Multiomics Point of Departure (moPOD) Modeling Supports an Adverse Outcome Pathway Network for Ionizing Radiation.

While adverse biological effects of acute high-dose ionizing radiation have been extensively investigated, knowledge on chronic low-dose effects is scarce. The aims of the present study were to identify hazards of low-dose ionizing radiation to Daphnia magna using multiomics dose-response modeling and to demonstrate the use of omics data to support an adverse outcome pathway (AOP) network development for ionizing radiation. Neonatal D. magna were exposed to γ radiation for 8 days. Transcriptomic analysis was performed after 4 and 8 days of exposure, whereas metabolomics and confirmative bioassays to support the omics analyses were conducted after 8 days of exposure. Benchmark doses (BMDs, 10% benchmark response) as points of departure (PODs) were estimated for both dose-responsive genes/metabolites and the enriched KEGG pathways. Relevant pathways derived using the BMD modeling and additional functional end points measured by the bioassays were overlaid with a previously published AOP network. The results showed that several molecular pathways were highly relevant to the known modes of action of γ radiation, including oxidative stress, DNA damage, mitochondrial dysfunction, protein degradation, and apoptosis. The functional assays showed increased oxidative stress and decreased mitochondrial membrane potential and ATP pool. Ranking of PODs at the pathway and functional levels showed that oxidative damage related functions had relatively low PODs, followed by DNA damage, energy metabolism, and apoptosis. These were supportive of causal events in the proposed AOP network. This approach yielded promising results and can potentially provide additional empirical evidence to support further AOP development for ionizing radiation.

Salidroside in the Treatment of NAFLD/NASH.

Non-alcoholic fatty liver disease (NAFLD) is the commonest reason for chronic liver diseases in the world and is commonly related to the hepatic manifestation of the metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is a deteriorating form of NAFLD, which can eventually develop into fibrosis, cirrhosis, and liver cancer. The reason for NAFLD/NASH development is complicated, such as liver lipid metabolism, oxidative stress, inflammatory response, apoptosis and autophagy, liver fibrosis and gut microbiota. Apart from bariatric surgery and lifestyle changes, officially approved drug therapy for NAFLD/NASH treatment is lacking. Salidroside (SDS) is a phenolic compound extensively distributed in the tubers of Rhodiola plants, which possesses many significant biological activities. This review summarized the related targets regulated by SDS in treating NAFLD/NASH. It is indicated that SDS could improve the status of NAFLD/NASH by ameliorating abnormal lipid metabolism, inhibiting oxidative stress, regulating apoptosis and autophagy, reducing inflammatory response, alleviating fibrosis and regulating gut microbiota. In conclusion, although the multiple bioactivities of SDS have been confirmed, the clinical data are inadequate and need to become the focus of attention in the later study.

Microstructural heterogeneity of the collagenous network in the loaded and unloaded periodontal ligament and its biomechanical implications.

The periodontal ligament (PDL) is a highly heterogeneous fibrous connective tissue and plays a critical role in distributing occlusal forces and regulating tissue remodeling. Its mechanical properties are largely determined by the extracellular matrix, comprising a collagenous fiber network interacting with the capillary system as well as interstitial fluid containing proteoglycans. While the phase-contrast micro-CT technique has portrayed the 3D microscopic heterogeneity of PDL, the topological parameters of its network, which is crucial to understanding the multiscale constitutive behavior of this tissue, has not been characterized quantitatively. This study aimed to provide new understanding of such microscopic heterogeneity of the PDL with quantifications at both tissue and collagen network levels in a spatial manner, by combining phase-contrast micro-CT imaging and a purpose-built image processing algorithm for fiber analysis. Both variations within a PDL and among the PDL with different shapes, i.e. round-shaped and kidney-shaped PDLs, are described in terms of tissue thickness, fiber distribution, local fiber densities, and fiber orientation (namely azimuthal and elevation angles). Furthermore, the tissue and collagen fiber network responses to mechanical loading were evaluated in a similar manner. A 3D helical alignment pattern was observed in the fiber network, which appears to regulate and adapt a screw-like tooth motion under occlusion. The microstructural heterogeneity quantified here allows development of sample-specific constitutive models to characterize the PDL's functional and pathological loading responses, thereby providing a new multiscale framework for advancing our knowledge of this complex limited mobility soft-hard tissue interface.

