Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the absence of regulation by B cells.

Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Here we found a greater number of aged CD11bhiL-selectinloCXCR4+ polymorphonuclear leukocytes (PMNs) in lung vasculature than in the peripheral circulation. Using pulmonary intravital microscopy, we observed lung PMNs physically interacting with B cells via ß2 integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in the lungs without systemic inflammation, which caused pathological fibrotic interstitial lung disease that was attenuated by the adoptive transfer of B cells or depletion of PMNs. Thus, the lungs are an intermediary niche in the PMN lifecycle wherein aged PMNs are regulated by B cells, which restrains their potential to cause pulmonary pathology.

Prevention of neointimal hyperplasia after coronary artery bypass graft via local delivery of sirolimus and rosuvastatin: network pharmacology and in vivo validation.

BACKGROUND: Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown. METHODS: We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery. RESULTS: We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis. CONCLUSIONS: Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG.

Dual Leucine Zipper Kinase Regulates Dscam Expression through a Noncanonical Function of the Cytoplasmic Poly(A)-Binding Protein.

Dual leucine zipper kinase (DLK) plays a pivotal role in the development, degeneration, and regeneration of neurons. DLK can regulate gene expression post-transcriptionally, but the underlying mechanism remains poorly understood. The Drosophila DLK, Wallenda (Wnd), regulates the expression of Down syndrome cell adhesion molecule (Dscam) to control presynaptic arbor growth. This regulation is mediated by the 3' untranslated region (3'UTR) of Dscam mRNA, which suggests that RNA binding proteins (RBPs) mediate DLK function. We performed a genome-wide cell-based RNAi screen of RBPs and identified the cytoplasmic poly(A)-binding protein, pAbp, as an RBP that mediates Wnd-induced increase in Dscam expression. Genetic analysis shows that Wnd requires pAbp for promoting presynaptic arbor growth and for enhancing Dscam expression. Our analysis revealed that Dscam mRNAs harbor short poly(A) tails. We identified a region in Dscam 3'UTR that specifically interacts with pAbp. Removing this region significantly reduced Wnd-induced increase in Dscam expression. These suggest that a noncanonical interaction of PABP with the 3'UTR of target transcripts is essential for DLK functions.SIGNIFICANCE STATEMENT The kinase DLK plays key roles in a multitude of neuronal responses, including axon development, neurodegeneration, and nerve injury. Previous studies show that DLK acts via mRNAs to regulate protein synthesis, but how DLK does so is poorly understood. This study demonstrates that DLK regulates the synthesis of Dscam through the poly(A)-binding protein PABP-C. Whereas PABP-C is known as a general translational activator, our study shows that DLK-mediated Dscam expression involves a noncanonical interaction between PABP-C and the Dscam mRNA, which leads to a selective regulation of Dscam translation by PABP-C. Thus, our study provides novel insights into the mechanisms that underlie the function of DLK and regulation of gene expression of PABP-C.

Mapping the conformational epitope of a therapeutic monoclonal antibody against HBsAg by in vivo selection of HBV escape variants.

BACKGROUND AND AIMS: Hepatitis B immunoglobulin (HBIG) has been routinely applied in the liver transplantation setting to block HBV reinfection of grafts. However, new monoclonal anti-HBV surface antibodies have been developed to replace HBIG. The epitopes of such monoclonal antibodies may affect the emergence of escape variants and deserve study. APPROACH AND RESULTS: The conformational epitope of sLenvervimab, a surrogate form of Lenvervimab, which is a monoclonal anti-HBsAg antibody currently under phase 3 trial, was investigated by selecting escape mutants from a human liver chimeric mouse. HBV-infected chimeric mice treated with sLenvervimab monotherapy showed an initial decline in circulating HBsAg levels, followed by a quick rebound in 1 month. Sequencing of circulating or liver HBV DNA revealed emerging variants, with replacement of amino acid E164 or T140, two residues widely separated in HBsAg. E164 HBV variants strongly resisted sLenvervimab neutralization in cell culture infection, and the T140 variant moderately resisted sLenvervimab neutralization. Natural HBV variants with amino-acid replacements adjacent to E164 were constructed and examined for sLenvervimab neutralization effects. Variants with K160 replacement also resisted neutralization. These data revealed the conformational epitope of sLenvervimab. CONCLUSIONS: Selection of antibody-escape HBV variants in human chimeric mice works efficiently. Analysis of such emerging variants helps to identify anchor amino-acid residues of the conformational epitope that are difficult to discover by conventional approaches.

Influence of Sociodemographic Factors, Health Conditions, and Activity on Participation in People With Spinal Cord Injury in South Korea.

OBJECTIVE: To verify the causal relationship between sociodemographic factors, health conditions, and activities that influence the participation of people with spinal cord injury (SCI) using International Spinal Cord Injury (InSCI) Survey data and to investigate the moderation effects of environmental restrictions and health care system concerns. DESIGN: Cross-sectional community survey and structural equation model. SETTING: SCI databases of the Korea National Rehabilitation Center and Korea Spinal Cord Injury Association. PARTICIPANTS: Community-dwelling adults (N=890) with SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The InSCI questionnaire domains included sociodemographic factors, health conditions, activity, participation, environmental restrictions, and health system concerns. Sociodemographic factors included age, education, and income. Health conditions included bowel dysfunction, respiratory problems, and pain, among others. Activity included "daily routine" and "using hands," among others. Participation included "interacting with people" and "intimate relationships," among others. Environmental restrictions included "public places" and "negative attitudes," among others. Health care system concerns included "nursing care" and "experience of being treated," among others. RESULTS: The hypothesis that health conditions would have a significant effect on activity was supported because 51% of the total variance in activity factors was explained by health condition factors. The hypothesis that activity would have a significant effect on participation was also supported because 63.4% of total variance in participation factors was explained by activity factors. The moderation effect tests supported the hypotheses that health conditions, activity, and participation would differ depending on the extent of environmental restrictions as well as the extent of health system concerns. CONCLUSIONS: When formulating policies and recommendations to promote the participation of people with SCI living in the South Korean community, the influence of environmental restrictions and health systems as well as the causal influence of health conditions and activity should be considered.

A postulated model for photoimmunopathogenesis of chronic actinic dermatitis around adaptive immunity, including Th17 cells, Tregs, TRMs, cytotoxic T cells, and/or common-γ chain receptor+ cells.

BACKGROUND/PURPOSE: The pathogenesis of chronic actinic dermatitis (CAD) is more complicated than other photodermatoses. However, the relationship between the clinical severity of CAD and the offending photocontact or contact allergens or both, and the correlations of CAD immunopathogenesis with the immunoregulatory molecules involved in adaptive immunity are yet to be investigated. METHODS: We performed phototesting with broad-spectrum ultraviolet (UV) B, UVA, and visible light to establish the presence of photosensitivity in 121 patients with CAD, together with photopatch and contact patch testing. Nine patients with CAD were selected according to their clinical severity score for CAD (CSS-CAD), and triple direct immunofluorescence analysis was performed with paraffin-embedded skin biopsy samples. RESULTS: As CSS-CAD was closely correlated with the multiplicity of photo(contact) allergens, particularly photoallergens, three or more photoallergens were detected in the severe CAD group (52.5%); less in the moderate group (32.8%); and only one in the mild group (14.8%; P = .025). In the groups showing greater severity of disease, the absolute numbers of IFN-γ+ , IL-17+ , CD4+, CD8+, common-γ chain receptor (common-γCR)+ , and CD69+ tissue-resident memory cells increased on average; there was also an increase in the CD4+/CD8+ cell ratio, with the more severely affected groups. However, the levels of TNF-α+ and FoxP3+ regulatory T (Treg) cells and the mean IL-17/IFN-γ cell ratio decreased in the more severely affected CSS-CAD subgroups. CONCLUSIONS: Based on the clinical analysis and immunopathogenic results, avoidance of excessive sun exposure, and topical and systemic blocking agents for photo(contact) allergens are recommended. Additionally, conventional immunomodulators and emerging agents including JAK-STAT inhibitors may be administered for CAD treatment in the future.

Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model.

We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B-embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.

Temporal stability of the hemodynamic response function across the majority of human cerebral cortex.

