Engineered Nanoparticles for Enhanced Antitumoral Synergy Between Macrophages and T Cells in the Tumor Microenvironment.

T cells and macrophages have the potential to collaborate to eliminate tumor cells efficiently. Macrophages can eliminate tumor cells through phagocytosis and subsequently activate T cells by presenting tumor antigens. The activated T cells, in turn, can kill tumor cells and redirect tumor-associated macrophages toward an antitumoral M1 phenotype. However, checkpoint molecules expressed on tumor cells impede the collaborative action of these immune cells. Meanwhile, monotherapy with a single immune checkpoint inhibitor (ICI) for either macrophages or T cells yields suboptimal efficacy in cancer patients. To address this challenge, here a nanoparticle capable of efficiently delivering dual ICIs to tumors for both macrophages and T cells is developed. These programmed cell death protein 1 (PD-1)-transfected macrophage membrane-derived nanoparticles (PMMNPs) can target tumors and provide signal-regulatory protein alpha and PD-1 to block CD47 and programmed cell death-ligand 1 (PD-L1), respectively, on tumor cells. PMMNPs enhance macrophage-mediated cancer cell phagocytosis and antigen presentation, promote T cell activation, and induce the reprogramming of macrophages toward an antitumoral phenotype. In syngeneic tumor-bearing mice, PMMNPs demonstrate superior therapeutic efficacy compared to nanoparticles delivering single ICIs and non-targeted delivery of anti-CD47 and anti-PD-L1 antibodies. PMMNPs capable of augmenting the antitumoral interplay between macrophages and T cells may offer a promising avenue for cancer immunotherapy.

Real-Time Tunable Gas Sensing Platform Based on SnO2 Nanoparticles Activated by Blue Micro-Light-Emitting Diodes.

Micro-light-emitting diodes (µLEDs) have gained significant interest as an activation source for gas sensors owing to their advantages, including room temperature operation and low power consumption. However, despite these benefits, challenges still exist such as a limited range of detectable gases and slow response. In this study, we present a blue µLED-integrated light-activated gas sensor array based on SnO2 nanoparticles (NPs) that exhibit excellent sensitivity, tunable selectivity, and rapid detection with micro-watt level power consumption. The optimal power for µLED is observed at the highest gas response, supported by finite-difference time-domain simulation. Additionally, we first report the visible light-activated selective detection of reducing gases using noble metal-decorated SnO2 NPs. The noble metals induce catalytic interaction with reducing gases, clearly distinguishing NH3, H2, and C2H5OH. Real-time gas monitoring based on a fully hardware-implemented light-activated sensing array was demonstrated, opening up new avenues for advancements in light-activated electronic nose technologies.

The Role of Prolactin in Amniotic Membrane Regeneration: Therapeutic Potential for Premature Rupture of Membranes.

Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and antioxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. PRL had a dose-dependent effect on hAESCs in vitro. PRL (500 ng/mL) significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the upregulation of CCN2 expression and downregulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via downregulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. The top 10 specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. PRL improves the viability and antioxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.

Association of loneliness with mental disorders in Korean adults: national mental health survey of Korea 2021.

PURPOSE: Loneliness is a risk factor for mental and physical disorders. Rapid individualization, with increasing associated social burden, is a contributing factor to loneliness among Koreans. This study aimed to investigate the relationship between loneliness and mental disorders, as well as to determine whether long-term loneliness is a factor predicting the occurrence of mental disorders in adults. METHODS: The National Mental Health Survey of Korea 2021, a nationally representative survey on mental disorders, was conducted. Responses from 5511 participants were collected using the Korean version of the Composite International Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders fourth edition, Structured Clinical Interview for Internet Gaming Disorder, and the World Health Organization Adult Attention-deficit Hyperactivity Disorder (ADHD) self-report scale. Loneliness and its duration were investigated among these participants. RESULTS: Loneliness was reported by approximately 2.9% of the general population. Loneliness was associated with an increased adulthood prevalence of alcohol use disorders, nicotine use disorders, depressive disorders, anxiety disorders, adult ADHD, and internet gaming disorders. Long-term loneliness was significantly associated with an elevated risk of alcohol use disorders, nicotine use disorders, depressive disorders, and anxiety disorders. Internet gaming disorder was associated with loneliness lasting > 1 year. CONCLUSION: Various adult psychiatric disorders were associated with loneliness. The significant dose-effect relationship indicated the importance of early detection of and intervention for loneliness to reduce its negative consequences on mental health.

