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Cardiotoxicity remains a major challenge in drug development, accounting for 45% of medication withdrawals due to cardiac ischemia and arrhythmogenicity. To overcome the limitations of traditional multielectrode array (MEA)-based cardiotoxicity assays, we developed a Nafion-coated NanoMEA platform with decoupled reference electrodes, offering enhanced sensitivity for electrophysiological measurements. The 'Decoupled' configuration significantly reduced polarization resistance (Rp) from 12.77 MΩ to 3.41 MΩ, improving charge transfer efficiency as demonstrated by electrochemical impedance spectroscopy and cyclic voltammetry. Additionally, the limit of detection significantly decreased from 0.175 MΩ (Coupled) to 0.040 MΩ (Decoupled), underscoring the system's enhanced sensitivity. Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we evaluated the effects of three proarrhythmic drugs: Ranolazine, Domperidone, and Sotalol. Under the decoupled condition, the platform exhibited reductions in IC50 values for Domperidone (0.71 μM-0.29 μM), Sotalol (7.61 μM-0.27 μM), and Ranolazine (53.08 μM-5.89 μM), demonstrating significantly improved drug detection sensitivity. Longitudinal analysis revealed significant alterations in key electrophysiological parameters, including beating period (BP), field potential duration (FPD), spike slope, and amplitude, which were consistent with the known pharmacological actions of these drugs. Further validation through action potential (AP) waveform analysis showed enhanced repolarization dynamics, confirming the platform's predictive capabilities. Our findings highlight the critical role of electrochemical topology in optimizing MEA performance. The NanoMEA system, featuring decoupled Nafion-coated electrodes, represents a robust and sensitive platform for cardiotoxicity screening, setting a new standard for preclinical drug safety assessment and advancing bioelectronic device design for cardiac research., Competing Interests: Declaration of competing interest Deok-Ho Kim is a co-founder and scientific advisory board member at Curi Bio, Inc. Todd. J. Herron is a consultant and scientific advisory board member at StemBioSys, Inc., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Spermatozoa must undergo a complex maturation process within the female genital tract known as capacitation. This process entails the phosphorylation or dephosphorylation of various proteins, and multiple signaling pathways are recognized to play a role. The present study aims to identify alterations in the expression of proteins related to the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway and assess sperm functions during capacitation. Mouse spermatozoa were incubated in a medium supplemented with bovine serum albumin to induce capacitation. Subsequently, we evaluated sperm motility, cell viability, capacitation status, and acrosome reaction. Consequently, we observed a significant increase in several kinematic parameters. Additionally, the capacitation status and acrosome reaction exhibited a time-dependent manner. Furthermore, we confirmed a significant increase in the phosphorylation of PI3K, PDK1, and p-AKT (Thr308), along with activation of PKA and tyrosine phosphorylation. These alterations in protein expression were found to correlate with capacitation status, acrosome reaction, and various kinematic parameters. Therefore, our findings show that the phosphorylation of PKA and PI3K/AKT pathway-related proteins during capacitation may plays a crucial role in regulating sperm function. These findings contribute to a better understanding of the molecular mechanisms and interactions of the PI3K/AKT signaling pathway in the capacitation process., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Clinically heterogeneous spectrum and molecular phenotypes of inflammatory bowel disease (IBD) remain to be comprehensively elucidated. This exploratory multi-omics study investigated the serum molecular profiles of Crohn's disease (CD) and ulcerative colitis (UC), in association with elevated fecal calprotectin and disease activity states. The serum proteome, metabolome, and lipidome of 75 treated IBD patients were profiled. Single- and multi-omic data analysis was performed to determine differential analytes and integrative biosignatures for biological interpretations. We found that chronic inflammation, phosphatidylcholines and bile acid homeostasis disturbances underlined the differences between CD and UC. Besides, elevated calprotectin was associated with higher levels of inflammatory proteins and sphingomyelins (SM) and lower levels of bile acids, amino acids, and triacylglycerols (TG). Relative to the remission disease state, the active form was characterized by decreased abundances of SMs and increased abundances of inflammatory proteins and TGs. We also observed that molecular changes upon treatment escalation were putatively related to altered levels of inflammatory response proteins, amino acids, and TGs. ISM1, ANGPTL4, chenodeoxycholate, Cer(18:1;2 O/24:1), and TG were identified as candidates subject to further investigation. Altogether, our study revealed that disturbances in immune response, bile acid homeostasis, amino acids, and lipids potentially underlie the clinically heterogeneous spectrum of IBD., 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.)

Ethnopharmacological Relevance: Cheonwangbosim-dan (CWBSD) as a traditional herbal medicine prescription has been used for cognitive dysfunction in terms of heart blood deficiency, however, there were few researches for cognitive dysfunction and its mode of action., Aim of the Study: This study was aimed to examine the effects of CWBSD on hypocholinergic-induced memory impaired mice and unveil its mechanism of action on cognitive function., Materials and Methods: The standardized CWBSD was used in the present study. Several behavioral tests, including Y-maze task, the Morris water maze task (MWM), novel object recognition test (NORT) and passive avoidance test (PAT), were employed with administration of CWBSD (150, 500 or 1500 mg/kg) in scopolamine-treated mice. After behavioral tests, the mice were sacrificed and the Western blot analysis and electrophysiological analysis were conducted to investigate the mechanism of CWBSD on ameliorating cognitive function., Results: The administration of CWBSD improved cognitive functions measured by the Y-maze task, MWM, NORT and PAT in scopolamine-induced cognitive impaired mice. This memory improvement effect was associated with the activation of protein kinase C zeta (PKCζ)/calcium-calmodulin-dependent protein kinase Ⅱ (CaMKⅡ)-extracellular signal-regulated kinase (ERK)-cAMP response element-binding protein (CREB)-brain-derived neurotropic factor (BDNF) pathway via N-methyl-D-aspartate receptor subtype 2B (NR2B), and the activation of this pathway increased long-term potentiation in the brain of mice., Conclusion: The administration of CWBSD could ameliorate spatial memory, recognition memory and long-term memory, and such ameliorating activities would be derived from the activation of NMDA receptor-associated pathway with increase of LTP in the brain. These results suggests that CWBSD would be a candidate for a new dementia treatment., 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 © 2025 Elsevier B.V. All rights reserved.)

Amphiphilic polymers form molecular monolayers at aqueous interfaces, stabilizing the discontinuity between two phases and acting as macromolecular surfactants. These polymer monolayers exhibit superior mechanical stability compared to traditional surfactants, making them useful in various applications, including structured liquids, drug delivery, lung surfactant therapy, protein encapsulation, extraction separation, and templates for synthesis. Despite their significance, the molecular-level understanding of the structure of polymer monolayers and their relationship to their physical properties remain obscure. Thus, understanding their structural behavior is crucial for controlling interfaces and tailoring system properties. At the air-water interface, polymer chains adopt two-dimensional (2D) Gaussian coil conformations, scalable by 2D-conformational polymer scaling theory and a few parameters such as temperature, surface concentration, and surface pressure (Π). Beyond a critical Π, polymer chains transition to 3D conformations, a critical but understudied phenomenon. This study investigated regioisomeric effects on these stereoscopic transitions using the poly(vinylpyridine) (PVP) polymer family. Despite sharing solubility parameters, steric differences in nitrogen positioning within the pyridine ring significantly influence solvation and stereoscopic conformational transitions. Alloying these regioisomeric polymers further enables fine-tuning of monolayer transitions and mechanical properties, providing deeper insights into the design and control of interfacial polymer systems.

Background: Livestock, particularly cattle, are crucial for biotechnology fields, such as genetic breeding, infectious diseases, bioreactors, and specific disease models. However, genetic engineering in cattle has lagged due to long gestation periods, single embryo pregnancies, and high rearing costs. Additionally, the slow validation of germline transmission and the absence of germline-competent embryonic stem cells hinder progress. With the development of genome editing technologies like ZFN, TALEN, and CRISPR-Cas9, recent advancements have shown that Cas9-expressing pigs and chickens have been successfully produced. We hypothesize that generating CRISPR/Cas9-expressing cattle and their resources will provide a powerful resource for bovine genome editing, advancing our understanding of bovine genetics and disease resistance., Results: In this study, two types of Cas9-expressing cattle were successfully produced: Cas9-RFP-fatty acid dehydrogenase I (FatI), Cas9-GFP-sgRNA for the prion protein (sgPRNP). Somatic cells from these cattle were induced to mutate multiple target genes when single-guide RNAs (sgRNAs) were transfected into the somatic cells. Additionally, semen from Cas9 expressing male cattle was frozen and used to fertilize wild-type oocytes, successfully transmitting the transgene (Cas9, reporter genes, FatI), and sgPRNP) to the next generation. Furthermore, the gene editing capabilities of Cas9, including knockout and high-efficiency knock-in, were confirmed in embryos derived from F1 semen through in vitro production., Conclusion: These data demonstrate, for the first time, that Cas9-expressing cattle were successfully born, and this transgene was transmitted to the next-generation calves (F1) and F2 embryos. In addition, somatic and germ cells derived from F0 and F1generations were used to evaluate the potential for gene editing (knockout and knock-in) in multiple genes. PRNP-mutated F1 cattle are currently being raised as a resistance model for bovine spongiform encephalopathy. These transgenic bovine models and their derivatives will serve as a valuable resource for both in vitro and in vivo genome editing, advancing our genetic understanding of bovine genomics and diseases., Competing Interests: Declarations. Ethics approval and consent to participate: This study was carried out in accordance with the guidelines for Institutional Animal Care and Use Committee of Seoul National University (IACUC # SNU-180403–1-2). Additionally, approval for the animal experiments was obtained from the Institutional Animal Care and Use Committee (IACUC #106) of the Gyeongsangbuk-do Livestock Research Institute, and all relevant national laws and policies regarding animal care and use were followed throughout. All procedures, including embryo transfer for animal production, animal care and rearing, genotyping through tissue sampling, blood collection, and sperm collection, were conducted with approval from the IACUC #106. The heifers were housed in a stanchion barn with adequate space and were fed according to the Korean feeding standard program. Rice straw, mineral blocks, and water were provided without restriction. All animal procedures, including blood collection and embryo transfer, were performed by a veterinarian. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Reducing the dimensionality in layered materials typically yields properties distinct from bulk properties. In systems with broken inversion symmetry, strong spin-orbit coupling induces relativistic electron interactions such as the Rashba-Edelstein effect (REE). Initially proposed in two-dimensional magnets, applying the REE theory to real three-dimensional systems poses challenges, necessitating experimental validation. In this study, we empirically ascertained an REE-induced intrinsic and extrinsic fundamental unity between two distinct and dissimilar phenomena, namely, charge-to-spin conversion and chiral-spin alignment. Atomically thin quasi-two-dimensional ferromagnetic materials were used to observe such universal unity by examining the thickness dependences of the Heisenberg exchange interaction, the Dzyaloshinskii-Moriya interaction, and spin-orbit torques. The results revealed a correlation that is highly consistent with the underlying theoretical REE model. These findings not only highlight the role of REE in fundamental physics but also illuminate the intricate impact of interfacial effects on magnetic materials.

