Pharmacokinetic/Pharmacodynamic assessment of the structural refinement of clopidogrel focusing on the balance between bioactivation and deactivation.

The delicate balance between ischemic and bleeding risks is a significant consideration in the administration of antiplatelet therapy. Clopidogrel and prasugrel, both members of the thienopyridine class of antiplatelet drugs, are well established for their variability in individual responsiveness and for a high number of bleeding events, respectively. The current study focuses on evaluating the pharmacokinetics and pharmacodynamics of a series of deuterated clopidogrel derivatives, leveraging insights gained from the structure-pharmacokinetic relationships in the development of thienopyridine drugs. Our approaches were based on the molecular skeleton of clopidogrel and adopted the C2-pharmacophore design from prasugrel. The selected C2-pharmacophore distinguishes itself from the acetyloxy substituent of prasugrel by exhibiting a moderated hydrolysis rate, resulting in a gentler formation of the active metabolite. An excessive and burst release of the active metabolite are therefore to be avoided, as it is believed to be associated with an increased risk of bleeding. Our proposed structural modification maintains the hydrolysis-sensitive methyl ester of clopidogrel but replaces it with a deuterated methyl group, which has been shown to effectively reduce metabolic deactivation. The evaluation of the clopidogrel derivatives has been primarily based on the criteria related to the exposure to active metabolites. Three promising compounds demonstrate higher biotransformation efficiency, similar Cmax, delayed Tmax, enhanced antiplatelet activity, and a lower risk of bleeding compared to clopidogrel, when administered at a dosage resulting in a similar exposure to the active metabolites. Significance Statement The pharmacokinetics and pharmacodynamics of a series of newly designed clopidogrel derivatives were assessed to validate the rationale for their structural modifications. Three promising compounds displayed balanced pharmacokinetics, characterized by slower deactivation compared to clopidogrel and a more gradual bioactivation than prasugrel. Under similar exposure to active metabolites, these compounds have demonstrated enhanced antiplatelet activity and a diminished risk of bleeding compared to clopidogrel. The D3-clopidogrel-ozagrel conjugate was found to exert a synergistic therapeutic effect.

PHLDA2 overexpression facilitates senescence and apoptosis via the mitochondrial route in human nucleus pulposus cells by regulating Wnt/ß-catenin signalling pathway.

Low back pain is a common clinical symptom of intervertebral disc degeneration (IVDD), which seriously affects the quality of life of the patients. The abnormal apoptosis and senescence of nucleus pulposus cells (NPCs) play important roles in the pathogenesis of IVDD. PHLDA2 is an imprinted gene related to cell apoptosis and tumour progression. However, its role in NPC degeneration is not yet clear. Therefore, this study was set to explore the effects of PHLDA2 on NPC senescence and apoptosis and the underlying mechanisms. The expression of PHLDA2 was examined in human nucleus pulposus (NP) tissues and NPCs. Immunohistochemical staining, magnetic resonance imaging imaging and western blot were performed to evaluate the phenotypes of intervertebral discs. Senescence and apoptosis of NPCs were assessed by SA-ß-galactosidase, flow cytometry and western blot. Mitochondrial function was investigated by JC-1 staining and transmission electron microscopy. It was found that the expression level of PHLDA2 was abnormally elevated in degenerated human NP tissues and NPCs. Furthermore, knockdown of PHLDA2 can significantly inhibit senescence and apoptosis of NPCs, whereas overexpression of PHLDA2 can reverse senescence and apoptosis of NPCs in vitro. In vivo experiment further confirmed that PHLDA2 knockdown could alleviate IVDD in rats. Knockdown of PHLDA2 could also reverse senescence and apoptosis in IL-1ß-treated NPCs. JC-1 staining indicated PHLDA2's knockdown impaired disruption of the mitochondrial membrane potential and also ameliorated superstructural destruction of NPCs as showed by transmission electron microscopy. Finally, we found the PHLDA2 knockdown promoted Collagen-II expression and suppressed MMP3 expression in NPCs by repressing wnt/ß-catenin pathway. In conclusion, the results of the present study showed that PHLDA2 promotes IL-1ß-induced apoptosis and senescence of NP cells via mitochondrial route by activating the Wnt/ß-catenin pathway, and suggested that therapy targeting PHLDA2 may provide valuable insights into possible IVDD therapies.

