Color stability and translucency of newly developed composites for splinting teeth.

This study aimed to investigate the colorimetric properties of newly developed composites for dental trauma splints using various staining solutions during the clinical splinting period. The clear shades of G-Fix (GF), Ortho Connect Flow (OC), Light Fix (LF), and Filtek Z350XT (FZ) were fabricated into 96 disk-shaped specimens. Specimens from each composite group were stored in distilled water, coffee, tea, and red wine solutions at 37ºC. CIE values were measured using a spectrophotometer at 24 h after specimen preparation and at 1 day, 1 week, 2 weeks, 3 weeks, and 4 weeks after storage in each solution. Color differences and translucency parameters were calculated using the initial and measured values. Within the experiment period, the color differences of GF, OC, and LF compared to the initial measurement were smaller than that for FZ for all staining solutions except distilled water. There were no significant color differences between the GF, OC, and LF groups.

Fully automated deep learning approach to dental development assessment in panoramic radiographs.

BACKGROUND: Dental development assessment is an important factor in dental age estimation and dental maturity evaluation. This study aimed to develop and evaluate the performance of an automated dental development staging system based on Demirjian's method using deep learning. METHODS: The study included 5133 anonymous panoramic radiographs obtained from the Department of Pediatric Dentistry database at Seoul National University Dental Hospital between 2020 and 2021. The proposed methodology involves a three-step procedure for dental staging: detection, segmentation, and classification. The panoramic data were randomly divided into training and validating sets (8:2), and YOLOv5, U-Net, and EfficientNet were trained and employed for each stage. The models' performance, along with the Grad-CAM analysis of EfficientNet, was evaluated. RESULTS: The mean average precision (mAP) was 0.995 for detection, and the segmentation achieved an accuracy of 0.978. The classification performance showed F1 scores of 69.23, 80.67, 84.97, and 90.81 for the Incisor, Canine, Premolar, and Molar models, respectively. In the Grad-CAM analysis, the classification model focused on the apical portion of the developing tooth, a crucial feature for staging according to Demirjian's method. CONCLUSIONS: These results indicate that the proposed deep learning approach for automated dental staging can serve as a supportive tool for dentists, facilitating rapid and objective dental age estimation and dental maturity evaluation.

Correlation between dental and skeletal maturity in Korean children based on dental maturity percentile: a retrospective study.

BACKGROUND: The correlation between dental maturity and skeletal maturity has been proposed, but its clinical application remains challenging. Moreover, the varying correlations observed in different studies indicate the necessity for research tailored to specific populations. AIM: To compare skeletal maturity in Korean children with advanced and delayed dental maturity using dental maturity percentile. DESIGN: Dental panoramic radiographs and cephalometric radiographs were obtained from 5133 and 395 healthy Korean children aged between 4 and 16 years old. Dental maturity was assessed with Demirjian's method, while skeletal maturity was assessed with the cervical vertebral maturation method. Standard percentile curves were developed through quantile regression. Advanced (93 boys and 110 girls) and delayed (92 boys and 100 girls) dental maturity groups were defined by the 50th percentile. RESULTS: The advanced group showed earlier skeletal maturity in multiple cervical stages (CS) in both boys (CS 1, 2, 3, 4, and 6) and girls (CS 1, 3, 4, 5, and 6). Significant differences, as determined by Mann-Whitney U tests, were observed in CS 1 for boys (p = 0.004) and in CS 4 for girls (p = 0.037). High Spearman correlation coefficients between dental maturity and cervical vertebral maturity exceeded 0.826 (p = 0.000) in all groups. CONCLUSION: A correlation between dental and skeletal maturity, as well as advanced skeletal maturity in the advanced dental maturity group, was observed. Using percentile curves to determine dental maturity may aid in assessing skeletal maturity, with potential applications in orthodontic diagnosis and treatment planning.

Paroxysmal dystonia results from the loss of RIM4 in Purkinje cells.

