeneity. RESULTS: 228 healthy and unhealthy participants were included across 12 studies resulted from the systematic search. One-third of studies had a moderate quality percentage while the rest had relatively high quality. The pooled correlation coefficient in meta-analysis showed a high correlation of more than 0.88 (0.71-1.05. 95 %CI) between SUV and Hawkins and more than 0.96 (0.88-1.03. 95 %CI) between Patlak and Hawkins within all subgroups, suggesting all methods yield similar results in healthy and unhealthy bone sites. SUV has the lowest precision error followed by Patlak while Hawkins method showed the highest precision error. CONCLUSION: Patlak is the best within research and SUV is better within clinical practice.

Effects of buccal thickness augmentation on bone remodeling after maxillary anterior implantation.

The biomechanics associated with buccal bone thickness (BBT) augmentation remains poorly understood, as there is no consistent agreement in the adequate BBT to avoid over-loading resorption or over-augmenting surgical difficulty. This study utilizes longitudinal clinical image data to establish a self-validating time-dependent finite element (FE)-based remodeling procedure to explore the effects of different buccal bone thicknesses on long-term bone remodeling outcomes in silico. Based upon the clinical computed tomography (CT) scans, a patient-specific heterogeneous FE model was constructed to enable virtual BBT augmentation at four different levels (0.5, 1.0, 1.5, and 2.0 mm), followed by investigation into the bone remodeling behavior of the different case scenarios. The findings indicated that although peri-implant bone resorption decreased with increasing initial BBT from 0.5 to 2 mm, different levels of the reduction in bone loss were associated with the amount of bone augmentation. In the case of 0.5 mm BBT, overloading resorption was triggered during the first 18 months, but such bone resorption was delayed when the BBT increased to 1.5 mm. It was found that when the BBT reached a threshold thickness of 1.5 mm, the bone volume can be better preserved. This finding agrees with the consensus in dental clinic, in which 1.5 mm BBT is considered clinically justifiable for surgical requirement of bone graft. In conclusion, this study introduced a self-validating bone remodeling algorithm in silico, and it divulged that the initial BBT affects the bone remodeling outcome significantly, and a sufficient initial BBT is considered essential to assure long-term stability and success of implant treatment.

Investigation on masticatory muscular functionality following oral reconstruction - An inverse identification approach.

The human masticatory system has received significant attention in the areas of biomechanics due to its sophisticated co-activation of a group of masticatory muscles which contribute to the fundamental oral functions. However, determination of each muscular force remains fairly challenging in vivo; the conventional data available may be inapplicable to patients who experience major oral interventions such as maxillofacial reconstruction, in which the resultant unsymmetrical anatomical structure invokes a more complex stomatognathic functioning system. Therefore, this study aimed to (1) establish an inverse identification procedure by incorporating the sequential Kriging optimization (SKO) algorithm, coupled with the patient-specific finite element analysis (FEA) in silico and occlusal force measurements at different time points over a course of rehabilitation in vivo; and (2) evaluate muscular functionality for a patient with mandibular reconstruction using a fibula free flap (FFF) procedure. The results from this study proved the hypothesis that the proposed method is of certain statistical advantage of utilizing occlusal force measurements, compared to the traditionally adopted optimality criteria approaches that are basically driven by minimizing the energy consumption of muscle systems engaged. Therefore, it is speculated that mastication may not be optimally controlled, in particular for maxillofacially reconstructed patients. For the abnormal muscular system in the patient with orofacial reconstruction, the study shows that in general, the magnitude of muscle forces fluctuates over the 28-month rehabilitation period regardless of the decreasing trend of the maximum muscular capacity. Such finding implies that the reduction of the masticatory muscle activities on the resection side might lead to non-physiological oral biomechanical responses, which can change the muscular activities for stabilizing the reconstructed mandible.

Structure activity relationships of chrysoeriol and analogs as dual c­Met and VEGFR2 tyrosine kinase inhibitors.

Vascular endothelial growth factor receptor 2 (VEGFR2) and c­Met are tyrosine kinases, which are involved in the tumorigenesis of various types of cancer. Previous studies have demonstrated that the elevated activation of c­Met is associated with the drug resistance of VEGFR2 inhibitors. Therefore, dual c­Met and VEGFR2 kinase inhibitors are expected to overcome VEGFR2 inhibitor resistance and subsequently lead to a superior therapeutic outcome to regular VEGFR2 inhibitors. In the present study, it was found that chrysoeriol, which can be extracted from several natural plants, was a potential dual c­Met and VEGFR2 kinase inhibitor. The results of docking experiments revealed that chrysoeriol was able to efficiently bind in the active site cavity of c­Met and VEGFR2. The results of enzymatic assays showed relatively high binding affinities of chrysoeriol to c­Met (Kd=12 µM) and VEGFR2 (Kd=11 µM). The structure activity relationships (SARs) of chrysoeriol and its analogs were investigated using pharmacological and molecular docking experiments. To the best of our best knowledge, the present study is the first to report a natural product with both c­Met and VEGFR2 inhibitory profiles, and provides insights into future dual c­Met and VEGFR2 kinase inhibitor development.

Biomechanical analysis of bone remodeling following mandibular reconstruction using fibula free flap.

Whilst the newly established biomechanical conditions following mandibular reconstruction using fibula free flap can be a critical determinant for achieving favorable bone union, little has been known about their association in a time-dependent fashion. This study evaluated the bone healing/remodeling activity in reconstructed mandible and its influence on jaw biomechanics using CT data, and further quantified their correlation with mechanobiological responses through an in-silico approach. A 66-year-old male patient received mandibular reconstruction was studied. Post-operative CT scans were taken at 0, 4, 16 and 28 months. Longitudinal change of bone morphologies and mineral densities were measured at three bone union interfaces (two between the fibula and mandibular bones and one between the osteotomized fibulas) to investigate bone healing/remodeling events. Three-dimensional finite element models were created to quantify mechanobiological responses in the bone at these different time points. Bone mineral density increased rapidly along the bone interfaces over the first four months. Cortical bridging formed at the osteotomized interface earlier than the other two interfaces with larger shape discrepancy between fibula and mandibular bones. Bone morphology significantly affected mechanobiological responses in the osteotomized region (R2 > 0.77). The anatomic position and shape discrepancy at bone union affected the bone healing/remodeling process.