Dose-response analysis between alcohol consumption and psoriasis: A systematic review and meta-analysis.

The association between psoriasis and alcohol consumption has been inconsistent across various studies. However, to the best of our knowledge, no dose-response meta-analysis has been performed to date. This study aims to investigate the association between alcohol consumption and psoriasis. The search was performed on July 27, 2021, using Embase and MEDLINE. The restricted cubic spline analysis was used to perform a dose-response analysis. We identified 3,904 studies, of which 48 studies with 1,702,847 individuals across 24 countries were included. Alcohol consumption was positively associated with psoriasis (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.27-1.70). In addition, a significantly increased OR for psoriasis was observed in males (OR, 1.84; 95% CI, 1.13-3.01) but not in females (OR, 1.22; 95% CI, 0.97-1.54). Based on eight studies, including three cohort and five case-control studies, the analysis revealed that with each additional gram of daily alcohol intake, the OR for psoriasis increased by 4%. We found a positive association between alcohol consumption and psoriasis. The association is more prominent in the group drinking more than 45 g of alcohol per day (3.2 alcoholic drink equivalent).

Molecular tools for recording and intervention of neuronal activity.

Observing the activity of neural networks is critical for the identification of learning and memory processes, as well as abnormal activities of neural circuits in disease, particularly for the purpose of tracking disease progression. Methodologies for describing the activity history of neural networks using molecular biology techniques first utilized genes expressed by active neurons, followed by the application of recently developed techniques including optogenetics and incorporation of insights garnered from other disciplines, including chemistry and physics. In this review, we will discuss ways in which molecular biological techniques used to describe the activity of neural networks have evolved along with the potential for future development.

Review of Scoring Systems for Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is an inflammatory disorder characterized by chronic deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in apocrine gland-bearing regions. Assessing its severity is challenging because of its clinical heterogeneity, lack of a standardized tool, and increasing severity scores. This article provides a chronological overview of HS grading scales to aid in the understanding and comparison of different scoring systems. A literature review of articles published in English on PubMed was conducted searched from 1989 to 2023. The review includes 15 scores that are the most relevant and widely used and acknowledges the existence of over 30 scoring systems for HS. The expanding landscape of HS scoring systems presents challenges when patients evaluated using different systems are compared. A universally accepted scoring system is required for consistent application across diverse populations. A comprehensive assessment should balance subjective and objective items, considering observer-reported signs and patient-reported symptoms to make meaningful treatment decisions.

Risk stratification for early mortality in newly diagnosed acute promyelocytic leukemia: a multicenter, non-selected, retrospective cohort study.

Introduction: Despite the current effective treatments for acute promyelocytic leukemia (APL), early mortality (EM), defined as death within 30 days of presentation, is a major hurdle to long-term survival. Methods: We performed a multicenter retrospective study to evaluate the incidence and clinical characteristics of EM in patients with newly diagnosed APL and to develop a risk stratification model to predict EM. Results: We identified 313 eligible patients diagnosed between 2000 and 2021 from five academic hospitals. The median age was 50 years (range 19-94), and 250 (79.9%) patients were <65 years. Most patients (n=274, 87.5%) received their first dose of all-trans retinoic acid (ATRA) within 24 hours of presentation. EM occurred in 41 patients, with a cumulative incidence of 13.1%. The most common cause of EM was intracranial hemorrhage (n=22, 53.6%), and most EMs (31/41, 75.6%) occurred within the first seven days of APL presentation. In a multivariable analysis, we identified three independent factors predicting EM: age ≥65 years (HR, 2.56), white blood cell count ≥8.0 x 109/L (HR, 3.30), and ATRA administration >24 hours of presentation (HR, 2.95). Based on these factors, patients were stratified into three categories with a significantly increasing risk of EM: 4.1% for low risk (54.3%; no risk factors; HR 1), 18.5% for intermediate risk (34.5%; 1 factor; HR 4.81), and 40.5% for high risk (11.2%; 2-3 factors; HR 13.16). Discussion: The risk of EM is still not negligible in this era of ATRA-based therapies. Our risk model serves as a clinically useful tool to identify high-risk patients for EM who may be candidates for novel treatments and aggressive supportive strategies.

Association between the skin microbiome and lichen striatus hypopigmentation: Cutibacterium acnes as a potential cause.

