Exploring the large chemical space in search of thermodynamically stable and mechanically robust MXenes via machine learning.

To effectively utilize MXenes, a family of two-dimensional materials, in various applications that include thermoelectric devices, semiconductors, and transistors, their thermodynamic and mechanical properties, which are closely related to their stability, must be understood. However, exploring the large chemical space of MXenes and verifying their stability using first-principles calculations are computationally expensive and inefficient. Therefore, this study proposes a machine learning (ML)-based high-throughput MXene screening framework to identify thermodynamically stable MXenes and determine their mechanical properties. A dataset of 23 857 MXenes with various compositions was used to validate this framework, and 48 MXenes were predicted to be stable by ML models in terms of heat of formation and energy above the convex hull. Among them, 45 MXenes were validated using density functional theory calculations, of which 23 MXenes, including Ti2CClBr and Zr2NCl2, have not been previously known for their stability, confirming the effectiveness of this framework. The in-plane stiffness, shear moduli, and Poisson's ratio of the 45 MXenes were observed to vary widely according to their constituent elements, ranging from 90.11 to 198.02 N m-1, 64.00 to 163.40 N m-1, and 0.19 to 0.58, respectively. MXenes with Group-4 transition metals and halogen surface terminations were shown to be both thermodynamically stable and mechanically robust, highlighting the importance of electronegativity difference between constituent elements. Structurally, a smaller volume per atom and minimum bond length were determined to be preferable for obtaining mechanically robust MXenes. The proposed framework, along with an analysis of these two properties of MXenes, demonstrates immense potential for expediting the discovery of stable and robust MXenes.

The Portal Venous Pulsatility Index and Main Portal Vein Diameter as Surrogate Markers for Liver Fibrosis in Nonalcoholic Fatty Liver Disease and Metabolic-Dysfunction-Associated Steatotic Liver Disease.

(1) Background: Despite numerous noninvasive methods for assessing liver fibrosis, effective ultrasound parameters remain limited. We aimed to identify easily measurable ultrasound parameters capable of predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and metabolic-dysfunction-associated steatotic liver disease (MASLD); (2) Methods: The data of 994 patients diagnosed with NAFLD via ultrasound at the Armed Forces Goyang Hospital were retrospectively collected from June 2022 to July 2023. A liver stiffness measurement (LSM) ≥ 8.2 kPa was classified as significant fibrosis. Liver steatosis with cardiometabolic risk factors was defined as MASLD. Two ultrasound variables, the portal venous pulsatility index (VPI) and main portal vein diameter (MPVD), were measured; (3) Results: Of 994 patients, 68 had significant fibrosis. Significant differences in VPI (0.27 vs. 0.34, p < 0.001) and MPVD (10.16 mm vs. 8.98 mm, p < 0.001) were observed between the fibrotic and non-fibrotic groups. A logistic analysis adjusted for age and body mass index (BMI) revealed that only VPI (OR of 0.955, p = 0.022, VPI on a 0.01 scale) and MPVD (OR of 1.501, p < 0.001) were significantly associated with significant liver fibrosis. In the MASLD cohort (n = 939), VPI and MPVD were associated with significant fibrosis. To achieve better accuracy in predicting liver fibrosis, we established a nomogram that incorporated MPVD and VPI. The established nomogram was validated in the test cohort, yielding an area under the receiver operating characteristic curve of 0.821 for detecting significant liver fibrosis; (4) Conclusions: VPI and MPVD, as possible surrogate markers, are useful in predicting significant fibrosis in patients with NAFLD and MASLD.

Impact of Overseas Deployment on Fatty Liver and Metabolic Diseases Among Korean Soldiers.

