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Background: Recent studies have reported the inhomogeneity in the light emitted by dental light-curing units (LCUs). It is essential to understand how this uneven light distribution affects the physical properties of resin-based composites (RBCs) at various points across their surfaces. This study aimed to evaluate the effect of LCU beam's inhomogeneity on the microhardness of RBCs with different shades and thicknesses., Methods: Four body (A1B, A2B, A3B, and A4B), one dentin (A3D), and one enamel shade (A3E) of RBC (Filtek Z350 XT) were examined. The specimens were fabricated in four thicknesses (1, 2, 3, and 4 mm) and subjected to a 40-second light-curing. Vickers microhardness testing was performed at the center point, and 3 mm left and right from the center at the bottom surface of each sample. The LCU beam profile was characterized using a beam profiler, while irradiance after specimen passage was measured using a spectrometer. One-way analysis of variance (ANOVA) and Tukey's post-hoc tests were used to analyze the effects of shades and thicknesses on irradiance and microhardness, respectively. One-way repeated-measures ANOVA was used to compare the microhardness across different points. Pearson's correlation analysis examined the relationship between irradiance and microhardness., Results: The beam profile of LCU revealed inhomogeneous light distribution. Light irradiance was decreased with both the increase in thickness and darker shade of the specimens (p < 0.05). Microhardness was found to decline with an increase in sample thickness (p < 0.05), and was consistently higher at the center point compared to the periphery, particularly in thicker (3 and 4 mm) and darker shades (A3B, A4B, and A3D). A positive correlation was found between the irradiance and microhardness across all evaluated points (p < 0.05)., Conclusions: Inhomogeneous light emission from LCU significantly influences the microhardness of RBC samples, depending on the thicknesses and shades. The findings underline the importance of considering LCU beam inhomogeneity in clinical settings to ensure optimal polymerization of RBC., (© 2024. The Author(s).)

Upon encountering allergens, CD4 + T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases., Competing Interests: Competing interests statement:The authors declare no competing interest.

This paper describes the development of an in-pipe inspection robot system designed for large-diameter water pipes. The robot is equipped with a Magnetic Flux Leakage (MFL) sensor module. The robot system is intended for pipes with diameters ranging from 900 mm to 1200 mm. The structure of the in-pipe inspection robot consists of the front and rear driving parts, with the inspection module located centrally. The robot is powered by 22 motors, including eight wheels with motors positioned at both the bottom and the top for propulsion. To ensure that the robot's center aligns with that of the pipeline during operation, lifting units have been incorporated. The robot is equipped with cameras and LiDAR sensors at the front and rear to monitor the internal environment of the pipeline. Pipeline inspection is conducted using the MFL inspection modules, and the robot's driving mechanism is designed to execute spiral maneuvers while maintaining contact with the pipeline surface during rotation. The in-pipe inspection robot is configured with wireless communication modules and batteries, allowing for wireless operation. Following its development, the inspection robot underwent driving experiments in actual pipelines to validate its performance. The field test bed used for these experiments is approximately 1 km in length. Results from the driving experiments on the field test bed confirmed the robot's ability to navigate various curvatures and obstacles within the pipeline. It is posited that the use of the developed in-pipe inspection robot can reduce economic costs and enhance the safety of inspectors when examining aging pipes.

This retrospective study aimed to evaluate the impact of radiation dose on the outcomes of stereotactic radiosurgery (SRS) for benign meningiomas and determine an optimal dosing strategy for balancing tumor control and treatment-related toxicity. Clinical data of 147 patients with 164 lesions treated between 2014 and 2022 were reviewed. Primary outcomes included progression-free survival (PFS), local control rate (LCR), and radiation-induced toxicity, with secondary outcomes focusing on LCR and radiation-induced peritumoral edema (PTE) in two dose groups (≥14 Gy and <14 Gy). The results revealed a median follow-up duration of 47 months, with 1-year, 2-year, and 5-year PFS rates of 99.3%, 96.7%, and 93.8%, respectively, and an overall LCR of 95.1%. Radiation-induced toxicity was observed in 24.5% of patients, primarily presenting mild symptoms. Notably, no significant difference in LCR was found between the two dose groups ( p = 0.628), while Group 2 (<14 Gy) exhibited significantly lower PTE ( p = 0.039). This study concludes that SRS with a radiation dose < 14 Gy demonstrates comparable tumor control with reduced toxicity, advocating consideration of such dosing to achieve a balance between therapeutic efficacy and safety.

Backgruound: Many studies have shown that Hashimoto's thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC., Methods: This study included two types of research., Results: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies., Results: Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT., Conclusion: This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

Hardware neuromorphic systems are crucial for the energy-efficient processing of massive amounts of data. Among various candidates, hafnium oxide ferroelectric tunnel junctions (FTJs) are highly promising for artificial synaptic devices. However, FTJs exhibit non-ideal characteristics that introduce variations in synaptic weights, presenting a considerable challenge in achieving high-performance neuromorphic systems. The primary objective of this study is to analyze the origin and impact of these variations in neuromorphic systems. The analysis reveals that the major bottleneck in achieving a high-performance neuromorphic system is the dynamic variation, primarily caused by the intrinsic 1/f noise of the device. As the device area is reduced and the read bias (V Read ) is lowered, the intrinsic noise of the FTJs increases, presenting an inherent limitation for implementing area- and power-efficient neuromorphic systems. To overcome this limitation, an adaptive read-biasing (ARB) scheme is proposed that applies a different V Read to each layer of the neuromorphic system. By exploiting the different noise sensitivities of each layer, the ARB method demonstrates significant power savings of 61.3% and a scaling effect of 91.9% compared with conventional biasing methods. These findings contribute significantly to the development of more accurate, efficient, and scalable neuromorphic systems., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

We investigated the interference of apical constriction position and diameter on the accuracy of electronic apex locators using 3D-printed tooth models. Single-rooted tooth models with the same length, canal taper and major foramen, but variation in apical constriction position or size, were designed and 3D-printed. A mounting model was custom-made for precise measurement of both marks (0.5 and APEX/0.0) of two electronic apex locators. The electronic measurements of both devices were correlated significantly to the major foramen rather than apical constriction. The mean measurements of the group with 0.45 mm in apical constriction width were significantly shorter than those of the other groups for both marks of the two devices (p < 0.05). The variations in apical constriction position and width negatively affected the precision of the 0.5 mark of the tested devices. The 0.0 or APEX mark was consistently located the major foramen., (© 2022 Australian Society of Endodontology Inc.)