Global research landscape and trends of cancer stem cells from 1997 to 2023: A bibliometric analysis.

Cancer stem cells (CSCs) are a subset of cells with self-renewal ability and tumor generating potential. Accumulated evidence has revealed that CSCs were shown to contribute to tumorigenesis, metastasis, recurrence and resistance to chemoradiotherapy. Therefore, CSCs were regarded as promising therapeutic targets in cancer. This study is the first to reveal the development process, research hotspots, and trends of entire CSCs research field through bibliometric methods. All relevant publications on CSCs with more than 100 citations (notable papers) and the 100 most cited papers (top papers) during 1997 to 2023 were extracted and analyzed. Cancer research published the largest number of papers (184 papers). The USA accounted for the most publications (1326 papers). Rich, JN was the author with the most publications (56 papers) and the highest M-index (3.111). The most contributive institution was the University of Texas System (164 papers). Before 2007, research mainly focused on the definition and recognition of CSCs. Between 2007 and 2016, with the emergence of the terms such as "sonic hedgehog," "metabolism," "oxidative phosphorylation," and "epithelial mesenchymal transition," research began to shift toward exploring the mechanisms of CSCs. In 2016, the focus transitioned to the tumor microenvironment and the ecological niches. The analysis of papers published in major journals since 2021 showed that "transcription," "inhibition," and "chemoresistance" emerged as new focused issues. In general, the research focus has gradually shifted from basic biology to clinical transformation. "Tumor microenvironment" and "chemo-resistance" should be given more attention in the future.

Dose rate dependent genotoxic and metabolic effects predict onset of impaired development and mortality in Atlantic salmon (S. salar) embryos exposed to chronic gamma radiation.

Release of radionuclides to the environment from either nuclear weapon and fuel cycles or from naturally occurring radionuclides (NORM) may cause long term contamination of aquatic ecosystems and chronic exposure of living organisms to ionizing radiation, which in turn could lead to adverse effects compromising the sustainability of populations. To address the effects of chronic ionizing radiation on the development of fish, Atlantic salmon embryos were exposed from fertilization until hatching (88 days, 550 day-degree) to dose rates from 1 to 30 mGy·h-1 gamma radiation (60Co). The lowest adopted dose rate was similar to the highest doses measured in some water bodies right after the Chernobyl accident (1 mGy·h-1), however, well above current environmentally realistic scenarios (20 µGy·h-1), or the threshold assumed for significant effects on fish population (40 µGy·h-1). Dose dependent effects were observed on survival, hatching, morbidity, DNA damage, antioxidant defenses, and metabolic status. Histopathological analysis showed dose rate dependent impairment of eye and brain tissues development and establishment of epidermal mucus cell layers accompanied by increased DNA damage at doses ≥1.3 Gy (dose rates ≥1 mGy·h-1). At ≥32.8 Gy (dose rates ≥20 mGy·h-1) deformities and developmental growth defects resulted in respective 46 and 95 % pre-hatch mortality. The 10 mGy·h-1 exposure (≥ 12 Gy total dose) caused significantly increased DNA damage, impaired eye development, and both premature and delayed hatching, while no deformities or effect on survival were observed. We observed a dose rate dependent reduction from dose rate ≥ 20 mGy·h-1 (≥ 27 Gy total dose) on antioxidant SOD, catalase and glutathione reductase enzyme activities. The reduction of antioxidant enzyme activities was in line with observed developmental delay and disturbance to time of hatching. Metabolomic profiles showed a clear shift at dose rates ≥10 mGy·h-1 (≥ 12 Gy total dose) in pathways related to oxidative stress, detoxification, DNA damage and repair. Due to gamma radiation exposure, a switch of central metabolism from glycolysis, citric acid cycle and lactate production towards pentose phosphate pathway indicated a rewiring mechanism for increased production of reductive equivalents to maintain redox homeostasis at the expense of energy output and thus embryonic development.