Full-length RIM1 and 2 are key components of the presynaptic active zone that ubiquitously control excitatory and inhibitory neurotransmitter release. Here, we report that the function of the small RIM isoform RIM4, consisting of a single C2 domain, is strikingly different from that of the long isoforms. RIM4 is dispensable for neurotransmitter release but plays a postsynaptic, cell-type specific role in cerebellar Purkinje cells that is essential for normal motor function. In the absence of RIM4, Purkinje cell intrinsic firing is reduced and caffeine-sensitive, and dendritic integration of climbing fibre input is disturbed. Mice lacking RIM4, but not mice lacking RIM1/2, selectively in Purkinje cells exhibit a severe, hours-long paroxysmal dystonia. These episodes can also be induced by caffeine, ethanol or stress and closely resemble the deficits seen with mutations of the PNKD (paroxysmal non-kinesigenic dystonia) gene. Our data reveal essential postsynaptic functions of RIM proteins and show non-overlapping specialized functions of a small isoform despite high homology to a single domain in the full-length proteins.

Non-Electroconductive Polymer Coating on Graphite Mitigating Electrochemical Degradation of PTFE for a Dry-Processed Lithium-Ion Battery Anode.

Polytetrafluoroethylene (PTFE)-based dry process for lithium-ion batteries is gaining attention as a battery manufacturing scheme can be simplified with drastically reducing environmental damage. However, the electrochemical instability of PTFE in a reducing environment has hampered the realization of the high-performance dry-processed anode. In this study, we present a non-electroconductive and highly ionic-conductive polymer coating on graphite to mitigate the electrochemical degradation of the PTFE binder and minimize the coating resistance. Poly(ethylene oxide) (PEO) and poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) (P(VDF-TrFE-CFE)) coatings on the anode material effectively inhibit the electron transfer from graphite to PTFE, thereby alleviating the PTFE breakdown. The graphite polymer coatings improved initial Coulombic efficiencies of full cells from 67.2% (bare) to 79.1% (PEO) and 77.8% (P(VDF-TrFE-CFE)) and increased initial discharge capacity from 157.7 mAh g(NCM)-1 (bare) to 185.1 mAh g(NCM)-1 (PEO) and 182.5 mAh g(NCM)-1 (P(VDF-TrFE-CFE)) in the full cells. These outcomes demonstrate that PTFE degradation in the anode can be surmounted by adjusting the electron transfer to the PTFE.

Neighbor List Artifacts in Molecular Dynamics Simulations.

Molecular dynamics (MD) simulations are widely used in biophysical research. To aid nonexpert users, most simulation packages provide default values for key input parameters. In MD simulations using the GROMACS package with default parameters, we found large membranes to deform under the action of a semi-isotropically coupled barostat. As the primary cause, we identified overly short outer cutoffs and infrequent neighbor list updates that resulted in missed nonbonded interactions. Small but systematic imbalances in the apparent pressure tensor then induce unphysical asymmetric box deformations that crumple the membrane. We also observed rapid oscillations in averages of the instantaneous pressure tensor components and traced these to the use of a dual pair list with dynamic pruning. We confirmed that similar effects are present in MD simulations of neat water in atomistic and coarse-grained representations. Whereas the slight pressure imbalances likely have minimal impact in most current atomistic MD simulations, we expect their impact to grow in studies of ever-larger systems with coarse-grained representation, in particular, in combination with anisotropic pressure coupling. We present measures to diagnose problems with missed interactions and guidelines for practitioners to avoid them, including estimates for appropriate values for the outer cutoff rl and the number of time steps nstlist between neighbor list updates.

The microRNA-mediated gene regulatory network in the hippocampus and hypothalamus of the aging mouse.

