Specialized pro-resolving mediator 7S MaR1 inhibits IL-6 expression via modulating ROS/p38/ERK/NF-κB pathways in PM10-exposed keratinocytes.

Keratinocytes are susceptible to airborne particulate matter (PM) exposure, resulting in human skin barrier dysfunction. Therefore, it is important to find useful reagents to resolve skin damages caused by PM. Here, we explored the protective effect of 7S MaR1, a specialized pro-resolving mediator derived from docosahexaenoic acid, on skin inflammation and the oxidative stress induced by PM with a diameter 10 µm or less (PM10) in human keratinocyte HaCaT cells. Interestingly, PM10-induced ROS generation was modulated by 7S MaR1 via the recovery of ROS scavenger genes. 7S MaR1 reduced PM10-induced IL-6 expression via modulating the p38/ERK/NF-κB signaling pathways. These results demonstrate that PM10 induces inflammatory cytokines, which can lead to skin diseases. In addition, 7S MaR1 can resolve inflammation caused by PM10-induced oxidative stress and inflammatory cytokines.

Minimal-gain-printed silicon nanolaser.

While there have been notable advancements in Si-based optical integration, achieving compact and efficient continuous-wave (CW) III-V semiconductor nanolasers on Si at room temperature remains a substantial challenge. This study presents an innovative approach: the on-demand minimal-gain-printed Si nanolaser. By using a carefully designed minimal III-V optical gain structure and a precise on-demand gain-printing technique, we achieve lasing operation with superior spectral stability under pulsed conditions and observe a strong signature of CW operation at room temperature. These achievements are attributed to addressing both fundamental and technological issues, including carrier diffusion, absorption loss, and inefficient thermal dissipation, through minimal-gain printing in the nanolaser. Moreover, our demonstration of the laser-on-waveguide structure emphasizes the integration benefits of this on-demand gain-printed Si nanolaser, highlighting its potential significance in the fields of Si photonics and photonic integrated circuits.

LSPR-susceptible metasurface platform for spectrometer-less and AI-empowered diagnostic biomolecule detection.

In response to the growing demand for biomolecular diagnostics, metasurface (MS) platforms based on high-Q resonators have demonstrated their capability to detect analytes with smart data processing and image analysis technologies. However, high-Q resonator meta-atom arrays are highly sensitive to the fabrication process and chemical surface functionalization. Thus, spectrum scanning systems are required to monitor the resonant wavelength changes at every step, from fabrication to practical sensing. In this study, we propose an innovative dielectric resonator-independent MS platform that enables spectrometer-less biomolecule detection using artificial intelligence (AI) at a visible wavelength. Functionalizing the focused vortex MS to capture gold nanoparticle (AuNP)-based sandwich immunoassays causes the resulting vortex beam profiles to be significantly affected by the localized surface plasmon resonance (LSPR) occurring between AuNPs and meta-atoms. The convolutional neural network algorithm was carefully trained to accurately classify the AuNP concentration-dependent focused vortex beam, facilitating the determination of the concentration of the targeted diagnostic biomolecule. Successful in situ identification of various biomolecule concentrations was achieved with over 99 % accuracy, indicating the potential of combining an LSPR-susceptible MS platform and AI for continuously tracking various chemical and biological compounds.

Novel Role of the ALPI Gene Associated with Constipation Caused by Complement Component 3 Deficiency.

Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (KDM5D), olfactory receptor 870 (Olfr870), pancreatic lipase (PNLIP), and alkaline phosphatase intestinal (ALPI). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.

Simultaneous electromechanical monitoring in engineered heart tissues using a mesoscale framework.

Engineered heart tissues (EHTs) generated from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent powerful platforms for human cardiac research, especially in drug testing and disease modeling. Here, we report a flexible, three-dimensional electronic framework that enables real-time, spatiotemporal analysis of electrophysiologic and mechanical signals in EHTs under physiological loading conditions for dynamic, noninvasive, longer-term assessments. These electromechanically monitored EHTs support multisite measurements throughout the tissue under baseline conditions and in response to stimuli. Demonstrations include uses in tracking physiological responses to pharmacologically active agents and in capturing electrophysiological characteristics of reentrant arrhythmias. This platform facilitates precise analysis of signal location and conduction velocity in human cardiomyocyte tissues, as the basis for a broad range of advanced cardiovascular studies.

Effect of high-flow nasal and buccal oxygenation on safe apnea time in children with open mouth: A randomized controlled trial.