Background: The clinical analgesic efficacy of iliopsoas plane block remains a subject of discussion. This study aimed to assess the analgesic efficacy of iliopsoas plane block under general anesthesia using multimodal analgesia., Methods: Fifty-six adult patients who underwent elective primary hip arthroplasty were enrolled. Patients were randomized to receive either a single-shot iliopsoas plane block (10 mL 0.75% ropivacaine with 1:200 000 epinephrine) or a sham block (10 mL normal saline). All patients received general anesthesia, multimodal analgesia (preoperative buprenorphine patch, 5 µg/h), intraoperative intravenous dexamethasone (8 mg) and nefopam (20 mg), and round-the-clock acetaminophen and celecoxib. The primary outcome was the numeric rating scale pain score at rest 6 hour after surgery., Results: Iliopsoas plane block did not have a notable advantage over the sham block in terms of pain relief at rest, as assessed by the numeric rating scale score, 6 hour after total hip arthroplasty (iliopsoas plane block: median, 4.0; IQR, 2.0-5.8; sham: median, 5.5; IQR, 2.3-6.8; median difference, -1.0; 95% CI -2.0 to 0.0; p≥0.999). Linear mixed model analysis showed no differences in pain scores, opioid consumption, quadriceps strength, or quality of recovery between the groups., Conclusions: Iliopsoas plane block did not improve postoperative analgesia following total hip arthroplasty under general anesthesia with a multimodal analgesic regimen. The blockade of sensory femoral branches supplying the anterior hip capsule using iliopsoas plane block may not yield additional benefits concerning patient outcomes in the aforementioned clinical context., Trial Registration Number: NCT05212038, https://clinicaltrials.gov/ct2/show/NCT05212038., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant EGFR-induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis., Materials and Methods: Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point., Results: We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as SCFA-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage., Conclusion: Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

The development of high-performance synaptic devices and organic floating gate memory is the most important innovation for electronics technology. Such devices possess huge potential in revolutionizing the storage and processing performance of data in applications that exhibit low power consumption, high areal density, and flexible substrate compatibility. However, achieving such a performance requires an effective charge trapping medium that can efficiently capture and retain charge carriers, essential for storing and processing information. There have been several candidates proposed for a potential charge trapping layer. In our analysis, we made use of a simple and cost-effective, solution-processed sol-gel AlO x as a charge trapping layer. We studied the properties of sol-gel AlO x thin films before and after annealing at different temperatures (pristine, 100, 200, 300, 400, and 500 °C) using X-ray diffraction, atomic force microscopy, and X-ray photoelectron spectroscopy. As the annealing temperature rises, it becomes apparent that the AlO x thin film produced via sol-gel undergoes the decomposition of organic residues and nitrate groups along with the transformation of aluminum hydroxide into aluminum oxide. At low temperatures, the organic floating gate device exhibited a wider hysteresis window (Δ V th ), which becomes negligible at high temperatures. This implies that the hysteresis window is affected by the presence of hydroxyl groups. Also, the investigation was done to enhance the device ability to simulate synaptic behavior by using a solution-processed sol-gel AlO x -based floating gate transistor. The channel conductance of a floating gate transistor is stored in synaptic weight, which is modulated by the applied positive and negative electrical pulse stimuli and annealing temperature of the sol-gel AlO x thin-film layer. The key properties of long-term potentiation and long-term depression characteristics such as dynamic range (DR) and nonlinearity (NL), which have a significant impact on the memory, adaptive learning, and decision-making ability of synaptic devices, were studied. The device subjected to annealing temperatures exceeding 200 °C exhibited favorable NL and DR at V G = ±20 V, compared to those annealed at other temperatures, in response to variations in the pulse width. Correspondingly, the devices that were annealed at 200 °C achieved the highest accuracy of ∼93.60% in the MNIST (Modified National Institute of Standards and Technology) deep neural network simulation at a pulse width of 200 ms, surpassing all other annealing conditions. These results underscore the role of the annealing temperature in optimizing device performance, particularly in fundamental aspects of synaptic behavior NL and the DR. This advancement paves the way for more efficient, flexible, and dense electronic devices.

Targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is promising in treating cancer in humans and offers potential for veterinary applications. However, no PD-L1 antibodies have been approved specifically for treating canine cancer. We aimed to develop PD-L1-specific antibodies using phage display technology for treating canine cancer. A synthetic antibody library was screened, and 18 high-affinity single-chain variable fragment clones were subsequently converted to the IgG format for enhancing binding affinity and functional stability. The clone #15 exhibited the highest binding affinity and most pronounced antitumor effects. The PD-1/PD-L1 interaction was inhibited by antibody #15. The binding and thermal stabilities of the antibodies were validated by flow cytometry and thermal stability assays, respectively. In NOG mice xenografted with canine osteosarcoma cells and treated with canine peripheral blood mononuclear cells and antibody #15, the tumor size and weight were reduced. Antibody #15 significantly increased apoptosis of tumor cells and lymphocyte populations. Therefore, anti-PD-L1 antibodies, particularly antibody #15, have substantial potential as novel immunotherapeutic agents against canine osteosarcoma. This study represents a significant advancement in veterinary oncology, with the potential of improving treatment outcomes for canine cancers and providing insights into similar strategies in human cancer therapy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Inflammation is essential for pathogen eradication and tissue repair; However, chronic inflammation can bring on multi-organ dysfunction due to an overproduction of reactive oxygen species (ROS). Among various anti-inflammatory agents, polyphenol-based nanotherapeutics offer potential advantages, including enhanced stability, targeted delivery, multiple therapeutic functions, and personalized therapy tailored to the severity. Despite these advantages, the development of biocompatible nanomedicines capable of selective accumulation in inflamed tissues and efficient inhibition of ROS-induced inflammatory signaling pathways remains a considerable challenge. In this study, a novel anti-inflammatory nanotherapeutic is engineered through the temperature-dependent condensation of polyphenolic catechin facilitated by hydrothermal reactions. The resulting catechin-condensed nanotherapeutic (CCN150), synthesized at a relatively low temperature, retains physicochemical and functional properties akin to its precursor, catechin, but with a marked enhancement in water solubility. CCN150 protects cells from oxidative stress by eliminating intracellular ROS and augmenting antioxidant enzymes. In vivo studies reveal that intravenously administered CCN150 predominantly accumulates in inflamed tissues, with minimal distribution to healthy regions. Furthermore, CCN150 effectively reduces systemic inflammation in mouse models by disrupting the cycles of ROS instigated by a pro-inflammatory oxidative milieu. Exhibiting negligible toxicity, CCN150 holds substantial promise for extensive therapeutic applications in the treatment of various ROS-mediated inflammatory diseases., (© 2025 Wiley‐VCH GmbH.)

