Federated attention consistent learning models for prostate cancer diagnosis and Gleason grading.

Artificial intelligence (AI) holds significant promise in transforming medical imaging, enhancing diagnostics, and refining treatment strategies. However, the reliance on extensive multicenter datasets for training AI models poses challenges due to privacy concerns. Federated learning provides a solution by facilitating collaborative model training across multiple centers without sharing raw data. This study introduces a federated attention-consistent learning (FACL) framework to address challenges associated with large-scale pathological images and data heterogeneity. FACL enhances model generalization by maximizing attention consistency between local clients and the server model. To ensure privacy and validate robustness, we incorporated differential privacy by introducing noise during parameter transfer. We assessed the effectiveness of FACL in cancer diagnosis and Gleason grading tasks using 19,461 whole-slide images of prostate cancer from multiple centers. In the diagnosis task, FACL achieved an area under the curve (AUC) of 0.9718, outperforming seven centers with an average AUC of 0.9499 when categories are relatively balanced. For the Gleason grading task, FACL attained a Kappa score of 0.8463, surpassing the average Kappa score of 0.7379 from six centers. In conclusion, FACL offers a robust, accurate, and cost-effective AI training model for prostate cancer pathology while maintaining effective data safeguards.

Coping with groundwater pollution in high-nitrate leaching areas: The efficacy of denitrification.

The Ningxia Yellow River irrigation area, characterized by an arid climate and high leaching of NO3--N, exhibits complex and unique groundwater nitrate (NO3--N) pollution, with denitrification serving as the principal mechanism for NO3--N removal. The characteristics of N leaching from paddy fields and NO3--N removal by groundwater denitrification were investigated through a two-year field observation. The leaching losses of total nitrogen (TN) and NO3--N accounted for 10.81-27.34% and 7.59-12.74%, respectively, of the N input. The linear relationship between NO3--N leaching and N input indicated that the fertilizer-induced emission factor (EF) of NO3--N leaching in direct dry seeding and seedling-raising and transplanting paddy fields was 8.2% (2021, R2 = 0.992) and 6.7% (2022, R2 = 0.994), respectively. The study highlighted that the quadratic relationship between the NO3--N leaching loss and N input (R2 = 0.999) significantly outperformed the linear relationship. Groundwater denitrification capacity was characterized by monitoring the concentrations of dinitrogen (N2) and nitrous oxide (N2O). The results revealed substantial seasonal fluctuations in excess N2 and N2O concentrations in groundwater, particularly following fertilization and irrigation events. The removal efficiency of NO3--N via groundwater denitrification ranged from 42.70% to 74.38%, varying with depth. Groundwater denitrification capacity appeared to be linked to dissolved organic carbon (DOC) concentration, redox conditions, fertilization, irrigation, and soil texture. The anthropogenic-alluvial soil with limited water retention accelerated the leaching of NO3--N into groundwater during irrigation. This process enhances the groundwater recharge capacity and alters the redox conditions of groundwater, consequently impacting groundwater denitrification activity. The DOC concentration emerged as the primary constraint on the groundwater denitrification capacity in this region. Hence, increasing carbon source concentration and enhancing soil water retention capacity are vital for improving the groundwater denitrification capacity and NO3--N removal efficiency. This study provides practical insights for managing groundwater NO3--N pollution in agricultural areas, optimizing fertilization strategies and improving groundwater quality.

A systematic evaluation of computation methods for cell segmentation.

Cell segmentation is a fundamental task in analyzing biomedical images. Many computational methods have been developed for cell segmentation, but their performances are not well understood in various scenarios. We systematically evaluated the performance of 18 segmentation methods to perform cell nuclei and whole cell segmentation using light microscopy and fluorescence staining images. We found that general-purpose methods incorporating the attention mechanism exhibit the best overall performance. We identified various factors influencing segmentation performances, including training data and cell morphology, and evaluated the generalizability of methods across image modalities. We also provide guidelines for choosing the optimal segmentation methods in various real application scenarios. We developed Seggal, an online resource for downloading segmentation models already pre-trained with various tissue and cell types, which substantially reduces the time and effort for training cell segmentation models.

Metabolomics Profiling Predicts Ventricular Arrhythmia in Patients with an Implantable Cardioverter Defibrillator.

