Evaluation of Drug Blood-Brain-Barrier Permeability Using a Microfluidic Chip.

The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue. We analyzed a model for predicting BBB permeability using the Emulate BBB-on-a-chip machine. Ten compounds were evaluated, and their permeabilities were estimated. Our study demonstrated that the permeability trends of ten compounds in our microfluidic-based system resembled those observed in previous animal and cell-based experiments. Furthermore, we established a general correlation between the partition coefficient (Kp) and the apparent permeability (Papp). In conclusion, we introduced a new paradigm for predicting BBB permeability using microfluidic-based systems.

Rational design, synthesis, biological evaluation, and molecular modeling of novel naphthamide derivatives possessing potent, reversible, and competitive inhibitory mode of action over human monoamine oxidase.

Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; with an IC50 value of 0.294 µM, compound 2c most potently inhibited MAO-A, while compound 2g exhibited most potent MAO-B inhibitory activity with an IC50 value of 0.519 µM. Compounds 2c and 2g showed selectivity index (SI) values of 6.02 for MAO-A and 2.94 for MAO-B, respectively. On the other hand, most compounds showed weak inhibitory activity against ChEs except 2a and 2h over butyrylcholinesterase (BChE). The most potent compounds 2c and 2g were found to be competitive and reversible MAO inhibitors based on kinetic and reversibility studies. Plausible interpretations of the observed biological effects were provided through molecular docking simulations. The drug-likeness predicted by SwissADME and Osiris property explorer showed that the most potent compounds (2a, 2c, 2g, and 2h) obey Lipinski's rule of five. Accordingly, in the context of neurological disorders, hybrids 2c and 2g may contribute to the identification of safe and potent therapeutic approaches in the near future.

Reliability and Safety of Super-Thin ALT Flap: A Comprehensive Evaluation of Perfusion-Related Complications and Donor Morbidity.

BACKGROUND: With an increasing need for thin flap, the use of super-thin anterolateral thigh (ALT) flaps, raised above the supra-superficial fascia, has drawn great attention. Controversy remains regarding whether such thin flap elevation could affect postoperative outcomes, encompassing perfusion-related complications (PRC) and donor morbidities. This study aimed to evaluate the outcomes of super-thin ALT flap-based reconstruction compared with those of suprafascially elevated flaps. METHOD: Patients who underwent free ALT flap-based reconstruction between March 2017 and June 2023 were reviewed, and categorized into two groups based on flap elevation plane; super-thin, and suprafascial. Development of PRC and donor morbidities including paresthesia, were compared. Independent associations of the elevation plane with complication profiles were evaluated. Further analyses were conducted using propensity-score matching. RESULTS: In total, 208 cases were analyzed: 80 super-thin and 128 suprafascial ALT flaps. Nineteen cases (9.1%) experienced PRC, including four total and 14 partial necrosis. The incidence of overall and each type of PRC did not differ based on flap elevation plane even after adjusting for other variables. The super-thin group exhibited significantly lower donor complications compared to the others, upheld in multivariable analyses. Elevating the flaps with a super-thin fashion allowed for a higher rate of preservation of the lateral femoral cutaneous nerve, resulting in a significantly lower rate of postoperative paresthesia. Similar associations were observed in the propensity-score matching analysis. CONCLUSIONS: Super-thin ALT flap elevation might not appear to increase PRC risk, while reduces donor complications, compared to suprafascial elevation.

Cumulative effect of unemployment on suicide mortality in South Korean workers (2018-2019).

BACKGROUND: While unemployment is known to increase the risk of suicide, its cumulative effect remains underexplored. This study investigates how unemployment affects suicide mortality and whether the effect varies based on the number of unemployment spells using two years of nationwide data. METHODS: Using the data from the National Statistical Office and Employment Insurance Database for 2018 and 2019, we identified an average of 2365 cases of suicide over two years among 7.76 million workers aged 25-64 years who had been employed within one year before their suicide. The number of unemployment spells was counted using the employment history of the past five years. We calculated crude suicide mortality rates per 100 000 population, age- and sex- standardized mortality rates (SMRs), and proportionate mortality rates (PMRs) for suicide. RESULTS: Over the two years, the crude suicide rate was 30.0 per 100 000 among the general population and 30.5 among workers. Workers with no unemployment spells in the past five years had a significantly lower SMR (0.44; 0.42-0.46), while those with four or more unemployment spells had a significantly higher SMR (3.13; 2.92-3.35) than the general population. These findings were consistent across all sex and age groups. Additionally, workers with four or more unemployment spells had a significantly higher PMR than the general population. CONCLUSION: The impact of unemployment on suicide mortality intensifies as the number of unemployment spells increases. These results underscore the necessity for additional social and psychological support along with economic assistance for individuals facing recurrent unemployment.

Association Between Subjective Masticatory Function and Mild Cognitive Impairment in Older Adults.

AIM: This study aimed to examine the effect of subjective masticatory function on the occurrence of mild cognitive impairment (MCI) by analysing the Korean Longitudinal Study of Ageing (KLoSA) data. METHODS: The study participants were 2954 KLoSA participants aged 60 years or older in the first wave (2006) who had normal cognitive function. The subjective masticatory function was determined using a survey item, and the responses were grouped into 3 categories, ie, good, moderate, and poor. The occurrence of MCI in the 3 groups was followed up until 2020. Cognitive function was assessed based on the Korean Mini-Mental State Examination score. Age, sex, education level, residence, health insurance type, smoking status, drinking status, and the number of chronic diseases were considered as potential confounders. To examine the occurrence of MCI according to subjective masticatory function, Cox proportional hazard regression analysis was performed. RESULTS: Cox proportional hazard regression models adjusted for confounders yielded the following results: in men, the risk of MCI was higher in those whose subjective masticatory function was moderate and poor, as compared to those with good subjective masticatory function (adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.12-1.58; aHR, 1.23; 95% CI, 1.04-1.46). In contrast, in women, subjective masticatory function did not significantly influence the occurrence of MCI (aHR, 1.05; 95% CI, 0.89-1.24; aHR, 1.08; 95% CI, 0.92-1.28). CONCLUSIONS: This study suggests that poor masticatory function may be a risk factor for MCI in older men.

Thin Free Perforator Flap as a Viable Option for Forefoot Reconstruction: Comprehensive Evaluation of Outcomes.

BACKGROUND: Reconstruction of forefoot defects often necessitates free tissue transfer due to the limited availability of local tissue. Microsurgical reconstruction of the forefoot remains challenging as it requires durable yet thin, soft tissue coverage for functional restoration. This study aimed to evaluate the efficacy of free thin perforator flaps for forefoot reconstruction, with a focus on functional outcomes. METHODS: Patients who underwent microsurgical forefoot reconstruction between March 2020 and September 2023 were reviewed. Development of postoperative complications and functional outcomes were evaluated. RESULTS: In total 53 patients were analyzed, with a mean age of 62.7 years. The most common etiology of defects was oncologic surgery, followed by chronic wound, with a majority involving the plantar side. Super-thin anterolateral thigh flap and superficial circumflex iliac artery perforator flap were predominantly used. The median thickness of the flap was 4.0 mm. Digital vessels were the most frequently used as recipients. All but one flap survived, resulting in a success rate of 98.1 percent. Postoperative flap-site complications developed in 20 patients, the majority of which were resolved with conservative treatment. The median hospital stay was 8.0 days, and the mean time for initiating weight-bearing ambulation was 12.4 days. In postoperative foot function index questionnaire survey, the overall score remained 9.41, showing minimal impairment, and did not differ according to defect size and locations. Secondary debulking operation was necessitated in seven patients. CONCLUSION: Use of thin free perforator flaps might provide reliable outcomes with rapid recovery and excellent postoperative function in the forefoot reconstruction.

Smartphone-based combined oral and whole-body exercise programme aimed at improving oral functions: A randomized clinical trial.

OBJECTIVES: To investigate the effects of a smartphone-based oral and whole-body exercise programme on oral function in older adults. METHODS: Individuals aged 65 years or above were randomized into three groups (non-app use, app use and control group), and a combined oral and whole-body exercise programme was conducted for 5 weeks. Oral muscle strength, saliva flow rate, Oral Health Impact Profile-14 (OHIP-14), and Geriatric Oral Health Assessment Index (GOHAI) were measured before and after the intervention. The changes in each group were analysed at the end of the programme using paired sample t-tests, and the differences among the groups were analysed using the chi-square test, Fisher's exact test and ANOVA. RESULTS: The anterior tongue strength increased by 2.80 kPa after the intervention in the non-app use group; however, the change was not statistically significant. In the app use group, the anterior tongue strength significantly increased by 4.48 kPa. The saliva flow rate increased by 0.54 and 0.71 g/min in the non-app and app use groups, respectively, after the intervention (p < 0.05), and the change was greater in the app use group than in the other groups (p < 0.01). There were no significant changes in the posterior tongue strength, cheek strength, OHIP-14 or GOHAI scores over the course of the study. CONCLUSIONS: A smartphone-based combined oral and whole-body exercise programme can improve anterior tongue strength and saliva flow rate in older participants. The programme, however, did not result in significant changes in posterior tongue strength, cheek strength and perceived oral health.

Dietary Poly-ß-Hydroxybutyrate Improved the Growth, Non-specific Immunity, Digestive Enzyme Activity, Intestinal Morphology, Phagocytic Activity, and Disease Resistance Against Vibrio parahaemolyticus of Pacific White Shrimp, Penaeus vannamei.

This study assessed the effects of dietary supplementation of poly-ß-hydroxybutyrate (PHB) on growth performance, feed efficiency, non-specific immunity, digestive enzyme capacity, phagocytic activity, hemocyte count, intestinal morphology, and disease resistance against Vibrio parahaemolyticus of Pacific white shrimp (Penaeus vannamei). Six diets were prepared by supplementing graded levels of PHB at 0.00, 0.25, 0.50, 1.00, 2.00, and 4.00% (Con, P0.25, P0.5, P1.0, P2.0, and P4.0, respectively). Triplicate groups of 90 shrimps (initial body weight 0.25 ± 0.01 g) per treatment were randomly assigned and fed an experimental diet for 56 days. The growth performance of shrimp was significantly improved by 1% dietary PHB supplementation. PHB-included diets fed shrimp showed significantly improved hepatopancreatic trypsin, chymotrypsin, and pepsin activities. Villus height was significantly increased with dietary PHB supplementation, and villus width was increased at a 1% inclusion level. P0.25, P0.5, and P4.0 groups significantly increased phenoloxidase activity, and the P2.0 group significantly increased anti-protease activity compared to the Con group. The survival of shrimp challenged against V. parahaemolyticus was higher in P0.5, P1.0, and P2.0 groups than in the Con diet. Dietary PHB supplementation improved weight gain, digestive enzyme activity, intestinal morphology, non-specific immunity, and disease resistance against V. parahaemolyticus of shrimp. According to the above observations, the optimal dietary PHB supplementation level for maximum weight gain would be 1% for Pacific white shrimp.

PT-Finder: A multi-modal neural network approach to target identification.

Efficient target identification for bioactive compounds, including novel synthetic analogs, is crucial for accelerating the drug discovery pipeline. However, the process of target identification presents significant challenges and is often expensive, which in turn can hinder the drug discovery efforts. To address these challenges machine learning applications have arisen as a promising approach for predicting the targets for novel chemical compounds. These methods allow the exploration of ligand-target interactions, uncovering of biochemical mechanisms, and the investigation of drug repurposing. Typically, the current target identification tools rely on assessing ligand structural similarities. Herein, a multi-modal neural network model was built using a library of proteins, their respective sequences, and active inhibitors. Subsequent validations showed the model to possess accuracy of 82 % and MPRAUC of 0.80. Leveraging the trained model, we developed PT-Finder (Protein Target Finder), a user-friendly offline application that is capable of predicting the target proteins for hundreds of compounds within a few seconds. This combination of offline operation, speed, and accuracy positions PT-Finder as a powerful tool to accelerate drug discovery workflows. PT-Finder and its source codes have been made freely accessible for download at https://github.com/PT-Finder/PT-Finder.

A comprehensive framework for the delimitation of species within the Bemisia tabaci cryptic complex, a global pest-species group.

Identifying cryptic species poses a substantial challenge to both biologists and naturalists due to morphological similarities. Bemisia tabaci is a cryptic species complex containing more than 44 putative species; several of which are currently among the world's most destructive crop pests. Interpreting and delimiting the evolution of this species complex has proved problematic. To develop a comprehensive framework for species delimitation and identification, we evaluated the performance of distinct data sources both individually and in combination among numerous samples of the B. tabaci species complex acquired worldwide. Distinct datasets include full mitogenomes, single-copy nuclear genes, restriction site-associated DNA sequencing, geographic range, host speciation, and reproductive compatibility datasets. Phylogenetically, our well-supported topologies generated from three dense molecular markers highlighted the evolutionary divergence of species of the B. tabaci complex and suggested that the nuclear markers serve as a more accurate representation of B. tabaci species diversity. Reproductive compatibility datasets facilitated the identification of at least 17 different cryptic species within our samples. Native geographic range information provides a complementary assessment of species recognition, while the host range datasets provide low rate of delimiting resolution. We further summarized different data performances in species classification when compared with reproductive compatibility, indicating that combination of mtCOI divergence, nuclear markers, geographic range provide a complementary assessment of species recognition. Finally, we represent a model for understanding and untangling the cryptic species complexes based on the evidence from this study and previously published articles.

Association of Neoadjuvant Chemotherapy With Postoperative Outcomes in Immediate Prepectoral Prosthetic Breast Reconstruction.

PURPOSE: Neoadjuvant chemotherapy (NACT) followed by total mastectomy and immediate reconstruction has become an important strategy in the treatment of breast cancer. Although the safety of subpectoral implant-based breast reconstruction with NACT has been extensively evaluated, the safety in prepectoral reconstruction has not been clearly elucidated. We aimed to evaluate the association of NACT with immediate prepectoral breast reconstruction outcomes. METHODS: A retrospective review of patients who underwent total mastectomy and immediate implant-based prepectoral breast reconstruction between May and December 2021 was conducted. Patients were categorized into 2 groups: those receiving NACT and those not receiving it. Postoperative complication rates were compared between the 2 groups. The independent association between NACT and the complication profiles was evaluated. Propensity score matching was also conducted. RESULTS: We analyzed 343 cases, including 85 who received NACT treatment and 258 who did not. Compared with the non-NACT group, the NACT group was younger, had a higher body mass index, and a higher rate of adjuvant radiotherapy. There were no differences in the rates of overall complications or type of complication between the 2 groups. In the multivariable logistic analyses, NACT did not show a significant association with the development of adverse outcomes. Similar results were observed in propensity score matching analyses. CONCLUSIONS: Our results suggest that receiving NACT may not have a significant detrimental effect on the postoperative outcomes of immediate prepectoral prosthetic reconstructions. Conducting prepectoral implant-based reconstruction in the setting of NACT might be safe and provide acceptable outcomes.

Revealing the pathogenesis of keloids based on the status: Active vs inactive.

Recently, the pathomechanisms of keloids have been extensively researched using transcriptomic analysis, but most studies did not consider the activity of keloids. We aimed to profile the transcriptomics of keloids according to their clinical activity and location within the keloid lesion, compared with normal and mature scars. Tissue samples were collected (keloid based on its activity (active and inactive), mature scar from keloid patients and normal scar (NS) from non-keloid patients). To reduce possible bias, all keloids assessed in this study had no treatment history and their location was limited to the upper chest or back. Multiomics assessment was performed by using single-cell RNA sequencing and multiplex immunofluorescence. Increased mesenchymal fibroblasts (FBs) was the main feature in keloid patients. Noticeably, the proportion of pro-inflammatory FBs was significantly increased in active keloids compared to inactive ones. To explore the nature of proinflammatory FBs, trajectory analysis was conducted and CCN family associated with mechanical stretch exhibited higher expression in active keloids. For vascular endothelial cells (VECs), the proportion of tip and immature cells increased in keloids compared to NS, especially at the periphery of active keloids. Also, keloid VECs highly expressed genes with characteristics of mesenchymal activation compared to NS, especially those from the active keloid center. Multiomics analysis demonstrated the distinct expression profile of active keloids. Clinically, these findings may provide the future appropriate directions for development of treatment modalities of keloids. Prevention of keloids could be possible by the suppression of mesenchymal activation between FBs and VECs and modulation of proinflammatory FBs may be the key to the control of active keloids.

Analysis of Self-Assembled Low- and High-Molecular-Weight Poly-L-Lysine-Ce6 Conjugate-Based Nanoparticles.

In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often exhibit poor physicochemical properties, including solubility, necessitating the development of nanoformulations. In this study, we developed two cationic peptide-based self-assembled nanomaterials by using a PDT agent, chlorin e6 (Ce6). To manufacture biocompatible nanoparticles based on peptides, we used the cationic poly-L-lysine peptide, which is rich in primary amines. We prepared low- and high-molecular-weight poly-L-lysine, and then evaluated the formation and performance of nanoparticles after chemical conjugation with Ce6. The results showed that both molecules formed self-assembled nanoparticles by themselves in saline. Interestingly, the high-molecular-weight poly-L-lysine and Ce6 conjugates (HPLCe6) exhibited better self-assembly and PDT performance than low-molecular-weight poly-L-lysine and Ce6 conjugates (LPLCe6). Moreover, the HPLCe6 conjugates showed superior cellular uptake and exhibited stronger cytotoxicity in cell toxicity experiments. Therefore, it is functionally beneficial to use high-molecular-weight poly-L-lysine in the manufacturing of poly-L-lysine-based self-assembling biocompatible PDT nanoconjugates.

Microbiomic association between the saliva and salivary stone in patients with sialolithiasis.

Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the primary treatment. This study explored the role of the salivary microbial communities in the formation of sialoliths. We conducted a comparative analysis of microbial communities present in the saliva and salivary stones, and sequenced the 16S rRNA gene in samples obtained from patients with sialoliths and from healthy individuals. Although the diversity in the saliva was high, the essential features of the microbial environment in sialoliths were low diversity and evenness. The association of microbial abundance between stones and saliva revealed a positive correlation between Peptostreptococcus and Porphyromonas, and a negative correlation for Pseudomonas in saliva. The functional potential differences between saliva and stones Bacterial chemotaxis and the citrate cycle were negatively correlated with most genera found in salivary stone samples. However, the functions required for organic compound degradation did not differ between the saliva samples. Although some microbes were shared between the sialoliths and saliva, their compositions differed significantly. Our study presents a novel comparison between salivary stones and salivary microbiomes, suggesting potential preventive strategies against sialolithiasis.

Microsurgical reconstruction using thoracoacromial vessels as recipients for complicated chest wall defects.

BACKGROUND: Free tissue transfer is often required for the reconstruction of complex and deep anterior chest wall wounds, for which the identification of suitable recipient vessels is crucial. Although the internal mammary arteries (IMAs) are a representative option, identifying secondary options when these vessels are compromised remains a challenge. This report evaluated the efficacy of using the thoracoacromial vessels (TAVs) as recipients for chest wall reconstruction by reviewing our experience. METHODS: We conducted a retrospective review of patients undergoing free-flap-based chest wall reconstruction using TAVs as recipient vessels from February 2020 to March 2023. Patient demographics and surgery-related characteristics data were collected. The primary outcome of interest was the occurrence of flap perfusion-related complications. RESULTS: In total, 12 cases utilized TAVs as recipients, primarily for defects following sternotomy, where bilateral IMA was unavailable due to prior surgery. The TAVs with reliable perfusion were consistently identified beneath the pectoralis major muscle. The anterolateral thigh flap was predominantly employed, with musculocutaneous or chimeric flaps introduced for bony defects. The mean pedicle length of the harvested flap was 7.2 cm (range, 3-13), and in cases with a vascular gap, the pedicle was extended using an arteriovenous interposition graft. This resulted in a mean pedicle length needed to reach recipient vessels of 9.9 cm (range, 6.5-19). All flaps survived, with only one experiencing partial necrosis. CONCLUSIONS: The TAV could be considered as an attractive alternative recipient vessel in microsurgical reconstruction of complicated chest wall defects when the use of IMA is not feasible.

Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity.

Background: Mast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored. Objectives: To elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity. Methods: Keloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids. Results: The scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples. Conclusions: scRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions.

Prognostic factors for tracheostomy early decannulation in acquired brain injury patients.

After severe brain injuries, a tracheostomy tube is usually inserted for respiratory support. This study aimed to clarify the prognostic factors for tracheostomy early decannulation in patients with acquired brain injuries. We retrospectively reviewed the medical records of inpatients with acquired brain injuries who underwent successful tracheostomy decannulation between March 2021 and June 2022. Fifty-six patients were included; median age was 68 (59-72) years; 28 (50%) were men; 28 (50%) underwent tracheostomy due to stroke. The median time to decannulation was 47 days. The patients were divided into the early and the late decannulation groups based on the median time, and compared. In univariate analysis, the early decannulation group had a higher BMI, peak cough flow, and acquired brain injuries due to trauma, and a lower penetration-aspiration scale score, duration of antibiotic use, and duration of oxygen use. Multivariate Cox regression analysis revealed that a higher initial peak cough flow [hazard ratio (HR) 1.142; 95% confidence interval (CI) 0.912-0.954; P  < 0.001] and lower duration of oxygen use (HR 0.930; 95% CI 0.502-0.864; P  = 0.016) were independent factors for early tracheostomy decannulation, with each unit increase in peak cough flow corresponding to a 14.2% increase and each additional day of duration of oxygen use corresponding to a 7.0% decrease in the likelihood of early decannulation. In conclusion, key prognostic factors for early tracheostomy decannulation were identified as the initial cough strength and duration of oxygen use. These results could play important role in decannulation plans for patients with tracheostomy tube.

Comparison of the problem-solving performance of ChatGPT-3.5, ChatGPT-4, Bing Chat, and Bard for the Korean emergency medicine board examination question bank.

Large language models (LLMs) have been deployed in diverse fields, and the potential for their application in medicine has been explored through numerous studies. This study aimed to evaluate and compare the performance of ChatGPT-3.5, ChatGPT-4, Bing Chat, and Bard for the Emergency Medicine Board Examination question bank in the Korean language. Of the 2353 questions in the question bank, 150 questions were randomly selected, and 27 containing figures were excluded. Questions that required abilities such as analysis, creative thinking, evaluation, and synthesis were classified as higher-order questions, and those that required only recall, memory, and factual information in response were classified as lower-order questions. The answers and explanations obtained by inputting the 123 questions into the LLMs were analyzed and compared. ChatGPT-4 (75.6%) and Bing Chat (70.7%) showed higher correct response rates than ChatGPT-3.5 (56.9%) and Bard (51.2%). ChatGPT-4 showed the highest correct response rate for the higher-order questions at 76.5%, and Bard and Bing Chat showed the highest rate for the lower-order questions at 71.4%. The appropriateness of the explanation for the answer was significantly higher for ChatGPT-4 and Bing Chat than for ChatGPT-3.5 and Bard (75.6%, 68.3%, 52.8%, and 50.4%, respectively). ChatGPT-4 and Bing Chat outperformed ChatGPT-3.5 and Bard in answering a random selection of Emergency Medicine Board Examination questions in the Korean language.

Anti-Tumor Efficacy of Oleuropein-Loaded ZnO/Au Mesoporous Silica Nanoparticle in 5-FU-Resistant Colorectal Cancer Cells.

Purpose: 5-fluorouracil (5-FU) is a first-line chemotherapeutic agent used to treat colorectal cancer (CRC). However, 5-FU induces drug resistance and activation of cancer stem cells (CSCs). In the present study, we designed a novel biocompatible nanomedicine system with high efficacy and biocompatibility by synthesizing mesoporous silica nanoparticle (MSN)-structured ZnO and gold ions. Oleuropein (OLP) is a phenolic compound derived from olive leaves that exerts anti-cancer effects. Therefore, we synthesized OLP-loaded ZnO/Au MSNs (ZnO/Au/OLP MSNs) and examined their anti-cancer effects on 5-FU-resistant CRC cells. Methods: ZnO/Au MSNs were synthesized and functionalized, and their physical and chemical compositions were characterized using UV-visible spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). Their effects were assessed in terms of cellular proliferation capacity, migration and invasion ability, colony-forming ability, spheroid-forming ability, reactive oxygen species (ROS) production, and mitochondrial membrane depolarization. Results: ZnO/Au MSNs were mostly composed of various ions containing ZnO and gold ions, had a spheroid phenotype, and exhibited no cytotoxicity. ZnO/Au/OLP MSNs reduced cell viability and CSC formation and induced apoptosis of 5-FU-resistant CRC cells via necrosis via ROS accumulation and DNA fragmentation. Conclusion: ZnO/Au/OLP MSNs exhibited anti-cancer activity by upregulating necrosis. These results revealed that ZnO/Au/OLP MSNs are a novel drug delivery system for 5-FU CRC therapy.