A Soft-Tissue Driven Bone Remodeling Algorithm for Mandibular Residual Ridge Resorption Based on Patient CT Image Data.

The role of the biomechanical stimulation generated from soft tissue has not been well quantified or separated from the self-regulated hard tissue remodeling governed by Wolff's Law. Prosthodontic overdentures, commonly used to restore masticatory functions, can cause localized ischemia and inflammation as they often compress patients' oral mucosa and impede local circulation. This biomechanical stimulus in mucosa is found to accelerate the self-regulated residual ridge resorption (RRR), posing ongoing clinical challenges. Based on the dedicated long-term clinical datasets, this work develops an in-silico framework with a combination of techniques, including advanced image post-processing, patient-specific finite element models and unsupervised machine learning Self-Organizing map algorithm, to identify the soft tissue induced RRR and quantitatively elucidate the governing relationship between the RRR and hydrostatic pressure in mucosa. The proposed governing equation has not only enabled a predictive simulation for RRR as showcased in this study, providing a biomechanical basis for optimizing prosthodontic treatments, but also extended the understanding of the mechanobiological responses in the soft-hard tissue interfaces and the role in bone remodeling.

Effects of mineralization on the hierarchical organization of collagen-a synchrotron X-ray scattering and polarized second harmonic generation study.

The process of mineralization fundamentally alters collagenous tissue biomechanics. While the structure and organization of mineral particles have been widely studied, the impact of mineralization on collagen matrix structure, particularly at the molecular scale, requires further investigation. In this study, synchrotron X-ray scattering (XRD) and polarization-resolved second harmonic generation microscopy (pSHG) were used to study normally mineralizing turkey leg tendon in tissue zones representing different stages of mineralization. XRD data demonstrated statistically significant differences in collagen D-period, intermolecular spacing, fibril and molecular dispersion and relative supramolecular twists between non-mineralizing, early mineralizing and late mineralizing zones. pSHG analysis of the same tendon zones showed the degree of collagen fibril organization was significantly greater in early and late mineralizing zones compared to non-mineralizing zones. The combination of XRD and pSHG data provide new insights into hierarchical collagen-mineral interactions, notably concerning possible cleavage of intra- or interfibrillar bonds, occlusion and reorganization of collagen by mineral with time. The complementary application of XRD and fast, label-free and non-destructive pSHG optical measurements presents a pathway for future investigations into the dynamics of molecular scale changes in collagen in the presence of increasing mineral deposition.

Clinical Effect of Lamivudine Combined with Leflunomide and Methylprednisolone Tablets in the Treatment of Hepatitis B Virus-Associated Glomerulonephritis and Its Influence on Renal Function Indicators.

BACKGROUND: In this study, the clinical effect of lamivudine combined with leflunomide and methylprednisolone in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN) and their influence on renal function indexes was explored. METHODS: Patients with HBV-GN were selected for retrospective analysis and divided into the group B and group A, with 41 cases in each group. The group B was given leflunomide and methylprednisolone, whereas the group A was supplemented with lamivudine. The level of 24 h proteinuria (PRO), albumin (ALB), beta2-microglobulin (ß2-MG), alanine aminotransferase (ALT), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in two groups was measured. The clinical efficacy, adverse reactions appetite, spirit, sleep and daily life scores of the two groups were recorded. RESULTS: With the extension of treatment time to end of the treatment, the level of 24 h PRO, ALB and ß2-MG in the group A significantly changed compared with that before treatment (p < 0.05). Moreover, the level of ALT, IFN-γ and IL-4 in the two groups significantly decreased compared with that before treatment, and the level of the three indexes in the group A decreased more significantly (p < 0.05). The total effective rate in the group A was higher than that in the group B (p < 0.05). The occurrence of adverse reactions showed no statistically significant difference between the two groups. After treatment, scores of appetite, spirit, sleep and daily living were increased in the two groups, and the increase in the group A was more significant than that in the group B (p < 0.05). CONCLUSIONS: Lamivudine combined with methylprednisolone and leflunomide treatment is conducive to clearing Hepatitis B virus (HBV) and improving renal function.