The Roles of Circular RNAs in Ischemic Stroke through Modulating Neuroinflammation.

Ischemic stroke (IS) remains a serious threat to human health. Neuroinflammatory response is an important pathophysiological process after IS. Circular RNAs (circRNAs), a member of the non-coding RNA family, are highly expressed in the central nervous system and widely involved in regulating physiological and pathophysiological processes. This study reviews the current evidence on neuroinflammatory responses, the role of circRNAs in IS and their potential mechanisms in regulating inflammatory cells, and inflammatory factors affecting IS damage. This review lays a foundation for future clinical application of circRNAs as novel biomarkers and therapeutic targets.

A subject-specific unsupervised deep learning method for quantitative susceptibility mapping using implicit neural representation.

Quantitative susceptibility mapping (QSM) is an MRI-based technique that estimates the underlying tissue magnetic susceptibility based on phase signal. Deep learning (DL)-based methods have shown promise in handling the challenging ill-posed inverse problem for QSM reconstruction. However, they require extensive paired training data that are typically unavailable and suffer from generalization problems. Recent model-incorporated DL approaches also overlook the non-local effect of the tissue phase in applying the source-to-field forward model due to patch-based training constraint, resulting in a discrepancy between the prediction and measurement and subsequently suboptimal QSM reconstruction. This study proposes an unsupervised and subject-specific DL method for QSM reconstruction based on implicit neural representation (INR), referred to as INR-QSM. INR has emerged as a powerful framework for learning a high-quality continuous representation of the signal (image) by exploiting its internal information without training labels. In INR-QSM, the desired susceptibility map is represented as a continuous function of the spatial coordinates, parameterized by a fully-connected neural network. The weights are learned by minimizing a loss function that includes a data fidelity term incorporated by the physical model and regularization terms. Additionally, a novel phase compensation strategy is proposed for the first time to account for the non-local effect of tissue phase in data consistency calculation to make the physical model more accurate. Our experiments show that INR-QSM outperforms traditional established QSM reconstruction methods and the compared unsupervised DL method both qualitatively and quantitatively, and is competitive against supervised DL methods under data perturbations.

Sluggish and Ion-Resilient Behavior of Interfacial Aqueous Layer on Single-Layer Graphene Oxide: Insights from In Situ Atomic Force Microscopy.

Understanding interfacial interactions of graphene oxide (GO) is important to evaluate its colloidal behavior and environmental fate. Single-layer GO is the fundamental unit of GO colloids, and its interfacial aqueous layers critically dictate these interfacial interactions. However, conventional techniques like X-ray diffraction are limited to multilayer systems and are inapplicable to single-layer GO. Therefore, our study employed atomic force microscopy to precisely observe the in situ dynamic behaviors of interfacial aqueous layers on single-layer GO. The interfacial aqueous layer height was detected at the subnanometer level. In real-time monitoring, the single-layer height increased from 1.17 to 1.70 nm within 3 h immersion. This sluggish process is different from the rapid equilibration of multilayer GO in previous studies, underscoring a gradual transition in hydration kinetics. Ion strength exhibited negligible influence on the single-layer height, suggesting a resilient response of the interfacial aqueous layer to ion-related perturbations due to intricate ion interactions and electrical double-layer compression. Humic acid led to a substantial increase in the interfacial aqueous layers, improving the colloidal stability of GO and augmenting its potential for migration. These findings hold considerable significance regarding the environmental behaviors of the GO interfacial aqueous layer in ion- and organic-rich water and soil.

Facile and efficient synthesis of sweater-ball shaped metal-organic framework/nickel sulfide nanoheterojunction for boosting electrochemical glucose sensing.

The synthesis of heterojunction materials is regarded as an efficient way to enhance catalytic activities in various catalytic reactions. However, the existing fabrication approaches often rely on complex multi-step synthesis process. In this work, we fabricate sweater-ball shaped nanostructured MOF/TMS (Ni-MOF/NiS1.03) heterojunction by one-pot, one-step solvothermal method. According to the results of discrete Fourier transform (DFT) calculations and experiments, the formation of Ni-MOF/NiS1.03 heterojunction interfaces improves electron transfer and charge redistribution, and increases the adsorption energy of glucose molecules as well, which is conducive to enhance electrochemical activity of electrode materials. The as-prepared Ni-MOF/NiS1.03 heterojunction exhibit enhanced glucose sensitivity, wide detection range and low detection limit. This study paves the way towards the development of MOF-based heterojunctions for electrochemical applications.

