Comparative profiling of the absorbed compounds and metabolites, and pharmacokinetic studies of Danshen-Chuanxiong herb pair in rat plasma and brain using liquid chromatography-tandem mass spectrometry.

Danshen-Chuanxiong (DS-CX) was a classic herb pair commonly used to treat ischemic stroke. Nevertheless, the metabolic conversion and pharmacokinetic behavior of DS-CX in vivo remains unclear. This work aimed to reveal the in vivo metabolic behavior of DS-CX through establishing metabolic profiles and performing multicomponent pharmacokinetics analysis. The mass defect filtering (MDF) strategy integrated with UHPLC-QTOF-MS was firstly developed to characterize the metabolites of DS-CX in rats' plasma and brain. Moreover, a sensitive UHPLC-QQQ-MS method was utilized to perform the comparative pharmacokinetic studies of major active ingredients of DS-CX in rats' plasma. A total of 111 exogenous compounds (29 prototype compounds and 82 metabolites) were identified in rat biological samples. The major metabolic pathways were hydroxylation, methylation, deoxidation, dehydration, hydrogenation, demethylation, hydrolysis, decarboxylation and glucuronidation binding reactions. According to the results of metabolites profiling, sixteen active compounds (8 phenolic acids, 5 phthalides and 3 tanshinones) were selected as markers for further comparative pharmacokinetics study. Compared with the oral administration of DS or CX alone, the higher Cmax of salvianolic acid B, crytotanshinone and tanshinone IIA; the shorter Tmax of lithospermic acid, rosmarinic acid and tanshinone IIA; as well as the higher AUC0-∞ of ferulic acid, rosmarinic acid, salvianolic acid B, senkyunolide I and crytotanshinone, could be found after co-administration of DS-CX (P < 0.05). This study provided the overall knowledge of metabolites profiling of DS-CX in vivo, which would help to understand the effective material basis and promote the clinical application of DC-CX herb pair.

CT surveillance for type 1 autoimmune pancreatitis: cumulative radiation dose and diagnostic performance for disease relapse.

OBJECTIVES: Long-term follow-up is essential for type 1 autoimmune pancreatitis (AIP) patients due to high relapse rates. The cumulative radiation dose from repeated CT scans during follow-up should not be ignored. We aim to investigate the cumulative radiation dose in AIP patients undergoing CT surveillance and the diagnostic performance of CT in detecting disease relapse. The diagnostic performance of MRI from a secondary cohort during the same period was also investigated. METHODS: This retrospective single-institutional study included 247 type 1 AIP patients with one or more follow-up CT scans, and 120 patients with MR follow-ups. Four metrics were utilized to report the radiation dose, including the volume computed tomography dose index, the dose length product, size-specific dose estimate and effective dose. The diagnostic performance for AIP relapse was assessed, taking the final clinical diagnosis in retrospect as the reference standard. RESULTS: With a median 2.3-year follow-up period, AIP patients followed up with CT exhibited a median cumulative radiation dose of 37.5 mSv. 11.3% of patients have accumulated doses exceeding 100 mSv. For the 169 patients followed over a year, 30.8% sustained an average annual radiation dose surpassing 20 mSv. The sensitivity/specificity/accuracy of CT for detecting abdominal organ relapse was 64.1%/99.6%/97.0%. For AIP patients followed up with MRI, the sensitivity for detecting disease relapse was 90.5%. CONCLUSION: Considering the accumulation of radiation dose in AIP patients and the insufficient sensitivity in detecting disease relapse with CT, safer and more sensitive imaging follow-up strategies should be explored. KEY POINTS: Question CT, as the primary imaging modality for autoimmune pancreatitis (AIP) follow-up, raises concerns regarding radiation exposure and lacks reported diagnostic performance in detecting AIP relapse. Findings CT in AIP follow-up causes significant cumulative radiation exposure and exhibits insufficient sensitivity in relapse detection. Clinical relevance Type 1 AIP necessitates long-term imaging follow-up, yet current guidelines lack consensus regarding the prioritization of CT or MRI for such follow-up. CT is widely used but has radiation concerns and limited sensitivity, calling for safer, efficient strategies.

Fully Interpretable Deep Learning Model Using IR Thermal Images for Possible Breast Cancer Cases.