Functional non-uniformity of periodontal ligaments tunes mechanobiological stimuli across soft- and hard-tissue interfaces.

The bone-periodontal ligament-tooth (BPT) complex is a unique mechanosensing soft-/hard-tissue interface, which governs the most rapid bony homeostasis in the body responding to external loadings. While the correlation between such loading and alveolar bone remodelling has been widely recognised, it has remained challenging to investigate the transmitted mechanobiological stimuli across such embedded soft-/hard-tissue interfaces of the BPT complex. Here, we propose a framework combining three distinct bioengineering techniques (i, ii, and iii below) to elucidate the innate functional non-uniformity of the PDL in tuning mechanical stimuli to the surrounding alveolar bone. The biphasic PDL mechanical properties measured via nanoindentation, namely the elastic moduli of fibres and ground substance at the sub-tissue level (i), were used as the input parameters in an image-based constitutive modelling framework for finite element simulation (ii). In tandem with U-net deep learning, the Gaussian mixture method enabled the comparison of 5195 possible pseudo-microstructures versus the innate non-uniformity of the PDL (iii). We found that the balance between hydrostatic pressure in PDL and the strain energy in the alveolar bone was maintained within a specific physiological range. The innate PDL microstructure ensures the transduction of favourable mechanobiological stimuli, thereby governing alveolar bone homeostasis. Our outcomes expand current knowledge of the PDL's mechanobiological roles and the proposed framework can be adopted to a broad range of similar soft-/hard- tissue interfaces, which may impact future tissue engineering, regenerative medicine, and evaluating therapeutic strategies. STATEMENT OF SIGNIFICANCE: A combination of cutting-edge technologies, including dynamic nanomechanical testing, high-resolution image-based modelling and machine learning facilitated computing, was used to elucidate the association between the microstructural non-uniformity and biomechanical competence of periodontal ligaments (PDLs). The innate PDL fibre network regulates mechanobiological stimuli, which govern alveolar bone remodelling, in different tissues across the bone-PDL-tooth (BPT) interfaces. These mechanobiological stimuli within the BPT are tuned within a physiological range by the non-uniform microstructure of PDLs, ensuring functional tissue homeostasis. The proposed framework in this study is also applicable for investigating the structure-function relationship in broader types of fibrous soft-/hard- tissue interfaces.

On interaction between fatigue of reconstruction plate and time-dependent bone remodeling.