Background: This study aims to evaluate temporal trends of advanced treatments and related clinical outcomes of ischemic stroke through a decade-long trend analysis, using data from a comprehensive, national, multicenter registry. We also seek to identify areas in need of improvement., Methods and Results: This analysis involved patients with ischemic stroke or transient ischemic attack registered prospectively in the CRCS-K-NIH (Clinical Research Center for Stroke in Korea-National Institute of Health) registry between 2011 and 2020. We examined temporal trends in risk factors, pathogenetic subtypes, acute management strategies, and outcomes for up to 1 year following a stroke. Generalized linear mixed models were used to account for center clustering. The average age of 77 662 patients increased 2.2 years in men and 2.4 years in women over the 10-year follow-up. Notably, in-hospital neurological deterioration, 3-month and 1-year mortality rate, and cumulative incidence of recurrent stroke within 1-year decreased over time after adjustments for age, sex, and initial stroke severity ( P <0.01). However, functional outcomes at 3 months and 1 year remained unchanged. Endovascular thrombectomy increased from 5.4% in 2011 to 10.6% in 2020. Use of anticoagulants for atrial fibrillation, dual antiplatelet therapy, statins, and stroke unit care also increased. Contrarily, the rate of intravenous thrombolysis showed a slight decline., Conclusions: This study points to a reduction in death and risk of recurrent stroke over the past decade, paralleling enhancement in acute and preventive stroke management. Nevertheless, the decline in the use of intravenous thrombolysis and the lack of improvement in functional outcomes following stroke are concerning trends that warrant thorough investigation.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer associated with a poor prognosis and decreased patient survival. It is intimately linked to AXL overexpression and AXL hyperactivation. Here, we explored the therapeutic potential of AX-0085, a small molecule AXL inhibitor. While AX-0085 was previously characterized in the context of lung adenocarcinoma, this study demonstrates its application in triple-negative breast cancer (TNBC) models. AX-0085 exhibited high binding affinity to the ATP binding site located beneath the conserved glycine-rich loop (P-loop) that links the β1 and β2 strands of the AXL kinase domain. Furthermore, it was demonstrated that the benzamide group of AX-0085 and LyS567's Nζ atom could generate a hydrogen bond. AX-0085 efficiently suppressed the AXL/GAS6 signaling pathway activation in TNBC cells in vitro, which in turn prevented AXL/GAS6 signaling-dependent pro-cancerous behavior like cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT). In TNBC, an AX-0085-induced cell cycle arrest that took place during the G1 phase reduced the expression of CYCLIN E and CDK2. Additionally, AX-0085 facilitated apoptotic cell death in TNBC. Treatment of AX-0085 on in vivo mouse xenografts transplanted with 4 T1 cells showed a significant tumor reduction. Thus, our findings demonstrate that AX-0085 has an effective therapeutic role in TNBC by inhibiting AXL activation., Competing Interests: Declaration of competing interest Two of the co-authors (Young Jun Park and Myeong Jun Choi) have financial interests in the Axceso Biopharma Co., Ltd. which has product and method-of-use patents pending on AX-0085. Invention title of patent: pytimido pyrimidinone compounds and pharmaceutical composition containing same, Patent application number: PCT/KR2021/012616, Control number: SOP51487/PCT, Other authors have no conflict., (Copyright © 2025. Published by Elsevier B.V.)

Background: Pterygium, abnormal growths of conjunctival tissue onto the cornea, are common ocular surface conditions with a high risk of recurrence after surgery and potential ophthalmic complications. The exact cause of pterygium remains unclear, and the triggers are still unknown. This study aims to investigate the relationship between pterygium and epigenetics to uncover the cause of pterygium and identify biomarkers for its diagnosis., Methods: We performed a ChIP-seq assay to compare genome-wide histone modification levels between normal conjunctiva and stage 3 pterygium samples., Results: In this study, we investigate the epigenetic profiles of patients with pterygium, focusing on histone H3 lysine 4 (H3K4) and lysine 9 (H3K9) trimethylation (me3). While H3K4me3 levels showed no significant genome-wide change, they were significantly altered in genes related to development and ocular diseases. Conversely, H3K9me3 levels were markedly elevated genome-wide, particularly at the promoters of 82 genes involved in developmental pathways. Furthermore, we identify six genes, ANK2, AOAH, CBLN2, CDH8, CNTNAP4, and DPP6, with decreased gene expression correlated with substantially increased H3K9me3, suggesting their potential as biomarkers for pterygium., Conclusion: This study represents the first report linking histone modification to pterygium progression, providing valuable insights into therapeutic strategies and potential drug targets., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consents were obtained from all participants. The study adhered to the principles outlined in the Declaration of Helsinki and received approval from the Institutional Review Boards of Korea University Anam Hospital (IRB No. 2022AN0503). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The efficacy of radiotherapy is often limited by insufficient radiosensitization and tumor radioresistance. This study reports a dual-functional hafnium oxide nanoplatform that combines high-Z radiosensitization with Bcl-2 gene silencing for enhanced cancer radiotherapy. The nanoplatform is developed by surface modification of hafnium oxide nanoparticles with polyethyleneimine, enabling efficient siRNA delivery while maintaining inherent high-Z radiosensitizing properties. Comprehensive physicochemical characterization confirmed the successful surface modification and stable siRNA complexation. Upon radiation exposure, the nanoplatform enhanced reactive oxygen species generation and DNA damage while simultaneously delivering Bcl-2 siRNA to suppress radioresistance mechanisms. In vitro studies revealed significant enhancement of radiation-induced cell death through synergistic effects of high-Z radiosensitization and Bcl-2 silencing, evidenced by increased γ-H2AX expression and apoptotic cell population. In a murine colon cancer model, the nanoplatform achieved remarkable tumor growth inhibition (80%) when combined with radiotherapy while exhibiting favorable biocompatibility in major organs. Mechanistic studies confirmed effective Bcl-2 downregulation and enhanced DNA damage in tumor tissues, validating this dual-functional therapeutic approach. This study presents a promising strategy for improving radiotherapy outcomes through the simultaneous enhancement of radiosensitization and suppression of radioresistance, potentially advancing the field of cancer radiotherapy., (© 2025 Wiley‐VCH GmbH.)

The exceptional theoretical capacity of potassium metal anodes (687 mA h g -1 ), along with their low electrochemical potential, makes potassium metal batteries (PMBs) highly attractive for achieving high energy density. This review first provides an overview of potassium metal anodes, including their origin, current development status, and distinctive advantages compared to other metal anodes. Then, it discusses the composition and characteristics of emerging breakthrough PMBs, such as K-S, K-O 2 , K-CO 2 batteries, and anode-free metal batteries. Subsequently, we delve into the pivotal challenges and theoretical research pertaining to PMBs, such as potassium metal nucleation/stripping, dendritic growth in PMBs, and unstable interfaces. Furthermore, we comprehensively examine the latest strategies in electrode design (including alloy, host, and current collector design), interface engineering (such as artificial solid electrolyte interphase layers, barrier layer design, and separator modification), and electrolyte optimization concerning nucleation, cycling stability, coulombic efficiency, and the development of PMBs. Finally, we introduce key characterization techniques, including in situ liquid phase secondary ion mass spectrometry, titration gas chromatography, neutron-based characterization, and computational simulation. This review will propel advancements in electrodes, separators, and electrolytes for innovative PMBs and other similar alkali metal batteries.

Purpose: To evaluate the feasibility of a three-point flanged optic piercing intrascleral fixation technique for replacing a dislocated multifocal intraocular lens (IOL)., Design: Retrospective cross-sectional study., Methods: In total, 13 eyes from 13 patients with a dislocated single-piece C-loop or double C-loop diffractive multifocal IOL were enrolled to undergo dislocated multifocal IOL replacement through three-point flanged optic piercing 120 degrees apart intrascleral fixation using 7-0 polypropylene sutures at 2.5 mm posterior to the limbus. Preoperative and postoperative uncorrected distance visual acuity (UDVA), postoperative uncorrected intermediate visual acuity (UIVA) at 66 cm, uncorrected near visual acuity (UNVA) at 40 cm, residual refractive errors, and the amount of IOL decentration were evaluated., Results: There were six multifocal IOLs and seven multifocal toric IOLs. There was a notable improvement in visual acuity, with the mean UDVA improving from 0.79 ± 0.72 logMAR preoperatively to 0.06 ± 0.08 logMAR postoperatively (P = 0.004). The mean postoperative UIVA and UNVA were 0.04 ± 0.05 and 0.10 ± 0.12 logMAR, respectively. The mean residual refractive sphere, cylinder, and spherical equivalent were -0.04 ± 0.48 D, -0.29 ± 0.25 CD, and -0.18 ± 0.47 D, respectively. The mean residual cylinder was -0.25 ± 0.25 CD in eyes with multifocal toric IOL fixation. The mean amount of IOL decentration was 0.22 ± 0.05 mm., Conclusion: The three-point flanged optic piercing intrascleral fixation technique for dislocated multifocal IOLs could provide good distance, intermediate, and near vision alongside excellent IOL centration., (Copyright © 2025 Indian Journal of Ophthalmology.)