BACKGROUND: Lichen striatus (LS) is an acquired skin disorder with a linear pattern along Blaschko's lines. It commonly occurs in childhood, and the lesions spontaneously regress within several months. OBJECTIVES: Although up to 50% of LS cases exhibit hypopigmentation that can persist for several months to years, it is unknown why LS is associated with such a high incidence of hypopigmentation compared to other inflammatory skin diseases. Therefore, this study aimed to analyse the differences in the skin microbiome between LS patients with and without hypopigmentation. METHODS: Differences in skin microbiome were analysed using whole genome sequencing of skin biopsies and subsequent bioinformatics analyses. RESULTS: Some microbes commonly found in hypopigmented skin disorders, including Cutibacterium acnes, were more abundant in patients with LS showing hypopigmentation than in those not showing hypopigmentation. CONCLUSIONS: The skin microbiota may be involved in the development of hypopigmentation in LS and may be considered a treatment target to reduce LS duration and hypopigmentation.

The safety of systemic Janus kinase inhibitors in atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

Janus kinase (JAK) inhibitors have been recently approved by the FDA and are widely used in the treatment of patients with atopic dermatitis. However, a comprehensive safety profile of JAK inhibitors in patients with atopic dermatitis has not been analysed. This study aimed to establish clinical evidence for the safety of systemic JAK inhibitors in patients with atopic dermatitis. Medline, Embase, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and International Clinical Trials Registry Platform (ICTRP) were considered for search databases. Randomized controlled trials reporting the adverse events of systemic therapy in patients with atopic dermatitis were included. The risk of 11 adverse events was compared between the JAK inhibitors and placebo groups. Fourteen randomized controlled trials were analysed published between 2019 and 2022. The JAK inhibitors included in the analysis were abrocitinib (10, 30, 100 and 200 mg), baricitinib (1, 2 and 4 mg) and upadacitinib (7.5, 15 and 30 mg). The risk of herpes zoster, headache, acne, elevated blood creatinine phosphokinase and nausea was significantly increased, but the risk of serious infection, non-melanoma skin cancer (NMSC), malignancies other than NMSC, major adverse cardiovascular event, venous thromboembolism and nasopharyngitis was not increased. This study provides comprehensive clinical evidence on the risk of various adverse events in patients with atopic dermatitis. However, since the follow-up periods of the studies analysed in this review were mostly limited to 16 weeks or less, it is recommended that comprehensive long-term observational studies be conducted to determine any potential adverse events associated with major cardiovascular events or malignancies, which typically have prolonged courses.

Enhancing Performance of Ultraviolet C Photodetectors Through Single-Domain Epitaxy of Monoclinic ß-Ga2 O3 Films and Tailored Anti-Reflection Coating.

Implementing high-performance ultraviolet C photodetectors (UVC PDs) based on ß-Ga2 O3 films is challenging owing to the anisotropic crystal symmetry between the epitaxial films and substrates. In this study, highly enhanced state-of-the-art photoelectrical performance is achieved using single-domain epitaxy of monoclinic ß-Ga2 O3 films on a hexagonal sapphire substrate. Unlike 3D ß-Ga2 O3 films with twin domains, 2D ß-Ga2 O3 films exhibit a single domain with a smooth surface and low concentration of point defects, which enable efficient charge separation by suppressing boundary-induced recombination. Furthermore, a tailored anti-reflection coating (ARC) is adopted as a light-absorbing medium to improve charge generation. The tailored nanostructure, which features a gradient refractive index, not only substantially reduces the reflection, but also suppresses the surface leakage current as a passivation layer. This study provides fundamental insights into the single-domain epitaxy of ß-Ga2 O3 films and the application of ARC for the development of high-performance UVC PDs.

A Case of Cavernous Sinus Syndrome Due to Extranodal Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma accounting for approximately one-third of all cases. DLBCL can present as a lymph node or extranodal tumor. Cavernous sinus (CS) is a small but complex structure in which various arteries, sympathetic plexuses, and cranial nerves are passing through. Cavernous sinus syndrome (CSS) results from any disease process that affects CS including tumor, vascular disease, infection, or inflammation. Herein, we report a case of extranodal DLBCL diagnosed by skin biopsy presenting as CSS. A 58-year-old male presented with a 3-week-old, gradually growing subcutaneous nodule on the left upper lip. He also suffered from ptosis, ophthalmoplegia, diplopia, and headache confined to the right side for 3 months. Histopathologic examination of the left upper lip showed dense dermal infiltration of atypical large tumor cells resembling centroblasts and immunoblasts. Immunohistochemistry studies revealed that the tumor cells were positive for CD20, BCL2, BCL6, MUM1, and MYC. After additional radiologic evaluation with positron emission tomography-computed tomography (PET-CT), brain magnetic resonance imaging, and orbital CT, he was finally diagnosed with extranodal DLBCL involving the right CS, oculomotor muscles, and left upper lip.