BACKGROUND: The prevalence of metabolic diseases is increasing worldwide and is influenced by multiple environmental, psychological, and dietary factors. As overseas deployment (OD) of Korean soldiers brings about changes in these factors, this study aimed to explore the impact of OD on metabolic diseases. MATERIALS AND METHODS: We collected paired health checkup data of Korean soldiers between January 2020 and December 2022, before and after their deployment. We analyzed changes in lipid profile, fasting glucose, and liver function biomarkers during OD and compared the prevalence of metabolic diseases before and after the OD. RESULTS: A total of 2,953 soldiers were enrolled. During OD, body weight, body mass index, total cholesterol, low-density lipoprotein, and fasting glucose levels decreased significantly. Furthermore, the prevalence of obesity, impaired fasting glucose, and nonalcoholic fatty liver disease decreased significantly from 45.78% to 33.49%, P < .001; 38.60% to 34.41%, P < .001; and 24.89% to 18.88%, P < .001, respectively. In a subgroup analysis of participants with long-term deployment (duration >365 days), only the prevalence of obesity decreased significantly during deployment, whereas the prevalence of hypertension and dyslipidemia increased. CONCLUSIONS: Metabolic biomarkers improved, and the prevalence of metabolic diseases decreased significantly during OD. However, personnel with long-term deployment did not experience significant improvements in these parameters. Further analysis is needed to identify the factors influencing these discrepancies.

Influence of Curved Video Laryngoscope Blade Sizes and Patient Heights on Video Laryngoscopic Views: A Randomized Controlled Trial.

This study aimed to compare the video laryngoscope views facilitated by curved blades 3 and 4 with an exploration of the relationship between these views and patient height. Conducted as a randomized controlled trial, this study enrolled adults scheduled for surgery under general anesthesia. Intubation procedures were recorded, and the percentage of glottic opening was measured before tube insertion. Multivariate analysis validated the impact of various factors, including blade size and patient height, on the percentage of glottic opening scores. A total of 192 patients were included. The median percentage of glottic opening scores for curved blades 3 and 4 were 100 and 83, respectively (p < 0.001). The unstandardized coefficient indicated a significant negative impact of blade 4 on the percentage of glottic opening scores (-13, p < 0.001). In the locally estimated scatterplot smoothing analysis, blade 3 exhibited a steady rise in glottic opening scores with increasing height, whereas blade 4 showed a peak followed by a decline around 185 cm. The unstandardized coefficient of height showed no significant association (0, p = 0.819). The study observed superior laryngoscopic views with blade 3 compared to blade 4. However, no significant association was found between laryngoscopic views and patient height.

Abused drug-induced intracranial self-stimulation is correlated with the alteration of dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens of mice.

Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors. Here, we used the ICSS model to evaluate the abuse potential of 18 abused drugs: 3-Fluoroethamphetamine (3-FEA); methylphenidate; cocaine; dextroamphetamine; alpha-Pyrrolidinobutyrophenone (α-PBT); 4'-Fluoro-4-methylaminorex (4-FPO); methamphetamine; larocaine; phentermine; paramethoxymethamphetamine (PMMA); phendimetrazine; N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48); Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB-13); 4-Ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210); Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018); N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe); N-[(2-Methoxyphenyl)methyl]-N-methyl-1-(4-methylphenyl)propan-2-amine (4-MMA-NBOMe); and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine (4-MeO-PCP). We determined dopamine transporter (DAT) availability in the medial prefrontal cortex (mPFC), striatum, and nucleus accumbens (NAc) after drug treatment. DAT availability in the mPFC and NAc significantly correlated with the ICSS threshold after drug treatment. Extracellular dopamine and calcium levels in PC-12 cells were measured following drug treatment. After drug treatment, Spearman rank and Pearson correlation analyses showed a significant difference between the extracellular dopamine level and the ICSS threshold. After drug treatment, Spearman rank correlation analysis showed a significant correlation between Ca2+ signaling and the ICSS threshold. A positive correlation exists between the ICSS threshold and DAT availability in the mPFC and NAc provoked by abused drugs. The relative potential of drug-induced reward-seeking behavior may be related to DAT availability-mediated extracellular dopamine levels in the mPFC and NAc.