Anaerobic bacteriolytic cancer therapy, whether delivered locally or systemically, frequently encounters challenges related to limited colonization within hypoxic pockets of central tumors and activation of innate immunity. Herein we have developed trans-arterial bacteria embolization therapy using bacterial embolic microspheres. C. novyi-NT spores loaded calcium alginate embolic microspheres demonstrated C. novyi-NT metabolites-mediated microsphere degradation, releasing vegetative C. novyi-NT bacterial in hypoxic condition. Transcatheter directed bacterial microsphere embolization therapy occludes tumor feeding vessels with infused bacterial embolic microspheres and enhances tumoral hypoxia. Notably, anaerobic bacterial metabolism responsive microsphere-bacterial embolization therapy achieved a complete tumor response with enhanced tumor-specific bacterial delivery and colonization, resulting in cancer cell killing across the entire tumor. In vivo tumor response and immunological profiling revealed that bacterial embolization uniquely enhances anti-cancer response, effectively engaging direct anaerobic bacterial oncolysis and adaptive and innate immune responses in a cooperative manner., 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 Ltd. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Conductive hydrogels feature reasonable electrical performance as well as tissue-like mechanical softness, thus positioning them as promising material candidates for soft bio-integrated electronics. Despite recent advances in materials and their processing technologies, however, facile patterning and monolithic integration of functional hydrogels (e.g., conductive, low-impedance, adhesive, and insulative hydrogels) for all-hydrogel-based soft bioelectronics still poses significant challenges. Here, we report material design, fabrication, and integration strategies for an electronic-skin (e-skin) patch based on functional hydrogels. The e-skin patch was fabricated by using photolithography-compatible functional hydrogels, such as poly(2-hydroxyethyl acrylate) (PHEA) hydrogel (substrate), Ag flake hydrogel (interconnection; conductivity: ∼571.43 S/cm), poly(3,4-ethylenedioxythiophene:polystyrene) (PEDOT:PSS) hydrogel (working electrode; impedance: ∼69.84 Ω @ 1 Hz), polydopamine (PDA) hydrogel (tissue adhesive; shear strength: ∼725.1 kPa), and poly(vinyl alcohol) (PVA) hydrogel (encapsulation). The properties of these functional hydrogels closely resemble those of human tissues in terms of water content and Young's modulus, enabling stable tissue-device interfacing in dynamically changing physiological environments. We demonstrated the efficacy of the e-skin patch through its application to accelerated healing and monitoring of skin wounds in mouse models - efficient fibroblast migration, proliferation, and differentiation promoted by electric field (EF) stimulation and iontophoretic drug delivery, and monitoring of the accelerated healing process through impedance mapping. The all-hydrogel-based e-skin patch is expected to create new opportunities for various clinically-relevant tissue interfacing applications., 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 Ltd. All rights reserved.)

Background: Advanced gastric cancer (AGC) is a leading cause of cancer-related deaths worldwide, with its treatment complicated by challenges such as high recurrence rates, severe side effects, and limited effectiveness of current therapies. Herbal medicine (HM) has emerged as an adjunct to palliative chemotherapy (PC), potentially improving tumor response and reducing side effects. This study conducted a meta-analysis to evaluate the effectiveness and safety of HM in palliative therapy for inoperable stage Ⅲ and Ⅳ AGC patients., Methods: Databases were searched until August 2023, encompassing 10 electronic databases, including PubMed, Embase, Cochrane Library, CNKI, and ScienceON. The inclusion criteria focused on randomized controlled trials (RCTs) combining herbal medicine with palliative therapy for patients with AGC. Primary outcomes assessed were tumor response rates, overall survival, adverse drug reactions (ADRs), and patients' quality of life (QoL)., Results: In our analysis of 101 RCTs comparing PC alone to PC combined with HM, the meta-analysis demonstrated statistically significant improvements in overall response rate (ORR), disease control rate (DCR), survival rates, as well as a reduction in adverse drug reactions (ADRs) and an enhancement in quality of life (QoL) for patients receiving HM in combination with PC ( p < 0.00001, I² = 0 %)., Conclusion: The combination of HM with PC significantly enhances tumor response and survival rates while reducing overall adverse drug reactions (ADRs) and improving quality of life (QoL) in patients with stage Ⅲ and Ⅳ AGC. HMs not only improve the efficacy of PC but also help alleviate side effects, including myelosuppression, digestive symptoms, nausea, vomiting, diarrhea, liver and renal injuries, and neurotoxicity.Protocol registration: PROSPERO, CRD 42022354133., (© 2025 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Dermal fillers comprising injectable hyaluronic acid (HA) are widely used for soft tissue augmentation, often using crosslinking agents such as 1,4-butanediol diglycidyl ether (BDDE) or poly (ethylene glycol) diglycidyl ether (PEGDE). Here, we assessed the physical properties, toxicity, and inflammatory reactions of HA fillers crosslinked with either BDDE (HA-BDDE filler) or PEGDE (HA-PEGDE filler) in in vitro and in vivo investigations. The HA-PEGDE filler exhibited higher G', tan δ, G*, and complex viscosity values compared to the HA-BDDE filler, while maintaining similar cohesivity. The filler extracts were used to evaluate cytotoxicity. HA-PEGDE filler extracts exhibited reduced cytotoxicity, oxidative stress, and inflammation in human keratinocytes (HaCaTs) and fibroblasts (HDFs) than that of HA-BDDE filler extracts. In animal studies, SKH1-hairless mice were injected subcutaneously with varying volumes of fillers and euthanized at 1- and 4-weeks post-injection. Compared with the HA-BDDE filler, the HA-PEGDE filler displayed favorable biocompatibility, decreased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression and reduced inflammatory cell infiltration. Our results demonstrate that the HA-PEGDE filler has comparable rheological properties and lower toxicity than the HA-BDDE filler, suggesting its suitability as an alternative in applications where minimal inflammatory response is crucial., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objective: To investigate the safety and effectiveness of dose-related ketorolac administration in children who underwent tonsillectomy., Data Sources: Data sourced from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases, encompassing literature from their inception until June 2024., Review Methods: The perioperative administration of ketorolac in comparison with a control group was included in this analysis. The outcomes assessed were postoperative pain levels; utilization patterns of analgesic medication in terms of quantity and frequency; and the incidence rates of postoperative nausea, vomiting, and bleeding., Results: Eighteen studies with 11,729 patients that investigated. The ketorolac treatment group with postoperative bleeding had a higher incidence of primary bleeding (significant bleeding and operative bleeding control) compared to the control group. However, ketorolac treatment did not affect the risk of secondary bleeding. Subgroup analysis showed that 0.9 to 1 mg/kg of ketorolac significantly increases primary operative control (odds ratio [OR] = 4.0700 [1.6352; 10.1302]; I 2  = 0.0%) and primary significant bleeding (OR = 2.3200 [1.1322; 4.7538]; I 2  = 0.0%). On the other hand, 0.5 mg/kg ketorolac did not show any influence on primary operative control. The administration of ketorolac (both 0.9-1 and 0.5 mg/kg) led to a significant decrease in postoperative pain (2-24 hours), nausea, and vomiting compared to the control group., Conclusion: Low-dose (0.5 mg/kg) ketorolac administration to children could significantly reduce the risk of primary significant bleeding and surgical hemostasis compared to high-dose administration (0.9-1.0 mg/kg). In addition, low-dose ketorolac administration could provide sufficient pain control and reduce postoperative nausea and vomiting., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background and Aims: Self-expandable metal stents (SEMS) are effective in alleviating malignant colorectal obstruction. However, bowel perforation following SEMS placement remains a significant concern, as it can adversely affect oncological outcomes. This study aimed to evaluate the recurrence and overall survival rates associated with SEMS-related bowel perforations., Methods: This multicenter, retrospective analysis included patients with obstructive colorectal cancer who underwent SEMS placement as a bridge to surgery. The data collection period spanned from January 2008 to May 2019, with patient matching in a 1:5 ratio based on age, sex, tumor location, pathological stage, and achievement of curative resection., Results: Among the 412 patients who received SEMS placement, 25 (6.1%) patients experienced SEMS-related perforations (perforation group), with 21 instances classified as overt and four as silent perforations. Compared with 125 matched controls (non-perforation group), the perforation group showed elevated rates of emergent surgery, open surgery, and stoma formation, as well as a reduced interval from SEMS placement to surgery. The 5-year recurrence rate was notably higher in the perforation group than in the no-perforation group (47.4% vs. 21.5%, p < 0.001), whereas the 5-year survival rate was not significantly different between groups (63.8% vs. 80.0%, p = 0.330)., Conclusions: SEMS-related perforation led to less favorable surgical outcomes and a higher rate of recurrence, although no notable impact on overall survival was observed. Considering the risk of perforation, these findings support the cautious use of SEMS as a bridge to surgery., Competing Interests: Declarations. Disclosures: Han Hee Lee, Dong Hyun Kim, Hyun Lim, Jung-Wook Kim, Yunho Jung, Hyun-Soo Kim, Hyung-Hoon Oh, Jin Won Kim, Kwang Bum Cho, Young-Eun Joo, and Bo-In Lee have no conflicts of interest or financial ties to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Cilostazol improves ischemic symptoms and prevents recurrence following cerebral infarction, and rosuvastatin reduces cholesterol levels. However, no reports exist on the pharmacokinetic interactions between these two drugs in healthy adults. This study evaluated the pharmacokinetic (PK) interactions and safety of cilostazol and rosuvastatin when co-administered to healthy male participants., Methods: A randomized, open-label, multiple-dosing, two-arm, two-period study was conducted. Arm A had 30 participants receiving 200 mg cilostazol daily and arm B had 27 participants receiving 20 mg rosuvastatin daily for 7 days. In period 2, both arms received a combination of 200 mg cilostazol and 20 mg rosuvastatin daily for 7 days following a 7-day washout period. Plasma concentrations of cilostazol, its metabolites, and rosuvastatin were quantified using liquid chromatography-tandem mass spectrometry., Results: Fifty-seven participants were randomized, and 44 completed the study. The geometric mean ratio (GMR) and 90% confidence intervals (CI) for maximum plasma concentration at steady state (C max,ss ) and area under the plasma concentration-time curve during the dosing interval at steady state (AUC tau,ss ) indicated no significant interaction between cilostazol and rosuvastatin. Safety assessments showed comparable profiles to individual drug administration, with no significant adverse events., Conclusion: The repeated co-administration of cilostazol and rosuvastatin in healthy male participants resulted in minor PK interactions and exhibited a safety and tolerability profile similar to those of the individual drugs. This suggested that the combined regimen is well tolerated and does not necessitate dose adjustments., Registration: ClinicalTrials.Gov identifier no. NCT06568133., Competing Interests: Declarations. Funding: This study was funded by Korea United Pharmaceutical Corporation, Seoul, Republic of Korea. Conflict of interest: Jung WT, Nam K-Y, and Roh JS are employees of Korea United Pharmaceutical Corporation, Seoul, Republic of Korea. Lee HJ, Moon J, and Kim KY are employees of Caleb Multilab Inc., Seoul, Republic of Korea. The other authors declare no conflicts of interest. Authors’ contributions: Conceptualization: Sunwoo J; data curation: Sunwoo J; formal analysis: Kim DH, Sunwoo J; investigation: Sunwoo J; methodology: Hong JH, Jung J-G; resources: Jung WT, Nam K-Y, Roh JS, Lee HJ, Moon J, Kim KY; supervision: Sunwoo J, Jung J-G; writing—original draft: Kim DH; writing—review and editing: Sunwoo J. Data availability statement: The data that support the findings of this study are available from Korea United Pharmaceutical Corporation, Seoul, Republic of Korea, but restrictions apply to the availability of these data, which were used under license for the current study and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of Korea United Pharmaceutical Corporation, Seoul, Republic of Korea. Ethics approval: The trial protocol (KUP-UI022-101) was approved by the Ministry of Food and Drug Safety (MFDS, Republic of Korea) and the Institutional Review Board (IRB) of Chungnam National University Hospital (IRB, CNUH 2016-12-033). All procedures performed in studies involving human participants were in accordance with Good Clinical Practice (ICH-GCP) guidelines, all pertinent Republic of Korea laws, and the ethical standards specified in the applicable version of the declaration of Helsinki. All volunteers gave their written informed consent prior to any study procedures. Consent to participate: All volunteers gave their written informed consent prior to any study procedures. Code availability: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Triazolium α-cyclodextrin click cluster-magnetic agarose bead conjugate ( + CCC-MAB) was used to enrich phosphatidylinositol bisphosphates in brain tissue. The enriched sample was phosphate-methylated and analyzed by MALDI-TOF-MS/MS in positive ion mode. + CCC-MAB effectively removed weak-binding interferences from the phosphoinositide extract and improved the signal-to-noise ratio. The MALDI-TOF-MS/MS fragment ion revealed sodium adducts of polar head groups, exhibiting a converse fragmentation pattern compared to LC-ESI fragmentation. Our  + CCC-MAB-based phosphoinositide enrichment method enabled MALDI-TOF-MS/MS to assign 38 peaks in brain tissue and identify two phosphatidylinositol monophosphates, fifteen bisphosphates, and two trisphosphates. To our knowledge, this is the first study to analyze phosphatidylinositol bisphosphates in brain tissue using specific PIP enrichment and phosphate-methylation with MALDI-TOF-MS/MS., 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. Published by Elsevier Inc.)