Aging leads to time-dependent functional decline of all major organs. In particular, the aging brain is prone to cognitive decline and several neurodegenerative diseases. Various studies have attempted to understand the aging process and underlying molecular mechanisms by monitoring changes in gene expression in the aging mouse brain using high-throughput sequencing techniques. However, the effect of microRNA (miRNA) on the post-transcriptional regulation of gene expression has not yet been comprehensively investigated. In this study, we performed global analysis of mRNA and miRNA expression simultaneously in the hypothalamus and hippocampus of young and aged mice. We identified aging-dependent differentially expressed genes, most of which were specific either to the hypothalamus or hippocampus. However, genes related to immune response-related pathways were enriched in upregulated differentially expressed genes, whereas genes related to metabolism-related pathways were enriched in downregulated differentially expressed genes in both regions of the aging brain. Furthermore, we identified many differentially expressed miRNAs, including three that were upregulated and three that were downregulated in both the hypothalamus and hippocampus. The two downregulated miRNAs, miR-322-3p, miR-542-3p, and the upregulated protein-encoding coding gene C4b form a regulatory network involved in complement and coagulation cascade pathways in the hypothalamus and hippocampus of the aging brain. These results advance our understanding of the miRNA-mediated gene regulatory network and its influence on signaling pathways in the hypothalamus and hippocampus of the aging mouse brain.

Histology and morphometry of the skin of purple spaghetti-eel Moringua raitaborua (Anguilliformes, Moringuidae).

The purple spaghetti-eel Moringua raitaborua lives on the sandy or muddy bottoms of estuaries, which are subject to rapid and wide changes in salinity, pH, and osmoregulatory and hypoxic conditions due to the influx of organic materials from sources of freshwater. The species has adapted to hypoxic environments by developing a thicker epidermis with stratified polygonal cells, club cells, two types of mucous cells (goblet and, oval cells), stratified cuboidal cells and dermis with abundant blood capillaries. Among them, histological modification of thinner dorsal, lateral, and ventral body skin to include abundant capillaries and well-developed dermal vascularization may provide cutaneous respiration, permitting survival in brackish waters with low levels of oxygen and variable environmental parameters.

Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase.

Prostate cancer remains the second leading cause of cancer death in men in Western cultures. A deeper understanding of the mechanisms by which prostate cancer cells divide to support tumor growth could help devise strategies to overcome treatment resistance and improve survival. Here, we identified that the mitotic AGC family protein kinase citron kinase (CIT) is a pivotal regulator of prostate cancer growth that mediates prostate cancer cell interphase progression. Increased CIT expression correlated with prostate cancer growth induction and aggressive prostate cancer progression, and CIT was overexpressed in prostate cancer compared with benign prostate tissue. CIT overexpression was controlled by an E2F2-Skp2-p27 signaling axis and conferred resistance to androgen-targeted treatment strategies. The effects of CIT relied entirely on its kinase activity. Conversely, CIT silencing inhibited the growth of cell lines and xenografts representing different stages of prostate cancer progression and treatment resistance but did not affect benign epithelial prostate cells or nonprostatic normal cells, indicating a potential therapeutic window for CIT inhibition. CIT kinase activity was identified as druggable and was potently inhibited by the multikinase inhibitor OTS-167, which decreased the proliferation of treatment-resistant prostate cancer cells and patient-derived organoids. Isolation of the in vivo CIT substrates identified proteins involved in diverse cellular functions ranging from proliferation to alternative splicing events that are enriched in treatment-resistant prostate cancer. These findings provide insights into the regulation of aggressive prostate cancer cell behavior by CIT and identify CIT as a functionally diverse and druggable driver of prostate cancer progression. SIGNIFICANCE: The poorly characterized protein kinase citron kinase is a therapeutic target in prostate cancer that drives tumor growth by regulating diverse substrates, which control several hallmarks of aggressive prostate cancer progression. See related commentary by Mishra et al., p. 4008.

Criteria for early diagnosis of mandibular third molar agenesis based on the developmental stages of mandibular canine, first and second premolars, and second molar: a retrospective cohort study.