Stakeholders' Perceptions Regarding Digital Therapeutics Reimbursement in South Korea: Qualitative Study.

Background: Digital therapeutics (DTx) are therapeutic interventions driven by software and directly provided to patients, allowing them to manage their health with ease in any setting. A growing interest in DTx has spurred a discussion concerning their reimbursement pathways. However, DTx are still at a premature stage, with insufficient evidence on effectiveness, efficiency, and safety. Currently, although industries desire to quickly enter the market, especially by getting their products reimbursed by the National Health Insurance (NHI) fund, the NHI is cautious about DTx due to their uncertainties. Thus, public discussion and social consensus are crucial in deciding whether to reimburse DTx by the NHI fund. Objective: This study examined multiple stakeholders' awareness and attitudes toward DTx and perceptions of regulatory pathways for adopting DTx. Methods: In-depth interviews were conducted with 11 stakeholders in South Korea (industry: n=4, health care: n=3, academia: n=2, and consumer: n=2) using semistructured guidelines. They were purposively sampled to identify individuals with expertise in DTx and NHI policies. The interviews were conducted either in person or via a videoconference for 45-70 minutes. Qualitative data were analyzed using directed content analysis, which uses interview guidelines as an analytical framework. Results: Findings were divided into three categories: (1) awareness and attitude toward DTx, (2) perception of whether DTx are worth entering the market and being reimbursed by the NHI fund, and (3) perception of how to enter the market and how to reimburse DTx by the NHI fund if they are worth it. Although consumer stakeholders were not familiar with the basic concept of DTx, the other stakeholders understood it thoroughly. However, all participants showed positive attitudes and acceptance of DTx. Most of them responded that DTx are worth entering the market, but they could not reach an agreement on the pathways for DTx to enter the market. Although participants were in favor of the reimbursement of DTx in principle, they responded that a conservative approach is required due to insufficient clinical evidence for DTx. Conclusions: We found that stakeholders in South Korea had positive attitudes toward DTx, perceived them as worth using, and agreed to allow them to enter the market. The main issue was not the problem of the technology itself but the difference in opinion as to the pathways for reimbursement. Therefore, this study concluded that the NHI fund, which is operated very conservatively, is insufficient to quickly adopt and implement DTx. Various reimbursement methods, including tax-based financing, raising innovation funds for new technologies, and pilot studies using the NHI fund, should be used to rapidly generate clinical evidence and reduce the uncertainties of DTx to secure a stable market.

High-fluence 1064nm Q-switched Nd:YAG laser treatment for ectopic Mongolian spot.

Q-switched neodymium-yttrium aluminum-garnet (Q-switched Nd:YAG) laser has been reported as an effective treatment for nevus of Ota and acquired bilateral nevus of Ota-like macules (ABNOM). Data on ectopic Mongolian spots have rarely been reported.The present study was performed to investigate the treatment efficacy of a high-fluence 1064 nm Q-switched Nd:YAG laser without tissue whitening in ectopic Mongolian spots.We included 61 patients with ectopic Mongolian spots, and 70 lesions were examined. Thirty-three lesions were treated with a high-fluence 1064 nm Q-switched Nd:YAG laser, and 38 lesions were observed without treatment. The results were assessed using a 5-quantile grading scale and melanin index using a Mexameter®.Mean follow-up duration was 14.1 ± 6.8 months for the treatment group and 17.8 ± 10.0 months for the observation group. Mean 5-quintile grading scale at final follow-up was statistically different (p < 0.001) between the two groups (treatment: 2.85 ± 1.00, observation: 0.49 ± 0.73). There was a significant difference (p < 0.001) in the Δ melanin index (initial melanin index - final melanin index) between the observation (7.1 ± 62.7) and treatment (156.7 ± 78.4) groups.High-fluence Q-switched Nd:YAG laser without tissue whitening showed good results and was well-tolerated in treating ectopic Mongolian spots.