BACKGROUND AND OBJECTIVE: The fibula free flap (FFF) has been extensively used to repair large segmental bone defects in the maxillofacial region. The reconstruction plate plays a key role in maintaining stability and load-sharing while the fibula unites with adjacent bone in the course of healing and remodeling. However, not all fibula flaps would fully unite, and fatigue of prosthetic devices has been recognized as one major concern for long-term load-bearing applications. This study aims to develop a numerical approach for predicting the fatigue life of the reconstruction plate by taking into account the effect of ongoing bone remodeling. METHODS: The patient-specific mandible reconstruction with a prosthetic system is studied in this work. The 3D finite element model with heterogeneous material properties obtained from clinical computerized tomography (CT) data is developed for bone, and eXtended Finite Element Method (XFEM) is adopted for the fatigue analysis of the plate. During the remodeling process, the changing apparent density and Young's modulus of bone are simulated in a step-wise fashion on the basis of Wolff's law, which is correlated with the specific clinical follow-up. The maximum biting forces were considered as the driving force on the bone remodeling, which are measured clinically at different time points (4, 16 and 28 months) after reconstruction surgery. RESULTS: Under various occlusal loadings, the interaction between fatigue crack growth and bone remodeling is investigated to gain new insights for the future design of prosthetic devices. The simulation results reveal that appropriate remodeling of grafted bone could extend the fatigue life of fixation plates in a positive way. On the other hand, the rising occlusal load associated with healing and remodeling could lead to fatigue fracture of fixation plate and potentially cause severe bone resorption. CONCLUSION: This study proposes an effective approach for more realistically predicting fatigue life of prosthetic devices subject to a tissue remodeling condition in-silico. It is anticipated to provide a guideline for deriving an optimal design of patient-specific prosthetic devices to better ensure longevity.

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.

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.

A machine learning-based multiscale model to predict bone formation in scaffolds.

Computational modeling methods combined with non-invasive imaging technologies have exhibited great potential and unique opportunities to model new bone formation in scaffold tissue engineering, offering an effective alternate and viable complement to laborious and time-consuming in vivo studies. However, existing numerical approaches are still highly demanding computationally in such multiscale problems. To tackle this challenge, we propose a machine learning (ML)-based approach to predict bone ingrowth outcomes in bulk tissue scaffolds. The proposed in silico procedure is developed by correlating with a dedicated longitudinal (12-month) animal study on scaffold treatment of a major segmental defect in sheep tibia. Comparison of the ML-based time-dependent prediction of bone ingrowth with the conventional multilevel finite element (FE2) model demonstrates satisfactory accuracy and efficiency. The ML-based modeling approach provides an effective means for predicting in vivo bone tissue regeneration in a subject-specific scaffolding system.

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.

Quantitative/qualitative analysis of adhesive-dentin interface in the presence of 10-methacryloyloxydecyl dihydrogen phosphate.

Dental adhesive provides effective retention of filling materials via adhesive-dentin hybridization. The use of co-monomers, such as 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP), is thought to be crucial for hybridization owing to their ionic-binding to calcium and co-polymerization in the polymerizable adhesives. Optimal hybridization partly depends on the mechanical properties of polymerized adhesives, which are likely to be proportional to the degree of conversion ratio. This study assessed the correlation between polymerization quality and mechanical properties at the adhesive-dentin interfaces in the presence or absence of 10-MDP. In situ Raman microspectroscopy and nanoindentation tests were used concurrently to quantify the degree of conversion ratio and dynamic mechanical properties across the adhesive-dentin interfaces. Despite the excellent diffusion and apparent higher degree of co-polymerization, 10-MDP reduced the elastic modulus of the interface. The higher viscoelastic properties of the adhesive are suggestive of poor polymerization, namely polymerization linearity related to the long carboxyl chain of 10-MDP. Such reduced mechanical integrity of hybridization could also be associated with the inhibition of nano-layering between 10-MDP and mineralized tissue in the presence of hydroxyethyl methacrylate (HEMA). This potential drawback of HEMA necessitates further qualitative/quantitative characterization of adhesive-dentin hybridization using a HEMA-free/low concentration experimental 10-MDP monomer, which theoretically possesses superior chemical bonding potential to the current HEMA-rich protocol.

In vivo effects of different orthodontic loading on root resorption and correlation with mechanobiological stimulus in periodontal ligament.