BACKGROUND: Permanent first molars with severe dental caries, developmental defects, or involved in oral pathologies are at risk of poor prognosis in children. Accordingly, using the third molar to replace the first molar can be a good treatment option when third molar agenesis is predicted early. Thus, this retrospective cohort study aimed to develop criteria for early detection of mandibular third molar (L8) agenesis based on the developmental stages of mandibular canine (L3), first premolar (L4), second premolar (L5), and second molar (L7). METHOD: Overall, 1,044 and 919 panoramic radiographs of 343 males and 317 females, respectively, taken between the ages of 6 and 12 years were included. All developmental stages of L3, L4, L5, L7, and L8 were analyzed based on the dental age, as suggested by Demirjian et al. The independent t-test was used to assess age differences between males and females. The rank correlation coefficients were examined using Kendall's tau with bootstrap analysis and Bonferroni's correction to confirm the teeth showing developmental stages most similar to those of L8s. Finally, a survival analysis was performed to determine the criteria for the early diagnosis of mandibular third molar agenesis. RESULTS: Some age differences were found in dental developmental stages between males and females. Correlation coefficients between all stages of L3, L4, L5, and L7 and L8 were high. In particular, the correlation coefficient between L7 and L8 was the highest, whereas that between L3 and L8 was the lowest. CONCLUSION: If at least two of the following criteria (F stage of L3, F stage of L4, F stage of L5, and E stage of L7) are met in the absence of L8 crypt, agenesis of L8 can be confirmed.

Rationally Designed Solution-Processible Conductive Carbon Additive Coating for Sulfide-based All-Solid-State Batteries.

Sulfide-based all-solid-state batteries (ASSBs) have emerged as promising candidates for next-generation energy storage systems owing to their superior safety and energy density. A conductive agent is necessarily added in the cathode composite of ASSBs to facilitate electron transport therein, but it causes the decomposition of the solid electrolyte and ultimately the shortening of lifetime. To resolve this dilemmatic situation, herein, we report a rationally designed solution-processible coating of zinc oxide (ZnO) onto vapor-grown carbon fiber as a conductive agent to reduce the contact between the carbon additive and the solid electrolyte and still maintain electron pathways to the active material. ASSBs with the carbon additive with an optimal coating of ZnO have markedly improved cycling performance and rate capability compared to those with the bare conductive agent, which can be attributed to hindering the decomposition of the solid electrolytes. The results highlight the usefulness of controlling the interparticle contacts in the composite cathodes in addressing the challenging interfacial degradation of sulfide-based ASSBs and improving their key electrochemical properties.

Nutrition and Theriogenology: A Glimpse Into Nutrition and Nutritional Supplementation During Gestation, Lactation, Weaning and Breeding Dogs and Cats.

Feeding during normal reproduction is often not thought of until there is a problem with conception or gestational losses. Energy demands of lactation and early puppy/kitten are of concern, particularly in large and giant breed dogs where mineral balance is crucial to normal development. There is a paucity of information around optimizing feeding during conception and gestation with many myths around ingredients which will be explored in this article along with supplements that may be able to support spermatogenesis and conception which primarily comes from the human literature and may have validity in times of difficult conception.

Carbamate JNK3 Inhibitors Show Promise as Effective Treatments for Alzheimer's Disease: In Vivo Studies on Mouse Models.

We have been developing new inhibitors for c-Jun N-terminal kinase 3 (JNK3) as a potential treatment for Alzheimer's disease (AD). We identified potential JNK3 inhibitors through pharmacodynamic optimization studies, including benzimidazole compounds 2 and 3, but their unreliable pharmacokinetic properties led us to develop carbamate inhibitors 2h and 3h. In vitro studies validated carbamate inhibitors 2h and 3h as potent and highly selective JNK3 inhibitors with favorable pharmacokinetic profiles. Oral administration of 2h and 3h to both APP/PS1 and 3xTg AD mouse models improved cognitive function, indicating their potential as effective treatments for Alzheimer's disease. Carbamate JNK3 inhibitor 3h, in particular, restored cognitive function to near-normal levels in the 3xTg mice model of AD and led to pTau reduction in the hippocampal tissues of 3xTg-AD mice during in vivo behavioral evaluations. We intend to further develop these carbamate JNK3 inhibitors in preclinical studies as a potential first-in-class treatment for AD.

Graph approaches for analysis of brain connectivity during dexmedetomidine sedation.

