Application of Halloysite Nanotubes in Bone Disease Remediation and Bone Regeneration

Customized patient therapy has been a major research focus in recent years. There are two research fields that have made a significant contribution to realizing individualized-based treatment: targeted drug delivery and three-dimensional (3D) printing technology. With benefit from the advances in nanotechnology and biomaterial science, various drug delivery systems have been established to provide precise control of therapeutic agents release in time and space. The emergence of three-dimensional (3D) printing technology enables the fabrication of complicated structures that effectively mimic native tissues and makes it possible to print patient-specific implants. My dissertation research used a clay nanoparticle, halloysite, to develop a drug delivery system and 3D scaffold which may contribute to individualized-based treatment. Halloysite nanotubes (HNTs) are naturally occurring tubular nanoparticles with a hollow lumen. They possess a high aspect ratio, thermal stability, and unique oppositely charged inner and outer surfaces. These inherent features enable them to be used as a bulk filler to improve the performance characteristics of many polymers. Besides, HNTs are biocompatible and have a demonstrated capacity to delivery growth factors, RNA, DNA and other chemical substances; therefore, HNTs have received extensive attention in the development of drug delivery systems. In this dissertation, HNTs were applied in the development of medical devices for bone disease remediation, tissue regeneration, and restoration of bone function. Osteomyelitis is a bone infection and mainly caused by Staphylococcus aureus (S. aureus). Gentamicin is the antibiotic commonly used to against gram- negative and positive bacteria, which includes S. aureus. When gentamicin was loaded into HNTs and incorporated with chitosan, the hybrid chitosan/HNTs hydrogels provided a sustained drug release and successfully inhibited the growth of S. aureus. Simultaneously, the addition of HNTs improved chitosan mechanical properties. Osteosarcoma is the most common cancer tumor occurring in bone tissue. Through surface modification, HNTs were conjugated with folic acid and fluorochrome (FITC). The bi-functionalized HNTs (bHNTs) were then doped with anticancer drugs, methotrexate (MTX). MTX-doped bHNTs showed a high drug loading efficiency and selectively targeted cancer cells. MTX-loaded bHNTs efficiently inhibited osteosarcoma proliferation without harm to normal type cells (pre-osteoblasts). Osteoporosis is the most common bone disease as the bone formation fails to keep up with the bone resorption rate. Bone fractures happen as a result of long-term bone defection. Three dimensional printed scaffolds that support bone regeneration could be a viable alternative to bone grafting, which is limited by insufficient supplies and issued with infection. Metal-doped HNTs were combined with PLA and printed with a specific pore size and porosity design. After surface modification, 3D printed HNTs/PLA scaffolds encouraged cell adhesion and osteogenic differentiation. Furthermore, surface coating of gentamicin had a long stock life to inhibit bacterial growth and promoted osteogenesis

The Strontium-Coated Clay Nanoparticles in Calcium Phosphate Cement for Biomedical Applications

Anusha Elumalai, Yangyang Luo, and Ahmed Humayun are graduate students in Molecular Science and Nanotechnology at Louisiana Tech University. Dr. David K. Mills is a professor in the School of Biological Sciences at Louisiana Tech University. The abstract for The Strontium-Coated Clay Nanoparticles in Calcium Phosphate Cement for Biomedical Applications can be downloaded by clicking on the blue download button

RIGID: Recurrent GAN Inversion and Editing of Real Face Videos

GAN inversion is indispensable for applying the powerful editability of GAN to real images. However, existing methods invert video frames individually often leading to undesired inconsistent results over time. In this paper, we propose a unified recurrent framework, named \textbf{R}ecurrent v\textbf{I}deo \textbf{G}AN \textbf{I}nversion and e\textbf{D}iting (RIGID), to explicitly and simultaneously enforce temporally coherent GAN inversion and facial editing of real videos. Our approach models the temporal relations between current and previous frames from three aspects. To enable a faithful real video reconstruction, we first maximize the inversion fidelity and consistency by learning a temporal compensated latent code. Second, we observe incoherent noises lie in the high-frequency domain that can be disentangled from the latent space. Third, to remove the inconsistency after attribute manipulation, we propose an \textit{in-between frame composition constraint} such that the arbitrary frame must be a direct composite of its neighboring frames. Our unified framework learns the inherent coherence between input frames in an end-to-end manner, and therefore it is agnostic to a specific attribute and can be applied to arbitrary editing of the same video without re-training. Extensive experiments demonstrate that RIGID outperforms state-of-the-art methods qualitatively and quantitatively in both inversion and editing tasks. The deliverables can be found in \url{https://cnnlstm.github.io/RIGID}Comment: ICCV202