Purpose: The first objective was to determine if dual-curing of resin cement with reduced light could affect interfacial adaptations of zirconia restoration. The second objective was to examine whether cement type and pretreatment method of universal adhesive affected interfacial adaptation. The final objective was to compare the polymerization degree of cement under different reduced-light conditions., Materials and Methods: Inlay cavities were prepared on extracted third molars. Translucent zirconia restorations were milled using Katana UTML (Kuraray Noritake) in three groups with restoration thicknesses of 1, 2, and 3 mm, respectively. Each group had three subgroups using different cementation methods. For subgroup 1, restorations were cemented with self-adhesive cement. For subgroup 2, universal adhesive was applied and light cured. After the restoration was seated with conventional resin cement, light curing was performed. For subgroup 3, after adhesive was applied, the restoration was seated with conventional resin cement. Light curing was performed for the adhesive and cement simultaneously. After thermocycling, interfacial adaptation at the restoration-tooth interface was investigated using swept-source optical coherence tomography imaging. Finally, polymerization shrinkage of the cement was measured using a linometer and compared under the conditions of different zirconia thicknesses and light-curing durations., Results: Interfacial adaptation varied signficantly depending on the zirconia thickness, pretreatment, polymerization mode and cements used (p < 0.05). The effects of the adhesive and polymerization shrinkage differed signficantly, depending on the reduced light under the zirconia (p < 0.05)., Conclusion: Lower curing-light irradiance may lead to inferior adaptation and lower polymerization of the cement. Polymerization of resin cement can differ depending on the light irradiance and exposure duration.

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment., (© 2023. The Author(s).)

Neuromorphic computing (NC) architecture inspired by biological nervous systems has been actively studied to overcome the limitations of conventional von Neumann architectures. In this work, we propose a reconfigurable NC block using a flash-type synapse array, emerging positive feedback (PF) neuron devices, and CMOS peripheral circuits, and integrate them on the same substrate to experimentally demonstrate the operations of the proposed NC block. Conductance modulation in the flash memory enables the NC block to be easily calibrated for output signals. In addition, the proposed NC block uses a reduced number of devices for analog-to-digital conversions due to the super-steep switching characteristics of the PF neuron device, substantially reducing the area overhead of NC block. Our NC block shows high energy efficiency (37.9 TOPS/W) with high accuracy for CIFAR-10 image classification (91.80%), outperforming prior works. This work shows the high engineering potential of integrating synapses and neurons in terms of system efficiency and high performance.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases. To explore the role of TonEBP, we examined kidney biopsy samples from patients with LN. Kidney TonEBP expression was found to be elevated in these patients compared to control patients - in both kidney cells and infiltrating immune cells. Kidney TonEBP mRNA was elevated in LN and correlated with mRNAs encoding inflammatory cytokines and the degree of proteinuria. In a pristane-induced SLE model in mice, myeloid TonEBP deficiency blocked the development of SLE and LN. In macrophages, engagement of various toll-like receptors (TLRs) that respond to damage-associated molecular patterns induced TonEBP expression via stimulation of its promoter. Intracellular signaling downstream of the TLRs was dependent on TonEBP. Therefore, TonEBP can act as a transcriptional cofactor for NF-κB, and activated mTOR-IRF3/7 via protein-protein interactions. Additionally, TonEBP-deficient macrophages displayed elevated efferocytosis and animals with myeloid deficiency of TonEBP showed reduced Th1 and Th17 differentiation, consistent with macrophages defective in TLR signaling. Thus, our data show that myeloid TonEBP may be an attractive therapeutic target for SLE and LN., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Concerns about indoor and outdoor air quality, industrial gas leaks, and medical diagnostics are driving the demand for high-performance gas sensors. Owing to their structural variety and large surface area, reducible metal oxides hold great promise for constructing a gas-sensing system. While many earlier reports have successfully obtained a sufficient response to various types of target gases, the selective detection of target gases remains challenging. In this work, a novel method, low-frequency noise (LFN) spectroscopy is presented, to achieve selective detection using a single FET-type gas sensor. The LFN of the sensor is accurately modeled by considering the charge fluctuation in both the sensing material and the FET channel. Exposure to different target gases produces distinct corner frequencies of the power spectral density that can be used to achieve selective detection. In addition, a 3D vertical-NAND flash array is used with the fast Fourier transform method via in-memory-computing, significantly improving the area and power efficiency rate. The proposed system provides a novel and efficient method capable of selectively detecting a target gas using in-memory-computed LFN spectroscopy and thus paving the way for the further development in gas sensing systems., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

This study was aimed to evaluate the effect of thickness (1, 2, 3, and 4 mm) on the translucency of resin-based composites (RBCs) and glass-ceramics, and compare the influence of the thickness of those materials on the translucency parameter (TP) value. The materials were divided into two groups, eight RBCs in Group 1 and five glass-ceramics in Group 2 and TP, ΔL*, Δa*, and Δb* were compared. Statistically significant differences were present in the 2, 3, and 4 mm in the TP, in the 2 and 4 mm in ΔL*, and in all thicknesses in Δa* and Δb* betweent the two groups. The TP of RBCs and glass-ceramics decreased as thickness increased, especially from 1 mm to 2 mm. The TP values of the RBCs were more significantly decreased as the thickness of the material increased from 2 mm to 4 mm than those of the glass-ceramics.

Objectives: This study evaluated the effect of adjacent gingival blood flow on detection of pulpal blood flow (PBF) using ultrasound Doppler flowmetry (UDF) through animal study., Materials and Methods: The study included 36 right and left maxillary the third incisors and canines in 9 experimental dogs. The study included 2 main steps: In the first step, the pulse sound level (PSL) was recorded on the cervical part of each tooth without flap elevation (Group 1), with flap elevation (Group 2), and after it was repositioned in place (Group 3). In the second step, the PSL was recorded on the cervical part of each tooth (Group 4), after pulpotomy (Group 5), after partial pulp extirpation (Group 6), after complete extirpation (Group 7), and after canal filling (Group 8). In Groups 5-8, the study was performed with and without flap elevation in the left and right teeth, respectively. The PSL was graded as follows: 0, inaudible; 1, heard faintly; and 2, heard well. The difference between each group was analyzed using Friedman's test with Wilcoxon signed-rank tests (α = 0.05)., Results: In step 1, the PSL results were Group 1 > 2 and 3. In step 2, there was no significant difference between the groups when the flap was not elevated, while PSL results were Group 4 > 5 ≥ 6 and 7 ≥ 8 when the flap was elevated., Conclusions: PBF is affected by gingival blood flow when measured with UDF. UDF measurements require isolation of gingiva from the tooth., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. The Korean Academy of Conservative Dentistry.)

Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4-6 took MED-01 (5.0 × 10 9 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that Lactobacillus plantarum was significantly increased in the vagina, whereas harmful bacteria such as Mobiluncus spp., Gardnerella vaginalis, and Atopobium vaginae were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota.