Implantable cardioverter defibrillators (ICDs) reduce sudden cardiac death (SCD) when patients experience life-threatening ventricular arrhythmias (LTVA). However, current strategies determining ICD patient selection and risk stratification are inefficient. We used metabolomics to assess whether dysregulated metabolites are associated with LTVA and identify potential biomarkers. Baseline plasma samples were collected from 72 patients receiving ICDs. Over a median follow-up of 524.0 days (range 239.0-705.5), LTVA occurred in 23 (31.9%) patients (22 effective ICD treatments and 1 SCD). After confounding risk factors adjustment for age, smoking, secondary prevention, and creatine kinase MB, 23 metabolites were significantly associated with LTVA. Pathway analysis revealed LTVA associations with disrupted metabolism of glycine, serine, threonine, and branched chain amino acids. Pathway enrichment analysis identified a panel of 6 metabolites that potentially predicted LTVA, with an area under the receiver operating characteristic curve of 0.8. Future studies are necessary on biological mechanisms and potential clinical use.

PhaseFIT: live-organoid phase-fluorescent image transformation via generative AI.

Organoid models have provided a powerful platform for mechanistic investigations into fundamental biological processes involved in the development and function of organs. Despite the potential for image-based phenotypic quantification of organoids, their complex 3D structure, and the time-consuming and labor-intensive nature of immunofluorescent staining present significant challenges. In this work, we developed a virtual painting system, PhaseFIT (phase-fluorescent image transformation) utilizing customized and morphologically rich 2.5D intestinal organoids, which generate virtual fluorescent images for phenotypic quantification via accessible and low-cost organoid phase images. This system is driven by a novel segmentation-informed deep generative model that specializes in segmenting overlap and proximity between objects. The model enables an annotation-free digital transformation from phase-contrast to multi-channel fluorescent images. The virtual painting results of nuclei, secretory cell markers, and stem cells demonstrate that PhaseFIT outperforms the existing deep learning-based stain transformation models by generating fine-grained visual content. We further validated the efficiency and accuracy of PhaseFIT to quantify the impacts of three compounds on crypt formation, cell population, and cell stemness. PhaseFIT is the first deep learning-enabled virtual painting system focused on live organoids, enabling large-scale, informative, and efficient organoid phenotypic quantification. PhaseFIT would enable the use of organoids in high-throughput drug screening applications.

Retracted: Ultra-processed food consumption and risk of dementia and Alzheimer's disease: Long-term results from the Framingham Offspring Study

Retraction: Wang, K, Tang, W, Hao, X, Zhao, J. Ultra-processed food consumption and risk of dementia and Alzheimer's disease: Long-term results from the Framingham Offspring Study. Alzheimer's Dement. 2023; 1­11. https://doi.org/10.1002/alz.13351. The above article, published online on 03 July 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor-in-Chief Dr. Donna M. Wilcock, the Alzheimer's Association and Wiley Periodicals LLC. The retraction has been agreed as the authors did not have the appropriate approvals in place from the National Heart, Lung and Blood Institute (NHLBI) for use of the data in this article. This contravenes the journal's policy on data use and the journal is issuing this retraction as a result.

Machine learning for cryosection pathology predicts the 2021 WHO classification of glioma.

BACKGROUND: Timely and accurate intraoperative cryosection evaluations remain the gold standard for guiding surgical treatments for gliomas. However, the tissue-freezing process often generates artifacts that make histologic interpretation difficult. In addition, the 2021 WHO Classification of Tumors of the Central Nervous System incorporates molecular profiles in the diagnostic categories, so standard visual evaluation of cryosections alone cannot completely inform diagnoses based on the new classification system. METHODS: To address these challenges, we develop the context-aware Cryosection Histopathology Assessment and Review Machine (CHARM) using samples from 1,524 glioma patients from three different patient populations to systematically analyze cryosection slides. FINDINGS: Our CHARM models successfully identified malignant cells (AUROC = 0.98 ± 0.01 in the independent validation cohort), distinguished isocitrate dehydrogenase (IDH)-mutant tumors from wild type (AUROC = 0.79-0.82), classified three major types of molecularly defined gliomas (AUROC = 0.88-0.93), and identified the most prevalent subtypes of IDH-mutant tumors (AUROC = 0.89-0.97). CHARM further predicts clinically important genetic alterations in low-grade glioma, including ATRX, TP53, and CIC mutations, CDKN2A/B homozygous deletion, and 1p/19q codeletion via cryosection images. CONCLUSIONS: Our approaches accommodate the evolving diagnostic criteria informed by molecular studies, provide real-time clinical decision support, and will democratize accurate cryosection diagnoses. FUNDING: Supported in part by the National Institute of General Medical Sciences grant R35GM142879, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the Partners' Innovation Discovery Grant, and the Schlager Family Award for Early Stage Digital Health Innovations.

