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Nitroimidazoles comprise a class of broad-spectrum anti-microbial drugs with efficacy against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. Among these drugs, metronidazole (MTZ) is commonly used with other antibiotics to prevent infection in open fractures. However, the effect of MTZ on bone remains understudied. In this paper, we evaluated six nitroimidazole drugs for their impact on osteoblast differentiation and identified MTZ as having the highest osteogenic effect. MTZ enhanced bone regeneration at the femur osteotomy site in osteopenic ovariectomized (OVX) rats at the human equivalent dose. Moreover, in OVX rats, MTZ significantly improved bone mass and strength and improved microarchitecture compared to the vehicle-treated rats, which was likely achieved by an osteogenic mechanism attributed to the stimulation of the Wnt pathway in osteoblasts. To mitigate the reported neurological and genotoxic effects of MTZ, we designed an injectable sustained-release in situ gel formulation of the drug that improved fracture healing efficacy by 3.5-fold compared to oral administration. This enhanced potency was achieved through a significant increase in the circulating half-life and bioavailability of MTZ. We conclude that MTZ exhibits osteogenic effects, further accentuated by our sustained-release delivery system, which holds promise for enhancing bone regeneration in open fractures. [ABSTRACT FROM AUTHOR]

Biomedical imaging devices, in general, have been made and used a lot lately to examine the insides of the body during diagnostic and analytic procedures. Biomedical imaging gives accurate information about metabolites, which can be used to find and classify diseases because it is not invasive. For the study of cervical cancer (CC), the pap smear is a crucial type of biological imaging. CC is a crucial reason to enhance the rate of women's mortalities. Proper screening of pap smear images is critical for assisting in the early detection and analysis of CC. Computer‐aided systems for cancerous cell recognition need well established artificial intelligence (AI) methods. In this study, we introduce an automated Cervical Precancerous Lesion Classification using Quantum Invasive Weed Optimization with Deep Learning (CPLC‐QIWODL) on biomedical pap smear images. The presented CPLC‐QIWODL technique examines the pap smear images for cervical cancer classification. To do so, the presented CPLC‐QIWODL technique pre‐processes the biomedical images using a Gabor filtering (GF) approach. Moreover, the CPLC‐QIWODL technique uses a deep convolutional neural network‐based SqueezeNet system for feature extraction. Furthermore, the hyperparameter tuning of the SqueezeNet methodology takes place using the QIWO technique, showing the novelty of the work. Finally, to classify CC, the deep variational autoencoder (DVAE) model is applied. The experimental result analysis of the CPLC‐QIWODL technique is tested using a benchmark medical image database. Extensive comparative results demonstrated the enhanced outcomes of the CPLC‐QIWODL technique over other existing algorithms, with a maximum accuracy of 99.07%. [ABSTRACT FROM AUTHOR]

A few ubiquitin ligases have been shown to target Runx2, the key osteogenic transcription factor and thereby regulate bone formation. The regulation of Runx2 expression and function are controlled both at the transcriptional and posttranslational levels. Really interesting new gene (RING) finger ubiquitin ligases of which RNF138 is a member are important players in the ubiquitin‐proteasome system, contributing to the regulation of protein turnover and cellular processes. Here, we demonstrated that RNF138 negatively correlated with Runx2 protein levels in osteopenic ovariectomized rats which implied its role in bone loss. Accordingly, RNF138 overexpression potently inhibited osteoblast differentiation of mesenchyme‐like C3H10T1/2 as well primary rat calvarial osteoblast (RCO) cells in vitro, whereas overexpression of catalytically inactive mutant RNF138Δ18‐58 (lacks RING finger domain) had mild to no effect. Contrarily, RNF138 depletion copiously enhanced endogenous Runx2 levels and augmented osteogenic differentiation of C3H10T1/2 as well as RCOs. Mechanistically, RNF138 physically associates within multiple regions of Runx2 and ubiquitinates it leading to its reduced protein stability in a proteasome‐dependent manner. Moreover, catalytically active RNF138 destabilized Runx2 which resulted in inhibition of its transactivation potential and physiological function of promoting osteoblast differentiation leading to bone loss. These findings underscore the functional involvement of RNF138 in bone formation which is primarily achieved through its modulation of Runx2 by stimulating ubiquitin‐mediated proteasomal degradation. Thus, our findings indicate that RNF138 could be a promising novel target for therapeutic intervention in postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

This editorial discusses the role of posttranslational modifications (PTMs) in cancer biology. It highlights various articles published in the journal "Frontiers in Oncology" that explore PTMs of key proteins and their association with cancer pathogenesis. The articles cover topics such as phosphorylation, ubiquitination, and acetylation, and their impact on protein functionality and cancer progression. The findings emphasize the importance of understanding PTMs in order to develop novel biomarkers and therapeutic targets for cancer treatment. [Extracted from the article]