The aggressive proliferation of tumor cells often requires increased glucose uptake and excessive anaerobic glycolysis, leading to the massive production and secretion of lactate to form a unique tumor microenvironment (TME). Therefore, regulating appropriate lactate levels in the TME would be a promising approach to control tumor cell proliferation and immune suppression. To effectively consume lactate in the TME, lactate oxidase (LOX) and catalase (CAT) were displayed onto Aquifex aeolicus lumazine synthase protein nanoparticles (AaLS) to form either AaLS/LOX or AaLS/LOX/CAT. These complexes successfully consumed lactate produced by CT26 murine colon carcinoma cells under both normoxic and hypoxic conditions. Specifically, AaLS/LOX generated a large amount of H 2 O 2 with complete lactate consumption to induce drastic necrotic cell death regardless of culture condition. However, AaLS/LOX/CAT generated residual H 2 O 2 , leading to necrotic cell death only under hypoxic condition similar to the TME. While the local administration of AaLS/LOX to the tumor site resulted in mice death, that of AaLS/LOX/CAT significantly suppressed tumor growth without any severe side effects. AaLS/LOX/CAT effectively consumed lactate to produce adequate amounts of H 2 O 2 which sufficiently suppress tumor growth and adequately modulate the TME, transforming environments that are favorable to tumor suppressive neutrophils but adverse to tumor-supportive tumor-associated macrophages. Collectively, these findings showed that the modular functionalization of protein nanoparticles with multiple metabolic enzymes may offer the opportunity to develop new enzyme complex-based therapeutic tools that can modulate the TME by controlling cancer metabolism., (© 2023. The Author(s).)

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to the development of osteoclast-specific therapeutic interventions., (© 2022. The Author(s), under exclusive licence to CSI and USTC.)

Hysterectomy is commonly performed for benign gynecological diseases. Minimally invasive surgical approaches offer several advantages. Unfortunately, few studies have compared the outcomes of different types of minimally invasive surgeries. Therefore, this study aimed to compare the surgical outcomes of robotic hysterectomy (RH) and conventional laparoscopic hysterectomy (CLH) in benign gynecologic diseases. We performed a retrospective cohort study at a single center between January 2014 and July 2022. A total of 397 patients (RH: 197 and CLH: 200) who underwent minimally invasive hysterectomy for benign diseases with uterine size exceeding 250 g were enrolled, and factors related to the surgical outcomes were compared. The median age was 46 (range, 35-74) years, and the median uterine weight was 400 (range, 250-2720) g. There were no significant differences between the two groups regarding age, body mass index, uterine weight, hospital stay, estimated blood loss, or operating time. Intraoperative and postoperative complication rates were not significantly different between the two groups. RH was not inferior to CLH in terms of perioperative and immediate postoperative outcomes in our study.

Purpose: Numerous studies have linked particulate matter2.5 (PM 2.5 ) to ocular surface diseases, but few studies have been conducted on the biological effect of PM 2.5 on the cornea. The objective of this study was to evaluate the harmful effect of PM2.5 on primary rat corneal epithelial cells (RCECs) in vitro and identify the toxic mechanism involved., Materials and Methods: Primary cultured RCECs were characterized by pan-cytokeratin (CK) staining. In PM2.5-exposed RCECs, cell viability, microarray gene expression, inflammatory cytokine levels, mitochondrial damage, DNA double-strand break, and signalling pathway were investigated., Results: Exposure to PM 2.5 induced cytotoxicity and morphological changes in RCECs. In addition, PM 2.5 markedly up-regulated pro-inflammatory mediators but down-regulated the wound healing-related transforming growth factor-β. Furthermore, PM 2.5 promoted mitochondrial reactive oxygen species (ROS) production and mediated cellular damage to mitochondria and DNA, whereas these cellular alterations induced by PM 2.5 were markedly suppressed by a potential ROS scavenger. Noteworthy, removal of ROS selectively down-regulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the activation of the nuclear factor-κB (NF-κB) p65 in PM 2.5 -stimulated cells. Additionally, SB203580, a p38 MAPK inhibitor, markedly suppressed these PM 2.5 -mediated cellular dysfunctions., Conclusions: Taken together, our findings show that PM 2.5 can promote the ROS/p38 MAPK/NF-κB signalling pathway and lead to mitochondrial damage and DNA double-strand break, which is ultimately caused inflammation and cytotoxicity in RCECs. These findings indicate that the ROS/p38 MAPK/NF-κB signalling pathway is one mechanism involved in PM 2.5 -induced ocular surface disorders.

Endothelial nitric oxide synthase (eNOS) decreases following inflammatory stimulation. As a master regulator of endothelial homeostasis, maintaining optimal eNOS levels is important during cardiovascular events. However, little is known regarding the mechanism of eNOS protection. In this study, we demonstrate a regulatory role for endothelial expression of 2'-5' oligoadenylate synthetase-like 1 (OASL1) in maintaining eNOS mRNA stability during athero-prone conditions and consider its clinical implications. A lack of endothelial Oasl1 accelerated plaque progression, which was preceded by endothelial dysfunction, elevated vascular inflammation, and decreased NO bioavailability following impaired eNOS expression. Mechanistically, knockdown of PI3K/Akt signaling-dependent OASL expression increased Erk1/2 and NF-κB activation and decreased NOS3 (gene name for eNOS) mRNA expression through upregulation of the negative regulatory, miR-584, whereas a miR-584 inhibitor rescued the effects of OASL knockdown. These results suggest that OASL1/OASL regulates endothelial biology by protecting NOS3 mRNA and targeting miR-584 represents a rational therapeutic strategy for eNOS maintenance in vascular disease., (© 2022. The Author(s).)