Oral cancer is notoriously painful. Activation of protease-activated receptor 2 (PAR 2 , encoded by F2RL1) by proteases in the cancer microenvironment is implicated in oral cancer pain. PAR 2 is a G protein-coupled receptor (GPCR) expressed on neurons and cells in the cancer microenvironment. Sustained signaling of PAR 2 from endosomes of neurons mediates sensitization and nociception. We focused on the differential contribution of PAR 2 on oral cancer cells and neurons to oral cancer pain and whether encapsulation of a PAR 2 inhibitor, AZ3451 in nanoparticles (NP) more effectively reverses PAR 2 activation. We report that F2RL1 was overexpressed in human oral cancers and cancer cell lines. Deletion of F2RL1 on cancer cells reduced cancer-associated mechanical allodynia. A third-generation polyamidoamine dendrimer, functionalized with cholesterol was self-assembled into NPs encapsulating AZ3451. NP encapsulated AZ3451 (PAMAM-Chol-AZ NPs) more effectively reversed activation of PAR 2 at the plasma membrane and early endosomes than free drug. The PAMAM-Chol-AZ NPs showed greater efficacy in reversing nociception than free drug, with respect to both level and duration, in three preclinical mouse models of oral cancer pain. The antinociceptive efficacy was confirmed with an operant orofacial assay. Genetic deletion of F2RL1 on cancer cells or F2rl1 on neurons each partially reversed mechanical cancer allodynia. The remaining nociception could be effectively reversed by PAMAM-Chol-AZ NPs. These findings suggest that PAR 2 on oral cancer cells and neurons contribute to oral cancer nociception and NPs loaded with a PAR 2 antagonist provide increased antinociception and improved oral function compared to free drug., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nigel W. Bunnett reports a relationship with Endosomal Therapeutics Inc that includes: equity or stocks. The other 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. Published by Elsevier Ltd.)

Objective: To assess prescribing trends of glucose-lowering medications in the last year of life among older adults with type 2 diabetes (T2D) and explore whether frailty is associated with differential prescribing., Research Design and Methods: In this observational cohort study of Medicare beneficiaries aged ≥67 years (2015-2019) with T2D, we assessed temporal trends in prescribing a glucose-lowering medication, stratified by frailty. The main outcome included glucose-lowering medication fills within 1 year of death., Results: Among 975,407 community-dwelling Medicare beneficiaries with T2D, the use of glucose-lowering medications within 1 year of death slightly increased from 71.4% during the first 6-month period in 2015 to 72.9% (standardized mean difference [SMD] -0.03) during the second 6-month period in 2019. The most pronounced increase in use was observed for metformin (40.7% to 46.5%, SMD -0.12), whereas the largest decrease was observed for sulfonylureas (37.0% to 31.8%, SMD 0.11). Overall glucose-lowering medication use decreased from 66.1% in the 9 to 12 months before death to 60.8% in the last 4 months of life (SMD 0.11; P < 0.01), driven by reduced noninsulin medication use. The use of short-acting and long-acting insulin both increased near death, with frailer individuals more likely to receive insulin. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists, although less common, became more frequent in more recent years., Conclusions: The use of glucose-lowering medications declined in the last year of life, mainly due to reduced noninsulin use. Insulin use increased near death, particularly among frailer individuals, highlighting the need for careful end-of-life management., (© 2025 by the American Diabetes Association.)

As the world grapples with the coronavirus-19 (COVID) pandemic, more reports are coming in regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in endotheliopathy. It is a vascular condition in which endothelial cell injury or damage inflicts anatomical and functional changes in the endothelium, significantly impacting the physiological process and function. Previously, it was assumed that SARS-CoV-2 infects respiratory epithelial cells via spike glycoproteins present on the surface of the virus. However, severe cases and different autopsy studies described the clandestine role of this virus in infecting endothelial cells other than epithelial cells. It was observed that SARS-CoV-2 targets the pulmonary and extrapulmonary systems to damage the microvasculature and affect respiratory functioning, resulting in the onset of endotheliopathy, thrombosis, inflammation, pulmonary edema, and fibrosis. Such deleterious events are the consequence of the hyperactive immune response initiated by the SARS-CoV-2 infection, leading to pulmonary and extrapulmonary complications. However, the molecular mechanism behind endotheliopathy and other complications caused by this virus is elusive and will be unraveled by covering recent literature in this mini-review., Competing Interests: Compliance with Ethical Standards. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite the remarkable outcome of open thoracoabdominal aortic repairs of high-volume aortic centers, generalized result that spans diverse clinical settings are needed in the era of thoracic endovascular aortic repair (TEVAR). This study explored the national real-world data focusing on the impact of cumulative surgical volume on the operative outcomes., Methods: Using data from the Korean National Health Insurance Service claims database, the cohort included adult patients who underwent open thoracoabdominal or descending thoracic aortic aneurysm repairs from 2008 to 2020. The primary outcome was operative mortality defined as 30-day mortality or in-hospital mortality. The secondary outcome was adverse early outcome defined as a composite measure of operative mortality, stroke, and spinal cord injury., Results: A total of 2,514 patients (mean age, 60.7 years; 615 (24.5%) female) were included in the study. Distribution of cases revealed a pronounced bias towards a limited number of larger centers: 1,724 surgeries (68.6%) were concentrated in 6 highest-volume centers. Operative mortality rates decreased with increasing surgical volume: 30.1% in institutions with <50 cases, 20.6% for 50-99, 15.0% for 100-299, and 10.5% for those with ≥300 cases (P<0.001). Multivariable analyses further revealed that higher hospital volume was associated with lower risks of operative mortality and adverse early outcomes., Conclusions: The early operative outcomes of open thoracoabdominal aortic aneurysm repairs were significantly influenced by the institutional volume of the operating centers, highlighting the indispensable role of experience and expertise. This suggests the strategic aggregation of cases towards specialized, high-volume centers to optimize surgical results., (Copyright © 2025. Published by Elsevier Inc.)

