FYVE2, a phosphatidylinositol 3-phosphate effector, interacts with the COPII machinery to control autophagosome formation in Arabidopsis.

Autophagy is an intracellular trafficking mechanism by which cytosolic macromolecules and organelles are sequestered into autophagosomes for degradation inside the vacuole. In various eukaryotes including yeast, metazoans, and plants, the precursor of the autophagosome, termed the phagophore, nucleates in the vicinity of the endoplasmic reticulum (ER) with the participation of phosphatidylinositol 3-phosphate (PI3P) and the coat protein complex II (COPII). Here we show that Arabidopsis thaliana FYVE2, a plant-specific PI3P-binding protein, provides a functional link between the COPII machinery and autophagy. FYVE2 interacts with the small GTPase Secretion-associated Ras-related GTPase 1 (SAR1), which is essential for the budding of COPII vesicles. FYVE2 also interacts with ATG18A, another PI3P effector on the phagophore membrane. Fluorescently tagged FYVE2 localized to autophagic membranes near the ER and was delivered to vacuoles. SAR1 fusion proteins were also targeted to the vacuole via FYVE2-dependent autophagy. Either mutations in FYVE2 or the expression of dominant-negative mutant SAR1B proteins resulted in reduced autophagic flux and the accumulation of autophagic organelles. We propose that FYVE2 regulates autophagosome biogenesis through its interaction with ATG18A and the COPII machinery, acting downstream of ATG2.

IL-10-induced modulation of macrophage polarization suppresses outer-blood-retinal barrier disruption in the streptozotocin-induced early diabetic retinopathy mouse model.

Diabetic retinopathy (DR) is associated with ocular inflammation leading to retinal barrier breakdown, vascular leakage, macular edema, and vision loss. DR is not only a microvascular disease but also involves retinal neurodegeneration, demonstrating that pathological changes associated with neuroinflammation precede microvascular injury in early DR. Macrophage activation plays a central role in neuroinflammation. During DR, the inflammatory response depends on the polarization of retinal macrophages, triggering pro-inflammatory (M1) or anti-inflammatory (M2) activity. This study aimed to determine the role of macrophages in vascular leakage through the tight junction complexes of retinal pigment epithelium, which is the outer blood-retinal barrier (BRB). Furthermore, we aimed to assess whether interleukin-10 (IL-10), a representative M2-inducer, can decrease inflammatory macrophages and alleviate outer-BRB disruption. We found that modulation of macrophage polarization affects the structural and functional integrity of ARPE-19 cells in a co-culture system under high-glucose conditions. Furthermore, we demonstrated that intravitreal IL-10 injection induces an increase in the ratio of anti-inflammatory macrophages and effectively suppresses outer-BRB disruption and vascular leakage in a mouse model of early-stage streptozotocin-induced diabetes. Our results suggest that modulation of macrophage polarization by IL-10 administration during early-stage DR has a promising protective effect against outer-BRB disruption and vascular leakage. This finding provides valuable insights for early intervention in DR.

Multinucleation resets human macrophages for specialized functions at the expense of their identity.

Macrophages undergo plasma membrane fusion and cell multinucleation to form multinucleated giant cells (MGCs) such as osteoclasts in bone, Langhans giant cells (LGCs) as part of granulomas or foreign-body giant cells (FBGCs) in reaction to exogenous material. How multinucleation per se contributes to functional specialization of mature mononuclear macrophages remains poorly understood in humans. Here, we integrate comparative transcriptomics with functional assays in purified mature mononuclear and multinucleated human osteoclasts, LGCs and FBGCs. Strikingly, in all three types of MGCs, multinucleation causes a pronounced downregulation of macrophage identity. We show enhanced lysosome-mediated intracellular iron homeostasis promoting MGC formation. The transition from mononuclear to multinuclear state is accompanied by cell specialization specific to each polykaryon. Enhanced phagocytic and mitochondrial function associate with FBGCs and osteoclasts, respectively. Moreover, human LGCs preferentially express B7-H3 (CD276) and can form granuloma-like clusters in vitro, suggesting that their multinucleation potentiates T cell activation. These findings demonstrate how cell-cell fusion and multinucleation reset human macrophage identity as part of an advanced maturation step that confers MGC-specific functionality.

Wound healing effect of polydeoxyribonucleotide derived from Hibiscus sabdariffa callus via Nrf2 signaling in human keratinocytes.