Orthodontic root resorption is a common side effect of orthodontic therapy. It has been shown that high hydrostatic pressure in the periodontal ligament (PDL) generated by orthodontic forces will trigger recruitment of odontoclasts, leaving resorption craters on root surfaces. The patterns of resorption craters are the traces of odontoclast activity. This study aimed to investigate resorptive patterns by: (i) quantifying spatial root resorption under two different levels of in vivo orthodontic loadings using microCT imaging techniques and (ii) correlating the spatial distribution pattern of resorption craters with the induced mechanobiological stimulus field in PDL through nonlinear finite-element analysis (FEA) in silico. Results indicated that the heavy force led to a larger total resorption volume than the light force, mainly by presenting greater individual crater volumes ( p < 0.001) than increasing crater numbers, suggesting that increased mechano-stimulus predominantly boosted cellular resorption activity rather than recruiting more odontoclasts. Furthermore, buccal-cervical and lingual-apical regions in both groups were found to have significantly larger resorption volumes than other regions ( p < 0.005). These clinical observations are complemented by the FEA results, suggesting that root resorption was more likely to occur when the volume average compressive hydrostatic pressure exceeded the capillary blood pressure (4.7 kPa).

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.

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.

Cloning and characterization of fatty acid-binding proteins (fabps) from Japanese seabass (Lateolabraxjaponicus) liver, and their gene expressions in response to dietary arachidonic acid (ARA).

In the present study, putative cDNA of five fabp isoforms, i.e., fabp1, fabp2, fabp3, fabp4, and fabp7, was cloned and characterized from the liver of Japanese seabass (Lateolabrax japonicus), and their expression in response to diets with different arachidonic acid (ARA) levels (0.05%, 0.22%, 0.37%, 0.60%, 1.38% and 2.32% of dry matter) was investigated following a feeding trial. The Japanese seabass fabps showed high identity to their orthologs in other fish species and mammals. However, a specific fabp of Japanese seabass showed much lower identity to other Japanese seabass fabps. fabp1 has high expressions in liver and intestine, whereas fabp2 is mainly expressed in the gastrointestinal tract. The highest expression level of fabp3, fabp4, and fabp7 was observed in muscle, eye, and liver respectively. Different tissue expression patterns of fabp2, fabp4, and fabp7 between Japanese seabass and other teleost may indicate specific evolutionary Fabp functions in Japanese seabass. Moderate levels of dietary ARA (0.37-0.60%) enhanced the gene expressions of fabp1 in liver and intestine, fabp2 in intestine, and fabp3 in intestine, whereas excess dietary ARA levels (1.38-2.323%) were ineffective. The highest level of dietary ARA (2.32%) increased only the expression of fabp3 in muscle compared to the control diet. Gene expressions of fabp3 and fabp7 in liver, and fabp4 in liver, intestine, and muscle were not significantly influenced by dietary ARA. To our knowledge, this is the first study investigating the regulation of fabp expressions by dietary ARA.

Multiobjective optimization of cartilage stress for non-invasive, patient-specific recommendations of high tibial osteotomy correction angle - a novel method to investigate alignment correction.

Medial opening wedge high tibial osteotomy (MOWHTO) is a surgical procedure to treat knee osteoarthritis associated with varus deformity. However, the ideal final alignment of the Hip-Knee-Ankle (HKA) angle in the frontal plane, that maximizes procedural success and post-operative knee function, remains controversial. Therefore, the purpose of this study was to introduce a subject-specific modeling procedure in determining the biomechanical effects of MOWHTO alignment on tibiofemoral cartilage stress distribution. A 3D finite element knee model derived from magnetic resonance imaging of a healthy participant was manipulated in-silico to simulate a range of final HKA angles (i.e. 0.2°, 2.7°, 3.9° and 6.6° valgus). Loading and boundary conditions were assigned based on subject-specific kinematic and kinetic data from gait analysis. Multiobjective optimization was used to identify the final alignment that balanced compressive and shear forces between medial and lateral knee compartments. Peak stresses decreased in the medial and increased in the lateral compartment as the HKA was shifted into valgus, with balanced loading occurring at angles of 4.3° and 2.9° valgus for the femoral and tibial cartilage respectively. The concept introduced here provides a platform for non-invasive, patient-specific preoperative planning of the osteotomy for medial compartment knee osteoarthritis.