Contrast-enhanced image-guided lead deployment for left bundle branch pacing.

BACKGROUND: Left bundle branch pacing (LBBP) is a novel conduction system pacing modality, but pacing lead deployment remains challenging. OBJECTIVES: This study aimed to evaluate the feasibility of visualization-enhanced lead deployment for LBBP implantation and to assess LBBP characteristics on the basis of lead tip location. METHODS: Successful LBBP with a well-defined lead tip location by visualization of the tricuspid value annulus in 20 patients was retrospectively analyzed to develop an image-guided technique to identify the LBBP target site. This technique was then prospectively tested in 60 patients who were randomized into 2 groups, one using the standard approach (the standard group) and the other using the image-guided technique (the visualization group). The procedural details, electrophysiological characteristics, and short-term follow-up were compared between groups. RESULTS: LBBP was successfully achieved in 28 patients in the standard group and in 29 in the visualization group. The procedural and fluoroscopic durations in the visualization group (66.76 ± 14.62 and 7.83 ± 2.05 minutes) were significantly shorter than those in the standard group (85.46 ± 20.19 and 11.11 ± 3.51 minutes) (P < .01). The number of lead deployment attempts in the visualization group was lower than that in the standard group (2.03 ± 1.18 vs 2.96 ± 1.17; P < .01), and the proportion of left bundle branch potential recorded was higher (79.3% vs 46.4%; P = .01). CONCLUSION: Using a visualization technique, the procedural and fluoroscopic durations for LBBP implantation were significantly shortened with fewer lead repositioning attempts.

A Comparison of the Electrophysiological and Anatomic Characteristics of Pacing Different Branches of the Left Bundle Conduction System.

Introduction: Left bundle branch pacing (LBBP) is a rapidly growing conduction system pacing technique. However, little is known regarding the electrophysiological characteristics of different types of LBBP. We aimed to evaluate the electrophysiological characteristics and anatomic lead location with pacing different branches of the left bundle branch. Methods: Consecutive bradycardia patients with successful LBBP were enrolled and classified into groups according to the paced electrocardiogram and the lead location. Electrocardiogram, pacing properties, vectorcardiogram, and lead tip location were analyzed. Results: Ninety-one patients were enrolled, including 48 with the left bundle trunk pacing (LBTP) and 43 with the left bundle fascicular pacing (LBFP). The paced QRS duration in the LBTP group was significantly shorter than that in the LBFP group (108.1 ± 9.9 vs. 112.9 ± 11.2 ms, p = 0.03), with a more rightward QRS transition zone (p = 0.01). The paced QRS area in the LBTP group was similar to that during intrinsic rhythm (35.1 ± 15.8 vs. 34.7 ± 16.6 µVs, p = 0.98), whereas in the LBFP group, the paced QRS area was significantly larger compared to intrinsic rhythm (43.4 ± 15.8 vs. 35.7 ± 18.0 µVs, p = 0.01). The lead tip site for LBTP was located in a small fan-shaped area with the tricuspid valve annulus summit as the origin, whereas fascicular pacing sites were more likely in a larger and more distal area. Conclusions: Pacing the proximal left bundle main trunk produced better electrical synchrony compared with pacing the distal left bundle fascicles. A visualization technique can facilitate achieving LBTP.

Phoenixmap: An Abstract Approach to Visualize 2D Spatial Distributions.

The multidimensional nature of spatial data poses a challenge for visualization. In this paper, we introduce Phoenixmap, a simple abstract visualization method to address the issue of visualizing multiple spatial distributions at once. The Phoenixmap approach starts by identifying the enclosed outline of the point collection, then assigns different widths to outline segments according to the segments' corresponding inside regions. Thus, one 2D distribution is represented as an outline with varied thicknesses. Phoenixmap is capable of overlaying multiple outlines and comparing them across categories of objects in a 2D space. We chose heatmap as a benchmark spatial visualization method and conducted user studies to compare performances among Phoenixmap, heatmap, and dot distribution map. Based on the analysis and participant feedback, we demonstrate that Phoenixmap 1) allows users to perceive and compare spatial distribution data efficiently; 2) frees up graphics space with a concise form that can provide visualization design possibilities like overlapping; and 3) provides a good quantitative perceptual estimating capability given the proper legends. Finally, we discuss several possible applications of Phoenixmap and present one visualization of multiple species of birds' active regions in a nature preserve.