There has been a growing interest in skin recovery in both the medical and cosmetics fields, leading to an increasing number of studies reporting diverse materials being utilized for this purpose. Among them, polydeoxyribonucleotide (PDRN) is known for its efficacy in skin repair processes, while Hibiscus sabdariffa (HS) is recognized for its antioxidant, hypolipidemic, and wound healing properties, including its positive impact on mammalian skin and cells. We hypothesized that these characteristics may have a germane relationship during the healing process. Consequently, we induced calli from HS and then extracted PDRN for use in treating human keratinocytes. PDRN (5 µg/mL) had considerable wound healing effects and wrinkle improvement effects. To confirm its function at the molecular level, we performed real-time polymerase chain reaction, western blotting, and immunocytochemistry. Furthermore, genes related to wound healing (MMP9, Nrf2, KGF, VEGF, SOD2, and AQP3) were significantly upregulated. Additionally, the protein expression of MMP9, AQP3, and CAT, which are closely related to wound healing and antioxidant cascades, was considerably enhanced. Based on cellular morphology and molecular-level evidence, we propose that PDRN from calli of HS can improve wound healing in human keratinocytes. Furthermore, its potential to serve as a novel material in cosmetic products is demonstrated.

Cone cell dysfunction attenuates retinal neovascularization in oxygen-induced retinopathy mouse model.

Aberrant neovascularization is the most common feature in retinopathy of prematurity (ROP), which leads to the retinal detachment and visual defects in neonates with a low gestational age eventually. Understanding the regulation of inappropriate angiogenic signaling benefits individuals at-risk. Recently, neural activity originating from the specific neural activity has been considered to contribute to retinal angiogenesis. Here, we explored the impact of cone cell dysfunction on oxygen-induced retinopathy (OIR), a mouse model commonly employed to understand retinal diseases associated with abnormal blood vessel growth, using the Gnat2cpfl3 (cone photoreceptor function loss-3) strain of mice (regardless of the sex), which is known for its inherent cone cell dysfunction. We found that the retinal avascular area, hypoxic area, and neovascular area were significantly attenuated in Gnat2cpfl3 OIR mice compared to those in C57BL/6 OIR mice. Moreover, the HIF-1α/VEGF axis was also reduced in Gnat2cpfl3 OIR mice. Collectively, our results indicated that cone cell dysfunction, as observed in Gnat2cpfl3 OIR mice, leads to attenuated retinal neovascularization. This finding suggests that retinal neural activity may precede and potentially influence the onset of pathological neovascularization.

A comprehensive genotype-phenotype study in 203 individuals with retinoblastoma.

Retinoblastoma is the most common intraocular tumor in children and is caused by biallelic inactivation of the RB1 gene. The identification of RB1 germline variants in patients with retinoblastoma and their families is critical for early diagnosis and prevention. In this study, genetic testing was conducted on the genomic DNA of 203 patients with retinoblastoma using a combined approach of direct sequencing and multiplex ligation-dependent probe amplification (MLPA) assays for genotype-phenotype correlation studies. Sixty-five germline variants were identified in 80 of the 203 patients, with 67 bilateral and 13 unilateral retinoblastoma cases. The variant detection rates in the bilateral and unilateral cases were 88% and 10%, respectively. Eighteen novel variants were identified. Variants were classified according to their presence, mutation pattern, location, molecular consequences, and pathogenicity. Subsequently, the genotypes and phenotypes of the 203 patients were evaluated. Variants were associated with age at diagnosis (p < 0.001), laterality (p < 0.001), and tumor size (p = 0.010). The molecular consequences of the variants were related to laterality (p < 0.001) and tumor size (p = 0.001). The pathogenicity of the variants was associated with age at diagnosis (p = 0.001), laterality (p = 0.0212), treatment response (p = 0.0470), and tumor size (p = 0.002). These results suggest that patient phenotypes are associated with the inherent characteristics of germline RB1 variants. These findings indicate the potential application of genetic testing results in clinical practice.

Palladium-Catalyzed/Copper-Mediated Decarbonylative Cross-Coupling of S-Pyrimidyl Thioesters for Biaryl Synthesis.