Objective: : Several studies have reported the therapeutic effects of phytoncides on various mental disorders. However, little is known about the therapeutic effects of phytoncides on mild cognitive impairment (MCI), a prodromal stage of dementia. In this pilot study, we aimed to clarify the effect of inhaled phytoncides on the cognitive function of patients clinically diagnosed with MCI., Methods: : In total, 21 patients with MCI were randomly assigned to either a saline (no-odor) or phytoncide group and subsequently inhaled saline or phytoncide for 30 minutes indoors, respectively. To evaluate changes in cognitive function, we implemented functional near-infrared spectroscopy along with the Stroop task and compared task performance and hemodynamic responses in the dorsolateral/ventrolateral part of the prefrontal cortex (DLPFC/VLPFC) before and after inhalation., Results: : While the saline group showed no significant difference in either task performance (Wilcoxon W = 18.50, p = 0.385) or hemodynamic response, a significant increase in Stroop task performance (Wilcoxon W = 1.50, p = 0.009) and hemodynamic attenuation in the left VLPFC (Wilcoxon W = 56.00, p = 0.042) were found in the phytoncide group after inhalation., Conclusion: : Since compensatory task-related prefrontal hyperactivation represents one of the neural indicators of cognitive dysfunction in MCI, our findings shed light on the beneficial effects of phytoncide on cognitive function in MCI.

Objective: We aimed to investigate the effectiveness of buspirone as an adjunctive therapy for alleviating anxiety symptoms in patients with depressive disorders who are already taking antidepressants., Methods: This was an open-label prospective multicenter non-interventional observational study conducted over 12 weeks. We enrolled 180 patients diagnosed with depressive disorders according to DSM-5 criteria and Hamilton Anxiety Rating Scale (HAMA) scores ≥ 18. Participants were already taking selective serotonin reuptake inhibitors or serotoninnorepinephrine reuptake inhibitors and were prescribed adjunctive buspirone. Efficacy was assessed using HAMA, Hamilton Depression Rating Scale (HAMD), Clinical Global Impression Scale-Improvement, Clinical Global Impression Scale-Severity, Sheehan Disability Scale (SDS), and WHO-5 Well-Being Index., Results: The efficacy analysis included 161 patients. HAMA scores decreased significantly from 25.2 ± 6.7 at baseline to 15.4 ± 8.6 at 12 weeks ( p < 0.001), whereas HAMD scores decreased from 19.4 ± 4.6 to 12.7 ± 5.7 ( p < 0.001). WHO-5 and SDS scores showed significant improvements. The HAMA response rate was 39.1% and the remission rate was 13.7% at 12 weeks. Adverse drug reactions were reported in 3.7% of participants. Subgroup analyses showed no significant differences in treatment response based on buspirone dosage, baseline anxiety/depression severity, or benzodiazepine use., Conclusion: Adjunctive buspirone therapy effectively improved anxiety symptoms in depressed patients taking antidepressants, regardless of baseline symptom severity or buspirone dosage. The treatment was well-tolerated with few adverse events. Future studies using a control group are needed.

Heart rate variability (HRV) of 10 participants was assessed to evaluate the impact of exposure to first- and second-hand smoke from heat-not-burn (HnB) products and conventional cigarettes on cardiovascular health and the autonomic nervous system. The nicotine and cotinine concentrations in the urine of smokers and non-smokers exposed to this smoke were also measured. Nicotine levels in the urine of smokers exposed to HnB products and conventional cigarettes averaged 71.76 and 229.36 ng/ml, respectively. Short-term analyses of HRV in both time- and frequency-domain were performed. There were no significant differences in HRV indicators between both groups at baseline. However, decreases in SDNN, rMSSD, TINN, and pNN50 (%) were observed in smokers exposed to both first- and second-hand smoke from HnB products and conventional cigarettes. No significant trends were noted in non-smokers. The frequency-domain analysis revealed a decrease in low frequency components among smokers., 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 © 2025 Elsevier B.V. All rights reserved.)

Backgrounds: The treatment of complex distal radius fractures, particularly those involving both intra-articular disruption and significant metaphyseal comminution, remains a considerable surgical challenge. While volar locking plates have become a widely accepted standard for stabilizing these fractures, alone they may not address all fracture patterns. This study presents a surgical approach that incorporates the use of a mini-plate to provide targeted support for the metaphyseal region. We hypothesize that combining a mini-plate for metaphyseal stabilization with a volar locking plate for overall fracture fixation will enhance the structural stability and radiologic outcomes of metaphyseal comminuted distal radius fractures., Subjects and Methods: Eight cases of distal radius fractures involving comminution extending to the metaphysis treated surgically at Samsung Changwon Hospital during 2013-2023 were retrospectively analyzed. All patients had distal radius fractures with severe comminution at the metaphysis, where an added mini-plate was used to fix the fragments before applying the final volar locking plate. Using patient medical records, the mechanism of injury; presence of osteoporosis; type of fracture; radiologic parameters, final range of motion of the wrist; Mayo score and Disabilities of the Arm, Shoulder, and Hand (DASH) scores were investigated., Results: The average age of the participants was 66 years. After a mean follow-up of 30.1 months, all patients achieved proper bone union. The median total range of motion of the wrist joint was 110.6° (40°-170°) at final follow-up. The radiographic parameters showed significant improvement postoperatively compared to preoperatively. The ulnar variance improved from a median of 5 mm to 0.5 mm (P = 0.013), the median teardrop angle increased from 33° to 59° (P = 0.012), and the median lateral palmar tilt improved from - 15.5° to 10.5° (P = 0.033). The median DASH score was 35.6 points, and the median Mayo score was 75.2 points., Conclusion: By initially securing larger metaphyseal fragments with mini-plates, we transform a comminuted metaphyseal fracture into a simpler fracture pattern. This approach stabilizes the metaphyseal region, maintains radial length, and facilitates subsequent reduction of intra-articular fractures, thereby simplifying the surgical procedure. This method is a valuable addition to the surgical treatment options for managing such challenging fractures., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the IRB committees of the Medical Research Institute of Samsung Changwon Hospital. (SCMC 2024–03-001). Written informed consent was obtained from all participants for research studies and presented data. All procedures were performed in accordance with the Declaration of Helsinki. Consent for publication: We confirmed that written informed consent to publish this manuscript was obtained from the study participants. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

GPR119 has emerged as a promising target for treating type 2 diabetes and associated obesity, as its stimulation induces the secretion of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide in the intestinal tract as well as the glucose-dependent release of insulin in pancreatic β-cells. We describe the design and synthesis of novel GPR119 agonists containing a 1,4-disubstituted cyclohexene scaffold. Compound 21b displayed nanomolar potency (EC 50 = 3.8 nM) for h GPR119 activation and demonstrated a hypoglycemic efficacy of 17.0% in an oral glucose tolerance test. The hypoglycemic effect of compound 21b , compared to sitagliptin, a DPP-4 inhibitor, showed the relatively higher efficacy in both FATZO and db/db mice. Additionally, compound 21b exhibited a significant reduction in body weight in a female diet-induced obese rat model, comparable to that of metformin. Furthermore, in vivo pharmacokinetic experiments revealed that compound 21b is a potential candidate for the treatment of type 2 diabetes and obesity.

Purpose: We aimed to investigate the causes and clinical features of compressive optic neuropathy in Koreans., Methods: We analyzed the medical records of patients diagnosed with compressive optic neuropathy from March 2014 to December 2023 to determine the cause of optic nerve compression, symptoms and symptom patterns at first visit, accompanying symptoms, and types of visual field defects, and visual prognosis after surgery. In addition, the results of visual field tests and optical coherence tomography were analyzed to determine the positivity rate of each test and factors affecting test results., Results: A total of 73 patients were diagnosed with compressive optic neuropathy, and the most common cause was pituitary tumor (n=37, 51%). In addition, meningioma (n=16, 22%), hemangioma (n=4, 5%), thyroid ophthalmopathy (n=4, 5%), and sinus tumor (n=2, 3%) followed. In terms of symptom pattern, many patients had vision and visual field defects that appeared gradually (n=41, 56%), but there were also quite a few patients whose symptoms appeared suddenly (n=17, 23%). The positivity rate of the diagnostic test was highest for visual field testing (89%). In pituitary tumors, tumor size affected diagnostic test results (P=0.010)., Conclusions: The most common cause of compressive optic neuropathy in Koreans was a pituitary tumor. Deterioration of visual function can also occur acutely, and visual field testing was useful for diagnosis.

A comprehensive understanding of isoniazid (INH)-mediated hepatotoxic effects is essential for developing strategies to predict and prevent severe liver toxicity in tuberculosis treatment. In this study, we used multi-omics profiling in vitro to investigate the toxic effects of INH, revealing significant involvement of endoplasmic reticulum (ER) stress, mitochondrial impairment, redox imbalance, and altered metabolism. Additional analysis using transcriptomics data from repeated time-course INH treatments on human hepatic microtissues revealed that cellular responses to ER stress and oxidative stress happened prior to disturbances in mitochondrial complexes. Mechanistic validation studies using time-lapse measurements of cytosolic and mitochondrial reactive oxygen species (ROS) revealed that INH initially triggered cytosolic ROS increasement and Nrf2 signaling pathway activation before mitochondrial ROS accumulation. Molecular imaging showed that INH subsequently disrupted mitochondrial function by impairing respiratory complexes I-IV and caused mitochondrial membrane proton leakage without affecting mitochondrial complex V, leading to mitochondrial depolarization and reduced ATP production. These disturbances enhanced mitochondrial fission and mitophagy. Our findings highlight the potential of inhibiting ER stress during early INH exposure to mitigate cytosolic and mitochondrial oxidative stress. We also revealed the critical role of Nrf2 signaling in protecting hepatocytes under INH-induced oxidative stress by maintaining redox homeostasis and enabling metabolic reprogramming through regulating antioxidant gene expression and cellular lipid abundance. Alternative antioxidant pathways, including selenocompound metabolism, HIF-1 signaling, and the pentose phosphate pathway, also responded to INH-induced oxidative stress. Collectively, our study emphasizes the importance of ER stress, redox imbalance, metabolic changes, and mitochondrial dysfunction that underlie INH-induced hepatotoxicity., 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 © 2025 Elsevier B.V. All rights reserved.)