Comprehensive plasma metabolites profiling reveals phosphatidylcholine species as potential predictors for cardiac resynchronization therapy response.

AIMS: This study aimed to identify the plasma metabolite fingerprint in patients with heart failure and to develop a prediction tool based on differential metabolites for predicting the response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We prospectively recruited 32 healthy individuals and 42 consecutive patients with HF who underwent CRT between January 2018 and January 2019. Peripheral venous blood samples, clinical data, and echocardiographic signatures were collected before CRT implantation. Liquid chromatography-mass spectrometry was used to perform untargeted metabolites profiling for peripheral plasma under ESI+ and ESI- modes. After 6 month follow-up, patients were categorized as CRT responders or non-responders based on the alterations of echocardiographic characteristics. Compared with healthy individuals, patients with HF had distinct metabolomic profiles under both ESI+ and ESI- modes, featuring increased free fatty acids, carnitine, ß-hydroxybutyrate, and dysregulated lipids with heterogeneous alterations such as phosphatidylcholines (PCs) and sphingomyelins. Disparities of baseline metabolomics profile were observed between CRT responders and non-responders under ESI+ mode but not under ESI- mode. Further metabolites analysis revealed that a group of 20 PCs metabolites under ESI+ mode were major contributors to the distinct profiles between the two groups. We utilized LASSO regression model and identified a panel of four PCs metabolites [including PC (20:0/18:4), PC (20:4/20:0), PC 40:4, and PC (20:4/18:0)] as major predictors for CRT response prediction. Among our whole population (n = 42), receive operating characteristics analysis revealed that the four PCs-based model could nicely discriminate the CRT responders from non-responders (area under the curve = 0.906) with a sensitivity of 83.3% and a specificity of 90.0%. Cross-validation analysis also showed a satisfactory and robust performance of the model with the area under the curve of 0.910 in the training dataset and 0.880 in the testing dataset. CONCLUSIONS: Patients with HF held significantly altered plasma metabolomics profile compared with the healthy individuals. Within the HF group, the non-responders had a distinct plasma metabolomics profile in contrast to the responders to CRT, which was characterized by increased PCs species. A novel predictive model incorporating four PCs metabolites performed well in identifying CRT non-responders. These four PCs might severe as potential biomarkers for predicting CRT response. Further validations are needed in multi-centre studies with larger external cohorts.

DNA methyltransferase 3B deficiency unveils a new pathological mechanism of pulmonary hypertension.

DNA methylation plays critical roles in vascular pathology of pulmonary hypertension (PH). The underlying mechanism, however, remains undetermined. Here, we demonstrate that global DNA methylation was elevated in the lungs of PH rat models after monocrotaline administration or hypobaric hypoxia exposure. We showed that DNA methyltransferase 3B (DNMT3B) was up-regulated in both PH patients and rodent models. Furthermore, Dnmt3b -/- rats exhibited more severe pulmonary vascular remodeling. Consistently, inhibition of DNMT3B promoted proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in response to platelet-derived growth factor-BB (PDGF-BB). In contrast, overexpressing DNMT3B in PASMCs attenuated PDGF-BB-induced proliferation/migration and ameliorated hypoxia-mediated PH and right ventricular hypertrophy in mice. We also showed that DNMT3B transcriptionally regulated inflammatory pathways. Our results reveal that DNMT3B is a previously undefined mediator in the pathogenesis of PH, which couples epigenetic regulations with vascular remodeling and represents a therapeutic target to tackle PH.

Plasma Metabolomic Profiles Differentiate Patients With Dilated Cardiomyopathy and Ischemic Cardiomyopathy.

Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) are common causes of heart failure (HF). Though they share similar clinical characteristics, their differential effects on cardiovascular metabolomics have yet to be elucidated. In this study, we applied a comprehensive metabolomics platform to plasma samples of HF patients with different etiology (38 patients with DCM and 18 patients with ICM) and 20 healthy controls. Significant differences in metabolomics profiling were shown among two cardiomyopathy groups and healthy controls. Two hundred thirty three dysregulated metabolites were identified between DCM vs. healthy controls, and 204 dysregulated metabolites between ICM patients and healthy controls. They have 140 metabolites in common, with fold-changes in the same direction in both groups. Pathway analysis found the commonalities of HF pathways as well as disease-specific metabolic signatures. In addition, we found that a combination panel of 6 metabolites including 1-pyrroline-2-carboxylate, norvaline, lysophosphatidylinositol (16:0/0:0), phosphatidylglycerol (6:0/8:0), fatty acid esters of hydroxy fatty acid (24:1), and phosphatidylcholine (18:0/18:3) may have the potential to differentiate patients with DCM and ICM.

Spermine promotes pulmonary vascular remodelling and its synthase is a therapeutic target for pulmonary arterial hypertension.

Pathological mechanisms of pulmonary arterial hypertension (PAH) remain largely unexplored. Effective treatment of PAH remains a challenge. The aim of this study was to discover the underlying mechanism of PAH through functional metabolomics and to help develop new strategies for prevention and treatment of PAH.Metabolomic profiling of plasma in patients with idiopathic PAH was evaluated through high-performance liquid chromatography mass spectrometry, with spermine identified to be the most significant and validated in another independent cohort. The roles of spermine and spermine synthase were examined in pulmonary arterial smooth muscle cells (PASMCs) and rodent models of pulmonary hypertension.Using targeted metabolomics, plasma spermine levels were found to be higher in patients with idiopathic PAH compared to healthy controls. Spermine administration promoted proliferation and migration of PASMCs and exacerbated vascular remodelling in rodent models of pulmonary hypertension. The spermine-mediated deteriorative effect can be attributed to a corresponding upregulation of its synthase in the pathological process. Inhibition of spermine synthase in vitro suppressed platelet-derived growth factor-BB-mediated proliferation of PASMCs, and in vivo attenuated monocrotaline-mediated pulmonary hypertension in rats.Plasma spermine promotes pulmonary vascular remodelling. Inhibiting spermine synthesis could be a therapeutic strategy for PAH.

Circulating Plasma Metabolomic Profiles Differentiate Rodent Models of Pulmonary Hypertension and Idiopathic Pulmonary Arterial Hypertension Patients.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe progressive disease with systemic metabolic dysregulation. Monocrotaline (MCT)-induced and hypoxia-induced pulmonary hypertension (PH) rodent models are the most widely used preclinical models, however, whether or not these preclinical models recapitulate metabolomic profiles of PAH patients remain unclear. METHODS: In this study, a targeted metabolomics panel of 126 small molecule metabolites was conducted. We applied it to the plasma of the 2 preclinical rodent models of PH and 30 idiopathic pulmonary arterial hypertension (IPAH) patients as well as 30 healthy controls to comparatively assess the metabolomic profiles of PAH patients and rodent models. RESULTS: Significantly different metabolomics profiling and pathways were shown among the 2 classical rodent models and IPAH patients. Pathway analysis demonstrated that methionine metabolism and urea cycle metabolism were the most significant pathway involved in the pathogenesis of hypoxia-induced PH model and MCT-induced model, respectively, and both of them were also observed in the dysregulated pathways in IPAH patients. CONCLUSIONS: These 2 models may develop PAH through different metabolomic pathways and each of the 2 classical PH model resembles IPAH patients in certain aspects.

3-Bromopyruvate Attenuates Experimental Pulmonary Hypertension via Inhibition of Glycolysis.