A palladium-catalyzed/copper-mediated cross-coupling of S-pyrimidinyl thioesters with arylboronic acids to yield biaryls is described. The reaction is likely to proceed via cleavage of the S-C(O) bond and subsequent release of CO, rather than via cleavage of the S-C(pyrimidine) bond and release of SCO, as supported by the results of both experimental and computational studies. The investigation of the reaction scope with various S-pyrimidinyl thioesters and arylboronic acids showed that the reaction is significantly affected by the substituent of the thioester and the presence of a chelatable ortho substituent was found to increase reaction efficiency.

Psychotropic Medications Promote Time-Dependent Reduction of Suicidal Ideation in Mood Disorder: A Prospective Cohort Study.

BACKGROUND: Despite a plethora of research on the topic, there is still no solid evidence that pharmacological treatment actually reduces the risk of suicide in patients with mental illness. In this study, we aimed to assess the effect of psychotropic medications on suicidal ideation in patients with major depressive disorder (MDD) and bipolar disorder (BPD) in two age groups: less than 25 years and 25 years and older. METHODS: We analyzed 312 patients with mood disorders with current suicidal thoughts or recent suicide attempts. We followed the participants from baseline for 6 months and assessed changes in suicidal ideation with Columbia-Suicide Severity Rating Scale (C-SSRS). The effect of psychotropic drug administration on suicidal ideation over time was analyzed using a linear mixed model. RESULTS: In patients aged 25 years and older with mood disorders, suicidal ideation was more severe when using psychotropic drugs than when not using them. However, suicidal ideation decreased rapidly over time. The time-dependent reduction in suicidal ideation was accelerated when using antidepressants and sedatives/hypnotics in adult MDD, and when using mood stabilizers in adult BPD. However, this effect was not observed in participants aged less than 25 years. CONCLUSION: Adequate psychotropic medication may reduce suicidal ideation in patients with mood disorders aged 25 years and older. Additional research on psychotropic drugs is needed to effectively reduce the risk of suicide among children and adolescents with mood disorders.

A prognostic value of estimated pulse wave velocity in idiopathic sudden sensorineural hearing loss.

PURPOSE: Arterial stiffness, represented by estimated pulse wave velocity (ePWV), is the independent surrogate marker for cardiovascular event. The aim of the study was to investigate the significance of ePWV in the treatment outcome of idiopathic sudden sensorineural hearing loss (SSNHL). METHODS: One hundred and ten patients with idiopathic SSNHL who hospitalized between April 2019 and March 2022 were evaluated. Arterial stiffness was calculated with formula for ePWV and other cardiovascular parameters of body mass index (BMI), and serum lipid level was determined. All patients received systemic high-dose steroid therapy and intratympanic steroid injections as a salvage management. Treatment outcome was assessed at 6 months after treatment, and classified as recovery and nonrecovery groups according to hearing recovery. RESULTS: The initial pure-tone hearing threshold was 72.6 ± 23.8 dB and final hearing threshold was 52.63 ± 31.10 dB. After treatment, 60 (54.5%) patients included in recovery group and other 50 (45.5%) were classified as nonrecovery group. Age, days of onset to treatment, BMI, waist circumference, and ePWV were higher in the nonrecovery group compared to recovery group in univariate analysis (p = 0.039, p = 0.049, p = 0.003, p = 0.004, p = 0.007, respectively). In multivariate analysis, days of onset to treatment, BMI, and ePWV were associated with recovery (p = 0.030, p = 0.007, p = 0.022). CONCLUSION: Higher ePWV, a measure of arterial stiffness, was associated with a poor hearing recovery of SSNHL.

Objective and subjective efficacy of hearing aids in patients with mild-to-moderate unilateral hearing loss: a prospective study.

PURPOSE: In patients with unilateral sensorineural hearing loss (USNHL), we explored both objective functional audiological gains and subjective satisfaction, indicating when a unilateral hearing aid is valuable. METHODS: Thirty-seven patients with mild-to-moderate USNHL (mean pure-tone thresholds between 25 and 70 dB) were prescribed unilateral hearing aids. Functional gain, the aided speech discrimination score (SDS), the Hearing in Noise Test (HINT) score, and the sound localization test score were collected, and a questionnaire (the Hearing Handicap Inventory for the Elderly, HHIE) completed after 1, 2, and 3 months of hearing aid use. We classified the participants as having 'no handicap' (HHIE < 17), 'mild-to-moderate handicap' (17-42), and 'significant handicap' (> 42). RESULTS: The decrease in handicap afforded by unilateral hearing aids was largest in the 'significant handicap' group (the HHIE total score fell from 59.1 to 37.2; P = 0.007). There were no between-group differences in either functional gain or the aided SDS. Only the 'significant handicap' group evidenced an improved HINT score; the composite signal-to-noise ratio (SNR) fell from - 1.5 to - 2.2 dB [S/N] (P = 0.023). The HHIE usefully indicated when a hearing aid alleviated the discomfort of USNHL; patients with unaided HHIE scores ≥ 20 evidenced significant decreases in the composite SNR (- 1.7 to - 2.0 dB [S/N]; P = 0.045). CONCLUSIONS: When considering whether to prescribe a unilateral hearing aid for patients with mild-to-moderate USNHL, it is helpful to use the HHIE to evaluate discomfort. If the total score is ≥ 20, a hearing aid is appropriate.