High ApoB/ApoA-I Ratio Predicts Post-Stroke Cognitive Impairment in Acute Ischemic Stroke Patients with Large Artery Atherosclerosis.

BACKGROUND: We aimed to investigate the association between the ApoB/ApoA-I ratio and post-stroke cognitive impairment (PSCI) in patients with acute stroke of large artery atherosclerosis etiology. METHODS: Prospective stroke registry data were used to consecutively enroll patients with acute ischemic stroke due to large artery atherosclerosis. Cognitive function assessments were conducted 3 to 6 months after stroke. PSCI was defined as a z-score of less than -2 standard deviations from age, sex, and education-adjusted means in at least one cognitive domain. The ApoB/ApoA-I ratio was calculated, and patients were categorized into five groups according to quintiles of the ratio. Logistic regression analyses were performed to assess the association between quintiles of the ApoB/ApoA-I ratio and PSCI. RESULTS: A total of 263 patients were included, with a mean age of 65.9 ± 11.6 years. The median NIHSS score and ApoB/ApoA-I ratio upon admission were 2 (IQR, 1-5) and 0.81 (IQR, 0.76-0.88), respectively. PSCI was observed in 91 (34.6%) patients. The highest quintile (Q5) of the ApoB/ApoA-I ratio was a significant predictor of PSCI compared to the lowest quintile (Q1) (adjusted OR, 3.16; 95% CI, 1.19-8.41; p-value = 0.021) after adjusting for relevant confounders. Patients in the Q5 group exhibited significantly worse performance in the frontal domain. CONCLUSIONS: The ApoB/ApoA-I ratio in the acute stage of stroke independently predicted the development of PSCI at 3-6 months after stroke due to large artery atherosclerosis. Further, a high ApoB/ApoA-I ratio was specifically associated with frontal domain dysfunction.

Predictive Modeling and Integrated Risk Assessment of Postoperative Mortality and Pneumonia in Traumatic Brain Injury Patients through Clustering and Machine Learning: Retrospective Study.

This study harnessed machine learning to forecast postoperative mortality (POM) and postoperative pneumonia (PPN) among surgical traumatic brain injury (TBI) patients. Our analysis centered on the following key variables: Glasgow Coma Scale (GCS), midline brain shift (MSB), and time from injury to emergency room arrival (TIE). Additionally, we introduced innovative clustered variables to enhance predictive accuracy and risk assessment. Exploring data from 617 patients spanning 2012 to 2022, we observed that 22.9% encountered postoperative mortality, while 30.0% faced postoperative pneumonia (PPN). Sensitivity for POM and PPN prediction, before incorporating clustering, was in the ranges of 0.43-0.82 (POM) and 0.54-0.76 (PPN). Following clustering, sensitivity values were 0.47-0.76 (POM) and 0.61-0.77 (PPN). Accuracy was in the ranges of 0.67-0.76 (POM) and 0.70-0.81 (PPN) prior to clustering and 0.42-0.73 (POM) and 0.55-0.73 (PPN) after clustering. Clusters characterized by low GCS, small MSB, and short TIE exhibited a 3.2-fold higher POM risk compared to clusters with high GCS, small MSB, and short TIE. In summary, leveraging clustered variables offers a novel avenue for predicting POM and PPN in TBI patients. Assessing the amalgamated impact of GCS, MSB, and TIE characteristics provides valuable insights for clinical decision making.

Postoperative Nausea and Vomiting Prediction: Machine Learning Insights from a Comprehensive Analysis of Perioperative Data.

Postoperative nausea and vomiting (PONV) are common complications after surgery. This study aimed to present the utilization of machine learning for predicting PONV and provide insights based on a large amount of data. This retrospective study included data on perioperative features of patients, such as patient characteristics and perioperative factors, from two hospitals. Logistic regression algorithms, random forest, light-gradient boosting machines, and multilayer perceptrons were used as machine learning algorithms to develop the models. The dataset of this study included 106,860 adult patients, with an overall incidence rate of 14.4% for PONV. The area under the receiver operating characteristic curve (AUROC) of the models was 0.60-0.67. In the prediction models that included only the known risk and mitigating factors of PONV, the AUROC of the models was 0.54-0.69. Some features were found to be associated with patient-controlled analgesia, with opioids being the most important feature in almost all models. In conclusion, machine learning provides valuable insights into PONV prediction, the selection of significant features for prediction, and feature engineering.