The brain‐computer interface (BCI) enables individuals with impairments to interact with the real world without relying on the neuromuscular pathway. BCI leverages artificial intelligence (AI) models for control. It can capture brain activity patterns associated with mental processes and convert them into commands for actuators. One promising application of BCI is in rehabilitation centres. When compared to traditional methods integrated with machine learning (ML) approaches that were initially explored in the past decade, there is a relatively limited number of studies utilizing deep learning (DL) approaches in BCI applications. A novel approach has been developed for the automatic recognition of motor imagery (MI) tasks. This article introduces the improved sparrow search algorithm with deep transfer learning‐based EEG motor imagery classification (ISSADTL‐EEGMIC) algorithm for BCIs. The presented ISSADTL‐EEGMIC algorithm primarily focuses on the automated classification of motor imagery tasks. To achieve this, the ISSADTL‐EEGMIC method first preprocesses EEG signals using the wavelet packet decomposition (WPD) technique. Additionally, it employs the neural architecture search network (NASNet) technique for feature extraction. Moreover, the ISSADTL‐EEGMIC model performs the classification process using the stacked sparse autoencoder (SSAE) model. Furthermore, hyperparameter optimization of the SSAE model is performed using the ISSA technique, which helps achieve maximum classification performance. The results from the simulation of the ISSADTL‐EEGMIC algorithm have been examined using two benchmark datasets. The experimental findings suggest that it outperforms recent approaches in terms of performance. [ABSTRACT FROM AUTHOR]

The present study aims to analyze the role of microRNA‐1 in the regulation of skeletal muscle loss under hypobaric hypoxia (HH). Male Sprague Dawley rats (n = 10) weighing 230–250 g are divided into two groups, control and HH exposure for 7 days at 25 000 ft. After the hypoxia exposure, the animals are sacrificed and hindlimb skeletal muscles are excised for further analysis. Studies found the potential role of miR‐1 (myomiR) as a biomarker under different atrophic conditions. Prolonged exposure to HH leads to enhanced expression of miR‐1 in skeletal muscle as compared to unexposed controls. The Bioinformatics approach is used to identify the validated targets and the biological processes of miR‐1. The target prediction tools identify PAX3 and HSP70 as major targets for miR‐1. Exposure to HH significantly reduces PAX3 and HSP70 expression during 7 days of HH exposure, which further enhances the activity of FOXO3, MSTN, and ATROGIN known for the progression of skeletal muscle atrophy in relation to control rats. This study indicates the increased expressions of miR‐1 and reduced expression of PAX3 and HSP70 lead to impaired myogenesis in skeletal muscle under HH. Further, enhanced expression of muscle degradation genes such as FOXO3, MSTN, and ATROGIN under HH exposure causes skeletal muscle protein loss. [ABSTRACT FROM AUTHOR]

This CBCT‐based study analysed morphometric relationships in Mesio‐Buccal (MB) roots of maxillary first molars (MFM). 133 MFM with two MB canals were assessed and classified using Vertucci's classification. MB roots' length and MB1‐MB2 canals inter‐orifice distances (IOD) were noted. The data were analysed using SPSS software. The most frequently present canal was type IV (59.4%) followed by type II (40.6%). Mean MB roots' length for canals exhibiting type IV was 9.26 ± 0.21 mm and of those exhibiting type II was 12.8 ± 0.42 mm. Statistically significant relationship was found between MB root length and canal type. Mean IOD for type II and type IV canals was 2.4 ± 0.47 and 3.8 ± 0.21 mm, respectively. Statistically significant relationship was found between IOD and canal type. Length of MB root and IOD had a significant association with canal type present in MFM. This knowledge can enhance clinicians' understanding of canal morphology which can increase predictability and success rate of endodontic treatment. [ABSTRACT FROM AUTHOR]

Background and Objectives: An understanding of the anatomical complexity of teeth is a significant factor for a successful endodontic treatment outcome. The aim of this study was to explore the frequency and pattern of distribution of radix entomolaris (RE) in mandibular first molars (MFMs) of a Saudi Arabian subpopulation using CBCT scans. Materials and Methods: This study was conducted at dental clinics of Qassim University from February to May 2023 by evaluating CBCT scans that were previously obtained for diagnostic purposes. Scans of Saudi national patients with bilaterally present MFMs and fully formed root apices were included. Conversely, scans with one/or two missing MFMs, MFMs with incomplete root apices, full- or partial-coverage prosthesis, endodontic treatment, and associated radicular resorption were excluded from study. A total of 303 CBCT scans with 606 bilateral MFMs were analyzed by two calibrated evaluators for the presence of, and type according to Song's typolgy of RE. The data were analyzed using SPPS-24. The descriptive variables were documented as frequencies and percentages. The chi-square test was used to determine the association between the prevalence of RE with the gender, jaw side and age group. Both inter-rater and intra-rater agreements were estimated for detecting and classifying RE using Cohen's kappa test. Results: The sample had 63.7% males and 36.3% females. The prevalence of RE was 6.6%, with Song's type III (57.5%) as the most common variant. Absolute agreement was noted between the raters about the presence of RE and very strong agreement was noted for the classification of the RE. Conclusions: RE is an uncommon finding among the mandibular first molars of the Saudi population without any gender and quadrant predilection. The clinicians' knowledge of the presence and Song's type of RE may contribute towards the enhancement of endodontic treatment outcomes. [ABSTRACT FROM AUTHOR]