Objectives: Ameloblastoma (AM) has been known as a benign but locally invasive tumour with high recurrence rates. Invasive behaviour of the AM results in destruction of the adjacent jawbone and the non-detectable remnants during surgery, interrupting the complete elimination of cancer cells., Methods: To explore novel targets for the tumour cell invasion, a transcriptomic analysis between AM and odontogenic keratocyst were performed through next-generation sequencing in detail., Results: Enrichment of CACNA1C gene (encoding Cav1.2) in AM, a subunit of the L-type voltage-gated calcium channel (VGCC) was observed for the first time. The expression and channel activity of Cav1.2 was confirmed by immunostaining and calcium imaging in the patient samples or primary cells. Verapamil, L-type VGCC blocker revealed suppression of the Ca 2+ -induced cell aggregation and collective invasion of AM cells in vitro. Furthermore, the effect of verapamil in suppressing AM invasion into the adjacent bone was confirmed through orthotopic xenograft model specifically., Conclusion: Taken together, Cav1.2 maybe considered to be a therapeutic candidate to decrease the collective migration and invasion of AM., (© 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Background: We aimed to evaluate the usefulness of YouTube videos for helping patients become informed about robotic myomectomy., Methods: We searched YouTube using "robotic myomectomy" and "Da Vinci myomectomy." Videos were sorted by view count, with the 150 most highly viewed videos being selected. From each video, content type, source, view count, video length, time on YouTube, likes, and dislikes were extracted. A scoring system was used to evaluate video quality., Results: The most prevalent content was recordings of actual surgical procedures of robotic myomectomy, and the most common provider was gynecologic surgeons. Videos directly related to robotic myomectomy were mainly provided by medical groups, had been present on YouTube for a significantly longer time ( p = 0.003), and had a higher rate of no responses from viewers ( p = 0.014) than videos indirectly related to robotic myomectomy. Videos uploaded by nonmedical groups had more likes, more dislikes, and a higher view ratio ( p = 0.029, 0.042, and 0.042, respectively). Scores reflecting video quality did not differ between the two groups. Multiple logistic regression revealed that low-quality videos (less than score 5) were significantly correlated with content indirectly related to robotic myomectomy, poor general quality, fewer views, fewer likes, and no response by viewers., Conclusions: Patients who want to get informed about robotic myomectomy on YouTube should exclude low-quality videos according to such parameters as content, views, and response by viewers. In addition, medical groups should provide videos of good quality for instructing patients about this procedure.

To evaluate the association between red blood cell (RBC) indices (mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], MCH concentration [MCHC], red cell distribution width [RDW], hemoglobin [Hb], hematocrit [Hct], and neutrophil-to-lymphocyte ratio [NLR]) and the severity of endometriosis. Data were obtained from the medical records of 200 patients with endometriosis (stage I/II and stage III/IV groups), and 100 patients with benign ovarian tumors (control group), treated between September 2011 and April 2021. The mean Hb and Hct were significantly lower in the stage III/IV group compared to those in the control and stage I/II group (P = .015 and P = .004, respectively). The mean MCV, MCH, and Hb at postoperative day (POD)#1 were significantly lower in the stage III/IV group compared to those in the control and stage I/II group (P = .007, P = .032, and P < .0001, respectively). In addition, NLR at POD#1 was significantly higher in stage III/IV group compared to that in the control and stage I/II group. Multivariate analysis revealed that younger age (≤38 years old), lower preoperative MCV (≤88.5 fL), lower POD#1 Hb (<11.6g/dL), and higher POD#1 NLR (>2.5) were independent risk factors of stage III/IV endometriosis. Lower levels of RBC indices, including preoperative MCV and postoperative Hb, and higher postoperative NLR were significantly associated with the severity of endometriosis, which is potentially derived from a dysregulation in iron metabolism and inflammation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Many patients seek information online, including on social media, regarding various health topics. This study aimed to investigate whether YouTube videos on endometriosis could be a useful source for the general population, surgical trainees, and specialists. A YouTube search was conducted on December 26, 2021, using the search terms "endometriosis," "endometrioma," and "endometriotic cyst." Videos were sorted by view count, and the 100 videos with the highest view counts were chosen. After excluding 48 videos for various reasons, 52 were included in the final analysis. The number of views, duration, likes and dislikes, content type, and source of each video were recorded. We referred to a previous study to evaluate video quality. The 52 videos related to endometriosis had a total of 35,220,141 views (median 233,688, range 48,874-10,452,366). Based on authorship, the videos were categorized into videos uploaded by the medical group and the nonmedical group. The medical group mainly uploaded videos directly related to endometriosis, such as explanations or detailed surgical procedures for endometriosis (26/27, 96%), whereas the nonmedical group mainly uploaded videos about personal experiences and others (24/25, 96%; P <.001). Evaluating the score by each type of content, videos containing personal experiences (median score 6, range 3-10) scored significantly lower than videos containing other content such as explanations of the disease (median score 14, range 7-18; P < .001) and surgical procedures (median score 9, range 5-17; P < .001). Analysis according to the source, the number of views and video power index was significantly higher in the videos uploaded by the nonmedical group (P < .05). YouTube is currently not an appropriate source for patients to gain information on endometriosis. Credible videos with accurate information and clear, high-quality operative clips with proper scientific commentary should be uploaded by medical professionals and medical institutions to critically and rapidly appraise the quality of online video-disseminated information on endometriosis. In addition, advanced filtering using categories by YouTube's staff appears to be necessary., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ischemic stroke is the leading cause of immortal disability and death worldwide. For treatment in the acute phase, it is necessary to control excessive reactive oxygen species (ROS) damage during ischemia/reperfusion (I/R). Microglia are well known to be closely associated with excessive ROS response in the early stage of I/R. However, the precise roles of microglia associated with mitigating ROS damage, and molecular markers of heterogenetic microglia in the I/R damaged brain has not been clarified. Here, we identified a new type of microglia associated with stroke in the I/R injured brain. Single-cell RNA sequencing (scRNA-seq) was used to assess transcriptional changes of microglia and immune cells in the contralateral (CL) and ipsilateral (IL) hemispheres after transient middle cerebral artery occlusion (tMCAO) surgery to mimic ischemic stroke. We classified a unique type of microglia with enhanced antioxidant function and markers similar to those of disease-associated microglia (DAM), designated them as stroke-associated microglia (SAM). The representative antioxidant enzyme, Peroxiredoxin-1 (Prdx1), was predominantly expressed in SAM and mediated ROS defense genes, including Txn1, Srx1, Mt1, and Mt2. In the Prdx1 -/- I/R damaged brain, we observed significantly increased infarction, as assessed by TTC staining, and FACS analysis detected severe microglial cell death. Importantly, scRNA transcriptomics data showed that the SAM population was specifically decreased in Prdx1 -/- mice and that these mice exhibited decreased ROS damage resistance. Inflammatory responses which were detected by ELISA and qPCR, were also increased in Prdx1 -/- IL hemispheres. Finally, Prdx1-dependent antioxidative SAM were found to be essential for increasing the transcription levels of stroke-protective molecules, such as osteopontin and ferritin. A novel microglia type (SAM) is specifically activated in response to stroke I/R injury, and that Prdx1 expression is required for the activation and enhanced antioxidant function of SAM., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The dental curing unit (DCU) has been reported to emit inhomogeneous light. However, there are no studies on which elements could affect the inhomogeneity of DCUs. This study aimed to analyze the effect of attenuating factors such as the aperture of the lens or neutral density (ND) filters on the DCU's beam profile and evaluate the effect of DCU's inhomogeneous beam profile on the microhardness distribution on composite resin specimens with different thicknesses., Methods: Radiant emittance and spectrum of eight DCUs were investigated with and without ND filters using different optical density (OD) values. Beam profiles of eight DCUs were photographed while increasing the OD values of the ND filter. The change in the beam profile while changing the f-number of the aperture and the OD value of the ND filters were recorded. The Vickers microhardness of Filtek Z350XT and SDR cured by Bluephase Style 20i with 1, 2, 3, and 4 mm specimens of nine points on each surface was measured., Results: Irradiance and spectrum of DCUs uniformly decreased after attenuation by the ND filters. The beam profile of the DCUs blurred when the f-number of the aperture was higher. The microhardness of Filtek Z350XT showed differences between the central and peripheral areas, and between the points under violet LED and the center on the bottom surface of the 4 mm specimen. The microhardness of the SDR did not show any differences., Significance: The inhomogeneity of the beam profile can be affected by attenuation conditions. DCU's inhomogeneous beam profile may have different effects on the composites depending on the thicknesses and types of composite resin used., Competing Interests: Conflicts of interest The authors denied any conflicts of interests related to this study., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Statement of Problem: The beam profile of a light polymerization unit shows an inhomogeneous distribution. Therefore, the light passing through indirect restorations may be inhomogeneous and affect the polymerization of the resin cement., Purpose: The purpose of this in vitro study was to investigate the effects of the inhomogeneous distribution of irradiance passing through a computer-aided design and computer-aided manufacturing (CAD-CAM) block on the microhardness of resin cement., Material and Methods: IPS e.max CAD (A3 LT, A3 HT), Celtra Duo (A3 LT), LAVA Ultimate (A3 LT), and Vita Enamic (A3 T) blocks were tested and cut into 1.0-, 1.5-, 2.0-, and 4.0-mm thicknesses (N=100). The resin cements were Variolink N base (light-polymerized) and RelyX U200 (dual-polymerized). The light transmission, irradiance, and beam profile of each block were measured. For microhardness measurement, 5 points (-4 mm, -2 mm, 0 mm, +2 mm, and +4 mm) that coincided with the distance from the center to the periphery of the tip were marked on the specimen's surface. At each point, microhardness was measured 24 hours after polymerization. Repeated measured 1-way ANOVA with the LSD test was performed to analyze the effect of measuring points on the microhardness (α=.05)., Results: The microhardness of the resin cements decreased with an increase of the CAD-CAM block thickness (P<.05). Resin cements under a 1-mm CAD-CAM block showed relatively uniform microhardness, whereas those under 2-mm and 4-mm blocks showed inhomogeneous microhardness (P<.05)., Conclusions: Inhomogeneous light transmission from a light polymerization unit through CAD-CAM blocks resulted in the nonuniform microhardness of resin cement., (Copyright © 2022 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Parkinson's disease is a neurodegenerative disease characterized by progressive dopaminergic neuronal loss. Motor deficits experienced by patients with Parkinson's disease are well documented, but non-motor symptoms, including mood disorders associated with circadian disturbances, are also frequent features. One common phenomenon is "sundowning syndrome," which is characterized by the occurrence of neuropsychiatric symptoms at a specific time (dusk), causing severe quality of life challenges. This study aimed to elucidate the underlying mechanisms of sundowning syndrome in Parkinson's disease and their molecular links with the circadian clock. We demonstrated that 6-hydroxydopamine (6-OHDA)-lesioned mice, as Parkinson's disease mouse model, exhibit increased depression- and anxiety-like behaviors only at dawn (the equivalent of dusk in human). Administration of REV-ERBα antagonist, SR8278, exerted antidepressant and anxiolytic effects in a circadian time-dependent manner in 6-OHDA-lesioned mice and restored the circadian rhythm of mood-related behaviors. 6-OHDA-lesion altered DAergic-specific Rev-erbα and Nurr1 transcription, and atypical binding activities of REV-ERBα and NURR1, which are upstream nuclear receptors for the discrete tyrosine hydroxylase promoter region. SR8278 treatment restored the binding activities of REV-ERBα and NURR1 to the tyrosine hydroxylase promoter and the induction of enrichment of the R/N motif, recognized by REV-ERBα and NURR1, as revealed by ATAC-sequencing; therefore, tyrosine hydroxylase expression was elevated in the ventral tegmental area of 6-OHDA-injected mice, especially at dawn. These results indicate that REV-ERBα is a potential therapeutic target, and its antagonist, SR8278, is a potential drug for mood disorders related to circadian disturbances, namely sundowning syndrome, in Parkinson's disease., (© 2022. The Author(s).)