Outer membrane protein A (OmpA) plays a vital role in the interactions between Acinetobacter baumannii and host cells. Autophagy is a defense mechanism that hinders the intracellular replication of bacteria, thereby safeguarding cells against microbial infections. While it has been observed that A. baumannii triggers cellular autophagy, the precise role of its virulence protein OmpA in this process remains uncertain. In this study, we investigated the effects of A. baumannii OmpA (AbOmpA) on autophagy and explored the underlying molecular mechanisms. We found that AbOmpA exerted its autophagy-suppressive effect through inhibition of CaMKK2 phosphorylation. Compared to the wild-type strain, the ompA -deletion mutant strain displayed considerably enhanced autophagy induction, via the AMPK-ULK1 pathway. AbOmpA hindered starvation-induced autophagy, while A. baumannii -Omp33 (AbOmp33) and Escherichia coli -OmpA (EcOmpA) did not. Importantly, we confirmed that exogenous AbOmpA suppressed autophagy through the CaMKK2-AMPK-ULK1 pathway during A. baumannii infection. These findings reveal a novel mechanism for AbOmpA-mediated autophagy evasion, providing new insights into the pathogenesis of A. baumannii infection.IMPORTANCE Acinetobacter baumannii is a significant clinical pathogen notorious for causing infections in hospitals. Its outer membrane protein A acts as a virulence factor and helps the bacteria evade host defenses. Autophagy is a defense mechanism that hinders the intracellular replication of bacteria. While it has been observed that A. baumannii triggers cellular autophagy, the precise role of its AbOmpA in this process remains uncertain. Our studies demonstrate the AbOmpA of A. baumannii inhibits the cellular defense process, autophagy, through the CaMKK2-AMPK-ULK1 signaling cascade, thereby enhancing bacterial survival. This insight into how AbOmpA bypasses autophagy sheds light on A. baumannii infection's novel virulence strategy and suggests possible treatments.

Objectives: To investigate the association between oral antiviral administration and post-acute sequelae of COVID-19 (PASC) risk in Korea., Methods: This retrospective cohort study used data from the Korea Disease Control and Prevention Agency and the Health Insurance Review and Assessment Service. We analyzed data from COVID-19 patients aged > 60 years from January to December 2022. The primary outcome was the occurrence of 27 PASCs within 30-120 days after COVID-19 diagnosis. The hazard ratio was calculated using the Cox proportional hazards model., Results: Nirmatrelvir/ritonavir significantly reduced the risk of cardiovascular diseases, including heart failure and cardiomyopathies (aHR, 0.86), cardiac dysrhythmias (aHR, 0.83), and ischemic stroke (aHR, 0.88). Moreover, it also lowered the risk of hospitalization due to respiratory diseases including chronic obstructive pulmonary disease (aHR, 0.92) and decreased renal disorders including dialysis needs (aHR, 0.57) and acute renal failure (aHR, 0.85). Molnupiravir reduced the risk of ischemic stroke (aHR, 0.84) and other cerebrovascular diseases (aHR, 0.84). Respiratory conditions decreased by approximately 13-14% (aHR, 0.87 and 0.86, respectively)., Conclusions: Nirmatrelvir/ritonavir and molnupiravir administration in ambulatory patients were associated with decreased PASC risk; thus, oral antivirals may mitigate the indirect SARS-CoV-2 infection effects., 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 © 2025. Published by Elsevier Ltd.)

Background and Aims: Emerging evidence supports artificial intelligence-enhanced electrocardiogram (AI-ECG) for detecting acute myocardial infarction (AMI), but real-world validation is needed. The aim of this study was to evaluate the performance of AI-ECG in detecting AMI in the emergency department (ED)., Methods: The Rule-Out acute Myocardial Infarction using Artificial intelligence Electrocardiogram analysis (ROMIAE) study is a prospective cohort study conducted in the Republic of Korea from March 2022 to October 2023, involving 18 university-level teaching hospitals. Adult patients presenting to the ED within 24 h of symptom onset concerning for AMI were assessed. Exposure included AI-ECG score, HEART score, GRACE 2.0 score, high-sensitivity troponin level, and Physician AMI score. The primary outcome was diagnosis of AMI during index admission, and the secondary outcome was 30 day major adverse cardiovascular event (MACE)., Results: The study population comprised 8493 adults, of whom 1586 (18.6%) were diagnosed with AMI. The area under the receiver operating characteristic curve for AI-ECG was 0.878 (95% CI, 0.868-0.888), comparable with the HEART score (0.877; 95% CI, 0.869-0.886) and superior to the GRACE 2.0 score, high-sensitivity troponin level, and Physician AMI score. For predicting 30 day MACE, AI-ECG (area under the receiver operating characteristic, 0.866; 95% CI, 0.856-0.877) performed comparably with the HEART score (0.858; 95% CI, 0.848-0.868). The integration of the AI-ECG improved risk stratification and AMI discrimination, with a net reclassification improvement of 19.6% (95% CI, 17.38-21.89) and a C-index of 0.926 (95% CI, 0.919-0.933), compared with the HEART score alone., Conclusions: In this multicentre prospective study, the AI-ECG demonstrated diagnostic accuracy and predictive power for AMI and 30 day MACE, which was similar to or better than that of traditional risk stratification methods and ED physicians., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) remains a significant global health concern, and therefore, understanding their functional outcomes is essential. The aim of this study was to investigate the 1-year functional outcomes of patients with aSAH., Methods: We retrospectively analyzed data of patients with aSAH from the Korean Stroke Cohort for Functioning and Rehabilitation study, up to 1 year post-onset. The cohort data were collected twice. The first data was collected from August 2012 through May 2015, and the second data was collected from January to December in 2020, from nine different hospitals. Assessments were performed from 7 days to 1 year. Disability, measured by modified Rankin Scale (mRS), was analyzed in terms of good outcome (mRS 0 or 1) and mortality. In addition, functional level was further assessed using Functional Independence Measure (FIM) in aSAH survivors at 1 year post-onset. A subgroup analysis was conducted, with participants further classified into two groups: one with mild-to-moderate disability (mRS 0-3) and another with severe disability (mRS 4 or 5), as reported 7 days after onset. Multiple imputation method was used to handle missing data. In addition, mixed-effects model was used to analyze the trajectory of FIM., Results: A total of 517 patients with aSAH were included. Of these, 246 (47.6%) showed mild-to-moderate disability and 271 (52.4%) showed severe disability at 7 days. At 1 year after onset, the mortality rate was 6.0% and the good outcome was reported in 76.2% of patients. In aSAH survivors at 1 year, FIM showed a significant improvement over time, with a significant difference demonstrated between the subgroups. Age, initial clinical severity, and cognitive function at 7 days were also identified as significant covariates., Conclusions: The majority of patients reporting mild-to-moderate disability at 7 days exhibited good functional outcome, and even among those with severe disability, there was a favorable outcome with continuous improvement in their functional levels. Therefore, proper assessments and effective management should be employed to achieve favorable functional outcomes among aSAH survivors., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Excess adiposity impairs immune function and host defense in obese individuals, but studies on this concept in fish remain limited. In aquaculture, rapid growth is often encouraged through intensive farming practices, leading to overfeeding and negatively impacting production. This study aimed to induce obesity in rainbow trout through overfeeding, exploring metabolic abnormalities, immune response alterations, and infection susceptibility via transcriptomic and metabolomic analyses. In the overfed group, fish were fed until they refused to eat, while the control group was fed according to recommended feeding rates for four weeks. Sampling was conducted at weeks 1, 2, and 4 for serological, histopathological, metabolomic, and transcriptomic analyses. After four weeks, mortality rates were compared following Aeromonas salmonicida challenge, and immunological changes assessed one day post-infection. Overfed fish exhibited significant increases in weight gain (WG), body mass index (BMI), elevated AST/ALT levels, hepatocyte hypertrophy, lipid droplet formation, and triglyceride accumulation. At 1, 2, and 4 wpf, the overfed group exhibited distinct metabolic changes, with key alterations in glycolysis/gluconeogenesis, lipid metabolism and amino acid metabolism. KEGG analysis of transcriptomic data revealed a significant decrease in complement and coagulation cascades, including C3, FB, FH, an FI, accompanied by heightened TNF and IL-17 signaling pathways, involving the upregulation of genes such as TNF-α, IL-1β, and IL-6, indicating an enhanced inflammatory response. The overfed group experienced higher mortality post-infection. Excess energy from overfeeding led to hepatic fat accumulation, liver damage, and reduced innate immune responses, particularly in complement activation. These physiological disruptions compromised immune function, highlighting the detrimental effects of overfeeding-induced obesity on fish health. This study offers critical insights into the immunological mechanisms linking obesity to increased disease susceptibility., Competing Interests: Declaration of competing interest The authors declared no competing interest exists., (Copyright © 2025. Published by Elsevier Ltd.)