The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review

Autoimmune diseases are usually complex and multifactorial, characterized by aberrant production of autoreactive immune cells and/or autoantibodies against healthy cells and tissues. However, the pathogenesis of autoimmune diseases has not been clearly elucidated. The activation, differentiation, and development of CD8+ T cells can be affected by numerous inflammatory cytokines, transcription factors, and chemokines. In recent years, epigenetic modifications have been shown to play an important role in the fate of CD8+ T cells. The discovery of these modifications that contribute to the activation or suppression of CD8+ cells has been concurrent with the increasing evidence that CD8+ T cells play a role in autoimmunity. These relationships have been studied in various autoimmune diseases, including multiple sclerosis (MS), systemic sclerosis (SSc), type 1 diabetes (T1D), Grave's disease (GD), systemic lupus erythematosus (SLE), aplastic anemia (AA), and vitiligo. In each of these diseases, genes that play a role in the proliferation or activation of CD8+ T cells have been found to be affected by epigenetic modifications. Various cytokines, transcription factors, and other regulatory molecules have been found to be differentially methylated in CD8+ T cells in autoimmune diseases. These genes are involved in T cell regulation, including interferons, interleukin (IL),tumor necrosis factor (TNF), as well as linker for activation of T cells (LAT), cytotoxic T-lymphocyte–associated antigen 4 (CTLA4), and adapter proteins. MiRNAs also play a role in the pathogenesis of these diseases and several known miRNAs that are involved in these diseases have also been shown to play a role in CD8+ regulation

Distinguish bipolar and major depressive disorder in adolescents based on multimodal neuroimaging:Results from the Adolescent Brain Cognitive Development study^®

Background: Major depressive disorder and bipolar disorder in adolescents are prevalent and are associated with cognitive impairment, executive dysfunction, and increased mortality. Early intervention in the initial stages of major depressive disorder and bipolar disorder can significantly improve personal health. Methods: We collected 309 samples from the Adolescent Brain Cognitive Development study, including 116 adolescents with bipolar disorder, 64 adolescents with major depressive disorder, and 129 healthy adolescents, and employed a support vector machine to develop classification models for identification. We developed a multimodal model, which combined functional connectivity of resting-state functional magnetic resonance imaging and four anatomical measures of structural magnetic resonance imaging (cortical thickness, area, volume, and sulcal depth). We measured the performances of both multimodal and single modality classifiers. Results: The multimodal classifiers showed outstanding performance compared with all five single modalities, and they are 100% for major depressive disorder versus healthy controls, 100% for bipolar disorder versus healthy control, 98.5% (95% CI: 95.4–100%) for major depressive disorder versus bipolar disorder, 100% for major depressive disorder versus depressed bipolar disorder and the leave-one-site-out analysis results are 77.4%, 63.3%, 79.4%, and 81.7%, separately. Conclusions: The study shows that multimodal classifiers show high classification performances. Moreover, cuneus may be a potential biomarker to differentiate major depressive disorder, bipolar disorder, and healthy adolescents. Overall, this study can form multimodal diagnostic prediction workflows for clinically feasible to make more precise diagnose at the early stage and potentially reduce loss of personal pain and public society

OsbZIP18, a Positive Regulator of Serotonin Biosynthesis, Negatively Controls the UV-B Tolerance in Rice

Serotonin (5-hydroxytryptamine) plays an important role in many developmental processes and biotic/abiotic stress responses in plants. Although serotonin biosynthetic pathways in plants have been uncovered, knowledge of the mechanisms of serotonin accumulation is still limited, and no regulators have been identified to date. Here, we identified the basic leucine zipper transcription factor OsbZIP18 as a positive regulator of serotonin biosynthesis in rice. Overexpression of OsbZIP18 strongly induced the levels of serotonin and its early precursors (tryptophan and tryptamine), resulting in stunted growth and dark-brown phenotypes. A function analysis showed that OsbZIP18 activated serotonin biosynthesis genes (including tryptophan decarboxylase 1 (OsTDC1), tryptophan decarboxylase 3 (OsTDC3), and tryptamine 5-hydroxylase (OsT5H)) by directly binding to the ACE-containing or G-box cis-elements in their promoters. Furthermore, we demonstrated that OsbZIP18 is induced by UV-B stress, and experiments using UV-B radiation showed that transgenic plants overexpressing OsbZIP18 exhibited UV-B stress-sensitive phenotypes. Besides, exogenous serotonin significantly exacerbates UV-B stress of OsbZIP18_OE plants, suggesting that the excessive accumulation of serotonin may be responsible for the sensitivity of OsbZIP18_OE plants to UV-B stress. Overall, we identified a positive regulator of serotonin biosynthesis and demonstrated that UV-B-stress induced serotonin accumulation, partly in an OsbZIP18-dependent manner