The hemodynamic response function (HRF) measured with functional magnetic resonance imaging is generated by vascular and metabolic responses evoked by brief (<4 s) stimuli. It is known that the human HRF varies across cortex, between subjects, with stimulus paradigms, and even between different measurements in the same cortical location. However, our results demonstrate that strong HRFs are remarkably repeatable across sessions separated by time intervals up to 3 months. In this study, a multisensory stimulus was used to activate and measure the HRF across the majority of cortex (>70%, with lesser reliability observed in some areas of prefrontal cortex). HRFs were measured with high spatial resolution (2-mm voxels) in central gray matter to minimize variations caused by partial-volume effects. HRF amplitudes and temporal dynamics were highly repeatable across four sessions in 20 subjects. Positive and negative HRFs were consistently observed across sessions and subjects. Negative HRFs were generally weaker and, thus, more variable than positive HRFs. Statistical measurements showed that across-session variability is highly correlated to the variability across events within a session; these measurements also indicated a normal distribution of variability across cortex. The overall repeatability of the HRFs over long time scales generally supports the long-term use of event-related functional magnetic resonance imaging protocols.

Association of Smoking Status With the Risk of Type 2 Diabetes Among Young Adults: A Nationwide Cohort Study in South Korea.

INTRODUCTION: The longitudinal evidence between detailed parameters of smoking status and type 2 diabetes among young adults has been limited. We evaluated this association in young Korean adults. METHODS: This nationwide cohort study included 3 026 551 adults aged 20 to 39 years who underwent Korean National Health Insurance Service health examinations in 2009 and were followed up until the end of 2017. The participants were categorized according to smoking status, smoking duration, and smoking amount. The hazard ratios (HRs) and 95% CIs for type 2 diabetes were estimated using multivariable Cox proportional hazard regression analysis. RESULTS: During 8.2 years of follow-up, 71 952 cases of type 2 diabetes newly developed. Compared with never-smokers, independently increased HRs of type 2 diabetes were observed in ex-smokers (1.06, 95% CI = 1.04-1.09) and current smokers (1.39, 1.36-1.42). In these two groups, the type 2 diabetes risk increased with greater smoking duration and amount (p for trend <.001). The HRs of type 2 diabetes were higher in current smokers than in ex-smokers at the same lifetime smoking amount. The associations between smoking status and incident type 2 diabetes were stronger in men, individuals who did not drink heavily, and those without obesity. CONCLUSIONS: Among young adults, past and current smoking was associated with an increased risk of type 2 diabetes, and there was a dose-response association of smoking amount and duration with type 2 diabetes development. Appropriate interventions to help young adults cease smoking may help reduce the incidence of type 2 diabetes. IMPLICATIONS: Smoking was associated with an increased risk of type 2 diabetes among young adults, and the risk was shown to increase as amount and duration of smoking increased. Ceasing smoking in young adults may help reduce the incidence of type 2 diabetes.

Comparison of diagnostic performance between FIB-4 and NFS in metabolic-associated fatty liver disease era.

AIMS: Fibrosis-4 index (FIB-4) and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) are the two most widely used non-invasive tools for screening of advanced fibrosis in subjects with NAFLD. Since metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed as a new category of fatty liver disease, we aimed to compare the diagnostic performance of FIB-4 and NFS in subjects with MAFLD and in various subgroups. METHODS: This study was designed as cross-sectional study. Data from 6775 subjects who underwent magnetic resonance elastography (MRE) and abdominal ultrasonography at the same time during a health check-up at 13 various health check-up centers were retrospectively reviewed. Advanced fibrosis was defined as an MRE value of ≥3.6 kPa. RESULTS: The area under the receiver operating characteristic curves (AUROCs) of FIB-4 and NFS for diagnosing advanced fibrosis were similar in subjects with MAFLD. However, the AUROC of NFS was lower than that of FIB-4 in the diabetic subgroup of MAFLD (0.809 in FIB-4 vs. 0.717 in NFS, p = 0.002). The performances of both FIB-4 and NFS were poor in the subgroup of MAFLD with significant alcohol intake. CONCLUSIONS: The overall diagnostic performance of FIB-4 and NFS for diagnosing advanced fibrosis did not differ among subjects with MAFLD. However, the performance of NFS was lower in the diabetes subgroup of MAFLD. The diagnostic performance of FIB-4 was better for fibrosis in various subgroups of MAFLD.

Surgical Findings and Outcomes of Endotension Following Endovascular Aneurysm Repair.