BACKGROUND: High-flow nasal oxygenation is reported to prolong duration of apnea while maintaining adequate oxygen saturation with the mouth closed. Also, buccal oxygenation is known to have similar effects in obese adults. We compared the effect of these two methods on prolongation of acceptable apnea time in pediatric patients with their mouth open. METHODS: Thirty-eight patients, aged 0-10 years were randomly allocated to either the high-flow nasal oxygenation group (n = 17) or the buccal oxygenation group (n = 21). After induction of anesthesia including neuromuscular blockade, manual ventilation was initiated until the expiratory oxygen concentration reached 90%. Subsequently, ventilation was paused, and the patient's head was extended, and mouth was opened. The HFNO group received 2 L·min-1·kg-1 of oxygen, and the BO group received 0.5 L·min-1·kg-1 of oxygen. We set a target apnea time according to previous literature. When the apnea time reached the target, we defined the case as "success" in prolongation of safe apnea time and resumed ventilation. When the pulse oximetry decreased to 92% before the target apnea time, it was recorded as "failure" and rescue ventilation was given. RESULTS: The success rate of safe apnea prolongation was 100% in the high-flow nasal oxygenation group compared to 76% in the buccal oxygenation group (p = .04). Oxygen reserve index, end-tidal or transcutaneous carbon dioxide partial pressure, and pulse oximetry did not differ between groups. CONCLUSION: High-flow nasal oxygenation is effective in maintaining appropriate arterial oxygen saturation during apnea even in children with their mouth open and is superior to buccal oxygenation. Buccal oxygenation may be a good alternative when high-flow nasal oxygenation is not available.

The Cryptococcus neoformans STRIPAK complex controls genome stability, sexual development, and virulence.

The eukaryotic serine/threonine protein phosphatase PP2A is a heterotrimeric enzyme composed of a scaffold A subunit, a regulatory B subunit, and a catalytic C subunit. Of the four known B subunits, the B"' subunit (known as striatin) interacts with the multi-protein striatin-interacting phosphatase and kinase (STRIPAK) complex. Orthologs of STRIPAK components were identified in C. neoformans, namely PP2AA/Tpd3, PP2AC/Pph22, PP2AB"'/Far8, STRIP/Far11, SLMAP/Far9, and Mob3. Structural modeling, protein domain analysis, and detected protein-protein interactions suggest C. neoformans STRIPAK is assembled similarly to the human and fungal orthologs. Here, STRIPAK components Pph22, Far8, and Mob3 were functionally characterized. Whole-genome sequencing revealed that mutations in STRIPAK complex subunits lead to increased segmental and chromosomal aneuploidy, suggesting STRIPAK functions in maintaining genome stability. We demonstrate that PPH22 is a haploinsufficient gene: heterozygous PPH22/pph22Δ mutant diploid strains exhibit defects in hyphal growth and sporulation and have a significant fitness disadvantage when grown in competition against a wild-type diploid. Deletion mutants pph22Δ, far8Δ, and mob3Δ exhibit defects in mating and sexual differentiation, including impaired hyphae, basidia, and basidiospore production. Loss of either PPH22 or FAR8 leads to growth defects at 30°C, severely reduced growth at elevated temperature, abnormal cell morphology, and impaired virulence. The pph22Δ and far8Δ mutants are also unable to grow in the presence of the calcineurin inhibitors cyclosporine A or FK506, and thus these mutations are synthetically lethal with loss of calcineurin activity. Conversely, mob3Δ mutants display increased thermotolerance, capsule production, and melanization, and are hypervirulent in a murine infection model. Taken together, these findings reveal that the C. neoformans STRIPAK complex plays an important role in genome stability, vegetative growth, sexual development, and virulence in this prominent human fungal pathogen.

Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse.

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.

Oxygen reserve index versus conventional peripheral oxygen saturation for prevention of hypoxaemia: A randomised controlled trial.

BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%.

Effect of positive end expiratory pressure on non-hypoxic apnea time and atelectasis during induction of anesthesia in infant: A randomized controlled trial.