Muscle Mass Adjusted for Body Weight Is Associated with Significant Liver Fibrosis in Young Adults with Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study from a Korean Military Hospital.

Background: Sarcopenia has been associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the correlation between liver fibrosis and muscle mass in young adults with NAFLD. Methods: We conducted a retrospective review of 88 Korean soldiers <35 years of age who underwent bioelectrical impedance analysis and liver stiffness measurements. A FibroScan-aspartate aminotransferase score >0.35 was used to determine the presence of liver fibrosis. Results: Among the 88 patients, 38 were classified as having significant fibrosis. In the univariate analysis, muscle mass percentage (MMP), muscle-to-fat ratio (MFR), waist-to-hip ratio (WHR), body mass index, impaired fasting glucose or diabetes mellitus, and alanine transaminase (ALT) level were all significantly associated with fibrosis (P<0.001). After adjusting for ALT level, height, and age, MMP and WHR were associated with fibrosis. Conclusion: In young adults, MMP and MFR were significantly associated with hepatic fibrosis.

Harnessing Machine Learning for Prediction of Postoperative Pulmonary Complications: Retrospective Cohort Design.

Postoperative pulmonary complications (PPCs) are significant causes of postoperative morbidity and mortality. This study presents the utilization of machine learning for predicting PPCs and aims to identify the important features of the prediction models. This study used a retrospective cohort design and collected data from two hospitals. The dataset included perioperative variables such as patient characteristics, preexisting diseases, and intraoperative factors. Various algorithms, including logistic regression, random forest, light-gradient boosting machines, extreme-gradient boosting machines, and multilayer perceptrons, have been employed for model development and evaluation. This study enrolled 111,212 adult patients, with an overall incidence rate of 8.6% for developing PPCs. The area under the receiver-operating characteristic curve (AUROC) of the models was 0.699-0.767, and the f1 score was 0.446-0.526. In the prediction models, except for multilayer perceptron, the 10 most important features were obtained. In feature-reduced models, including 10 important features, the AUROC was 0.627-0.749, and the f1 score was 0.365-0.485. The number of packed red cells, urine, and rocuronium doses were similar in the three models. In conclusion, machine learning provides valuable insights into PPC prediction, significant features for prediction, and the feasibility of models that reduce the number of features.

Age-Related Variations in Postoperative Pain Intensity across 10 Surgical Procedures: A Retrospective Study of Five Hospitals in South Korea.

Age-related differences in pain perception have been reported in various contexts; however, their impact on postoperative pain intensity remains poorly understood, especially across different surgical procedures. Data from five hospitals were retrospectively analyzed, encompassing patients who underwent 10 distinct surgical procedures. Numeric rating scale scores were used to assess the worst postoperative pain intensity during the 24 h after surgery. The multivariate linear regression model analyzed the relationship between age and pain intensity. Subgroup analyses were performed according to sex and patient-controlled analgesia (PCA). This study included 41,187 patients. Among the surgeries studied, lumbar spine fusion (ß = -0.155, p < 0.001) consistently and significantly exhibited a decrease in worst postoperative pain with increasing age. Similar trends were observed in cholecystectomy (ß = -0.029, p < 0.001) and several other surgeries; however, the results were inconsistent across all analyses. Surgeries with higher percentages of PCA administration had lower median worst-pain scores. In conclusion, age may affect postoperative pain intensity after specific surgeries; however, a comprehensive understanding of the complex interplay between age, surgical intervention, and pain intensity is required. Pain management strategies should consider various factors, including age-related variations.

miR-429 Suppresses Endometrial Cancer Progression and Drug Resistance via DDX53.

(1) Background: To examine miR-429-meditated DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 (DDX53) function in endometrial cancer (EC). (2) Methods: DDX53 and miR-429 levels were measured using quantitative real-time polymerase chain reaction and western blotting assays, cell invasion and migration using Transwell invasion and wound healing assays, and cell proliferation using colony-forming/proliferation assays. A murine xenograft model was also generated to examine miR-429 and DDX53 functions in vivo. (3) Results: DDX53 overexpression (OE) promoted key cancer phenotypes (proliferation, migration, and invasion) in EC, while in vivo, DDX53 OE hindered tumor growth in the murine xenograft model. Moreover, miR-429 was identified as a novel miRNA-targeting DDX53, which suppressed EC proliferation and invasion. (4) Conclusions: DDX53 and miR-429 regulatory mechanisms could provide novel molecular therapies for EC.

The Impact of Blood Transfusion in Developing Postoperative Delirium in Patients with Hip Fracture Surgery.

BACKGROUND: Many studies have been conducted to explore the risk factors associated with postoperative delirium (POD) in order to understand its underlying causes and develop prevention strategies, especially for hip fracture surgery. However, the relationship between blood transfusion and POD has been heatedly debated. The purpose of this study was to evaluate the risk factors of POD and the relationship between blood transfusions and the occurrence of POD in hip fracture surgery through big data analysis. METHODS: Medical data (including medication history, clinical and laboratory findings, and perioperative variables) were acquired from the clinical data warehouse (CDW) of the five hospitals of Hallym University Medical Center and were compared between patients without POD and with POD. RESULTS: The occurrence of POD was 18.7% (228 of 2398 patients). The risk factors of POD included old age (OR 4.38, 95% CI 2.77-6.91; p < 0.001), American Society of Anesthesiology physical status > 2 (OR 1.84 95% CI 1.4-2.42; p < 0.001), dementia (OR 1.99, 95% CI 1.53-2.6; p < 0.001), steroid (OR 0.53 95% CI 0.34-0.82; p < 0.001), Antihistamine (OR 1.53 95% CI 1.19-1.96; p < 0.001), and postoperative erythrocyte sedimentation rate (mm/h) (OR 0.97 95% CI 0.97-0.98; p < 0.001) in multivariate logistic regression analysis. The postoperative transfusion (OR 2.53, 95% CI 1.88-3.41; p < 0.001) had a significant effect on the incidence of POD. CONCLUSIONS: big data analytics using a CDW was a good option to identify the risk factors of POD and to prevent POD in hip fracture surgery.

The Role of ROR1 in Chemoresistance and EMT in Endometrial Cancer Cells.

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.

Effectiveness of orthopedic implant removal surgery in patients with no implant-related symptoms after fracture union of isolated lower extremity shaft fractures: patient-centered evaluation.

INTRODUCTION: Routine orthopedic implant removal surgery (OIRS) in patients with no implant-related symptoms after union is controversial. Various factors, such as various fracture sites, fracture types, and accompanying fractures at other sites, act as error variables in the evaluation of routine OIRS. The purpose of this study is to evaluate the benefits of orthopedic implant removal surgery (OIRS) in patients with no implant-related symptoms such as infection and soft tissue irritation after union of isolated lower extremity shaft fractures from a patient-centered evaluation MATERIALS AND METHODS: Eighty-four patients who achieved fracture union after internal fixation of femoral shaft or tibial shaft fractures (March 2004 to December 2018) and who showed no implant-related symptoms were evaluated retrospectively. Minimum post-OIRS follow-up period was 1 year. Thirty-eight patients were treated with intramedullary nail and 13 were treated with plate and screws for femoral shaft fracture. Twenty patients were treated with intramedullary nail and 13 were treated with plate and screws for tibial shaft fracture. All patients subsequently underwent OIRS. Quality of life (QoL) and lower extremity pain using visual analogue scale (VAS) were evaluated 1 day before OIRS. Patient satisfaction with the OIRS, VAS, and QoL were assessed at least 1 year after OIRS using the SF-36 questionnaire. RESULTS: The physical component score, mental component score, and scores of all eight domains showed significant improvement after OIRS (p < 0.01). Patients with femoral shaft fractures tended to have lower pre- and post-OIRS SF-36 scores than those with tibial shaft fracture. Among patients with femoral shaft fracture, SF-36 scores were comparable in the nail and plate groups. Among patients with tibial shaft fracture, nail group showed relatively better QoL than the plate group, before and after OIRS in spite of several complications such as formation of scar tissue, nerve damage, and refracture. CONCLUSIONS: Patients with no implant-related symptoms showed significant improvement in QoL and satisfaction after OIRS. This suggests that OIRS is beneficial from the patients' evaluation. LEVEL OF EVIDENCE: Therapeutic Level II.

Design of Surface-Aligned Main-Chain Liquid-Crystal Networks Prepared under Ambient, Light-Free Conditions Using the Diels-Alder Cycloaddition.

Surface-aligned liquid-crystal networks (LCNs) offer a solution for developing functional materials capable of performing a range of tasks, including actuation, shape memory, and surfaces patterning. Here we show that Diels-Alder cycloaddition can be used to prepare the backbone of planar aligned LCNs under mild ambient conditions without the addition of additives or UV irradiation. The mechanical properties of the networks have robust viscoelastic modulus and stiffness with a reversible local free volume change upon physical aging. This study shows new opportunities to design surface-aligned LCNs based on additive free step-growth Diels-Alder polymerization and enables the potential to incorporate a wider range of photochromic materials into LCNs.

Association of Serum Liver Enzymes with Brain Amyloidopathy and Cognitive Performance.

Background: Alzheimer's disease (AD) is characterized by amyloid-ß (Aß) plaque accumulation and neurofibrillary tangles in the brain. Emerging evidence has suggested potential interactions between the brain and periphery, particularly the liver, in regulating Aß homeostasis. Objective: This study aimed to investigate the association of serum liver enzymes with brain amyloidopathy and cognitive performance in patients with complaints of cognitive decline. Methods: A total of 1,036 patients (mean age 74 years, 66.2% female) with subjective cognitive decline, mild cognitive impairment, AD dementia, and other neurodegenerative diseases were included using the Smart Clinical Data Warehouse. Amyloid positron emission tomography (PET) imaging, comprehensive neuropsychological evaluations, and measurements of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, and albumin, were assessed. After propensity score matching, logistic and linear regression analyses were used to investigate the associations between liver enzymes, amyloid status, and cognitive performance. Additionally, a machine learning approach was used to assess the classification performance of liver enzymes in predicting amyloid PET positivity. Results: Lower ALT levels and higher AST-to-ALT ratios were significantly associated with amyloid PET positivity and AD diagnosis. The AST-to-ALT ratio was also significantly associated with poor memory function. Machine learning analysis revealed that the classification performance of amyloid status (AUC = 0.642) for age, sex, and apolipoprotein E ɛ4 carrier status significantly improved by 6.2% by integrating the AST-to-ALT ratio. Conclusions: These findings highlight the potential association of liver function on AD and its potential as a diagnostic and therapeutic implications.

Immunomodulatory Effects of Primed Tonsil-Derived Mesenchymal Stem Cells on Atopic Dermatitis via B Cell Regulation.

Mesenchymal stem cells (MSCs) ameliorate T-and B cell-mediated immune responses. In particular, tonsil-MSCs (T-MSCs) are attractive candidates for practical and clinical applications because of their ease of acquisition and relatively low immunogenicity compared with other MSC sources. The use of MSCs as a therapeutic tool in atopic dermatitis (AD) has been investigated, but that of T-MSCs remains to be explored. Therefore, we investigated the immunomodulatory effects of primed T-MSCs in AD pathogenesis. In our animal study, primed T-MSCs showed greater immunological suppressive effects than naïve T-MSCs. Additionally, in vitro, the proliferation of B cells was downregulated by the addition of primed T-MSCs compared with naïve T-MSCs. The activation of B cells to differentiate into antibody-secreting cells and produce IgE was also reduced when primed T-MSCs were added. Moreover, under CD40-knockdown conditions, we found that CD40 in primed T-MSCs played a critical role as a regulator of B cell activation and was mediated by the non-canonical NF-κB pathway. Therefore, our findings suggest a promising role for primed T-MSCs in the treatment of AD by regulating B cell-mediated inflammatory responses, which are dependent on CD40 expression on primed T-MSCs mediated through the non-canonical NF-κB pathway.

Meta-Analysis of Survival Effects of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1).

Background and Objectives: Identification and targeting of membrane proteins in tumor cells is one of the key steps in the development of cancer drugs. The receptor tyrosine kinase-like orphan receptor (ROR) type 1 is a type-I transmembrane protein expressed in various cancer tissues, which is in contrast to its limited expression in normal tissues. These characteristics make ROR1 a candidate target for cancer treatment. This study aimed to identify the prognostic value of ROR1 expression in cancers. Materials and Methods: We conducted a comprehensive systematic search of electronic databases (PubMed) from their inception to September 2021. The included studies assessed the effect of ROR1 on overall survival (OS) and progression-free survival (PFS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using Revman version 5.4 with generic inverse-variance and random effects modeling. Results: A total of fourteen studies were included in the final analysis. ROR1 was associated with worse OS (HR 1.95, 95% confidence interval (CI) 1.50−2.54; p < 0.001) with heterogeneity. The association between poor OS and ROR1 expression was high in endometrial cancer, followed by ovarian cancer, and diffuse large B cell lymphoma. In addition, ROR1 was associated with poor PFS (HR 1.84, 95% CI 1.60−2.10; p < 0.001), but heterogeneity was not statistically significant. In subgroup analysis, high ROR1 expression showed a significantly higher rate of advanced stage or lymph node metastasis. Conclusions: This meta-analysis provides evidence that ROR1 expression is associated with adverse outcome in cancer survival. This result highlights ROR1 as a target for developmental therapeutics in cancers.

ROS- and pH-Responsive Polydopamine Functionalized Ti3C2Tx MXene-Based Nanoparticles as Drug Delivery Nanocarriers with High Antibacterial Activity.

Premature drug release and poor controllability is a challenge in the practical application of tumor therapy, which may lead to poor chemotherapy efficacy and severe adverse effects. In this study, a reactive oxygen species (ROS)-cleavable nanoparticle system (MXene-TK-DOX@PDA) was designed for effective chemotherapy drug delivery and antibacterial applications. Doxorubicin (DOX) was conjugated to the surface of (3-aminopropyl)triethoxysilane (APTES)-functionalized MXene via an ROS-cleavable diacetoxyl thioketal (TK) linkage. Subsequently, the surfaces of the MXene nanosheets were coated with pH-responsive polydopamine (PDA) as a gatekeeper. PDA endowed the MXene-TK-DOX@PDA nanoparticles with superior biocompatibility and stability. The MXene-TK-DOX@PDA nanoparticles had an ultrathin planar structure and a small lateral size of approximately 180 nm. The as-synthesized nanoparticles demonstrated outstanding photothermal conversion efficiency, superior photothermal stability, and a remarkable extinction coefficient (23.3 L g-1 cm-1 at 808 nm). DOX exhibited both efficient ROS-responsive and pH-responsive release performance from MXene-TK-DOX@PDA nanoparticles due to the cleavage of the thioketal linker. In addition, MXene-TK-DOX@PDA nanoparticles displayed high antibacterial activity against both Gram-negative Escherichia coli (E. coli) and Gram-positive Bacillus subtilis (B. subtilis) within 5 h. Taken together, we hope that MXene-TK-DOX@PDA nanoparticles will enrich the drug delivery system and significantly expand their applications in the biomedical field.