Microplastics (MPs) and nanoplastics (NPs) have attracted worldwide attention as potential environmental pollutants. However, toxic effects of exposure to MPs and NPs on organisms at developmental stages have not been elucidated yet. In this study, zebrafish embryos at early stage were used to evaluate potential toxic effects of exposure to MPs with diameter of 1 μm and NPs with diameter of 0.4 μm. Solution containing NPs was optically more transparent than solution containing MPs at the same mass concentration. However, exposure to NPs induced significantly higher mortality rate of zebrafish embryos than exposure to MPs. Exposure to MPs or NPs caused pathological changes of caudal vein plexus. In addition, caudal tissues were impaired with inhibition of intact growth of zebrafish embryos. Peripheral microcirculation at caudal region was significantly deteriorated by exposure to MPs or NPs. However, systematic perfusion was still maintained with preservation of RBC velocity profiles regardless of exposure to MPs or NPs. This study provides a new insight to the use of plastics, demonstrating that exposure to MPs or NPs can lead to developmental disorder with significant impairment of growth and peripheral microcirculation dysfunction., (Copyright © 2021. Published by Elsevier Ltd.)

To compare the clinical significance of 3-month cytogenetic and molecular monitoring, we analyzed 1,410 paired cytogenetic and molecular data from 705 chronic-phase chronic myeloid leukemia patients. Based on early cytogenetic response (ECyR, Ph+≤35 %) and molecular response (EMR, BCR-ABL1 IS ≤10 %) at 3 months, the patients were divided into four groups (group 1: ECyR + EMR, n = 560; group 2: no ECyR + EMR, n = 27; group 3: ECyR + no EMR, n = 55; group 4: no ECyR + no EMR, n = 63). By 10 years, major molecular response (MMR), deep molecular response (MR4.5), overall survival (OS), and progression-free survival (PFS) rates were significantly high in group 1 (P < 0.001). Comparing groups 2 and 3, the MMR (P = 0.096), MR4.5 (P = 0.945), OS (P = 0.832), and PFS (P = 0.627) rates tended to be higher in group 2, although not significantly. Thus, the cytogenetic assay can not only be useful but its addition may also provide a more precise prediction of MR4.5., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

While their function, as immune checkpoint molecules, is well known, B7-family proteins also function as regulatory molecules in bone remodeling. B7-H3 is a receptor ligand of the B7 family that functions primarily as a negative immune checkpoint. While the regulatory function of B7-H3 in osteoblast differentiation has been established, its role in osteoclast differentiation remains unclear. Here we show that B7-H3 is highly expressed in mature osteoclasts and that B7-H3 deficiency leads to the inhibition of osteoclastogenesis in human osteoclast precursors (OCPs). High-throughput transcriptomic analyses reveal that B7-H3 inhibition upregulates IFN signaling as well as IFN-inducible genes, including IDO. Pharmacological inhibition of type-I IFN and IDO knockdown leads to reversal of B7-H3-deficiency-mediated osteoclastogenesis suppression. Although synovial-fluid macrophages from rheumatoid-arthritis patients express B7-H3, inhibition of B7-H3 does not affect their osteoclastogenesis. Thus, our findings highlight B7-H3 as a physiologic positive regulator of osteoclast differentiation and implicate type-I IFN-IDO signaling as its downstream mechanism., (© 2021. The Author(s).)