Mechanism underlying and prevention of electrode migration in cochlear implants.

PURPOSE: We investigate the clinical manifestations, mechanisms, and methods of preventing electrode migration in Cochlear Implantation (CI) patients, based on our practical experience with this problem. STUDY DESIGN: This is a retrospective study in a single center. METHODS: We retrospectively reviewed electrode migration in 4 (0.75%) of 532 patients who underwent CI at our tertiary institution from January 2002 to December 2022. Pre- and post-operative pure-tone audiometry, word recognition score, aided functional gain test, and sound field speech intelligibility test were evaluated. RESULTS: All four patients underwent CIs with the straight electrode type. The following events or symptoms were observed in the patients before confirming electrode migration: an increase in high-frequency thresholds during the post-operative aided functional gain test and a decline in scores on the sound field speech intelligibility test. Electrode migration was confirmed through transocular view X-ray or temporal bone computer tomography. Two patients showed coiled electrodes within the mastoid cavity; while in the others, the electrodes were observed to be floating inside the cavity. To prevent migration of electrodes due to these issues, we mixed bone paste collected during the drilling of the mastoid cavity with glue and used it to secure the electrodes in place. CONCLUSION: Electrode migration can result in a decrease in hearing ability and may necessitate a revision surgery to adjust the electrode placement. The main factors affecting electrode placement include the position of electrode within the mastoid cavity and the elasticity of straight electrodes. It is important for surgeons to recognize the factors that increase the risk of electrode migration and to take preventative measures to reduce this risk.

Tinnitus reduction after active bone-conduction implantation in patients with single-sided deafness: a prospective multicenter study.

PURPOSE: Single-sided deafness (SSD) presents significant challenges for patients, including compromised sound localization, reduced speech recognition, and often, tinnitus. These issues are typically addressed using interventions such as cochlear implantation (CI) and bone conduction implant (BCI). However, evidence regarding the efficacy of BCI in reducing tinnitus in SSD patients remains limited. This study explored the ability of a novel active transcutaneous BCI (Bonebridge BCI602) to alleviate tinnitus in SSD patients. STUDY DESIGN: Prospective cohort multicenter study. SETTING: Tertiary referral hospitals. METHODS: A prospective multicenter study of 30 SSD patients was conducted. The patients were divided into two groups: those with (n = 19) and without (n = 11) tinnitus. Audiometric assessments, subjective questionnaires including the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Bern Benefit in Single-Sided Deafness (BBSS), and tinnitus evaluations with the Tinnitus Handicap Inventory (THI) and tinnitogram were conducted before and after BCI surgery. RESULTS: THI scores after surgery were significantly reduced in SSD patients with tinnitus. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups; however, the former group exhibited a significantly greater improvement in the APHAB questionnaire score. According to tinnitograms, the loudness of tinnitus decreased, particularly in patients with ipsilateral tinnitus. Patients with residual hearing had greater reductions in their THI scores. However, three patients without residual hearing had a relative worsening of tinnitus after surgery. CONCLUSION: The Bonebridge BCI602 effectively reduced tinnitus in SSD patients, particularly in those with residual hearing. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups. These findings demonstrate the therapeutic potential of BCI for managing SSD and associated tinnitus.

Assessment of the Quality of Sinus Elevation with Lateral Window Approach Procedure Videos on YouTube: A Content-quality Analysis.