Therapeutic effect of notoginseng saponins before and after fermentation on blood deficiency rats.

Notoginseng saponins (NS) are the active ingredients in Panax notoginseng (Burk.) F.H. Chen (PN). NS can be transformed depending on how the extract is processed. Fermentation has been shown to produce secondary ginsenosides with increased bioavailability. However, the therapeutic effect of fermented NS (FNS) requires further study. The present study compared the compositions and activities of FNS and NS in blood deficiency rats, which resembles the symptoms of anemia in modern medicine, induced by acetylphenylhydrazine and cyclophosphamide. A total of 32 rats were randomly divided into control, model, FNS and NS groups. A blood deficiency model was established and then treatment was orally administered for 21 days. The results of component analysis indicated that some saponins transformed during the fermentation process resulting in a decrease of notoginsenoside R1, and ginsenosides Rg1, Rb1 and Re, and an increase in ginsenosides Rd, Rh2, compound K, protopanaxadiol and protopanaxatriol. The animal results showed that both FNS and NS increased the number of white blood cells (WBCs), red blood cells, hemoglobin, platelets and reticulocytes, and the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO) and thrombopoietin (TPO), decreased the G0/G1 phase and increased G2/M phase, and decreased the apoptosis rate of bone marrow (BM) cells, which suggested a contribution to the recovery of hematopoietic function of the BM cells. FNS and NS increased the protein expression levels of the cytokines IL-4, IL-10, IL-12, IL-13, TGF-ß, IL-6, IFN-γ and TNF-α, and the mRNA expression levels of transcription factors GATA binding protein 3 and T-box expressed in T cell (T-bet). FNS and NS treatment also increased the number of CD4+ T cells, and decreased the enlargement of the rat spleen and thymus atrophy, which indicated a protective effect on the organs of the immune system. The results of the present study demonstrated that compared with NS, FNS showed an improved ability to increase the levels of WBCs, lymphocytes, GM-CSF, EPO, TPO, aspartate aminotransferase, IL-10, IL-12, IL-13 and TNF-α, and the mRNA expression levels of T-bet, and decrease alanine aminotransferase levels. The differences seen for FNS treatment could arise from their improved bioavailability compared with NS, due to the larger proportion of hydrophobic ginsenosides produced during fermentation.

Molecular phylogenetics of the Umbelopsis genus-identification of new species and evaluation of their oil application value.

AIMS: The aim of this study was to reconstruct the evolutionary framework of the genus Umbelopsis by using modern taxonomic strategies and evaluating the quality of oil and prospective uses of three distinct species. METHODS AND RESULTS: Three species of Umbelopsis were identified based on morphological characteristics and phylogenetic evidence obtained from three genes (ITS, LSU, and ACT). A new species of Umbelopsis was described and illustrated, and subsequently named U. ophiocordycipiticola. The characteristics of U. ophiocordycipiticola exhibited sporangia with a diameter ranging from 8 to 17 µm. and sporangiospores that were oval to ellipsoidal in shape, irregularly angular, with dimensions of ∼1.9-2.9 × 1.7-3.0 µm. Gas chromatography and mass spectrometry (GC-MS) were used to examine the composition of fatty acids. Notably, U. ophiocordycipiticola showed a significantly higher oil content of 50.89% in dry cell weight (DCW) compared to U. vinacea and U. ramanniana. The mean proportion of polyunsaturated fatty acids (PUFAs) in U. ophiocordycipiticola was 32.38%, and the maximum levels of γ-linolenic acid (GLA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in U. ophiocordycipiticola were found to be 14.51, 0.24, 0.54, and 0.53%, respectively. The biodiesel quality from all three species complied with applicable standards set by the American Association for Testing and Materials (ASTM 6751) and the Brazilian National Petroleum Agency (ANP 255). CONCLUSIONS: The establishment of a novel species, U. ophiocordycipiticola, was strongly supported by morphological and molecular evidence. Umbelopsis ophiocordycipiticola exhibited a high-value PUFA content. Additionally, three Umbelopsis species demonstrated good quality for biodiesel production.

Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.

Unlocking the link between temporomandibular disorders and suicide ideation in pre-orthodontic patients: A moderated mediation model of depression and anxiety.

BACKGROUND: Temporomandibular disorders (TMD) are a series of musculoskeletal diseases with high prevalence. A few studies have reported the correlation between TMD and suicide ideation (SI). However, the underlying mechanism of the relationship lacks in-depth exploration. METHODS: A cross-sectional study was conducted among 954 pre-orthodontic patients. TMD assessment was based on the quintessential five TMD symptoms (5Ts) questionnaire. Anxiety, depression and pain catastrophizing was evaluated by Seven-item Generalized Anxiety Disorder Scale (GAD-7), Nine-item Patient Health Questionnaire (PHQ-9), and Pain Catastrophizing Scale (PCS), respectively. Correlational and moderated mediated analysis was preformed to demonstrate the relationship between TMD and SI. RESULTS: In pre-orthodontic patients, 31.87 % reported having TMD symptoms and 6.50 % declared SI during the past two weeks. The SI prevalence was 10.53 % in participants with TMD and 4.62 % in those without TMD. Intra-articular TMD, rather than pain-related TMD were especially related with SI. Individuals with TMD had higher risk to SI (rs = 0.112, adjusted OR = 2.213, p < 0.001). The effect of TMD on SI was fully mediated through depression (ß = 0.445, 95 % CI = [0.326, 0.563]). Anxiety exerted a negative moderating effect on the depression-SI relation (ß = -0.033, 95 % CI = [-0.047, -0.019]). LIMITATIONS: This study was a single-centered and cross-sectional survey. The data collection relied on self-reporting methods. CONCLUSIONS: A positive link between TMD and SI was disclosed. The effect of TMD on SI was fully mediated through depression with anxiety as a negative moderator.

Brain Age Prediction Based on Quantitative Susceptibility Mapping Using the Segmentation Transformer.

The process of brain aging is intricate, encompassing significant structural and functional changes, including myelination and iron deposition in the brain. Brain age could act as a quantitative marker to evaluate the degree of the individual's brain evolution. Quantitative susceptibility mapping (QSM) is sensitive to variations in magnetically responsive substances such as iron and myelin, making it a favorable tool for estimating brain age. In this study, we introduce an innovative 3D convolutional network named Segmentation-Transformer-Age-Network (STAN) to predict brain age based on QSM data. STAN employs a two-stage network architecture. The first-stage network learns to extract informative features from the QSM data through segmentation training, while the second-stage network predicts brain age by integrating the global and local features. We collected QSM images from 712 healthy participants, with 548 for training and 164 for testing. The results demonstrate that the proposed method achieved a high accuracy brain age prediction with a mean absolute error (MAE) of 4.124 years and a coefficient of determination (R2) of 0.933. Furthermore, the gaps between the predicted brain age and the chronological age of Parkinson's disease patients were significantly higher than those of healthy subjects (P<0.01). We thus believe that using QSM-based predicted brain age offers a more reliable and accurate phenotype, with the potentiality to serve as a biomarker to explore the process of advanced brain aging.

IMJENSE: Scan-Specific Implicit Representation for Joint Coil Sensitivity and Image Estimation in Parallel MRI.

Parallel imaging is a commonly used technique to accelerate magnetic resonance imaging (MRI) data acquisition. Mathematically, parallel MRI reconstruction can be formulated as an inverse problem relating the sparsely sampled k-space measurements to the desired MRI image. Despite the success of many existing reconstruction algorithms, it remains a challenge to reliably reconstruct a high-quality image from highly reduced k-space measurements. Recently, implicit neural representation has emerged as a powerful paradigm to exploit the internal information and the physics of partially acquired data to generate the desired object. In this study, we introduced IMJENSE, a scan-specific implicit neural representation-based method for improving parallel MRI reconstruction. Specifically, the underlying MRI image and coil sensitivities were modeled as continuous functions of spatial coordinates, parameterized by neural networks and polynomials, respectively. The weights in the networks and coefficients in the polynomials were simultaneously learned directly from sparsely acquired k-space measurements, without fully sampled ground truth data for training. Benefiting from the powerful continuous representation and joint estimation of the MRI image and coil sensitivities, IMJENSE outperforms conventional image or k-space domain reconstruction algorithms. With extremely limited calibration data, IMJENSE is more stable than supervised calibrationless and calibration-based deep-learning methods. Results show that IMJENSE robustly reconstructs the images acquired at 5× and 6× accelerations with only 4 or 8 calibration lines in 2D Cartesian acquisitions, corresponding to 22.0% and 19.5% undersampling rates. The high-quality results and scanning specificity make the proposed method hold the potential for further accelerating the data acquisition of parallel MRI.