Background: Despite mechanical and technical improvements in laparoscopic and robot-assisted (LAR) rectal cancer procedures, the absence of prognostic disparities among various approaches cannot improve the quality of TME. The present study re-evaluated robot-assisted total mesorectal excision (TME) procedures to determine whether these procedures may reveal technical faults that may increase the rate of local recurrence (LR)., Methods: This study enrolled 886 consecutive patients with rectal cancer, who underwent curative robot-assisted LAR at Asan Medical Center (Seoul, Korea) between July 2010 and August 2017 (the first vs second period; n = 399 vs 487). The quality of TME and lateral pelvic mesorectal excision (LPME) were analyzed, as were LR rates and survival outcomes., Results: Complete TME and LPME were achieved in 89.2% and 80.1% of these patients, respectively, with ≤ 1% having incomplete TME excluding intramesorectal excision. LR rates were 13.5 and 14.5 times higher in patients with incomplete TME and LPME, respectively, than in patients with complete TME and LPME (14.8% vs 1.1% and 8.7% vs 0.6%; p < 0.001 each by univariate analyses). Multivariate analyses showed that defective LPME was independently associated with incomplete TME and vice versa (p < 0.001). Cox regression analysis showed that defective LPME was independently correlated with reduced 5-year disease-free survival rate (hazard ratio, 1.563; 95% confidence interval, 1.052-2.323; p = 0.027)., Conclusions: LR in rectal cancer patients was largely due to incomplete LPME, which was significantly associated with incomplete TME. Complete LPME may enhance the likelihood of complete TME, reducing LR rates., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Chronic inflammation is a hallmark of atherosclerosis and macrophages play a central role in controlling inflammation at all stages of atherosclerosis. In atherosclerosis, macrophages and monocyte-derived macrophages are continuously exposed to cholesterol, oxidized lipids, cell debris, cytokines, and chemokines. Not only do these stimuli induce a specific macrophage phenotype, but they also interact extensively, leading to macrophage heterogeneity in atherosclerotic plaques. Herein, we review the diverse phenotypes of macrophages, the mechanisms underlying macrophage activation, and the contributions of macrophages to atherosclerosis in this context. We also summarize recent studies on foamy macrophages and monocyte-derived macrophages in plaque during disease progression. We provide a comprehensive overview of transcriptional, epigenetic, and metabolic reprogramming of macrophages and discuss the emerging concepts of targeting cytokines and macrophages to modulate atherosclerosis., Competing Interests: Conflict of Interest: The author has no conflicts of interest to declare., (Copyright © 2021 The Korean Society of Lipid and Atherosclerosis.)

Tillandsia usneoides in epiphytic bromeliads takes up water through absorptive trichomes on the shoot surface under extreme environmental conditions. Although previous studies revealed the way by which T. usneoides absorbs water and prevents water loss, its water transport remains unclear. We characterized structures of trichome wings of T. usneoides. Wing length-to-thickness ratio of 136 and trichome interval (d)-to-wing length (l) ratio (d/l) smaller than 1 caused the water film to flatten the wings sequentially, resulting in domino-like water transport. A hinge-like linkage between wing and outer ring cells and the wing size longer than the elastocapillary length (L EC ) brought about this unique reconfiguration, which is the flattening and recovery of wings. Tillandsia usneoides transported water rapidly on the surface as the water film propagated on the exterior trichomes with flexible wings and the transport distance at the macroscopic scale grew as t x with x = 0.68 ± 0.04, unlike the conventional scaling of t 0.5 . Empirical and theoretical investigations proved our assumption that external water transport with the domino-like effect predominated over internal vascular transport. Biomimetic trichome wings simulated the domino-like water transport, highlighting the important role of flexible wing arrays., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

A salient feature of mammalian sleep is the alternation between rapid eye movement (REM) and non-REM (NREM) sleep. However, how these two sleep stages influence each other and thereby regulate the timing of REM sleep episodes is still largely unresolved. Here, we developed a statistical model that specifies the relationship between REM and subsequent NREM sleep to quantify how REM sleep affects the following NREM sleep duration and its electrophysiological features in mice. We show that a lognormal mixture model well describes how the preceding REM sleep duration influences the amount of NREM sleep till the next REM sleep episode. The model supports the existence of two different types of sleep cycles: Short cycles form closely interspaced sequences of REM sleep episodes, whereas during long cycles, REM sleep is first followed by an interval of NREM sleep during which transitions to REM sleep are extremely unlikely. This refractory period is characterized by low power in the theta and sigma range of the electroencephalogram (EEG), low spindle rate and frequent microarousals, and its duration proportionally increases with the preceding REM sleep duration. Using our model, we estimated the propensity for REM sleep at the transition from NREM to REM sleep and found that entering REM sleep with higher propensity resulted in longer REM sleep episodes with reduced EEG power. Compared with the light phase, the buildup of REM sleep propensity was slower during the dark phase. Our data-driven modeling approach uncovered basic principles underlying the timing and duration of REM sleep episodes in mice and provides a flexible framework to describe the ultradian regulation of REM sleep in health and disease., Competing Interests: The authors have declared that no competing interests exist.

Few studies have used a longitudinal approach to describe the immune response to SARS-CoV-2 infection. Here, we perform single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment shows distinct changes in cell proportions and characteristics compared to uninfected control, at 2 and 5 days post-infection (dpi). Macrophages are classified into 10 distinct subpopulations with transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, notably at 2 dpi. Moreover, trajectory analysis reveals gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identifies a macrophage subpopulation that has rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we find that M1 or M2 macrophages show distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection., (© 2021. The Author(s).)