Although the lateral window approach allows for greater graft material delivery and bone formation, it is more challenging and invasive, prompting keen interest among dentists to master this method. YouTube is increasingly used for medical training; however, concerns regarding the quality of instructional videos exist. This study proposes new criteria for evaluating YouTube videos on maxillary sinus elevation with the aim of establishing standards for assessing instructional content in the field. We sourced 100 maxillary sinus elevation videos from YouTube and, following exclusion criteria, analyzed 65 remaining videos. The video characteristics, content quality, and newly developed criteria were evaluated. Statistical analyses, employing ordinal logistic regression, identified the factors influencing the quality of instructional videos and evaluated the significance of our new criteria. Although video interaction and view rate exhibited positive relations to content quality, they were not significant ( P =0.818 and 0.826, respectively). Notably, videos of fair and poor quality showed a significant negative relation ( P <0.001). Audio commentary, written commentary, and descriptions of preoperative data displayed positive but statistically insignificant relationships ( P =0.088, 0.228, and 0.612, respectively). The comparison of video evaluation results based on the developed criteria with content quality scores revealed significant negative relationships for good, fair, and poor videos ( P <0.001, Exp(B)=-4.306, -7.853, -10.722, respectively). Among the various video characteristics, only image quality showed a significant relationship with content quality. Importantly, our newly developed criteria demonstrated a significant relationship with video content quality, providing valuable insights for assessing instructional videos on maxillary sinus elevation and laying the foundation for robust standards.

Cutting-Edge HEK293T Protein-Integrated Lipid Nanostructures: Boosting Biocompatibility and Efficacy.

Recently, artificial exosomes have been developed to overcome the challenges of natural exosomes, such as production scalability and stability. In the production of artificial exosomes, the incorporation of membrane proteins into lipid nanostructures is emerging as a notable approach for enhancing biocompatibility and treatment efficacy. This study focuses on incorporating HEK293T cell-derived membrane proteins into liposomes to create membrane-protein-bound liposomes (MPLCs), with the goal of improving their effectiveness as anticancer therapeutics. MPLCs were generated by combining two key elements: lipid components that are identical to those in conventional liposomes (CLs) and membrane protein components uniquely derived from HEK293T cells. An extensive comparison of CLs and MPLCs was conducted across multiple in vitro and in vivo cancer models, employing advanced techniques such as cryo-TEM (tramsmission electron microscopy) imaging and FT-IR (fourier transform infrared spectroscopy). MPLCs displayed superior membrane fusion capabilities in cancer cell lines, with significantly higher cellular uptake. Additionally, MPLCs maintained their morphology and size better than CLs when exposed to FBS (fetal bovine serum), suggesting enhanced serum stability. In a xenograft mouse model using HeLa and ASPC cancer cells, intravenous administration of MPLCs MPLCs accumulated more in tumor tissues, highlighting their potential for targeted cancer therapy. Overall, these results indicate that MPLCs have superior tumor-targeting properties, possibly attributable to their membrane protein composition, offering promising prospects for enhancing drug delivery efficiency in cancer treatments. This research could offer new clinical application opportunities, as it uses MPLCs with membrane proteins from HEK293T cells, which are known for their efficient production and compatibility with GMP (good manufacturing practice) standards.

Ultrasound-assisted efficient and convenient method of extracting valuable metals (Ni, Co, and Cd) from waste Ni-Cd batteries using DL-malic acid.

Recycling waste Ni-Cd batteries has received much attention recently because of the serious environmental pollution they cause and to avoid the dissipation of valuable metals. Despite significant research, it is still difficult to efficiently recycle valuable and hazardous metals from waste Ni-Cd batteries in an economical and environmentally friendly manner. This study employed a novel process utilizing ultrasound-assisted leaching to recover Ni, Cd, and Co from waste nickel-cadmium (Ni-Cd) batteries. Organic DL-malic acid served as the leaching agent and H2O2 was employed as an oxidizing agent. The effects of various factors on the recovery efficiency of Ni, Cd, and Co, such as leaching temperature, time, DL-malic acid concentration, pulp density, H2O2 concentration, and ultrasound frequency, were also examined. To predict the chemical compounds present before and after the recycling experiments, the solid residues from the metal extraction were analyzed using XRD, XPS, FE-SEM, and EDS element mapping. Concurrently, ICP-OES was utilized to determine the metal content in the leachate. Under optimized conditions of 90 °C, 90 min, 2M DL-malic acid, 160 mL/g pulp density, and 20% ultrasound frequency, over 83% of Ni, 94% of Cd, and 98% of Co were effectively leached from the waste Ni-Cd battery powder. The leaching kinetics of Ni, Cd, and Co followed the surface chemical reaction control model. The activation energies (Ea) for Ni, Cd, and Co leaching were 21.34, 20.47, and 18.38 kJ/mol, respectively. The findings suggest that ultrasound-assisted leaching is an efficient, cost-effective, environmentally friendly, and sustainable alternative for extracting precious and hazardous metals from waste Ni-Cd batteries. Additionally, it reduces industrial chemical usage and enhances waste management sustainability.