BACKGROUND: Endotension is one of the detrimental complications after endovascular aneurysm repair (EVAR) and surgical management has been considered as standard of care. However, there is a paucity of data regarding the findings, and outcomes of such surgical intervention. The aim of this study was to investigate intraoperative findings and outcomes of surgical treatment for endotension after EVAR. METHODS: Between January 2005 and October 2018, of the 708 patients who underwent EVAR for aneurysm aortic aneurysm; 12 patients (mean age of 76.1; range 66-88) who underwent open repair for endotension were retrospectively analyzed. The anatomical characteristics of the aorta and surgical findings were reviewed. The rates of early and late procedural complications, and overall mortality were evaluated. RESULTS: The median interval between the EVAR and surgical conversion was 45.9 months (range 17.1-46.9). Three of the twelve patients underwent emergency surgery due to aneurysm rupture. The median aneurysm sac size, the proximal neck diameter, and the proximal neck length before EVAR were 64 mm, 23.5 mm, and 30.5 mm, respectively, that changed before open repair to 93.5 mm (P = 0.02), 25 mm (P = 0.011), and 23 mm (P = 0.003), respectively. In four of the twelve patients, radiographically undetected endoleak was identified during surgery to be Type Ia, Ib, II, and III, respectively. The rates of early and late procedural complications, and overall mortality were 8.3%, 8.3% and 8.3%, respectively. CONCLUSIONS: Patients with endotension have a risk of delayed endoleak and aneurysm rupture; secondary intervention should be performed in such cases to prevent fatal complications. Surgical treatment appears to be a curative treatment for endotension with favorable outcomes. In addition, the possibility of an undetected endoleak should be considered as a potential cause of endotension.

Retinotopic variations of the negative blood-oxygen-level dependent hemodynamic response function in human primary visual cortex.

Functional magnetic resonance imaging (fMRI) measures blood-oxygen-level-dependent (BOLD) contrast that is generally assumed to be linearly related to excitatory neural activity. The positive hemodynamic response function (pHRF) is the positive BOLD response (PBR) evoked by a brief neural stimulation; the pHRF is often used as the impulse response for linear analysis of neural excitation. Many fMRI studies have observed a negative BOLD response (NBR) that is often associated with neural suppression. However, the temporal dynamics of the NBR evoked by a brief stimulus, the negative HRF (nHRF), remains unclear. Here, a unilateral visual stimulus was presented in a slow event-related design to elicit both pHRFs in the stimulus representation (SR), and nHRFs elsewhere. The observed nHRFs were not inverted versions of the pHRF previously reported. They were characterized by a stronger initial negative response followed by a significantly later positive peak. In contralateral primary visual cortex (V1), these differences varied with eccentricity from the SR. Similar nHRFs were observed in ipsilateral V1 with less eccentricity variation. Experiments with the blocked version of the same stimulus confirmed that brain regions presenting the unexpected nHRF dynamics correspond to those presenting a strong NBR. These data demonstrated that shift-invariant temporal linearity did not hold for the NBR while confirming that the PBR maintained rough linearity. Modeling indicated that the observed nHRFs can be created by suppression of both blood flow and oxygen metabolism. Critically, the nHRF can be misinterpreted as a pHRF due to their similarity, which could confound linear analysis for event-related fMRI experiments.NEW & NOTEWORTHY We investigate dynamics of the negative hemodynamic response function (nHRF), the negative blood-oxygen-level-dependent (BOLD) response (NBR) evoked by a brief stimulus, in human early visual cortex. Here, we show that the nHRFs are not inverted versions of the corresponding pHRFs. The nHRF has complex dynamics that varied significantly with eccentricity. The results also show shift-invariant temporal linearity does not hold for the NBR.

The Lung Microvasculature Is a Functional Immune Niche.

Lung capillaries, best known for vital gas exchange, also contribute to neutrophil margination, a phenomenon resulting in large numbers of pulmonary vascular neutrophils. Importantly, the functional relevance of neutrophil margination is unknown. Recent advances in microscopy have altered our understanding of why neutrophils marginate. Specifically, data show that lung capillaries provide a unique anatomical site for neutrophils to capture bloodstream pathogens, which contrasts the conventional monophagocytic-dominated vascular host defense of the spleen and liver. Moreover, lung capillaries provide an efficient site for direct cell-cell communication required for the induction of apoptosis in aged neutrophils. These new ideas transform our views of the pulmonary circulation as a site for immediate neutrophil-mediated host defense and regulation of their life cycle.

SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma.