Purpose: To investigate whether laparoscopic ovarian cystectomy (LOC) affects ovarian reserve., Patients and Methods: In 46 premenopausal women, who underwent either LOC (study group, n=26) or laparoscopic myomectomy (LM) (control group, n=20), serum anti-Mullerian hormone (AMH) levels were measured pre-operatively (AMH0), and postoperatively at 7 days (AMH1), 2 months (AMH2), and 6 months (AMH3). Changes in AMH from baseline level (AMH0) in each group were compared., Results: AMH0 did not differ between the two groups (3.5 ± 3.33 in LOC vs 2.4 ± 2.72 in LM, P =0.250). AMH1, AMH2, and AMH3 in each group were also similar. However, a significant decline of AMH (ie more than 50% decrease compared to AMH0) at postoperative 6 months occurred more frequently in the LOC group than in the LM group. In the sub-analysis of the LOC group, a significant decline of AMH at postoperative 2 months and 6 months was highly correlated with bilateral ovarian tumors ( P =0.001)., Conclusion: Compared to LM, serum AMH level showed a minimal decrease after 1 week following LOC, which did not revert to normal over 6 months of follow-up. In addition, a significant decline of ovarian reserve at postoperative 6 months was significantly more frequent in the LOC group, suggesting that LOC may have more adverse effects on ovarian reserve compared to the LM (control) group. Thus, care is required during the LOC procedure, specifically in women with bilateral tumors., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Cho et al.)

Graphene-based nanomaterials (GBNs) have been widely used in various fields nowadays. However, they are reported to be highly toxic to some aquatic organisms. However, the multi-organ toxicity caused by pristine graphene (pG) and graphene oxide (GO) to the developing zebrafish (Danio rerio) larvae or juvenile and the underlying mechanisms is not fully known. Therefore, in the present study, the effect of pG and GO with environmental concentrations (0, 5, 10, 15, 20, and 25 μg/L of pG; 0, 0.1, 0.2, 0.3, and 0.4 mg/mL of GO) on multi-organ system in developing zebrafish larvae was experimentally assessed. The pG and GO were found to accumulate in the brain tissue that also caused significant changes in the heart beat and survival rate. The sizes of hepatocytes were reduced. Altered axonal integrity, affecting axon length and pattern in "Tg(mbp:eGFP) transgenic lines" was also observed. In addition, the results indicated pathological effects in major organs and with disrupted mitochondrial structure was quite obvious. The pG and GO bioaccumulation leads to multi organ toxicity in zebrafish larvae. In future, the existence of the current study can be extrapolated to other aquatic system in general and in particularly to humans., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.

Plants have a special structure, torus-margo (TM) pit, which comprises a thickened torus at the center encircled by a highly porous margo. It is regarded as a key evolutionary structure to enable stable water transport, minimizing the air spread in the vessels. However, its valve-like dynamics to regulate two-phase flows still remains unclear even at a single pit level. Here, we study the air spreading dynamics using a bioinspired model of this soft pit valve. We divide it into the initial onset and the consecutive air-spreads, and propose the criteria of TM structures as the valve-like function. To delay the onset of air spread, the margo region should be thin and deformable enough to seal the pit aperture with the torus before the air penetration. Even after the onset, the membranes whose maximum pore size is smaller than its thickness can avoid continuous air-spread. The criteria also fit properly into botanical data on the morphologies of TM pits, implying that their valve-like behaviors may alleviate the tradeoff between hydraulic safety and efficiency at the single pit level. Our study would help to understand of the mechanistic pit-level strategy and also can provide insight into fluidic systems to control interfacial phenomena.

With the worsening water scarcity problem, seawater desalination has been receiving gradually increasing attention. Ion adsorptive desalination was introduced as one of the seawater desalination techniques. In our previous study, metal-organic framework (MOF)-incorporated single-network alginate (MOF-Alg(Cu)) beads were used to adsorb ions in seawater. In the present study, MOF-incorporated Cu-based alginate/PVA hydrogel (MOF-Alg(Cu)/PVA) beads were fabricated to enhance the ion adsorption desalination technique. Cu-based MOFs were successfully synthesized in situ on an interpenetrating polymer network (IPN). Given that the IPN hydrogel beads have high stability, the amount of MOF particles extracted during the adsorption of ions is reduced. The fabricated MOF-Alg(Cu)/PVA beads exhibit efficient removal of dissolved ions in artificial seawater and NaCl solution with varied concentrations. The ion adsorption characteristics were evaluated on the basis of adsorption kinetics, adsorption isotherms, and dosage of adsorbent. The repeat cycle tests show that more than half of the ion removal efficiency was maintained after 10 cycle tests. The concentration of artificial seawater was reduced to 1500 ppm by employing MOF-Alg(Cu)/PVA beads through a multistage experiment. Compared with other seawater desalination techniques, the proposed adsorptive desalination technique using MOF-Alg(Cu)/PVA beads will pave the way for developing a new ecofriendly and energy-saving approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Although gait disturbances are relatively common symptoms in diabetic polyneuropathy (DPN), few studies have quantitatively analyzed gait and posture in DPN patients. This study aimed to analyze gait and posture quantitatively in DPN patients and to determine the association between clinical and electrophysiological parameters and gait and posture parameters., Methods: Sixty-four DPN patients were enrolled in this study. DPN was clinically assessed using the Toronto clinical neuropathy score (TCNS). All participants underwent nerve conduction study (NCS), three-dimensional motion analysis, and static posturography. We evaluate the correlation of gait and posture parameters with electrophysiological and clinical parameters., Results: Foot height, step length, and stride length among gait parameters were inversely correlated with the TCNS. Anteroposterior range during eyes-closed and mediolateral distance and range during eyes-open and eyes-closed were inversely correlated with the sensory nerve action potential amplitude in the sural nerve. Mediolateral distance during eyes-open and eyes-closed was correlated with the compound muscle action potential amplitude in the peroneal nerve., Conclusions: Gait parameters are associated with clinical parameters, and postural parameters are associated with electrophysiological parameters, particularly sensory NCS. Gait and postural analysis can be a useful tool for assessing the neurological status in DPN patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The purpose of this study was to examine and compare color and translucency stability of three-dimensional (3D) printable dental materials for crown and bridge restorations. Five different materials were investigated, and twelve disc-shaped specimens of two different thicknesses (1 and 2 mm) were prepared using a digital light processing 3D printer. Color measurements were made according to the CIELAB color scale (L*, a*, and b*) using a spectrophotometer 1 h, 1 day, 1 week, one month, and six months after post-curing of the materials, and the translucency parameter (TP) was calculated. The L*, a*, b*, and TP values were compared among the different materials and storage periods using repeated measures analysis of variance. Color and translucency changes of the specimens after the different storage periods were compared with 1 h measurements to determine whether they exceeded clinically perceivable thresholds. The L*, a*, b*, and TP values showed significant differences according to the storage periods, as well as among the materials. Until one month, some materials demonstrated distinct color differences, while others showed small color differences below a clinically perceivable threshold. The translucency differences were not clinically perceivable for any specimen. After six months, all specimens demonstrated large color changes, whereas the changes in translucency were relatively small. In conclusion, the color of 3D printable dental materials changed with time, and the differences varied with the materials used. On the contrary, the changes in translucency were small. Overall, the materials became darker, more yellowish, and more opaque after six months of water storage.