INTRODUCTION: This study aimed to assess the impact of positive-end-expiratory pressure (PEEP) on the non-hypoxic apnea time in infants during anesthesia induction with an inspired oxygen fraction of 0.8. METHODS: This age stratified randomized controlled trial included patients under 1 year of age. Preoxygenation was performed using an inspired oxygen fraction of 0.8 for 2 min. Inspired oxygen fraction of 0.8 was administered via a face mask with volume-controlled ventilation at a tidal volume of 6 mL.kg-1, with or without 7 cmH2O of PEEP. Tracheal intubation was performed after 3 min of ventilation; however, it was disconnected from the breathing circuit. Ventilation was resumed once the pulse oximetry readings reached 95%. The primary outcome was the non-hypoxic apnea time, defined as the time from the cessation of ventilation to achieving a pulse oximeter reading of 95%. The secondary outcome measures included the degree of atelectasis assessed by ultrasonography and the presence of gastric air insufflation. RESULTS: Eighty-four patients were included in the final analysis. In the positive end-expiratory pressure group, the atelectasis score decreased (17.0 vs. 31.5, p < .001; mean difference and 95% CI of 11.6, 7.5-15.6), while the non-hypoxic apnea time increased (80.1 s vs. 70.6 s, p = .005; mean difference and 95% CI of -9.4, -16.0 to -2.9), compared to the zero end-expiratory pressure group, among infants who are 6 months old or younger, not in those aged older than 6 months. DISCUSSION: The application of positive end-expiratory pressure reduced the incidence of atelectasis and extended the non-hypoxic apnea time in infants who are 6 months old or younger. However, it did not affect the incidence of atelectasis nor the non-hypoxic apnea time in patients aged older than 6 months.

Risk factors for chloral hydrate sedation failure in pediatric patients: a retrospective analysis.

BACKGROUND: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea. METHODS: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications. RESULTS: A total of 6,691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1,457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225/1457] vs. 6.2% [322/5234]; P < 0.001, odds ratio: 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05). CONCLUSIONS: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.

3D mobile regression vision transformer for collateral imaging in acute ischemic stroke.

PURPOSE: The accurate and timely assessment of the collateral perfusion status is crucial in the diagnosis and treatment of patients with acute ischemic stroke. Previous works have shown that collateral imaging, derived from CT angiography, MR perfusion, and MR angiography, aids in evaluating the collateral status. However, such methods are time-consuming and/or sub-optimal due to the nature of manual processing and heuristics. Recently, deep learning approaches have shown to be promising for generating collateral imaging. These, however, suffer from the computational complexity and cost. METHODS: In this study, we propose a mobile, lightweight deep regression neural network for collateral imaging in acute ischemic stroke, leveraging dynamic susceptibility contrast MR perfusion (DSC-MRP). Built based upon lightweight convolution and Transformer architectures, the proposed model manages the balance between the model complexity and performance. RESULTS: We evaluated the performance of the proposed model in generating the five-phase collateral maps, including arterial, capillary, early venous, late venous, and delayed phases, using DSC-MRP from 952 patients. In comparison with various deep learning models, the proposed method was superior to the competitors with similar complexity and was comparable to the competitors of high complexity. CONCLUSION: The results suggest that the proposed model is able to facilitate rapid and precise assessment of the collateral status of patients with acute ischemic stroke, leading to improved patient care and outcome.

Spatially-constrained and -unconstrained bi-graph interaction network for multi-organ pathology image classification.

In computational pathology, graphs have shown to be promising for pathology image analysis. There exist various graph structures that can discover differing features of pathology images. However, the combination and interaction between differing graph structures have not been fully studied and utilized for pathology image analysis. In this study, we propose a parallel, bi-graph neural network, designated as SCUBa-Net, equipped with both graph convolutional networks and Transformers, that processes a pathology image as two distinct graphs, including a spatially-constrained graph and a spatially-unconstrained graph. For efficient and effective graph learning, we introduce two inter-graph interaction blocks and an intra-graph interaction block. The inter-graph interaction blocks learn the node-to-node interactions within each graph. The intra-graph interaction block learns the graph-to-graph interactions at both global- and local-levels with the help of the virtual nodes that collect and summarize the information from the entire graphs. SCUBa-Net is systematically evaluated on four multi-organ datasets, including colorectal, prostate, gastric, and bladder cancers. The experimental results demonstrate the effectiveness of SCUBa-Net in comparison to the state-of-the-art convolutional neural networks, Transformer, and graph neural networks.

Retraction Notice to: Decreased Lung Tumor Development in SwAPP Mice through the Downregulation of CHI3L1 and STAT 3 Activity via the Upregulation of miRNA342-3p.

[This retracts the article DOI: 10.1016/j.omtn.2019.02.007.].