Optimal tracking performance of networked control systems under communication constraints.

This paper investigates the optimal tracking performance (OTP) of multiple-input multiple-output discrete-time communication-constrained systems by thinking about Denial of Service (DoS) attacks, codecs and additive Gaussian white noise under energy constraints. The non-cooperative relationship between DoS attacks and intrusion detection systems (IDS) is analyzed using repeated game theory. A penalty mechanism is constructed to force the attackers to adopt a cooperative strategy, thus improving the system performance. Partial factorization and spectrum decomposition are used to provide the OTP for systems. The results demonstrate that the systems' OTP are linked to intrinsic characteristics like non-minimum phase zeros and unstable poles. Finally, concrete examples are shown that the results are accurate.

Revolutionizing Solid-State NASICON Sodium Batteries: Enhanced Ionic Conductivity Estimation through Multivariate Experimental Parameters Leveraging Machine Learning.

Na superionic conductor (NASICON) materials hold promise as solid-state electrolytes due to their wide electrochemical stability and chemical durability. However, their limited ionic conductivity hinders their integration into sodium-ion batteries. The conventional approach to electrolyte design struggles with comprehending the intricate interactions of factors impacting conductivity, encompassing synthesis parameters, structural characteristics, and electronic descriptors. Herein, we explored the potential of machine learning in predicting ionic conductivity in NASICON. We compile a database of 211 datasets, covering 160 NASICON materials, and employ facile descriptors, including synthesis parameters, test conditions, molecular and structural attributes, and electronic properties. Random forest (RF) and neural network (NN) models were developed and optimized, with NN performing notably better, particularly with limited data (R2=0.820). Our analysis spotlighted the pivotal role of Na stoichiometric count in ionic conductivity. Furthermore, the NN algorithm highlighted the comparable significance of synthesis parameters to structural factors in determining conductivity. In contrast, the impact of electronegativity on doped elements appears less significant, underscoring the importance of dopant size and quantity. This work underscores the potential of machine learning in advancing NASICON electrolyte design for sodium-ion batteries, offering insights into conductivity drivers and a more efficient path to optimizing materials.

SHED-derived exosomes attenuate trigeminal neuralgia after CCI of the infraorbital nerve in mice via the miR-24-3p/IL-1R1/p-p38 MAPK pathway.

BACKGROUND: Microglial activation in the spinal trigeminal nucleus (STN) plays a crucial role in the development of trigeminal neuralgia (TN). The involvement of adenosine monophosphate-activated protein kinase (AMPK) and N-methyl-D-aspartate receptor 1 (NMDAR1, NR1) in TN has been established. Initial evidence suggests that stem cells from human exfoliated deciduous teeth (SHED) have a potential therapeutic effect in attenuating TN. In this study, we propose that SHED-derived exosomes (SHED-Exos) may alleviate TN by inhibiting microglial activation. This study sought to assess the curative effect of SHED-Exos administrated through the tail vein on a unilateral infraorbital nerve chronic constriction injury (CCI-ION) model in mice to reveal the role of SHED-Exos in TN and further clarify the potential mechanism. RESULTS: Animals subjected to CCI-ION were administered SHED-Exos extracted by differential ultracentrifugation. SHED-Exos significantly alleviated TN in CCI mice (increasing the mechanical threshold and reducing p-NR1) and suppressed microglial activation (indicated by the levels of TNF-α, IL-1ß and IBA-1, as well as p-AMPK) in vivo and in vitro. Notably, SHED-Exos worked in a concentration dependent manner. Mechanistically, miR-24-3p-upregulated SHED-Exos exerted a more significant effect, while miR-24-3p-inhibited SHED-Exos had a weakened effect. Bioinformatics analysis and luciferase reporter assays were utilized for target gene prediction and verification between miR-24-3p and IL1R1. Moreover, miR-24-3p targeted the IL1R1/p-p38 MAPK pathway in microglia was increased in CCI mice, and participated in microglial activation in the STN. CONCLUSIONS: miR-24-3p-encapsulated SHED-Exos attenuated TN by suppressing microglial activation in the STN of CCI mice. Mechanistically, miR-24-3p blocked p-p38 MAPK signaling by targeting IL1R1. Theoretically, targeted delivery of miR-24-3p may offer a potential strategy for TN.