Sedation is commonly used to relieve fear and anxiety during procedures. Dexmedetomidine (DEX), approved by the US Food and Drug Administration in 1999 for short-term sedation, is a selective alpha2-adrenoreceptor agonist. The use of DEX is increasing due to minimal respiratory depression and easy and quick awakening from sedation. Its sedative mechanisms are suggested to be related to changes in the interaction between brain regions. In this study, we used graph theory to investigate whether the altered network connection is associated with sedation. Electroencephalogram (EEG) recordings of 32 channels were acquired during awake and DEX-induced sedation for 20 participants. We extracted EEG epochs from the awake and the DEX sedation state. Using the graph theory, we compared the changes in the network connection parameters with the awake state. We observed that the slopes in 1/f dynamics, which indicate overall brain network characteristics, were greater during DEX-induced sedation compared to the awake state, suggesting a transition towards a random network behavior. In addition, network connections from the perspective of information processing were significantly disturbed in the alpha frequency band, unlike other frequency bands augmenting network connections. The alpha frequency band plays a prominent role in the function and interaction of cognitive activities. These results collectively indicate that changes in the brain network critical to cognition during DEX administration may also be related to the mechanism of sedation.

Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease.

Despite innumerable efforts to develop effective therapeutics, it is difficult to achieve breakthrough treatments for Alzheimer's disease (AD), and the main reason is probably the absence of a clear target. Here, we reveal c-Jun N-terminal kinase 3 (JNK3), a protein kinase explicitly expressed in the brain and involved in neuronal apoptosis, with a view toward providing effective treatment for AD. For many years, we have worked on JNK3 inhibitors and have discovered 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile-based JNK3 inhibitors with superb potency (IC50 < 1.0 nM) and excellent selectivity over other protein kinases including isoforms JNK1 (>300 fold) and JNK2 (∼10 fold). Based on in vitro biological activity and DMPK properties, the lead compounds were selected for further in vivo studies. We confirmed that repeat administration of JNK3 inhibitors improved cognitive memory in APP/PS1 and the 3xTg mouse model. Overall, our results show that JNK3 could be a potential target protein for AD.

Structural optimization of novel Ras modulator for treatment of Colorectal cancer by promoting ß-catenin and Ras degradation.

Ras protein has been considered a fascinating target for anticancer therapy because its malfunction is closely related to cancer. However, Ras has been considered undruggable because of the failure to regulate its malfunction by controlling the Ras activation mechanism. Recently, Lumakras targeting the G12C mutation was approved, and therapeutic interest in Ras for anticancer therapy has been rejuvenated. Here, we present a series of compounds that inhibit Ras via a unique mechanism of action that exploits the relationship between the Wnt/ß-catenin pathway and Ras. KYA1797K (1) binds to axin to stabilize the ß-catenin destruction complex that causes the phosphorylation and subsequent degradation of Ras, similar to canonical ß-catenin regulation. Based on the chemical structure of 1, we performed a structural optimization and identified 3-(2-hydroxyethyl)-5-((6-(4-nitrophenyl)pyridin-2-yl)methylene)thiazolidine-2,4-dione (13d) as the most potent compound. 13d displayed antitumor effects in a colorectal cancer model with enhanced inhibition activity on Ras. The results of this study suggest that the further development of 13d could contribute to the development of Ras inhibitors with novel mechanisms of action.

Probing the optical near-field of plasmonic nano structure using scanning thermal microscopy.

Scanning thermal microscopy (SThM) enables to obtain thermal characteristic information such as temperature and thermal conductivity from the signals obtained by scanning a thermometer probe over a sample surface. Particularly, the precise control of the thermometer probe makes it possible to study near-field radiative heat transfer by measuring the near-field thermal energy, which implies that when light is used as a local heat source, photothermal energy can be detected from the optical near-field by approaching the probe in the near-field region. In this study, SThM is applied to generate sub-wavelength near-field optical image in the plasmonic grating coupler. Herein, by controlling the surface plasmon polariton generation, we show that the dominant component of SThM signal is from the optical response rather than the thermal response. The obtained near-field optical images have a spatial resolution of 40 nm and signal to noise ratio of up to 19.8. In addition, field propagation images in theZ-direction can be visualised with the precise control of the distance between the thermometer probe and the sample.