BACKGROUND: Vasculogenic mimicry (VM) is the formation of an alternative circulatory system by aggressive tumor cells. The characteristics of VM and its underlying mechanism in oral squamous cell carcinoma (OSCC) remain unclear. This study aims to determine the relationship between VM in OSCC tissues and clinical outcomes and to investigate the biological role of SOX7 in VM in OSCC cells. METHODS: CD31/PAS staining was performed to evaluate VM in OSCC tissue. The relationships between VM and clinicopathological variables, and VM and SOX7 levels were analyzed. The correlation between SOX7 levels and cancer cohorts was investigated using in silico analysis. VM formation assay was performed to observe VM in vitro. To investigate the role of SOX7 in VM formation, SOX7 was transiently over-expressed in SCC-9 cells. VM-modulating genes were identified by Western blotting. RESULTS: We found a positive correlation between VM and lymph node metastasis and patient survival in OSCC (p = 0.003). In silico analysis from The Cancer Genome Atlas and Gene Expression Omnibus database showed that down-regulation of SOX7 expression was significantly correlated with OSCC patients (p = 0.0187) and lymph node metastasis (p = 0.0017). We also found that the presence of VM in OSCC tissue was inversely associated with SOX7 expression (p = 0.020). We observed that overexpression of SOX7 impaired VM formation by reducing the expression of VE-cadherin, thereby inhibiting cell migration and invasion. CONCLUSION: These results suggest that SOX7 plays an important role in the regulation of VM formation and may inhibit OSCC metastasis.

The Extensive Usage of the Facial Image Threshing Machine for Facial Emotion Recognition Performance.

Facial emotion recognition (FER) systems play a significant role in identifying driver emotions. Accurate facial emotion recognition of drivers in autonomous vehicles reduces road rage. However, training even the advanced FER model without proper datasets causes poor performance in real-time testing. FER system performance is heavily affected by the quality of datasets than the quality of the algorithms. To improve FER system performance for autonomous vehicles, we propose a facial image threshing (FIT) machine that uses advanced features of pre-trained facial recognition and training from the Xception algorithm. The FIT machine involved removing irrelevant facial images, collecting facial images, correcting misplacing face data, and merging original datasets on a massive scale, in addition to the data-augmentation technique. The final FER results of the proposed method improved the validation accuracy by 16.95% over the conventional approach with the FER 2013 dataset. The confusion matrix evaluation based on the unseen private dataset shows a 5% improvement over the original approach with the FER 2013 dataset to confirm the real-time testing.

Luteolin-3'-O-Phosphate Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Regulating NF-κB/MAPK Cascade Signaling in RAW 264.7 Cells.

Luteolin (LT), present in most plants, has potent anti-inflammatory properties both in vitro and in vivo. Furthermore, some of its derivatives, such as luteolin-7-O-glucoside, also exhibit anti-inflammatory activity. However, the molecular mechanisms underlying luteolin-3'-O-phosphate (LTP)-mediated immune regulation are not fully understood. In this paper, we compared the anti-inflammatory properties of LT and LTP and analyzed their molecular mechanisms of action; we obtained LTP via the biorenovation of LT. We investigated the anti-inflammatory activities of LT and LTP in macrophage RAW 264.7 cells. We confirmed from previously reported literature that LT inhibits the production of nitric oxide and prostaglandin E2, as well as the expression of inducible NO synthetase and cyclooxygenase-2. In addition, expressions of inflammatory genes and mediators, such as tumor necrosis factor-α, interleukin-6, and interleukin-1ß, were suppressed. LTP showed anti-inflammatory activity similar to LT, but better anti-inflammatory activity in all the experiments, while also inhibiting mitogen-activated protein kinase and nuclear factor-kappa B more effectively than LT. At a concentration of 10 µM, LTP showed differences of 2.1 to 44.5% in the activity compared to LT; it also showed higher anti-inflammatory activity. Our findings suggest that LTP has stronger anti-inflammatory activity than LT.

Depth relationships and measures of tissue thickness in dorsal midbrain.

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distances from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for delineating depth for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.

Selective Phase Control of Dopant-Free Potassium Sodium Niobate Perovskites in Solution.