Orthodontic Patients with Poor Oral Health-Related Quality of Life are More Likely to Have Emotional Distress: A Cross-Sectional Study.

Objective: This study aims to investigate the relationship between oral health-related quality of life (OHRQoL) and emotional distress (ED), including anxiety and depression, in orthodontic patients. Methods: A cross-sectional study was conducted involving 603 orthodontic patients, consisting of 401 females (66.5%) with a mean age of 24.15 ± 7.72 and 202 males (33.5%) with a mean age of 24.16 ± 7.72. A questionnaire containing questions of demographic information, the Oral Health Impact Profile (OHIP-14) and the Huaxi emotional-distress index (HEI) was employed to assess OHRQoL and ED. According to the HEI score, the respondents were divided into ED group (HEI > 8) and non-ED group (HEI ≤ 8). Data were analyzed using Kolmogorov-Smirnov test, Mann-Whitney test and logistic regression analysis with the significance level set at p < 0.05. Results: The prevalence of poor OHRQoL and ED of the study sample was 28.4% and 19.57%, respectively. There was a significantly higher prevalence of ED among poor OHRQoL patients (35.67%) compared to those with good OHRQoL (13.19%) (p < 0.001). Poor OHRQoL and risky drinking behavior addressed higher significant correlation with ED patients than non-ED patients (p < 0.05). There were no statistical differences in other factors such as gender, age, and appliance type (p > 0.05). Poor OHRQoL orthodontic patients were at a higher risk of suffering from anxiety and depression compared to those with good OHRQoL (age-risky drinking behavior-sex-adjusted: OR = 4.00; all p < 0.001). Conclusion: Oral health-related quality of life (OHRQoL) is related to emotional stress. Namely, patients with poor OHRQoL are more likely to experience anxiety and depression. As a result, orthodontists should consistently assess the emotional well-being and OHROoL of patients over the treatment course for better treatment outcomes.

An outcomes-based module education via flipped classroom enhances undergraduate oral histopathology learning.

INTRODUCTION: Oral histopathology is a bridge course connecting oral basic medicine and clinical dentistry. However, the application of outcomes-based education via flipped classroom (FC) in oral histopathology has not been well explored. This study has assessed the efficacy of outcomes-based education via FC in undergraduate oral histopathology module learning in Nanjing Medical University of China. MATERIALS AND METHODS: A total of 214 third-year students were enrolled and assigned to the FC group of the batch 2022-23 (n = 110) and the traditional classroom (TC) group of the batch 2021-22 (n = 104) to participate the oral histopathology sessions respectively in the study. The FC group were required to preview the online course materials pre-class, followed by in-class quizz, in-class interactive group discussion, and slides microscopic observation. The outcomes-based formative and summative assessments for FC were designed. The TC group attended traditional laboratory class for the same glass slides microscopic observation. In addition, a questionnaire was performed to investigate the satisfaction of learning. Along with this, the performances of FC group in written theory tests and oral histopathology slide tests were compared with TC group. RESULTS: Students in the FC group gained significantly final higher scores of the course than those in the TC group (score: 83.79 ± 11 vs. 76.73 ± 10.93, P<0.0001). Data from the student questionnaires indicated a preference for outcomes-based module education via FC. In the questionnaires, most students considered outcomes-based module education via FC to be beneficial to learning motivation, knowledge comprehension, critical thinking and teamwork. FC group had a higher level of satisfaction with oral histopathology teaching than TC group (satisfaction score: 4.599 ± 0.1027 vs. 4.423 ± 0.01366, P<0.01). CONCLUSION: An outcomes-based module education via FC has a promising effect on undergraduate oral histopathology education.