BACKGROUND: The shift of metabolism from mitochondrial oxidative phosphorylation to glycolysis and mitochondria binding partner of hexokinase are features common to cancer. These have been seen in pulmonary hypertension (PH) as well. An inhibitor of hexokinase 2 (HK 2), the small molecule 3-bromopyruvate (3-BrPA) is an incredibly powerful and swift-acting anticancer agent. However, whether it could be of potential benefit to PH has still been unknown. METHODS: Sprague-Dawley rats with monocrotaline (MCT)-induced PH were administered 2 oral doses of 3-BrPA (15 and 30 mg/kg/day, respectively) for 14 days. Hemodynamic parameters were obtained by right heart catheterization. Histopathology, immunohistochemistry, transmission electron microscopy, flow cytometry, and assessments of relative protein expressions were conducted. RESULTS: Compared with MCT treatment, 3-BrPA decreased mean pulmonary arterial pressure and pulmonary vascular resistance, and increased cardiac output. 3-BrPA significantly suppressed proliferation in addition to enhancing apoptosis of pulmonary artery smooth muscle cells, attenuating small pulmonary artery remodeling and right ventricular hypertrophy. Treatment with 3-BrPA markedly reduced the mitochondrial membrane potential and restored mitochondrial structure. Furthermore, 3-BrPA significantly inhibited HK 2 expression but not HK 1. The expression of both pyruvate dehydrogenase kinase and lactate dehydrogenase was decreased whereas that of pyruvate dehydrogenase and cytosolic cytochrome c was upregulated with 3-BrPA administration. CONCLUSION: This study demonstrates the reversal of PH by 3-BrPA is related to alteration in glycolysis and improved mitochondria function, indicating the "metabolic targeting" as a rational therapeutic strategy for PH.

Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. METHOD: A single subcutaneous injection of monocrotaline (MCT) (60 mg kg- 1) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. RESULTS: Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. CONCLUSION: The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile.

CareerVis: Hierarchical Visualization of Career Pathway Data.

We present our CareerVis system, an interactive visualization tool to aid career education for high school and freshman college students. In additional to its practical use, we believe our design approach has potential to inspire the design community to develop simple visualizations that convey complex information to novice users.

Preparation of well-distributed titania nanopillar arrays on Ti6Al4V surface by induction heating for enhancing osteogenic differentiation of stem cells.

Great effort has recently been devoted to the preparation of nanoscale surfaces on titanium-based implants to achieve clinically fast osteoinduction and osseointegration, which relies on the unique characteristics of the nanostructure. In this work, we used induction heating treatment (IHT) as a rapid oxidation method to fabricate a porous nanoscale oxide layer on the Ti6Al4V surface for better medical application. Well-distributed vertical nanopillars were yielded by IHT for 20-35 s on the alloy surface. The composition of the oxides contained rutile/anatase TiO2 and a small amount of Al2O3 between the TiO2 grain boundaries (GBs). This technology resulted in a reduction and subsequent increase of surface roughness of 26-32 nm when upregulating the heating time, followed by the successive enhancement of the thickness, wettability and adhesion strength of the oxidation layer to the matrix. The surface hardness also distinctly rose to 554 HV in the IHT-35 s group compared with the 350 HV of bare Ti6Al4V. The massive small-angle GBs in the bare alloy promoted the formation of nanosized oxide crystallites. The grain refinement and deformation texture reduction further improved the mechanical properties of the matrix after IHT. Moreover, in vitro experiments on a mesenchymal stem cell (BMSC) culture derived from human bone marrow for 1-7 days indicated that the nanoscale layers did not cause cytotoxicity, and facilitated cell differentiation in osteoblasts by enhancing the gene and osteogenesis-related protein expressions after 1-3 weeks of culturing. The increase of the IHT time slightly advanced the BMSC proliferation and differentiation, especially during long-term culture. Our findings provide strong evidence that IHT oxidation technology is a novel nanosurface modification technology, which is potentially promising for further clinical development.

A bioactive coating with submicron-sized titania crystallites fabricated by induction heating of titanium after tensile deformations.

Thermal oxidation technology was widely investigated as one of effective surface modification method for improving the bioactivity and biocompatibility of titanium and its alloys. In this work, the induction heat oxidization method, a fast, efficient, economical and environmental protective technology, was applied to prepare the submicron-morphological oxide coating with variable rutile TiO2 equiaxed crystallites on the surface of pure Ti substrates after cold-drawing with 10-20% deformations. The results showed the plastic-deformed Ti cylinders recrystallized during induction heating treatment (IHT) for 10-20s which resulted in evolution of microstructures as well as slight improvement of microhardness. The surface characteristics of TiO2 crystallites in oxidation layers were determined by the microstructural evolutions of Ti substrate in terms of the nucleation and growth of TiO2 crystallites. Specially, the oxidized surface with 50-75nm roughness and more uniform and finer equiaxed oxide grains remarkablely improved the apatite deposition after bioactive evaluation in 1.5 × SBF for 7 days. This work provided a potential method to create controlled bioactive oxide coatings with submicro-/nano-scaled TiO2 crystallites on titanium substrate in terms of the role of metallographic microstructure in the formation process of titanium oxides.