As one of the perovskite families, potassium sodium niobates (K1-xNax)NbO3 (KNN) have been gaining tremendous attention due to their various functional properties which can be largely determined by their crystallographic phase and composition. However, a selective evolution of different phases for KNN with controlled composition can be difficult to achieve, especially in solution chemical synthesis because of its strong tendency to stabilize into orthorhombic phase at conventional synthetic temperature. We herein developed a facile solution approach to control the phase and composition of dopant-free KNN particles selectively through the modification of reaction parameters. A conventional hydrothermal synthesis method yielded orthorhombic KNN particles, while the monoclinic phase, which has never been observed in a bulk counterpart, was kinetically generated by the compositional modification of an intermediate phase under a high-intensity ultrasound irradiation. Cubic KNN particles were stabilized when ethylene glycol was used as a co-solvent together with deionized water through bonding between ethylene glycol molecules and the surface of the KNN. Composite-structured piezoelectric harvesters were fabricated using each phase of KNN particles and the ß-phase poly(vinylidene fluoride-co-trifluoroethylene) polymer. Maximum output power was found for the harvester containing orthorhombic KNN particles. This facile synthetic methodology could pave a new pathway for fabricating numerous phase-controlled materials.

Dipeptide YA is Responsible for the Positive Effect of Oyster Hydrolysates on Alcohol Metabolism in Single Ethanol Binge Rodent Models.

Accumulative alcohol hangovers cause liver damage through oxidative and inflammatory stress. Numerous antioxidant and anti-inflammatory reagents have been developed to reduce alcohol hangovers, but these reagents are still insignificant and have limitations in that they can cause liver toxicity. Oyster hydrolysate (OH), another reagent that has antioxidant and anti-inflammatory activity, is a product extracted through an enzymatic hydrolysis process from oysters (Crassostrea gigas), which can be easily eaten in meals. This study was aimed at determining the effects of OH on alcohol metabolism, using a single high dose of ethanol (EtOH) administered to rodents, by monitoring alcohol metabolic enzymes, oxidative stress signals, and inflammatory mediators. The effect of tyrosine-alanine (YA) peptide, a main component of OH, on EtOH metabolism was also identified. In vitro experiments showed that OH pretreatment inhibited EtOH-induced cell death, oxidative stress, and inflammation in liver cells and macrophages. In vivo experiments showed that OH and YA pre-administration increased alcohol dehydrogenase, aldehyde dehydrogenase, and catalase activity in EtOH binge treatment. In addition, OH pre-administration alleviated CYP2E1 activity, ROS production, apoptotic signals, and inflammatory mediators in liver tissues. These results showed that OH and YA enhanced EtOH metabolism and had a protective effect against acute alcohol liver damage. Our findings offer new insights into a single high dose of EtOH drinking and suggest that OH and YA could be used as potential marine functional foods to prevent acute alcohol-induced liver damage.

The effect of knee joint rotation in the sagittal and axial plane on the measurement accuracy of coronal alignment of the lower limb.

BACKGROUND: Although the measurement of coronal alignment of the lower limb on conventional full-length weight-bearing anteroposterior (FLWAP) radiographs was reported to be influenced by the knee joint rotation, no comparative analysis was performed considering the effects of knee joint rotation on the sagittal and axial planes simultaneously using the three-dimensional images while taking into account the actual weight-bearing conditions. The aim of this study was to investigate the effect of knee joint rotation on the measurement accuracy of coronal alignment of the lower limb on the FLWAP radiograph. METHODS: Radiographic images of 90 consecutive patients (180 lower limbs) who took both the FLWAP radiograph and the EOS image were retrospectively reviewed. The relationship among delta values of mechanical tibiofemoral angle (mTFA) between the FLWAP radiographs and the EOS images (ΔmTFA), knee flexion/extension angle (sagittal plane rotation) on the EOS images, and patellar rotation (axial plane rotation) on the FLWAP radiographs were analyzed. Further, subgroup analysis according to each direction of knee joint rotation was performed. RESULTS: There was a significant correlation between ΔmTFA and sagittal plane rotation (r = 0.368, P <  0.001), whereas axial plane rotation was not correlated. In the analysis according to the direction, statistically significant correlation was observed only in the knee flexion group (r = 0.399, P <  0.001). The regression analysis showed a significant linear relationship between ΔmTFA and sagittal plane rotation (r2 = 0.136, P <  0.001). Additional subgroup analysis in patients with the patellar rotation greater than 3% showed a similar result of a linear relationship between ΔmTFA and sagittal plane rotation (r2 = 0.257, P <  0.001), whereas no statistically significant relationship was found in patients with the patellar rotation less than 3%. CONCLUSION: The measurement accuracy of coronal alignment of the lower limb on the FLWAP radiographs would be influenced by knee flexion, specifically when there is any subtle rotation of the knee joint in the axial plane. A strict patellar forward position without axial plane rotation of the knee could provide accurate results of the measurement even if there is a fixed flexion contracture of the knee.