Stratum-Confined Solid-State Reaction (SC-SSR) toward Colloidal Silicon-Based Hollow Nanostructures for Bioapplications.

Silicon nanostructures (SiNSs) can provide multifaceted bioapplications; but preserving their subhundred nm size during high-temperature silica-to-silicon conversion is the major bottleneck. The SC-SSR utilizes an interior metal-silicide stratum space at a predetermined radial distance inside silica nanosphere to guide the magnesiothermic reduction reaction (MTR)-mediated synthesis of hollow and porous SiNSs. In depth mechanistic study explores solid-to-hollow transformation encompassing predefined radial boundary through the participation of metal-silicide species directing the in-situ formed Si-phase accumulation within the narrow stratum. Evolving thin-porous Si-shell remains well protected by the in-situ segregated MgO emerging as a protective cast against the heat-induced deformation and interparticle sintering. Retrieved hydrophilic SiNSs (<100 nm) can be conveniently processed in different biomedia as colloidal solutions and endocytosized inside cells as photoluminescence (PL)-based bioimaging probes. Inside the cell, rattle-like SiNSs encapsulated with Pd nanocrystals can function as biorthogonal nanoreactors to catalyze intracellular synthesis of probe molecules through C-C cross coupling reaction.

Risk of pancreatic cancer after acute pancreatitis: A population-based matched cohort study.

BACKGROUND: We investigated the short- and long-term risks of pancreatic cancer after the diagnosis of acute pancreatitis. METHODS: This population-based matched-cohort study used data from the Korean National Health Insurance Service database. Patients with acute pancreatitis (n = 25,488) were matched with the control group (n = 127,440) based on age, sex, body mass index, smoking status, and diabetes. We estimated the hazard ratios for developing pancreatic cancer in both groups using Cox regression analysis. RESULTS: During a median follow-up of 5.4 years, pancreatic cancer developed in 479 patients (1.9%) in the acute pancreatitis group and 317 patients (0.2%) in the control group. Compared with the control group, the risk of pancreatic cancer in the acute pancreatitis group was very high within the first 2 years, which gradually decreased over time. The hazard ratio for the risk of developing pancreatitis was 8.46 (95% confidence interval, 5.57-12.84) at 1-2 years, and then decreased to 3.62 (95% confidence interval, 2.26-4.91) at 2-4 years. However, even after 8-10 years, the hazard ratio was still statistically significantly increased to 2.80 (95% confidence interval, 1.42-5.53). After 10 years, there was no significant difference in the risk of pancreatic cancer between the two groups. CONCLUSIONS: The risk of pancreatic cancer increases rapidly after acute pancreatitis diagnosis, gradually declines after 2 years, and remains elevated for up to 10 years. Further studies are needed to determine the long-term effects of acute pancreatitis on the risk of pancreatic cancer.

Ultrasonographic monitoring of fetal eye growth parameters throughout gestation in the common marmoset (Callithrix jacchus).

The common marmoset (Callithrix jacchus) is considered an ideal species for developing genetically modified nonhuman primates (NHP) models of human disease, particularly eye disease. They have been proposed as a suitable bridge between rodents and other NHP models due to their similar ophthalmological features to humans. Prenatal ultrasonography is an accurate and reliable diagnostic tool for monitoring fetal development and congenital malformation. We monitored fetal eye growth and development using noninvasive ultrasonography in 40 heads of clinically normal fetuses during pregnancy to establish the criteria for studying congenital eye anomalies in marmosets. The coronal, sagittal, and transverse planes were useful to identify the facial structures for any associated abnormalities. For orbital measurements, biorbital distance (BOD), ocular diameter (OD), interorbital distance (IOD), and total axial length (TAL) were measured in the transverse plane and carefully identified for intraorbital structures. As a result, high correlations were observed between delivery-based gestational age (GA) and biparietal diameter (BPD), BOD, OD, and TAL. The correlation assessments based on BOD provide more reliable results for monitoring eye growth and development in normal marmosets than any other parameters since BOD has the highest correlation coefficient according to both delivery-based GA and BPD among ocular measurements. In conclusion, orbital measurements by prenatal ultrasonography provide reliable indicators of marmoset eye growth, and it could offer early diagnostic criteria to facilitate the development of eye disease models and novel therapies such as genome editing technologies in marmosets.