Accurate exclusion of kidney regions affected by susceptibility artifact in blood oxygenation level-dependent (BOLD) images using deep-learning-based segmentation.

Susceptibility artifact (SA) is common in renal blood oxygenation level-dependent (BOLD) images, and including the SA-affected region could induce much error in renal oxygenation quantification. In this paper, we propose to exclude kidney regions affected by SA in gradient echo images with different echo times (TE), based on a deep-learning segmentation approach. For kidney segmentation, a ResUNet was trained with 4000 CT images and then tuned with 60 BOLD images. Verified by a Monte Carlo simulation, the presence of SA leads to a bilinear pattern for the segmented area of kidney as function of TE, and the segmented kidney in the image of turning point's TE would exclude SA-affected regions. To evaluate the accuracy of excluding SA-affected regions, we compared the SA-free segmentations by the proposed method against manual segmentation by an experienced user for BOLD images of 35 subjects, and found DICE of 93.9% ± 3.4%. For 10 kidneys with severe SA, the DICE was 94.5% ± 1.7%, for 14 with moderate SA, 92.8% ± 4.7%, and for 46 with mild or no SA, 94.3% ± 3.8%. For the three sub-groups of kidneys, correction of SA led to a decrease of R2* of 8.5 ± 2.8, 4.7 ± 1.8, and 1.6 ± 0.9 s-1, respectively. In conclusion, the proposed method is capable of segmenting kidneys in BOLD images and at the same time excluding SA-affected region in a fully automatic way, therefore can potentially improve both speed and accuracy of the quantification procedure of renal BOLD data.

Inorganic Selenium Transformation into Organic Selenium by Monascus purpureus.

Selenium (Se) is a trace element that plays a crucial role in metabolism; a lack of selenium reduces the body's resistance and immunity, as well as causes other physiological problems. In this study, we aim to identify favorable conditions for improving organic selenium production. The functional microbe Monascus purpureus, which is widely used in food production, was employed to optimize selenium-enriched culture conditions, and its growth mode and selenium-enriched features were investigated. Spectrophotometry, inductively coupled plasma optical emission spectrometry (ICP-OES), and HPLC (High-Performance Liquid Chromatography) were used to determine the effects of various doses of sodium selenite on the selenium content, growth, and metabolism of M. purpureus, as well as the conversion rate of organic selenium. The best culture parameters for selenium-rich M. purpureus included 7.5 mg/100 mL of selenium content in the culture medium, a pH value of 6.8, a culture temperature of 30 °C, and a rotation speed of 180 rpm. Under ideal circumstances, the mycelia had a maximum selenium concentration of approximately 239.17 mg/kg, with organic selenium accounting for 93.45%, monacoline K production reaching 70.264 mg/L, and a secondary utilization rate of external selenium of 22.99%. This study revealed a novel biological route-selenium-rich M. purpureus fermentation-for converting inorganic selenium into organic selenium.

Long-Term Exposure of Graphene Oxide Suspension to Air Leading to Spontaneous Radical-Driven Degradation.

Understanding the environmental transformation and fate of graphene oxide (GO) is critical to estimate its engineering applications and ecological risks. While there have been numerous investigations on the physicochemical stability of GO in prolonged air-exposed solution, the potential generation of reactive radicals and their impact on the structure of GO remain unexplored. In this study, using liquid-PeakForce-mode atomic force microscopy and quadrupole time-of-flight mass spectroscopy, we report that prolonged exposure of GO to the solution leads to the generation of nanopores in the 2D network and may even cause the disintegration of its bulk structure into fragment molecules. These fragments can assemble themselves into films with the same height as the GO at the interface. Further mediated electrochemical analysis supports that the electron-donating active components of GO facilitate the conversion of O2 to •O2- radicals on the GO surface, which are subsequently converted to H2O2, ultimately leading to the formation of •OH. We experimentally confirmed that attacks from •OH radicals can break down the C-C bond network of GO, resulting in the degradation of GO into small fragment molecules. Our findings suggest that GO can exhibit chemical instability when released into aqueous solutions for prolonged periods of time, undergoing transformation into fragment molecules through self-generated •OH radicals. This finding not only sheds light on the distinctive fate of GO-based nanomaterials but also offers a guideline for their engineering applications as advanced materials.