Background: The differential diagnosis of ovarian cancer is important, and there has been ongoing research to identify biomarkers with higher performance. This study aimed to evaluate the diagnostic utility of combinations of cancer markers classified by machine learning algorithms in patients with early stage ovarian cancer, which has rarely been reported., Methods: In total, 730 serum samples were assayed for lactate dehydrogenase (LD), neutrophil-to-lymphocyte ratio (NLR), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), and risk of ovarian malignancy algorithm (ROMA). Among them, 53 were diagnosed with early stage ovarian cancer, and the remaining 677 were diagnosed with benign disease., Results: The areas under the receiver operating characteristic curves (ROC-AUCs) of the ROMA, HE4, CA125, LD, and NLR for discriminating ovarian cancer from non-cancerous disease were .707, .680, .643, .657, and .624, respectively. ROC-AUC of the combination of ROMA and LD (.709) was similar to that of single ROMA in the total population. In the postmenopausal group, ROC-AUCs of HE4 and CA125 combined with LD presented the highest value (.718). When machine learning algorithms were applied to ROMA combined with LD, the ROC-AUC of random forest was higher than that of other applied algorithms in the total population (.757), showing acceptable performance., Conclusion: Our data suggest that the combinations of ovarian cancer-specific markers with LD classified by random forest may be a useful tool for predicting ovarian cancer, particularly in clinical settings, due to easy accessibility and cost-effectiveness. Application of an optimal combination of cancer markers and algorithms would facilitate appropriate management of ovarian cancer patients.

Background: Macrophages produce many inflammation-associated molecules, released by matrix metalloproteinases, such as adhesion molecules, and cytokines, as well, which play a crucial role in atherosclerosis. In this context, we investigated the relationship between Ninjurin-1 (Ninj1 [nerve injury-induced protein]), a novel matrix metalloproteinase 9 substrate, expression, and atherosclerosis progression., Methods: Ninj1 expression and atherosclerosis progression were assessed in atherosclerotic aortic tissue and serum samples from patients with coronary artery disease and healthy controls, and atheroprone apolipoprotein e-deficient ( Apoe -/- ) and wild-type mice, as well. Apoe -/- mice lacking systemic Ninj1 expression ( Ninj1 -/- Apoe -/- ) were generated to assess the functional effects of Ninj1. Bone marrow transplantation was also used to generate low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice that lack Ninj1 specifically in bone marrow-derived cells. Mice were fed a Western diet for 5 to 23 weeks, and atherosclerotic lesions were investigated. The anti-inflammatory role of Ninj1 was verified by treating macrophages and mice with the peptides Ninj1 1 -56 (ML56) and Ninj1 26 -37 (PN12), which mimic the soluble form of Ninj1 (sNinj1)., Results: Our in vivo results conclusively showed a correlation between Ninj1 expression in aortic macrophages and the extent of human and mouse atherosclerotic lesions. Ninj1 -deficient macrophages promoted proinflammatory gene expression by activating mitogen-activated protein kinase and inhibiting the phosphoinositide 3-kinase/Akt signaling pathway. Whole-body and bone marrow-specific Ninj1 deficiencies significantly increased monocyte recruitment and macrophage accumulation in atherosclerotic lesions through elevated macrophage-mediated inflammation. Macrophage Ninj1 was directly cleaved by matrix metalloproteinase 9 to generate a soluble form that exhibited antiatherosclerotic effects, as assessed in vitro and in vivo. Treatment with the sNinj1-mimetic peptides, ML56 and PN12, reduced proinflammatory gene expression in human and mouse classically activated macrophages, thereby attenuating monocyte transendothelial migration. Moreover, continuous administration of mPN12 alleviated atherosclerosis by inhibiting the enhanced monocyte recruitment and inflammation characteristics of this disorder in mice, regardless of the presence of Ninj1., Conclusions: Ninj1 is a novel matrix metalloproteinase 9 substrate in macrophages, and sNinj1 is a secreted atheroprotective protein that regulates macrophage inflammation and monocyte recruitment in atherosclerosis. Moreover, sNinj1-mediated anti-inflammatory effects are conserved in human macrophages and likely contribute to human atherosclerosis.

The purpose of this study was to investigate whether tooth-brushing with a microcurrent was effective in inducing dentinal tubule occlusion. The specific aims of the study were (1) to evaluate the effectiveness of tooth-brushing with a microcurrent on dentinal tubule occlusion by using scanning electron microscopy (SEM); and (2) to compare the dentinal fluid flow rate after tooth-brushing with a microcurrent by using a sub-nanoliter-scaled fluid flow measuring device (NFMD). All experimental groups showed partially occluded dentinal tubules and crystal-like structures at a specific microcurrent intensity indicated that tooth-brushing with a microcurrent could efficiently occlude dentinal tubules. The decrease in dentinal fluid flow rate in the tooth-brushing with microcurrents group indicated that dentinal tubules were occluded and the flow of dentinal fluid had decreased.

Objectives: The first objective of this study was to determine if the luting material used for resin nanoceramic inlay affects interfacial adaptation. The second was to investigate whether pretreatment and the adhesive curing method before cementation affects interfacial adaptation. The final objective was to compare activation modes of luting material., Methods: Class I cavities were prepared on extracted human third molars. Resin nanoceramic inlays were fabricated using Lava Ultimate CAD/CAM block (3 M). For the control groups, inlays were cemented using Panavia V5 (Kuraray Noritake). For the experimental groups, teeth were randomly divided into five experimental groups with four subgroups using different self-adhesive cements (SACs). Cement in Group I was dual-cured without pretreatment. In Group II, the cement was dual-cured after polyacrylic acid treatment of the tooth cavity. In Groups III and IV, the cement was dual-cured after universal dentin adhesive treatment with pre-cure and co-cure methods. In Group V, the inlay was cemented in self-cure mode. After thermocycling, interfacial adaptation at the inlay-tooth interface was measured using swept-source optical coherence tomography (SS-OCT) imaging. Finally, polymerization shrinkage strain of the luting material was measured and compared., Results: Interfacial adaptation differed depending on the luting material. After application of a universal adhesive, some subgroups showed improved interfacial adaptation. Interfacial adaptation and polymerization shrinkage strain differed significantly depending on activation mode., Significance: Interfacial adaptation for a resin nanoceramic inlay can differ according to the type of SAC and activation mode. For some SACs, application of a universal adhesive before cementation improves interfacial adaptation., (Copyright © 2020 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs.