Search

Jae Hyun Park,1 Yeh Hong Ho,2 Kotchamol Manonukul3 1Dana Plastic Surgery Clinic, Seoul, Korea; 2Dana Taipei Hair Transplantation Clinic, Taipei City, 106, Taiwan, People’s Republic of China; 3V Design Hair by Dana International, Vibhavadi Hospital, Bangkok, 10900, ThailandCorrespondence: Jae Hyun Park, Dana Plastic Surgery Clinic, 10F Samju Building, Gangnamdaero 606, Gangnamgu, Seoul, Korea, Tel +82-2-512-0922, Fax +82-2-512-0942, Email jay8384@naver.comPurpose: Hair transplantation using the sharp implanter method is increasing in popularity. However, there has been little discussion pertaining to surgical know-how or specific techniques that increase efficiency and precision. We describe surgical techniques that enable dense packing in a swift and efficient fashion with the sharp implanter method using photos and videos.Patients and Methods: Grafts were placed using the sharp implanter method while adhering to several important principles. Eleven principles regarding the following aspects of hair transplant surgery were explained: gripping the implanter, graft placing technique that minimizes graft popping and tissue trauma when using the implanter, efficient team surgery system with assistant staff, direction and sequence of graft insertion, effective regimen for using epinephrine to control bleeding, selection of appropriately sized implanter tip, selection and usage of wide and narrow channel implanter tips, importance and methods of depth control, and staff training.Results: High graft survival and dense and natural hair density can be obtained with the sharp implanter method when performed in compliance with the principles described here.Conclusion: Appropriate use of the sharp implanter technique allows efficient and rapid graft insertion and achieves natural outcomes.Keywords: hair follicle, hair transplant, implanter, sharp implanter, alopecia

Gelsolin is known as one of the actin-binding proteins capable of severing and capping filamentous actin, and of undergoing structural changes in the presence of calcium ions to interact with actin filaments. In this study, single-particle 3D reconstruction using electron microscopy (EM) revealed that, in the presence of calcium, the structure of gelsolin undergoes structural changes before interacting with actin. These differences are subtle with similarities, as confirmed by the EM map. According to the results of the molecular dynamics simulations, these nuanced structural differences primarily manifest at the domain level when calcium is present. These results provide structural evidence that, in the presence of calcium, gelsolin enters a phase of conformational preparation to transition into the active state. This process enables gelsolin to bind to actin, whereupon gelsolin undergoes more drastic structural changes upon interaction with actin filaments, which allows it to participate in binding and severing to regulate the cytoskeleton. This is the first visualization of full-length gelsolin, and helps to clarify crucial aspects of the as of yet incompletely understood interaction between gelsolin and actin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antimicrobial peptides (AMPs) are a current solution to combat antibiotic resistance, but they have limitations, including their expensive production process and the induction of cytotoxic effects. We have developed novel AMP candidate (peptide 3.1) based on indolicidin, among the shortest naturally occurring AMP. The antimicrobial activity of this peptide is demonstrated by the minimum inhibitory concentration, while the hemolysis tests and MTT assay indicate its low cytotoxicity. In optical diffraction tomography, red blood cells treated with peptide 3.1 showed no discernible effects, in contrast to indolicidin. However, peptide 3.1 did induce cell lysis in E. coli, leading to a reduced potential for the development of antibiotic resistance. To investigate the mechanism underlying membrane selectivity, the structure of peptide 3.1 was analyzed using nuclear magnetic resonance spectroscopy and molecular dynamics simulations. Peptide 3.1 is structured with an increased distinction between hydrophobic and charged residues and remained in close proximity to the eukaryotic membrane. On the other hand, peptide 3.1 exhibited a disordered conformation when approaching the prokaryotic membrane, similar to indolicidin, leading to its penetration into the membrane. Consequently, it appears that the amphipathicity and structural rigidity of peptide 3.1 contribute to its membrane selectivity. In conclusion, this study may lead to the development of Peptide 3.1, a promising commercial candidate based on its low cost to produce and low cytotoxicity. We have also shed light on the mechanism of action of AMP, which exhibits selective toxicity to bacteria while not damaging eukaryotic cells., (© 2024 International Union of Biochemistry and Molecular Biology.)

In-sensor computing has gained attention as a solution to overcome the von Neumann computing bottlenecks inherent in conventional sensory systems. This attention is due to the ability of sensor elements to directly extract meaningful information from external signals, thereby simplifying complex data. The advantage of in-sensor computing can be maximized with the sampling principle of a restricted Boltzmann machine (RBM) to extract significant features. In this study, a stochastic photo-responsive neuron is developed using a TiN/In-Ga-Zn-O/TiN optoelectronic memristor and an Ag/HfO 2 /Pt threshold-switching memristor, which can be configured as an input neuron in an in-sensor RBM. It demonstrates a sigmoidal switching probability depending on light intensity. The stochastic properties allow for the simultaneous exploration of various neuron states within the network, making identifying optimal features in complex images easier. Based on semi-empirical simulations, high recognition accuracies of 90.9% and 95.5% are achieved using handwritten digit and face image datasets, respectively. In addition, the in-sensor RBM effectively reconstructs abnormal face images, indicating that integrating in-sensor computing with probabilistic neural networks can lead to reliable and efficient image recognition under unpredictable real-world conditions.

We compared axial length (AL) measurements using spectral-domain optical coherence tomography (SD-OCT)-based and partial coherence interferometry (PCI)-based biometry in eyes with various chorioretinal diseases. Medical records were retrospectively analyzed in 123 eyes from 73 patients who underwent AL measurements using SD-OCT and PCI. AL values were highly consistent by both measurements (ICC = 0.996 in SD-OCT and 0.995 in PCI-based biometry). The mean difference in AL between the two instruments was - 0.09 ± 0.17 mm, which was significant (P < 0.001). There was a strong correlation between the measurements obtained using the two instruments (r = 0.982, P < 0.001). The 95% limits of agreement were - 0.43 to 0.25 mm, and the agreement of AL in the Bland-Altman analysis showed a difference. The difference in measurements was not associated with the difference in central retinal thickness (r = 0.033, P = 0.720). However, the presence of an epiretinal membrane affected the difference in measurements, unlike in other chorioretinal diseases (P = 0.014). SD-OCT-based biometry showed a good correlation with PCI-based biometry in the measurement of AL; however, the mean AL between the two instruments was significantly different. Therefore, AL measurements made using SD-OCT-based and PCI-based biometry are not interchangeable., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

It has been three decades since the development of vestibular-evoked myogenic potential (VEMP) test. Now is an opportune moment to review clinical usefulness of the VEMP testing in audiovestibular disorders. This review was developed from peer-reviewed articles published in those journals listed on Journal Citation Reports. Initially, 2323 articles were retrieved from 1992 to 2023. Following the guidelines (PRISMA 2020 statement) for reporting reviews, 71 relevant papers were ultimately selected. In conclusion, the integration of acoustic, vibratory, and galvanic stimuli in eliciting cervical VEMP (cVEMP) and ocular VEMP (oVEMP) provides a more thorough identification of the lesion site. When combined with audiometry and caloric testing, the inner ear test battery is highly effective in precisely identifying the affected area, evaluating residual function, and predicting the outcomes of audiovestibular disorders. Furthermore, both cVEMP and oVEMP tests help elucidate the mechanism of audiovestibular disorders, indicating an evolving understanding in this field., Competing Interests: Conflict of interest statement None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Predose trough concentrations (C trough ) of intravenous infliximab (IV-IFX) during maintenance therapy are associated with therapeutic outcomes in patients with Crohn's disease (CD). A subcutaneous formulation of infliximab (SC-IFX) has shown high C trough values due to its favourable pharmacokinetics., Aims: To evaluate the association of C trough of SC-IFX with therapeutic outcomes and the threshold of SC-IFX C trough for achieving mucosal healing (MH) and transmural healing (TH) in patients with CD., Methods: We performed this cross-sectional study in patients with CD who had received SC-IFX maintenance therapy for ≥ 6 months. We measured SC-IFX C trough immediately before SC-IFX injection. We performed ileocolonoscopy/single-balloon enteroscopy and/or magnetic resonance enterography within 3 months of SC-IFX C trough measurement. MH was defined as SES-CD-ulcerated surface subscore of 0. TH was defined as simplified MaRIA score of 0., Results: We enrolled 124 patients with MH in 77.9% (74/95) and TH in 36.3% (37/102). SC-IFX C trough was significantly higher in patients with MH (24.1 vs.16.9 μg/mL; p = 0.001) and TH (26.0 vs. 20.5 μg/mL; p = 0.007) than in those without. ROC analysis identified that the threshold of SC-IFX C trough for MH and TH were 17.5 and 30.3 μg/mL, respectively. Multivariate logistic regression showed that SC-IFX C trough was significantly associated with MH (OR 1.16; 95% CI 1.05-1.27; p = 0.002) and TH (OR 1.08; 95% CI 1.02-1.14; p = 0.005)., Conclusions: SC-IFX C trough was positively associated with MH (≥ 18 μg/mL) and TH (≥ 30 μg/mL) in patients with CD, which may guide treatment decisions to optimise therapeutic response in the era of treat-to-target., (© 2024 John Wiley & Sons Ltd.)

Background/aims: Combi-elastography is a B-mode ultrasound-based method in which two elastography modalities are utilized simultaneously to assess metabolic dysfunction-associated steatotic liver disease (MASLD). However, the performance of combi-elastography for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and determining fibrosis severity is unclear. This study compared the diagnostic performances of combi-elastography and vibration-controlled transient elastography (VCTE) for identifying hepatic steatosis, fibrosis, and high-risk MASH., Methods: Participants who underwent combi-elastography, VCTE, and liver biopsy were selected from a prospective cohort of patients with clinically suspected MASLD. Combi-elastography-related parameters were acquired, and their performances were evaluated using area under the receiver-operating characteristic curve (AUROC) analysis., Results: A total of 212 participants were included. The diagnostic performance for hepatic steatosis of the attenuation coefficient adjusted by covariates from combi-elastography was comparable to that of the controlled attenuation parameter measured by VCTE (AUROC, 0.85 vs 0.85; p=0.925). The performance of the combi-elastography-derived fibrosis index adjusted by covariates for diagnosing significant fibrosis was comparable to that of liver stiffness measured by VCTE (AUROC, 0.77 vs 0.80; p=0.573). The activity index from combi-elastography adjusted by covariates was equivalent to the FibroScan-aspartate aminotransferase score in diagnosing high-risk MASH among participants with MASLD (AUROC, 0.72 vs 0.74; p=0.792)., Conclusions: The performance of combi-elastography is similar to that of VCTE when evaluating histology of MASLD.

Red tides occurring off the southern coast of Korea impact the marine ecosystem and aquaculture industries. Zooplankton are crucial in the food web, connecting primary producers to higher predators and interact diversely with red tide organisms. This study explores dynamics of the zooplankton community over seven years including three red tide and four non-red tide years in Tongyeong using metabarcoding. In non-red tide years, zooplankton diversity showed typical seasonal patterns, increasing from June to early October. However, during red tide years, diversity remained high, with a shift in species composition-decreased Copepoda and increased Branchiopoda, Echinodermata, Malacostraca, and Annelida. Diversity indices were significantly higher in red tide years across all periods except for the richness in "after" that showed an insignificant higher value. The differences in zooplankton assemblages across periods were influenced by surface temperatures and the density of the red tide-causing alga Margalefidinium polykrikoides. Eight species emerged as indicator species and showed direct correlations with M. polykrikoides and among them, seven species were indicator species for red tide occurrence years. The ecological characteristics of M. polykrikoides blooms and their recurrent occurrences over several decades suggest that zooplankton may adapt to the toxins and use these blooms as spawning cues. Overall, this study provides comprehensive understanding on changes in zooplankton communities during red tide events, offering novel insights into their ecology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aims: : The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage., Methods: : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data., Results: : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI., Conclusions: : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

Objectives: This study aimed to investigate the association between circulating interleukin-6 (IL-6) levels and Behçet's disease (BD), and associations between polymorphisms in IL-6 gene and BD susceptibility., Method: A search of relevant articles was conducted in the Medline, Embase, and Web of Sciences databases. Subsequently, a meta-analysis was performed to assess circulating IL-6 levels in both the BD and control groups. Additionally, we investigated the association between the functional IL-6 promoter -174 G/C polymorphism and the risk of developing BD., Results: Nineteen studies involving 923 patients with BD and 910 controls were included in this meta-analysis. The results demonstrated a significant elevation in circulating IL-6 levels in the BD group than in the control group (standardized mean difference [SMD] = 1.600, 95 % confidence interval [CI] = 0.732-2.496, P<0.001). Furthermore, IL-6 levels were significantly higher in the active disease group than in the inactive disease group (SMD=1.292, 95 % CI=0.059-2.525, P<0.001). Intriguingly, the meta-analysis revealed an association between BD and the IL-6 CC+CG genotype in Arabs (odds ratio [OR] = 0.588, 95 % CI=0.393-0.881, P=0.010), whereas no such association was observed in European or Asian populations., Conclusions: Our meta-analysis revealed significantly higher circulating IL-6 levels in patients with BD and found evidence of association between IL and 6 promoter -174 G/C and BD susceptibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: An understanding of the phenotypes and endotypes of atopic dermatitis (AD) is essential for developing precision therapies. Recent studies have demonstrated evidence for the gut-skin axis in AD., Objective: To determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms based on multi-omics analyses., Methods: Latent class trajectory analysis was used to AD phenotype in 2247 children who were followed until 9 years of age from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) birth cohort study. Multi-omics analyses (microbiome, metabolites, and gut epithelial cell transcriptome) using stool samples collected at 6 months of age were performed to elucidate the underlying mechanisms of AD phenotypes., Results: Five AD phenotypes were classified as follows: never/infrequent, early-onset transient, intermediate-transient, late-onset, and early-onset persistent. Early-onset persistent and late-onset phenotypes showed increased risks of food allergy and wheezing treatment ever, with bronchial hyperresponsiveness only evident in the early-onset persistent phenotype. Multi-omics analyses revealed a significantly lower relative abundance of Ruminococcus gnavus and a decreased gut acetate level in the early-onset persistent phenotype, with potential associations to ACSS2, JAK-STAT signaling, and systemic Th2 inflammation. The early-onset transient phenotype was associated with AMPK and/or chemokine signaling regulation, whereas the late-onset phenotype was linked with IL-17 and barrier dysfunction., Conclusions: Multi-omics profiling in early life may offer insights into different mechanisms underlying AD phenotypes in children., (Copyright © 2024. Published by Elsevier Inc.)

Alzheimer's disease (AD) is characterized by cognitive decline and memory loss, involving mechanisms such as tau hyperphosphorylation and mitochondrial dysfunction. Increasing evidence suggests that age-related alterations in metabolite levels are crucial for the pathogenesis of AD. Here, we analyzed serum metabolites from mice of various ages (2, 4, 14, and 21 months old) using mass spectrometry. We identified palmitoyl-L-carnitine as a key metabolite with significantly increased levels in aged mice. In vitro experiments with SH-SY5Y neuronal cells demonstrated that palmitoyl-L-carnitine treatment enhanced tau phosphorylation, increased mitochondrial fission, and elevated intracellular calcium levels. Furthermore, the increased levels of tau phosphorylation were significantly reduced by the inhibition of GSK-3β, CDK5, and calpain, indicating that tau kinases activated by calcium overload are directly involved in the increase of tau phosphorylation. Considering that mitochondrial fission is related to mitochondrial dysfunction, we propose that the elevated level of serum palmitoyl-L-carnitine during aging contributes to AD pathology through these pathways. These findings highlight the significant role of lipid metabolism in neurodegeneration and offer potential therapeutic targets for age-related diseases, including AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yoon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aluminum scandium nitride (AlScN) has emerged as a promising candidate for next-generation ferroelectric memories, offering a much higher remanent charge density than other materials with a stable ferroelectric phase. However, the inherently high coercive field requires a substantial decrease in film thickness to lower the operating voltage. Significant leakage currents present a severe challenge during the thickness scaling, especially when maintaining compatibility with complementary-metal-oxide-semiconductor (CMOS) fabrication standards. This study adopts a HfN 0.4 bottom electrode, which minimizes lattice mismatch with Al 0.7 Sc 0.3 N (ASN), forming a coherent bottom interface that effectively reduces leakage currents even at thickness < 5 nm. CMOS-compatible HfN 0.4 /ASN/TiN stack, deposited without vacuum break between each layer, demonstrates exceptional scalability, confirming the ferroelectricity of ASN films at thicknesses down to 3 nm. The coercive voltage is decreased to 4.35 V, significantly advancing low-voltage AlScN devices that align with CMOS standards., (© 2024 Wiley‐VCH GmbH.)

Chiral inorganic nanomaterials hold significant promise for various applications, including enantioselective catalysis, polarization-controlling optical devices, metamaterials, and enantioselective molecular sensors. In our previous work, we presented a method for synthesizing chiral Au 432 helicoid III (Au helicoids) from peptides and amino acids, where helical gaps are intricately arranged with 432 symmetry within single cubic nanoparticles. In this study, we have achieved the fabrication of chiral silica molds through Au etching subsequent to the silica coating of Au helicoids. We demonstrate that these molds serve as geometrically confined reactors capable of producing chiral Ag, Pd, and Pt 432 helicoid III (Ag, Pd, and Pt helicoids). The morphology of the synthesized Ag, Pd, and Pt helicoids closely resembles that of the Au helicoids, exhibiting a superior g-factor compared to other reported chiral structures of each material. Notably, the Ag and Pd helicoids are found to be single-crystalline, with high-index planes exposed within the gaps. We believe that this silica mold-based approach can be generalized to synthesize chiral nanomaterials of various metal and even oxide materials.

Alkali-free aluminoborosilicate glasses without (GDMC-Si) and with La 2 O 3 addition (GDMC-La) were fabricated with an aim to develop low dielectric glass fibers for use in printed circuit boards (PCBs) as a reinforcing material in high-speed 5G/6G telecommunications application. This study presents the structural, thermo-physical, and dielectric properties of the glasses. The decrease in glass transition temperature (T g ) and the increase in coefficient of thermal expansion (CTE) were found by the addition of SiO 2 and La 2 O 3 in the present glass system, which are due to the depolymerization of the glass networks confirmed by the FTIR analysis. The dielectric constants (Dk) and the dissipation factors (Df) of the glasses were investigated at a high frequency of 10 GHz. The Dk values of the GDMC-Si and GDMC-La glass systems reached a minimum of 4.50 and 4.75, while their Df values reached a minimum of 2.86 × 10 -3 and 3.01 × 10 -3 , respectively. Notably, the Dk and Df values of the present glasses were lower than the commercial E-glass (Dk: 6.9, Df: 7.0 × 10 -3 at 10 GHz) and L-glass (Dk: 4.8, Df: 3.0 × 10 -3 at 10 GHz). Glass fibers with a diameter of 10 μm were successfully drawn by the continuous melt-spinning process and their mechanical properties were investigated., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Small cell lung cancer (SCLC) is aggressive with limited therapeutic options. Despite recent advances in targeted therapies and immunotherapies, therapy resistance is a recurring issue, which might be partly due to tumor cell plasticity, a change in cell fate. Nonetheless, the mechanisms underlying tumor cell plasticity and immune evasion in SCLC remain elusive. CRACD, a capping protein inhibitor that promotes actin polymerization, is frequently inactivated in SCLC. Cracd knockout (KO) transforms preneoplastic cells into SCLC tumor-like cells and promotes in vivo SCLC development driven by Rb1, Trp53, and Rbl2 triple KO. Cracd KO induces neuroendocrine (NE) plasticity and increases tumor cell heterogeneity of SCLC tumor cells via dysregulated NOTCH1 signaling by actin cytoskeleton disruption. CRACD depletion also reduces nuclear actin and induces EZH2-mediated H3K27 methylation. This nuclear event suppresses the MHC-I genes and thereby depletes intratumoral CD8+ T cells for accelerated SCLC tumorigenesis. Pharmacological blockade of EZH2 inhibits CRACD-negative SCLC tumorigenesis by restoring MHC-I expression and immune surveillance. Unsupervised single-cell transcriptomics identifies SCLC patient tumors with concomitant inactivation of CRACD and downregulated MHC-I pathway. This study defines CRACD, an actin regulator, as a tumor suppressor that limits cell plasticity and immune evasion and proposes EZH2 blockade as a viable therapeutic.

Filler morphology control is critical for enhancing the gas separation performance of mixed matrix membranes (MMMs). A vertical transport channel using the crystal twinning phenomenon is designed on the zeolitic imidazolate framework (ZIF) nanoplate. Twinned ZIF-8 (TZIF-8) nanoplate is prepared by controlling the shape of ZIF-L from nanosheet to twinned flake, followed by conversion into the ZIF-8 phase. With the addition of TZIF-8 in 6FDA-DAM polymer, propylene/propane selectivity is dramatically enhanced, showing propylene permeability of 40 Barrer and propylene/propane selectivity of 82. The separation performance surpasses the performance of MMMs reported so far, and the selectivity is comparable to that of polycrystalline ZIF-8 membranes. A transport mechanism study using mathematical models implies that the percolated twin fillers create rapid and selective gas channels for desired molecules and substantial tortuous pathways for undesired molecules., (© 2024 Wiley‐VCH GmbH.)

Introduction: Despite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations., Methods: RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co-expression network, gene-set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography., Results: DGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD-associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell-mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data., Discussion: Our results in a Korean population suggest Aβ deposition-associated genes are enriched in NK cell-mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies., Highlights: Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network modules were associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβ deposition. Dysregulated genes were related to a NK cell-mediated immunity., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

This study sought to investigate the association between interleukin-10 (IL10) polymorphisms and susceptibility to Sjögren's syndrome. A systematic search of the Medline, Embase and Web of Science databases was conducted to identify relevant articles from inception to April 2024. No restrictions were placed on race, ethnicity or geographic area, but only studies published in English were included. A meta-analysis was conducted to evaluate the association among the IL10-1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms, as well as their haplotypes and the risk of developing Sjögren's syndrome. The included studies involved 998 Sjögren's syndrome patients and 1576 controls. Ten studies were included in the meta-analysis. Meta-analysis of the IL10-1082 G/A polymorphism revealed no significant association with Sjögren's syndrome (odds ratio [OR] = 1.115, 95% confidence interval [CI]: 0.888-1.401, p = 0.343), with stratification by ethnicity yielding consistent results for Europeans and Latin Americans. Similarly, the IL10-819 C/T polymorphism was not associated with Sjögren's syndrome in any study subjects (OR = 0.859, 95% CI: 0.648-1.138, p = 0.290). The IL10-592 C allele also exhibited no association with Sjögren's syndrome (OR = 1.131, 95% CI: 0.776-1.646, p = 0.522). However, the GCC carrier status demonstrated a significant association with Sjögren's syndrome across all study subjects (OR = 1.496, 95% CI: 1.200-1.865, p < 0.001), particularly in Europeans (OR = 1.444, 95% CI: 1.085-1.921, p = 0.012) and Latin Americans (OR = 1.324, 95% CI: 1.115-2.366, p = 0.012). A significant protective effect of the homozygous ATA/ATA haplotype on Sjögren's syndrome was found in Europeans (OR = 0.320, 95% CI: 0.121-0.846, p = 0.022). This meta-analysis indicates a significant link between carrying the GCC haplotype of the IL10-1082 G/A, -819 C/T and -592 C/A polymorphisms and an increased susceptibility to Sjögren's syndrome. Conversely, the homozygous ATA/ATA haplotype appears to confer protection against the risk of Sjögren's syndrome, particularly in European populations., (© 2024 John Wiley & Sons Ltd.)

Avian influenza viruses (AIVs) pose a significant threat to global poultry production, necessitating effective control strategies to mitigate economic losses and ensure animal welfare. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of immune responses, yet their roles in AIV-infected chickens remain poorly understood. This study aimed to investigate the expression profiles of lncRNAs and their targets in Vietnamese Ri chickens infected with the highly pathogenic AIV (HPAIV) H5N1. Through RNA sequencing, we identified novel lncRNAs and analyzed differentially expressed (DE) transcripts at 1 and 3 days post-infection (dpi) in chicken lung tissue. Our results revealed a higher number of DE lncRNAs and mRNAs at 1 dpi and 3 dpi, respectively, compared to control, with resistant chickens exhibiting a notably stronger immune response than susceptible chickens at 3 dpi. Functional analysis implicated these lncRNAs in immune-related pathways crucial for host responses to H5N1 viral infection. Furthermore, we identified lncRNA-mRNA interactions associated with antiviral responses and immune function. Notably, several genes involved in antiviral resistance and immune responses showed higher expression in resistant chickens, confirming their stronger antiviral response. Overall, our study provides insights into the role of lncRNAs in the host's response to HPAIV H5N1 infection in chickens and highlights potential candidates for further investigation into host-pathogen interactions. These findings could drive the development of novel control strategies for AIVs, significantly enhancing poultry health and biosecurity., Competing Interests: Declaration of competing interests The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Ultrasensitive, rapid, and reliable biomolecular sensing is essential for biomedical diagnostics, requiring real-time monitoring and detection of trace samples. Optical sensing, particularly plasmonic biosensing, meets these demands through noninvasive, high-sensitivity detection based on the interaction between light and molecules. Here, we present novel plasmonic metamaterial-based sensing strategy, utilizing the circular dichroism (CD) response of grating-coupled surface plasmon resonance (SPR) from chiral nanoparticle grating structure (i.e., 2D helicoid crystal) on gold substrate. Strong chiroptic response of helicoids has been effectively expanded to produce a remarkable CD/ g reflection response in the SPR mode, achieved by spectral coupling of SPR with localized surface plasmon resonance (LSPR) in helicoids. This CD response, derived from the differential of left and right circularly polarized light, corrects optical fluctuations, enhancing sensitivity and reliability. Our SPR-CD-based approach achieves a sensitivity of 379.2 nm/RIU and detection limit of a few mM for d-glucose, offering a new paradigm for high-performance optical biosensors.

The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 ATS Workshop on Precision Cut Lung Slices (PCLS) brought together 35 experts to discuss and address the role of human tissue-derived PCLS as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, along with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts. The current document recommends standard reporting criteria and emphasizes the requirement for careful collection and integration of clinical metadata. We further discuss current clinically relevant readouts that can be applied to PCLS and highlight recent developments and future steps for implementing novel technologies for PCLS modeling and analysis. The collection and correlation of clinical metadata and multiomic analysis will further advent the integration of this preclinical platform into patient endotyping and the development of tailored therapies for lung disease patients.

This study explored the anti-pruritic and immunomodulatory effects of Coix sprouts extract, focusing on histamine release and IL-31 cytokine production in HMC-1 cells. The extract significantly inhibited both factors, indicating its potential for pruritus relief. In a pruritus induction mouse model, Coix sprouts extract outperformed prednisolone in anti-pruritus effectiveness, also improving skin lesions and inhibiting mast cell infiltration. The extract suppressed tryptase expression, reduced release, inhibited mast cell proliferation, and lowered nitric oxide production, suggesting anti-inflammatory properties. Coix sprouts extract shows promise in suppressing inflammation and pruritus, making it a valuable candidate for clinical use. Additionally, the analysis of coixol content in Coix sprouts revealed variations in growth time, indicating their potential as functional materials with anti-pruritus and immune-enhancing applications.

Public health and clinical medicine should identify and characterize modifiable risk factors for skin cancer in order to facilitate primary prevention. In existing literature, the impact of occupational exposure on skin cancer, including malignant melanoma and non-melanoma skin cancers, has been extensively studied. This review summarizes the available epidemiological evidence on the significance of occupational risk factors and occupations associated with a higher risk in skin cancer. The results of this review suggest that there is sufficient epidemiological evidence to support the relationship between the increased risk of non-melanoma skin cancers and occupational exposure to solar radiation, ultraviolet radiation, ionizing radiation, arsenic and its compounds, and mineral oils. Occupational exposure to pesticides and polychlorinated biphenyls appears to provide sufficient epidemiological evidence for melanoma, and a higher risk of melanoma has been reported among workers in petroleum refining and firefighters. This comprehensive analysis will establish a foundation for subsequent investigations and developing targeted interventions of focused preventive measures against skin cancer among the working population., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Parkinson's disease is a progressive neurodegenerative disease with well-documented motor symptoms as well as less recognised, but significant, non-motor symptoms. These non-motor symptoms include prodromal pain and peripheral neuropathy, the causes of which are unknown. We investigated the role of DJ-1/PARK7, a Parkinson's disease-associated gene, in prodromal pain and peripheral neuropathy. Using DJ-1 deficient mice, we conducted comprehensive sensory tests, cutaneous staining, molecular analyses and electrophysiological studies on mouse and human primary sensory neurons from dorsal root ganglia. We found that these mice exhibited cold hypersensitivity, oxidative stress, and neuropathy of the cutaneous fibres of primary sensory neurones before any motor impairments were observed. Mechanistically, DJ-1 in primary sensory neurones regulated this hypersensitivity and neuropathy via TRPA1 signalling. Interestingly, we discovered that DJ-1 also plays a role in the progression of chemotherapy-induced peripheral neuropathies. Pain and mechanisms associated with these neuropathies were exacerbated in DJ-1 deficient mice but were significantly reduced by the pharmacological activation of DJ-1. Importantly, we also confirmed the expression of DJ-1 and its therapeutic potential in human primary sensory neurons. Thus, we uncover a peripheral mechanism of DJ-1 and propose that it may serve as a new target for developing therapeutic approaches for Parkinson's disease-linked and other painful neuropathies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Hormonal regulation during food ingestion and its association with pain prompted the investigation of the impact of glucagon-like peptide-1 (GLP-1) on transient receptor potential vanilloid 1 (TRPV1). Both endogenous and synthetic GLP-1, as well as a GLP-1R antagonist, exendin 9-39, reduced heat sensitivity in naïve mice. GLP-1-derived peptides (liraglutide, exendin-4, and exendin 9-39) effectively inhibited capsaicin (CAP)-induced currents and calcium responses in cultured sensory neurons and TRPV1-expressing cell lines. Notably, exendin 9-39 alleviated CAP-induced acute pain, as well as chronic pain induced by complete Freund's adjuvant (CFA) and spared nerve injury (SNI), in mice without causing hyperthermia associated with other TRPV1 inhibitors. Electrophysiological analyses revealed that exendin 9-39 binds to the extracellular side of TRPV1, functioning as a noncompetitive inhibitor of CAP. Exendin 9-39 did not affect proton-induced TRPV1 activation, suggesting its selective antagonism. Among the exendin 9-39 fragments, exendin 20-29 specifically binds to TRPV1, alleviating pain in both acute and chronic pain models without interfering with GLP-1R function. Our study revealed a novel role for GLP-1 and its derivatives in pain relief, suggesting exendin 20-29 as a promising therapeutic candidate., (© 2024. The Author(s).)

Background: Acute bronchiolitis is a common cause of hospitalization during infancy that carries significant morbidity and mortality rates., Purpose: This study compared the efficacy of different treatment modalities for infants with bronchiolitis in terms of hospital stay and clinical severity scores., Methods: The PubMed database was searched for relevant studies. Eligibility criteria included double-blind randomized controlled trial design, assessment of the effect of treatment on bronchiolitis in infants under 2 years of age, and publication in English from inception through July 31, 2020. The primary efficacy outcome was the length of hospital stay, while the secondary outcome was the clinical severity score. The standardized treatment effect and standard error of the effect size were calculated., Results: We identified 45 randomized controlled trials of 24 pairwise comparisons. These 45 trials included 5,061 participants and investigated 13 types of interventions (12 active, 1 placebo). Inhalation therapy with epinephrine (standard mean difference [SMD], -0.41; 95% confidence interval [CI], -0.8 to -0.03) and hypertonic saline (SMD, -0.29; 95% CI, -0.55 to -0.03) reduced the length of hospital stay compared with normal saline. Hypertonic saline was the most effective at improving the clinical severity score (SMD, -0.52; 95% CI, -0.95 to -0.10)., Conclusion: Inhalation therapy with epinephrine and hypertonic saline reduced the length of hospital stay and the clinical severity of bronchiolitis among infants under 2 years of age.

Purpose: Interest in the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has recently increased. Although measurement tools have been devised for IBD in general, there is no specific tool for measuring the QoL of patients with ulcerative colitis (UC). Therefore, we developed a QoL questionnaire specifically for patients with UC., Materials and Methods: The Korean Ulcerative Colitis-Specific Questionnaire (K-UCSQ) was developed through item generation, raw-scale construction, focus group meetings, and multi-center field tests. Two hundred patients with UC were recruited for a field test of the K-UCSQ, and subsequent responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) were also obtained. After performing factor analyses to ensure construct validity, the K-UCSQ was finalized as a four-domain, 28-item questionnaire. Subsequent analyses evaluated the reliability of the K-UCSQ in terms of Cronbach's alpha, concurrent validity in comparison with the pre-established IBDQ, and predictive validity of the area under the ROC curve (AUC) for clinically relevant QoL outcomes., Results: A Cronbach's alpha of 0.94 showed excellent reliability. Furthermore, correlation analyses demonstrated the concurrent validity of the K-UCSQ in comparison with the IBDQ. The K-UCSQ also showed high validity in predicting the perceived overall health (AUC of 0.812 vs. 0.797 using the IBDQ) and past 2-week QoL (AUC of 0.864 vs. 0.859 using the IBDQ)., Conclusion: The newly developed K-UCSQ is concise, bathroom problem-emphasizing, and UC-specific, suggesting that it could be a valid and reliable UC-specific instrument for QoL measurement., Competing Interests: Byong Duk Ye has received research grants from Celltrion and Pfizer Korea; consulting fees from AbbVie Korea, BMS Pharmaceutical Korea Ltd., Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Curacle, Daewoong Pharm, Ferring Korea, IQVIA, Janssen Korea, Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Medtronic Korea, Nano-Entek, ORGANOID SCIENCES LTD., Pfizer Korea, Samsung Bioepis, Takeda, and Takeda Korea; and speaking fees from AbbVie Korea, Celltrion, Cornerstones Health, Curacle, Daewoong Pharm, Ferring Korea, IQVIA, Janssen Korea, Pfizer Korea, and Takeda Korea. The other authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Oxidative stress and mitochondrial dysfunction play critical roles in neurodegenerative diseases. Glutathione (GSH), a key brain antioxidant, helps to neutralize reactive oxygen species (ROS) and maintain redox balance. We investigated the effectiveness of L-cysteine (L-Cys) in preventing apoptosis induced by the ROS generator 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in mouse hippocampal neuronal HT22 cells, as well as alleviating memory and cognitive impairments caused by the GSH synthesis inhibitor L-buthionine sulfoximine (BSO) in mice. DMNQ-induced apoptotic events in HT22 cells, including elevated cytosolic and mitochondrial ROS levels, DNA fragmentation, endoplasmic reticulum stress, and mitochondrial damage-mediated apoptotic pathways were dose-dependently abrogated by L-Cys (0.5-2 mM). The reduced intracellular GSH level, caused by DMNQ treatment, was restored by L-Cys cotreatment. Although L-Cys did not significantly restore GSH in the presence of BSO, it prevented DMNQ-induced ROS elevation, mitochondrial damage, and apoptosis. Furthermore, compared to N-acetylcysteine and GSH, L-Cys had higher 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical-scavenging activity. L-Cys also restored mitochondrial respiration capacity in DMNQ-treated HT22 cells by reversing mitochondrial fission-fusion dynamic balance. BSO administration (500 mg/kg/day) in mice led to neuronal deficits, including memory and cognitive impairments, which were effectively mitigated by oral L-Cys (15 or 30 mg/kg/day). L-Cys also reduced BSO-induced ROS levels in the mice hippocampus and cortex. These findings suggest that even though it does not contribute to intracellular GSH synthesis, exogenous L-Cys protects neuronal cells against oxidative stress-induced mitochondrial damage and apoptosis, by acting as a ROS scavenger, which is beneficial in ameliorating neurocognitive deficits caused by oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest relevant to this study., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: This study aimed to evaluate and compare the clinico-radiographic outcomes between two techniques for acute Lisfranc fracture-dislocation with a large, displaced second metatarsal base plantar fracture: isolated Lisfranc screw fixation versus Lisfranc joint fixation with dorsoplantar miniscrew fixation of the second metatarsal base., Methods: We retrospectively compared the clinico-radiographic outcome between patients who underwent isolated Lisfranc screw fixation (Group 1, 26 patients) and those who underwent Lisfranc joint fixation with dorsoplantar miniscrew fixation of the second metatarsal base (Group 2, 23 patients). The main outcome measurements were the postoperative distance between the medial cuneiform and second metatarsal base on standing anteroposterior foot radiographs, known as the C1-M2 distance. Residual diastasis was defined as C1-M2 distance ≥ 2 mm on the affected side compared with that on the contralateral side. We also assessed the Foot and Ankle Ability Measure (FAAM)-activities of daily living (ADL) and sports subscale scores at three, six and ≥ 18 months postoperatively., Results: At the final follow-up, the mean C1-M2 distance on the affected side compared with that on the contralateral side was significantly greater in Group 1 than in Group 2 (3.9 versus 0.7 mm, P = 0.027). Furthermore, Group 1 showed a higher incidence of residual diastases at the final follow-up (69.2%) than the Group 2 (13.0%, P < 0.001). The FAAM-ADL scores at the final follow-up did not differ significantly between the groups (P = 0.518), but the FAAM Sports score was significantly higher in Group 2 than in Group 1 (P = 0.001)., Conclusions: The postoperative C1-M2 distance was better maintained with Lisfranc joint fixation with dorsoplantar miniscrew fixation of the second metatarsal base than with isolated Lisfranc screw fixation. We recommend that surgeons exercise caution when dealing with a second metatarsal plantar fracture and consider performing secure fixation using the dorsoplantar miniscrew technique for improved clinical outcomes., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Typically used household chemicals comprise numerous compounds. Determining mixture toxicity, as observed when using household chemicals containing multiple substances, is of considerable importance from a regulatory perspective. Upon examining the toxic effects of household chemical mixtures, we observed that hydramethylnon combined with tetramethrin resulted in synergistic toxicity. To determine the unknown toxicity mechanism of hydramethylnon, which carries the risk of inhalation exposure when using household chemicals, we conducted a further investigation using BEAS-2B cells, a human bronchial epithelial cell line. Hydramethylnon-induced cytotoxicity was determined following 24 and 48 h of exposure using the water-soluble tetrazolium 1 and lactate dehydrogenase assays. To elucidate the toxicity mechanism, we utilized flow cytometry and measured the levels of apoptosis-related proteins and caspase activities. Given that hydramethylnon, as an insecticide, disrupts the mitochondrial electron transfer chain, we analyzed the relevant mechanisms, including mitochondrial superoxide levels as well as the mitochondrial membrane potential (MMP). Hydramethylnon dose-dependently induced BEAS-2B cell apoptosis via the intrinsic pathway. Furthermore, it significantly increased mitochondrial superoxide levels and disrupted the MMP. Pre-treatment with a caspase inhibitor (Z-DEVD-FMK) confirmed that hydramethylnon induced caspase-dependent apoptosis. Apoptosis, a key event in the toxicological process of chemicals, can lead to lung diseases, including fibrosis and cancer. The results of the present study suggest a mechanism of toxicity of hydramethrylnon, an organofluorine biocide whose toxicity has been little studied, to the lung epithelium. Considering the potential risks associated with inhalation exposure, these results highlight the need for careful management and regulation of hydramethylnon., Competing Interests: Declaration of competing interest The authors declare that they do not possess any personal relationships or competing financial interests that would impact the work reported in the paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Avian influenza virus (AIV) infections first affect the respiratory tract of chickens. The epithelial cells activate the host immune system, which leads to the induction of immune-related genes and the production of antiviral molecules against external environmental pathogens. In this study, we used chicken tracheal epithelial cells (TECs) in vitro model to investigate the immune response of the chicken respiratory tract against avian respiratory virus infections., Methods: Eighteen-day-old embryonic chicken eggs were used to culture the primary chicken TECs. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC) analysis of epithelial cell-specific gene makers were performed to confirm the characteristics, morphology, and growth pattern of primary cultured chicken TECs. Moreover, to investigate the cellular immune response to AIV infection or polyinosinic-polycytidylic acid (poly [I:C]) treatment, the TECs were infected with the H5N1 virus or poly (I:C). Then, immune responses were validated by RT-qPCR and western blotting., Results: The TECs exhibited polygonal morphology and formed colony-type cell clusters. The RT-qPCR results showed that H5N1 infection induced a significant expression of antiviral genes in TECs. We found that TECs treated with poly (I:C) and exposed to AIV infection-mediated activation of signaling pathways, leading to the production of antiviral molecules (e.g., pro-inflammatory cytokines and chemokines), were damaged due to the loss of junction proteins. We observed the activation of the nuclear factor kappa B and mitogen-activated protein kinase (MAPK) pathways, which are involved in inflammatory response by modulating the release of pro-inflammatory cytokines and chemokines in TECs treated with poly (I:C) and pathway inhibitors. Furthermore, our findings indicated that poly (I:C) treatment compromises the epithelial cell barrier by affecting junction proteins in the cell membrane., Conclusion: Our study highlights the utility of in vitro TEC models for unraveling the mechanisms of viral infection and understanding host immune responses in the chicken respiratory tract.

Early diagnosis of pregnancy is directly related to cost-effective livestock production. We produced a rat monoclonal antibody (mAb) against synthesized porcine early pregnancy factor (pEPF) using conventional hybridoma technology and used it as a tool for the detection of early pregnancy in Duroc sows. The rat pEPF-mAb showed reactivity to uterine tissues of pregnant sows 20 or 30 days post-mating (day 0 defined as the day of mating) and non-pregnant sows (confirmed signs of estrus) in western blotting. Immunohistochemical analysis confirmed that pEPF was located in the stromal and grand epithelial tissues of pregnant sows 20 or 30 days post-mating. In the enzyme-linked immunosorbent assay, pEPF expression in urine and blood showed similar results, with the highest expression observed in pregnant sows 20 days post-mating, whereas there was no significant difference in expression levels between non-pregnant sows and pregnant sows 30 days post-mating. The pEPF-mAb-based pregnancy diagnostic kit can be applied to pig urine samples non-invasively collected at 20 days post-mating with 70 % accuracy. Further improvements to the kit's diagnostic performance may lead to substantial benefits for the swine industry, facilitating more efficient and accurate reproductive management., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the author(s)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Tinnitus is one of the irritating symptoms that should be addressed in adolescents. Since tinnitus affects mental health, it is important to treat it. However, identifying the cause of tinnitus is very challenging and the treatment strategies of tinnitus are controversial. The objective of this study was to identify the prevalence of tinnitus in adolescents and systemic diseases as risk factors of adolescent tinnitus to find evidence for new treatment strategies., Materials and Methods: We extracted the subjects and data using the 5th Korea National Health and Nutrition Examination Survey from 2010 to 2012. One thousand five hundred ninety-three adolescents with bilateral normal tympanic membranes and availability of the results of physical, laboratory and audiological examinations, were selected. We evaluated their systemic diseases based on these results and assessed the association of tinnitus with demographic factors, systemic diseases and hearing levels., Results: The prevalence of tinnitus in Korean adolescents was 21.7%. The hearing level was not associated with tinnitus. Tinnitus was significantly associated with age (p = 0.005), 25(OH)-D level (p = 0.007) and anaemia (p = 0.003). After controlling the other factors, age (p = 0.045), 25(OH)-D level (p = 0.041) and anaemia (p = 0.019) were independently related to tinnitus., Conclusion: Tinnitus in adolescents was significantly associated with age, vitamin D and anaemia. Physicians should consider the higher likelihood of these deficiencies or diseases in adolescent tinnitus patients. Additionally, recognizing these associations may be helpful in developing treatment strategies for adolescent tinnitus., (© 2024 John Wiley & Sons Ltd.)

Intra-neuronal accumulation of hyper-phosphorylated tau as neurofibrillary tangles (NFT) is a hallmark of Alzheimer's disease (AD). To prevent the aggregation of phosphorylated tau in neurons, decreasing the phosphorylated tau protein levels is important. Here, we examined the biological effects of rottlerin, a phytochemical compound extracted from the Kamala tree, Mallotus philippinensis, on phosphorylated tau levels. Notably, rottlerin decreased the levels of intracellular phosphorylated and total tau. A marked increase in the LC3-II, a hallmark of autophagy, was observed in these cells, indicating that rottlerin strongly induced autophagy. Interestingly, rottlerin induced the phosphorylation of Raptor at S792 through the activation of adenosine-monophosphate activated-protein kinase (AMPK), which likely inhibits the mammalian target of rapamycin complex 1 (mTORC1), thus resulting in the activation of transcription factor EB (TFEB), a master regulator of autophagy. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) activity increased in the presence of rottlerin. The decrease of phosphorylated tau levels in the presence of rottlerin was ameliorated by the knockdown of TFEB and partially attenuated by the knockout of the Nrf2 gene. Taken together, rottlerin likely enhances the degradation of phosphorylated tau through autophagy activated by TFEB and Nrf2. Thus, our results suggest that a natural compound rottlerin could be used as a preventive and therapeutic drug for AD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Both vestibular schwannoma (VS) and Meniere's disease (MD) patients underwent hydrops MRI to clarify the relationship between VS and endolymphatic hydrops (EH)., Methods: Eighty patients with VS or MD underwent an inner ear test battery followed by hydrops MRI, and were then divided into 3 groups. Group A comprised 58 MD patients (62 ears) with positive EH but negative VS. Group B included 18 VS patients (18 ears) with negative EH, while Group C consisted of 4 patients (4 ears) who had VS concomitant with EH. Another 14 MD patients who tested negative for EH on hydrops MRI were initially excluded from this cohort, but were later included for comparison., Results: The decreasing prevalence of EH at the cochlea, saccule and utricle in Group A was identified in 59 (95%), 42 (68%) and 40 (65%) ears, respectively, mimicking a declining sequence of abnormality rates running from audiometry (86%), cervical vestibular-evoked myogenic potential (cVEMP) test (55%) to the ocular (oVEMP) test (53%). However, such decreasing trend was not identified in Groups B and C. In Groups C and A combined, 4 (6%) of 62 EH patients had concomitant VS. Conversely, 4 (18%) of 22 VS patients in Groups C and B combined had concurrent EH., Conclusion: A very low (6%) rate of VS in EH patients indicates that VS in EH patients may be coincidental. In contrast, EH was identified in 18% prevalence of VS patients, mirroring the 22% prevalence of cochlear EH demonstrated in VS donors through histopathological studies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Human blood vessel organoids (hBVOs) offer a promising platform for investigating vascular diseases and identifying therapeutic targets. In this study, we focused on in vitro modeling and therapeutic target finding of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of hereditary stroke disorder caused by mutations in the NOTCH3 gene. Despite the identification of these mutations, the underlying pathological mechanism is elusive, and effective therapeutic approaches are lacking. CADASIL primarily affects the blood vessels in the brain, leading to ischemic strokes, migraines, and dementia. By employing CRISPR/Cas9 base-editing technology, we generated human induced pluripotent stem cells (hiPSCs) carrying Notch3 mutations. These mutant hiPSCs were differentiated into hBVOs. The NOTCH3 mutated hBVOs exhibited CADASIL-like pathology, characterized by a reduced vessel diameter and degeneration of mural cells. Furthermore, we observed an accumulation of Notch3 extracellular domain (Notch3ECD), increased apoptosis, and cytoskeletal alterations in the NOTCH3 mutant hBVOs. Notably, treatment with ROCK inhibitors partially restored the disconnection between endothelial cells and mural cells in the mutant hBVOs. These findings shed light on the pathogenesis of CADASIL and highlight the potential of hBVOs for studying and developing therapeutic interventions for this debilitating human vascular disorder., (© 2024. The Author(s).)

Designing current collectors and constructing efficient artificial solid electrolyte interphase (SEI) layers are promising strategies for achieving dendrite-free Li deposition and practical applications in Li metal batteries (LMBs). Electrodeposition is advantageous for large-scale production and allows the direct formation of current collectors without binders, making them immediately usable as electrodes. In this study, an adherent Cu 2 S thin-layer on Cu foil is synthesized through anodic electrodeposition from a Na 2 S solution in a one-step process, followed by the generation of Li 2 S layers as artificial SEI layers via a conversion reaction (3DLi 2 S-Cu foil). The Li 2 S layers move from the 3D Cu surface to the deposited Li surface, facilitating uniform and dense Li deposition. The 3DLi 2 S-Cu foil structure demonstrates stable cycling performance over 350 cycles in an asymmetric cell, with a capacity of 1 mAh cm -2 at 1 mA cm -2 . Moreover, symmetric cells with 5 mAh cm -2 of deposited Li exhibit a stable cycle life for over 1200 h. When paired with commercial LiFePO 4 (LFP), the full cells show substantially enhanced cyclability, regardless of the amount of deposited Li. This study provides new insights into the construction of artificial SEIs for facilitating commercial applications., (© 2024 Wiley‐VCH GmbH.)

Background/aims: Proton pump inhibitors (PPIs) play a crucial role in managing laryngopharyngeal reflux (LPR), but the optimal dosing regimen remains unclear. We aim to compare the effectiveness of the same total PPI dose administered twice daily versus once daily in LPR patients., Methods: We conducted a prospective randomized controlled trial at a tertiary referral hospital, enrolling a total of 132 patients aged 19 to 79 with LPR. These patients were randomly assigned to receive either a 10 mg twice daily (BID) or a 20 mg once daily (QD) dose of ilaprazole for 12 weeks. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were assessed at 8 weeks and 16 weeks. The primary endpoint was the RSI response, defined as a reduction of 50% or more in the total RSI score from baseline. We also analyzed the efficacy of the dosing regimens and the impact of dosing and duration on treatment outcomes., Results: The BID group did not display a higher response rate for RSI than the QD group. The changes in total RSI scores at the 8-week and 16- week visits showed no significant differences between the 2 groups. Total RFS alterations were also comparable between both groups. Each dosing regimen demonstrated significant decreases in RSI and RFS., Conclusions: Both BID and QD PPI dosing regimens improved subjective symptom scores and objective laryngoscopic findings. There was no significant difference in RSI improvement between the 2 dosing regimens, indicating that either dosing regimen could be considered a viable treatment option.

Introduction: End-stage lung disease causes cardiac remodeling and induces electrocardiogram (ECG) changes. On the other way, whether lung transplantation (LTx) in end-stage lung disease patients are associated with ECG change is unknown. The object of this study was to investigate ECG changes before and after LTx in end-stage lung disease patients and whether these changes had clinical significance., Method: This was a single-center retrospective cohort study of 280 end-stage lung disease patients who consecutively underwent LTx at a tertiary referral hospital. ECG findings before LTx and within 1 week and 1, 3, and 6 months after LTx were obtained and analyzed. To find clinical meaning, the ECG at 1 month after LTx was analyzed according to 1-year survival (survivor vs non-survivor groups). Survival data were estimated using the Kaplan-Meier method., Results: Significant differences were observed in the PR interval, QRS duration, QT interval, QTc interval, and heart rate before LTx and 1 month after LTx; the PR interval, QRS duration, QTc interval, and heart rate were decreased. Particularly, the QTc interval was significantly decreased 1 month after LTx, whereas there was no significant change in the QTc interval from 1 to 6 months thereafter. The PR interval, QT interval, QTc interval, and heart rate were significantly different between the survivor and non-survivor groups. The serial changes in QTc interval before LTx and 1 and 3 months after LTx were also significantly different between the survivor and non-survivor groups ( p = 0.040 after adjusting for age and body mass index). Upon dividing the patients based on the range of QTc interval change ≤ -8 ms, >-8-10 ms, >10-35 ms, >35 ms), the survival rate was significantly lower in the group whose QTc interval at 1 month after LTx decreased by > 35 m ( p = 0.019)., Conclusion: LTx in patients with end-stage lung disease may induce ECG changes. Patients whose QTc interval at 1 month after LTx decreased by > 35 ms have a significantly higher 1-year mortality rate. Hence, these ECG changes may have clinical and prognostic significance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Leem, Yu, Sung, Chung, Kim, Woo, Kim, Park, Kim, Yang, Kim, Lee, Kim, Kim, Joung, Park and Lee.)

Extracellular vesicles (EVs) are promising for molecular diagnostics, but current analyses are limited by the rarity and compositional heterogeneity of EV protein expression. Therefore, single EV profiling methods require high sensitivity, multiplexing, and throughput to address these issues. Here a single EV analysis technique that utilizes squeezable methacrylated hyaluronic acid hydrogel microparticles (MHPs) is described as a scaffold to immobilize EVs and perform an integrated rolling circle amplification (RCA) assay for an ultra-sensitive and multiplex analysis of single EV proteins. EVs are prepared into MHPs in a high-throughput manner with droplet microfluidics and optimally labeled with antibody-oligonucleotide conjugates in MHPs without steric limitations. By designing MHPs with high compressibility, single EV protein signals are amplified as RCA products that can be aligned on the same plane by physically squeezing MHPs and visualized with low magnification. This method provides a simple and scalable single EV imaging analysis pipeline for identifying multiplex marker expression patterns from single EVs. For validation, the single EV heterogeneity of highly expressed cancer cell markers is profiled across different cancer cell lines. These findings exemplify squeezable MHPs as a robust platform with high sensitivity, multiplexing, and scalability for resolving single EV heterogeneity and advancing molecular assay technologies., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Airborne particulate matter less than 10 µm in diameter (PM10) is recognized as a significant environmental risk factor for hemorrhagic stroke (HS), as evidenced by epidemiological studies that link PM10 with the heightened cerebrovascular mortality related to HS. Nonetheless, the molecular mechanisms underlying this association remain unknown. Cerebral aneurysm (CA), an etiological factor of HS, is characterized by a bulge resulting from the abnormal loss of the muscular layer of a cerebral artery, comprising brain vascular endothelial cell (BVEC) and vascular smooth muscle cell (VSMC). BVEC exhibiting an inflammatory phenotype is critical for VSMC death within the cerebrovasculature. Here, we elucidate a molecular mechanism by which PM10 augments necroptotic death of VSMC as a consequence of intercellular effects arising from FasL inflammatory cytokine, which is derived from BVEC. Notably, BVEC exposed to PM10 upregulates FasL through ATM-NF-κB signaling, in response to oxidative DNA damage. This genotoxic stress is attributed to pro-oxidant action of aluminum, the prevalent element in PM10. Furthermore, respiratory exposure to PM10 in mice precipitates early onset of CA development through necroptotic VSMC death in cerebral artery, by activating FasL expression in BVEC. In conclusion, this study provides molecular evidence establishing a direct association between PM10 pollution and an elevated risk of stroke, particularly HS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)