Effectiveness of Computer-Mediated Educational Counseling for Tinnitus Relief: A Randomized Controlled Trial.

Counseling can help alleviate tinnitus-caused emotional distress and correct misconceptions, making it an effective rehabilitation option for people with tinnitus. Advances in communication technology have increased the demand for computer-mediated tinnitus counseling; however, the effectiveness of such counseling in reducing tinnitus is unclear. Thus, this study aimed to determine the tinnitus-relieving effects of computer-mediated counseling. Thirty-six participants with tinnitus were randomly assigned to online counseling (15 participants) or video-based counseling (21 participants) groups, defining how remote counseling was conducted. Tinnitus counseling, comprising 100 items, lasted 2 weeks and was separated into six sessions for the online counseling group and 8-9 items daily for 12 days for the video-based counseling group. The effectiveness of counseling was determined based on score changes between baseline and 2-week follow-up using the Korean version of the Tinnitus Primary Function Questionnaire and Visual Analog Scales for annoyance and loudness. While no significant improvements were observed in other domains, average emotional aspect-related scores showed significant improvements in both groups. Regarding individual results, four and seven participants in the online and video-based counseling groups reported significant improvements in the emotional domain, respectively. Overall, computer-mediated educational counseling might be a rehabilitation option for individuals with tinnitus.

Effective and safe pediatric sedation.

Pediatric sedation is a crucial tool for minimizing pain and anxiety during procedures and examinations in children. However, it is not without risks. This review provides a comprehensive review of pediatric sedation, including both established practices and recent advancements. A thorough pre-procedural evaluation is crucial to mitigate these risks. Skilled healthcare professionals trained in pediatric sedation are paramount to ensure a safe and effective procedure. The choice of sedative medication depends on various factors, such as the type of procedure and the patient's medical condition. Medications, used alone or in combination, offer sedation with varying onset times and durations. Non-pharmacological approaches can complement pharmacological sedation and further reduce potential complications. Preventing sedation-related complications requires a multidisciplinary approach. This includes collaborative decision-making, vigilant monitoring throughout the procedure, and a focus on patient safety. Recovery involves ensuring the child returns to their baseline status before discharge, following established criteria. In conclusion, successful pediatric sedation hinges on a comprehensive strategy. This strategy encompasses a thorough evaluation, skilled personnel, appropriate medication selection, vigilant monitoring, and a focus on patient safety throughout the process. By following these steps, we can minimize risks and achieve successful outcomes.

Effect of epidural anesthesia on the optic nerve sheath diameter in patients with pre-eclampsia: a prospective observational study.

INTRODUCTION: Optic nerve sheath diameter (ONSD) reflects intracranial pressure and is increased in pre-eclampsia. Administrating a significant volume of epidural solution into the epidural space can potentially increase ONSD. We investigated the impact of epidural local anesthetic injection on ONSD in patients with pre-eclampsia. METHODS: Patients with pre-eclampsia (n=11) and normotensive pregnant women (n=11) received de novo epidural anesthesia for cesarean delivery. We administered 21 mL of an epidural solution containing 2% lidocaine and 50 µg fentanyl into the lumbar epidural space in incremental doses. ONSD was measured at baseline, 3, 10, and 20 min after completing the epidural injection, after delivery, and at the end of surgery. Primary outcome was the change in ONSD from baseline to 3 min after epidural injection in patients with pre-eclampsia and normotensive pregnant women. Serial changes in the ONSD were analyzed using a linear mixed model. RESULTS: At baseline and 3 min after epidural drug injection, ONSD was significantly larger in patients with pre-eclampsia than in normotensive mothers (5.7 vs 4.1 mm, p=0.001 and 5.4 vs 4.1 mm, p<0.001, respectively). However, there were no significant changes in ONSD at 3 min after injection from baseline in either group (p>0.999). Linear mixed model demonstrated that ONSD did not change after epidural anesthesia in either group (p=0.279 and p=0.347, respectively). CONCLUSIONS: Despite a higher baseline ONSD in pre-eclampsia, epidural anesthesia did not further increase ONSD. Our findings indicate that epidural anesthesia can be safely administered in patients with pre-eclampsia at risk of increased intracranial pressure, without other intracranial pathology. TRIAL REGISTRATION NUMBER: NCT04095832.

Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells.

The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1ß, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFß, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

Erratum: Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin.

[This corrects the article e22 in vol. 21, PMID: 34277112.].