Multi-parametric MRI-based peritumoral radiomics on prediction of lymph-vascular space invasion in early-stage cervical cancer

PURPOSEThis retrospective study aims to evaluate the use of multi-parametric magnetic resonance imaging (MRI) in predicting lymph-vascular space invasion (LVSI) in early-stage cervical cancer using radiomics methods.METHODSA total of 163 patients who underwent contrast-enhanced T1-weighted (CE T1W) and T2-weighted (T2W) MRI scans at 3.0T were enrolled between January 2014 and September 2019. Radiomics features were extracted and selected from the tumoral and peritumoral regions at different dilation distances outside the tumor. Mann–Whitney U test, the least absolute shrinkage and selection operator logistic regression, and logistic regression was applied to select the predictive features and develop the radiomics signature. Univariate analysis was performed on the clinical characteristics. The radiomics nomogram was constructed incorporating the radiomics signature and the selected important clinical predictor. Prediction performance of the radiomics signature, clinical model, and nomogram was evaluated with the area under the curve (AUC), specificity, sensitivity, calibration, and decision curve analysis (DCA).RESULTSA total of 5 features that were selected from the peritumoral regions with 3- and 7-mm dilation distances outside tumors in CE T1W and T2W MRI, respectively, showed optimal discriminative performance. The radiomics signature comprising the selected features was significantly associated with the LVSI status. The radiomics nomogram integrating the radiomics signature and degree of cellular differentiation exhibited the best predictability with AUCs of 0.771 (specificity (SPE)=0.831 and sensitivity (SEN)=0.581) in the training cohort and 0.788 (SPE=0.727, SEN=0.773) in the validation cohort. DCA confirmed the clinical usefulness of our model.CONCLUSIONOur results illustrate that the radiomics nomogram based on MRI features from peritumoral regions and the degree of cellular differentiation can be used as a noninvasive tool for predicting LVSI in cervical cancer

Clinical efficacy and safety of robotic retroperitoneal lymph node dissection for testicular cancer: a systematic review and meta-analysis

BackgroundRetroperitoneal lymph node dissection (RPLND) is an effective treatment for testicular tumors. In recent years, with the development of robotics, many urological procedures performed via standard laparoscopy have been replaced by robots. Our objective was to compare the safety and efficacy of robotic retroperitoneal lymph node dissection (R-RPLND) versus Non-robotic retroperitoneal lymph node dissection (NR-RPLND) in testicular cancer.MethodsPubmed, Embase, Scopus, Cochrane Library, and Web of Science databases were searched for literature on robotic surgery for testicular germ cell tumors up to April 2023. The statistical and sensitivity analyses were performed using Review Manager 5.3. Meta-analysis was performed to calculate mean difference (MD), odds ratio(OR), and 95% confidence interval (CI) effect indicators.ResultsEight studies with 3875 patients were finally included in this study, 453 with R-RPLND and 3422 with open retroperitoneal lymph node dissection (O-RPLND)/laparoscopic retroperitoneal lymph node dissection (L-RPLND). The results showed that R-RPLND had lower rates of intraoperative blood loss (MD = -436.39; 95% CI -707.60 to -165.19; P = 0.002), transfusion (OR = 0.06; 95% CI 0.01 to 0.26; P = 0.0001), total postoperative complication rates (OR = 0.39; 95% CI 0.21 to 0.70; P = 0.002), and length of stay (MD=-3.74; 95% CI -4.69 to -2.78; P<0.00001). In addition, there were no statistical differences between the two groups regarding perioperative and oncological outcomes regarding total operative time, the incidence of postoperative complications grade≥III, abnormal ejaculation rate, lymph node yield, and postoperative recurrence rate.ConclusionsThe R-RPLND and O-RPLND/L-RPLND provide safe and effective retroperitoneal lymph node dissection for testicular cancer. Patients with R-RPLND have less intraoperative bleeding, shorter hospitalization period, fewer postoperative complications, and faster recovery. It should be considered a viable alternative to O-RPLND/L-RPLND.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023411696