Objectives: This study aimed to assess the efficacy of sialendoscopy in retrieving non-palpable submandibular stones located in the hilum or deeper parenchyma compared to traditional non-endoscopic transoral stone removal techniques., Methods: Seventy patients with non-palpable submandibular hilar or intraparenchymal stones underwent sialendoscopy-assisted stone removal (SASR). Seventeen patients with hilar stones treated with non-endoscopic transoral stone removal (TOSR) were the control group. Parameters evaluated included stone characteristics (size, number, location, mobility, and accessibility) as well as outcomes (success rate, operation time, complications, recurrence, and functional recovery)., Results: The SASR group had four stones in the intraparenchymal glands, two of which were located inferior to the mylohyoid. Complete stone removal was achieved in 69 out of 70 patients (98.57%) in the SASR group. However, one patient had a sialolith measuring less than 2 mm in the intraparenchymal and inferior to mylohyoid that could not be removed. TOSR procedures were exclusively performed to remove hilar stones. Nevertheless, one patient in the TOSR group was unsuccessful in retrieving a 5-mm hilar stone, resulting in an overall success rate of 94.12%. The operation duration was much longer in the SASR group than in the TOSR group. However, the TOSR group had a significantly higher incidence of acute complications (41.18%), such as swelling, pain, or tongue numbness, compared to the SASR group (7.14%)., Conclusion: Sialendoscopy is a valuable adjunct to the transoral combined approach for retrieving non-palpable submandibular stones, especially those in the hilum or deeper parenchyma. A precise preoperative assessment of stone location is crucial for determining the appropriate surgical intervention., Study Design: Retrospective review., Setting: Two academic tertiary medical centers., (© 2025 The American Laryngological, Rhinological and Otological Society, Inc.)

Conjugated polymer design via random terpolymerization with irregular backbones has emerged as a strategy for stretchable organic electronics, requiring diverse molecular architectures to balance charge carrier mobility (μ) and stretchability. In this study, diketopyrrolopyrrole (DPP)-based conjugated polymers with 0%, 5%, and 10% Pechmann dye (PDy) units, denoted as DP-T0, DP-T5, and DP-T10, respectively, are introduced, and explore the impact of PDy on structural mobility and stretchability through experimental and computational analyses. Electrical measurements reveal hole mobilities ranging from 0.01 to 0.08 cm 2 V⁻¹ s⁻¹, with a slight decrease as PDy content increases. Stretchability tests indicate significant improvements in DP-T5 and DP-T10 due to their loosely packed lamellar structures. Notably, DP-T5 achieves a crack onset strain (ε c ) of 250% and a polarization dichroic ratio (PDR) of 2.4 under 200% strain, leading to a mobility ratio (μ 200 /μ 0 ) exceeding 5. These results demonstrate that PDy incorporation enhances the mechanical stretchability of DPP-based conjugated polymers while maintaining reasonable electronic performance. This work highlights the potential of PDy-based random terpolymerization for developing stretchable polymer semiconductors., (© 2025 Wiley‐VCH GmbH.)

Objective: Odontoid fractures in older adults often lead to substantial morbidity and mortality. This study explores the outcomes of water-based endoscope-assisted anterior odontoid screw (AOS) fixation, a minimally invasive technique, in managing these fractures., Methods: Six patients (5 men, 1 woman) underwent endoscope-assisted AOS fixation for displaced odontoid fractures. Surgical procedures and follow-up assessments were reviewed retrospectively. Inclusion criteria included type IIa or type IIb odontoid fractures with potential nonunion/instability., Results: Surgical procedures demonstrated no intraoperative complications. The mean operation time was 82 minutes (69-107 minutes), with an average estimated blood loss of 28 mL (10-50 mL). Among the 5 patients followed for >6 months, 4 (80%) showed successful fusion through computed tomography. Screw-related complications were observed in 1 patient., Conclusions: AOS fixation is advocated for managing unstable odontoid fractures and providing strength and fracture union rates without impending cervical motion. Incorporating minimally invasive approaches, particularly endoscopic techniques, has garnered interest. The novel endoscope-assisted AOS fixation method, unlike prior approaches, begins with endoscopic guidance and minimal incisions, potentially reducing the risk of neurovascular injury. This novel technique shows promise as an effective strategy for addressing unstable odontoid fractures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nanocrystalline perovskites have driven significant progress in metal halide perovskite light-emitting diodes (PeLEDs) over the past decade by enabling the spatial confinement of excitons. Consequently, three primary categories of nanocrystalline perovskites have emerged: nanoscale polycrystalline perovskites, quasi-2D perovskites, and perovskite nanocrystals. Each type has been developed to address specific challenges and enhance the efficiency and stability of PeLEDs. This review explores the representative material design strategies for these nanocrystalline perovskites, correlating them with exciton recombination dynamics and optical/electrical properties. Additionally, it summarizes the trends in progress over the past decade, outlining four distinct phases of nanocrystalline perovskite development. Lastly, this review addresses the remaining challenges and proposes a potential material design to further advance PeLED technology toward commercialization., (© 2025 Wiley‐VCH GmbH.)

Sodium-ion batteries (SIBs) attract significant attention due to their potential as an alternative energy storage solution, yet challenges persist due to the limited energy density of existing cathode materials. In principle, redox-active organic materials can tackle this challenge because of their high theoretical energy densities. However, electrode-level energy densities of organic electrodes are compromised due to their poor electron/ion transport and severe dissolution. Here, we report the use of a low-bandgap, conductive, and highly insoluble layered metal-free cathode material for SIBs. It exhibits a high theoretical capacity of 355 mAh g -1 per formula unit, enabled by a four-electron redox process, and achieves an electrode-level energy density of 606 Wh kg -1 electrode (90 wt % active material) along with excellent cycling stability. It allows for facile two-dimensional Na + diffusion, which enables a high intrinsic rate capability. Growth of the active cathode material in the presence of as little as 2 wt % carboxyl-functionalized carbon nanotubes improves charge transport and charge transfer kinetics and further enhances the power performance. Altogether, these allow the construction of SIB cells built from an affordable, sustainable organic small molecule, which provide a cathode energy density of 472 Wh kg -1 electrode when charging/discharging in 90 s and a top specific power of 31.6 kW kg -1 electrode .

Background: Many older adults with trauma have pre-existing serious illness like dementia, frailty, and organ insufficiency and are candidates for palliative care to improve outcomes and reduce downstream healthcare utilization. We hypothesize that baseline pain, depressive symptoms, and unpaid caregiving needs are associated with increased healthcare utilization in the year after trauma admission in seriously ill older adults., Methods: Using the Health and Retirement Study (2008-2018) linked to Medicare claims, we identified adults aged ≥66 years admitted for trauma. We assessed pre-admission pain (none/mild vs moderate/severe), depressive symptoms (no-Center for Epidemiologic Studies Depression Scale (CES-D) <3 vs yes-CES-D ≥3) and unpaid caregiving needs (none vs any); and hospital characteristics: trauma center designation and palliative care service. The χ 2 tests were used for categorical variables, and t-tests were used for continuous variables. Associations of pain, depressive symptoms, unpaid caregiving needs with healthcare utilization were tested with negative binomial and Poisson regression models., Results: Among 1693 older adults with serious illness, a third (35.7%) were older than 85 years, two-thirds were female (67.5%), and almost all were White (88.7%). Before trauma, 36.4% reported moderate/severe pain, 40.2% reported depressive symptoms (CES-D >3), and 34.9% reported any amount of hours/week of unpaid caregiving needs. Adjusted analyses demonstrated that compared with those without depressive symptoms, seriously ill older adults with depressive symptoms were less likely to be alive (incidence rate ratio (IRR) 0.61, 95% CI 0.41 to 0.91), had more emergency room visits (IRR 1.62, 95% CI 1.15 to 2.27), and more hospital visits (IRR 1.48, 95% CI 1.08 to 2.03) in the year after admission. Adjusted analyses of association of pain and caregiving with healthcare utilization were not significant., Conclusions: Seriously ill older trauma patients with depressive symptoms have increased healthcare utilization in the year after discharge. Palliative care interventions may improve patient outcomes and reduce postdischarge healthcare utilization., Level of Evidence: III., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Toll-like receptor 5 (TLR5) plays a critical role beyond its traditional function in innate immunity, significantly impacting metabolic regulation and liver health. Previously, we reported that TLR5 activation extends the healthspan and lifespan of aging mice. This study demonstrates that TLR5 deficiency leads to pronounced metabolic abnormalities with age, primarily affecting liver metabolic functions rather than intestinal inflammation. Comprehensive RNA sequencing analysis revealed that TLR5 deficiency induces gene expression changes in liver tissue similar to those caused by the methionine-choline deficient (MCD) diet, particularly affecting lipid metabolism and circadian rhythm-related genes. TLR5 knockout (TLR5 KO) mice displayed an increased propensity for liver fibrosis and lipid accumulation under the MCD diet, exacerbating liver pathology. Both hepatocytes and hepatic stellate cells in TLR5 KO mice were functionally impacted, leading to metabolic dysfunction and fibrosis. These findings suggest that TLR5 could be a significant target for addressing metabolic diseases that arise and worsen with aging. Furthermore, understanding the mechanisms by which TLR5 activation extends healthspan could provide valuable insights into therapeutic strategies for enhancing longevity and managing age-related metabolic disorders., (© 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)