Plasmon-exciton couplings in the MoS2/AuNP plasmonic hybrid structure.

The understanding and engineering of the plasmon-exciton coupling are necessary to control the innovative optoelectronic device platform. In this study, we investigated the intertwined mechanism of each plasmon-exciton couplings in monolayer molybdenum disulfide (MoS2) and plasmonic hybrid structure. The results of absorption, simulation, electrostatics, and emission spectra show that interaction between photoexcited carrier and exciton modes are successfully coupled by energy transfer and exciton recombination processes. Especially, neutral exciton, trion, and biexciton can be selectively enhanced by designing the plasmonic hybrid platform. All of these results imply that there is another degree of freedom to control the individual enhancement of each exciton mode in the development of nano optoelectronic devices.

Scalp acupuncture for stroke: A protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Scalp acupuncture (SA) is a new acupuncture method that connects head acupoints and aculines, and many systematic reviews (SRs) have been published on its use against neuropsychiatric diseases. However, no overview of SRs on the effectiveness of SA in stroke recovery has been conducted. Therefore, our overview aims to evaluate the methodological bias and reliability of the conclusions of SRs regarding SA for stroke recovery and help clinical decision-makers translate this research into clinical policy and practice. METHODS: We will consider SRs and meta-analyses of randomized controlled trials to evaluate the effects of SA on stroke recovery. Two reviewers will identify relevant studies, extract data information, and assess the methodological quality using the Assessment of Multiple Systematic Reviews-2 tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses report checklist will also be included in the study to assess the quality of the reports. We will use evaluations of the Grading of Recommendations Assessment, Development and Evaluation of the authors of the included SRs. The Risk of Bias in Systematic Review tool will be used to assess the risk of bias of SRs. The screening of SRs, eligibility evaluation, data extraction, methodological quality, and quality of evidence will be conducted by independent reviewers in pairs. The outcomes of interest include the Modified Edinburgh-Scandinavian Stroke Scale, Ability of Daily Living, Functional Independence Measure, Barthel index, Fugl-Meyer assessment, clinical effective rate, and adverse events. Data will be extracted using predefined forms designed to summarize the important characteristics of each review. The evidence will be a descriptive synthesis of the type and content of the intervention and the results reported. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSIONS: We expect to organize evidence from multiple SRs on the effectiveness of SA for stroke recovery and synthesize the findings in an accessible and useful documentation.

High-speed, large dynamic range spectral domain interrogation of fiber-optic Fabry-Perot interferometric sensors.

We report high-speed, large dynamic range spectral domain interrogation of fiber-optic Fabry-Perot (FP) interferometric sensors. An optical interrogation system employing a piezoelectric FP tunable filter and an array of fiber-Bragg gratings for wavelength referencing is developed to acquire the reflection spectrum of FP sensors at a high interrogation speed with a wide wavelength range. A 98 nm wavelength interrogation range was obtained at the resonance frequency of ∼110kHz of the FP tunable filter. At this frequency, the resolution of the FP cavity length measurement was 1.8 nm. To examine the performance of the proposed high-speed spectral domain interrogation scheme, two diaphragm-based fiber-tip FP sensors (a pressure sensor and acoustic sensor) were interrogated. The pressure measurement results show that the high-speed spectral domain interrogation method has the advantages of being robust to light intensity fluctuations and having a much larger dynamic range compared with the conventional intensity-based interrogation method. Moreover, owing to its capability of measuring the absolute FP cavity length, the proposed interrogation system mitigates the sensitivity drift that intensity-based interrogation often suffers from. The acoustic measurement results demonstrate that the high-speed spectral domain interrogation method is capable of high-frequency acoustic measurements of up to 20 kHz. This work will benefit many applications that require high-speed interrogation of fiber-optic FP interferometric sensors.