Anti-Pollutant Activity of Porphyra yezoensis Water Extract and Its Active Compound, Porphyra 334, against Urban Particulate Matter-Induced Keratinocyte Cell Damage.

Urban particulate matter (UPM) causes skin aging and inflammatory reactions by influencing skin cells through the aryl hydrocarbon receptor (AhR) signaling pathway. Porphyra yezoensis (also known as Pyropia yezoensis), a red alga belonging to the Bangiaceae family, is an edible red seaweed. Here, we examined the anti-pollutant effect of P. yezoensis water extract. While UPM treatment induced xenobiotic response element (XRE) promoter luciferase activity, P. yezoensis water extract reduced UPM-induced XRE activity. Next, we isolated an active compound from P. yezoensis and identified it as porphyra 334. Similar to the P. yezoensis water extract, porphyra 334 attenuated UPM-induced XRE activity. Moreover, although UPM augmented AhR nuclear translocation, which led to an increase in cytochrome P450 1A1 (CYP1A1) mRNA levels, these effects were reduced by porphyra 334. Moreover, UPM induced the production of reactive oxygen species (ROS) and reduced cell proliferation. These effects were attenuated in response to porphyra 334 treatment. Furthermore, our results revealed that the increased ROS levels induced by UPM treatment induced transient receptor potential vanilloid 1 (TRPV1) activity, which is related to skin aging and inflammatory responses. However, porphyra 334 treatment reduced this reaction by inhibiting ROS production induced by CYP1A1 activation. This indicates that porphyra 334, an active compound of P. yezoensis, attenuates UP-induced cell damage by inhibiting AhR-induced ROS production, which results in a reduction in TRPV1 activation, leading to cell proliferation. This also suggests that porphyra 334 could protect the epidermis from harmful pollutants.

Acoustic Analysis of Speech for Screening for Suicide Risk: Machine Learning Classifiers for Between- and Within-Person Evaluation of Suicidality.

BACKGROUND: Assessing a patient's suicide risk is challenging for health professionals because it depends on voluntary disclosure by the patient and often has limited resources. The application of novel machine learning approaches to determine suicide risk has clinical utility. OBJECTIVE: This study aimed to investigate cross-sectional and longitudinal approaches to assess suicidality based on acoustic voice features of psychiatric patients using artificial intelligence. METHODS: We collected 348 voice recordings during clinical interviews of 104 patients diagnosed with mood disorders at baseline and 2, 4, 8, and 12 months after recruitment. Suicidality was assessed using the Beck Scale for Suicidal Ideation and suicidal behavior using the Columbia Suicide Severity Rating Scale. The acoustic features of the voice, including temporal, formal, and spectral features, were extracted from the recordings. A between-person classification model that examines the vocal characteristics of individuals cross sectionally to detect individuals at high risk for suicide and a within-person classification model that detects considerable worsening of suicidality based on changes in acoustic features within an individual were developed and compared. Internal validation was performed using 10-fold cross validation of audio data from baseline to 2-month and external validation was performed using data from 2 to 4 months. RESULTS: A combined set of 12 acoustic features and 3 demographic variables (age, sex, and past suicide attempts) were included in the single-layer artificial neural network for the between-person classification model. Furthermore, 13 acoustic features were included in the extreme gradient boosting machine learning algorithm for the within-person model. The between-person classifier was able to detect high suicidality with 69% accuracy (sensitivity 74%, specificity 62%, area under the receiver operating characteristic curve 0.62), whereas the within-person model was able to predict worsening suicidality over 2 months with 79% accuracy (sensitivity 68%, specificity 84%, area under receiver operating characteristic curve 0.67). The second model showed 62% accuracy in predicting increased suicidality in external sets. CONCLUSIONS: Within-person analysis using changes in acoustic features within an individual is a promising approach to detect increased suicidality. Automated analysis of voice can be used to support the real-time assessment of suicide risk in primary care or telemedicine.