Breast cancer remains a global health problem requiring effective diagnostic methods for early detection, in order to achieve the World Health Organization's ultimate goal of breast self-examination. A literature review indicates the urgency of improving diagnostic methods and identifies thermography as a promising, cost-effective, non-invasive, adjunctive, and complementary detection method. This research explores the potential of using machine learning techniques, specifically Bayesian networks combined with convolutional neural networks, to improve possible breast cancer diagnosis at early stages. Explainable artificial intelligence aims to clarify the reasoning behind any output of artificial neural network-based models. The proposed integration adds interpretability of the diagnosis, which is particularly significant for a medical diagnosis. We constructed two diagnostic expert models: Model A and Model B. In this research, Model A, combining thermal images after the explainable artificial intelligence process together with medical records, achieved an accuracy of 84.07%, while model B, which also includes a convolutional neural network prediction, achieved an accuracy of 90.93%. These results demonstrate the potential of explainable artificial intelligence to improve possible breast cancer diagnosis, with very high accuracy.

The dysfunction of complement and coagulation in diseases: the implications for the therapeutic interventions.

The complement system, comprising over 30 proteins, is integral to the immune system, and the coagulation system is critical for vascular homeostasis. The activation of the complement and coagulation systems involves an organized proteolytic cascade, and the overactivation of these systems is a central pathogenic mechanism in several diseases. This review describes the role of complement and coagulation system activation in critical illness, particularly sepsis. The complexities of sepsis reveal significant knowledge gaps that can be compared to a profound abyss, highlighting the urgent need for further investigation and exploration. It is well recognized that the inflammatory network, coagulation, and complement systems are integral mechanisms through which multiple factors contribute to increased susceptibility to infection and may result in a disordered immune response during septic events in patients. Given the overlapping pathogenic mechanisms in sepsis, immunomodulatory therapies currently under development may be particularly beneficial for patients with sepsis who have concurrent infections. Herein, we present recent findings regarding the molecular relationships between the coagulation and complement pathways in the advancement of sepsis, and propose potential intervention targets related to the crosstalk between coagulation and complement, aiming to provide more valuable treatment of sepsis.

Physiological, biochemical, and transcriptomic alterations in Castor (Ricinus communis L.) under polyethylene glycol-induced oxidative stress.

BACKGROUND: Castor is an important industrial raw material. Drought-induced oxidative stress leads to slow growth and decreased yields in castor. However, the mechanisms of drought-induced oxidative stress in castor remain unclear. Therefore, in this study, physiological, biochemical, and RNA-seq analyses were conducted on the roots of castor plants under PEG-6000 stress for 3 d and 7 d followed by 4 d of hydration. RESULTS: The photosynthetic rate of castor leaves was inhibited under PEG-6000 stress for 3 and 7 d. Biochemical analysis of castor roots stressed for 3 d and 7 d, and rehydrated for 4 d revealed that the activities of APX and CAT were highest after only 3 d of stress, whereas the activities of POD, GR, and SOD peaked after 7 d of stress. RNA-seq analysis revealed 2926, 1507, and 111 differentially expressed genes (DEGs) in the roots of castor plants under PEG-6000 stress for 3 d and 7 d and after 4 d of rehydration, respectively. GO analysis of the DEGs indicated significant enrichment in antioxidant activity. Furthermore, KEGG enrichment analysis of the DEGs revealed significantly enriched metabolic pathways, including glutathione metabolism, fatty acid metabolism, and plant hormone signal transduction. WGCNA identified the core genes PP2C39 and GA2ox4 in the navajowhite1 module, which was upregulated under PEG-6000 stress. On the basis of these results, we propose a model for the response to drought-induced oxidative stress in castor. CONCLUSIONS: This study provides valuable antioxidant gene resources, deepening our understanding of antioxidant regulation and paving the way for further molecular breeding of castor plants.

Fast Determination of Propofol in Human Plasma Using C18-Functionalized Magnetic Nanomaterials Followed by Supercritical Fluid Chromatography.

Novel C18-functionalized magnetic nanomaterials; i.e., C18@poly-styrene-divinylbenzene-glycidyl methacrylate-Fe3O4 (C18@PS-DVB-GMA-Fe3O4) have been synthesized by using N, N-dimethyloctadecylamine as modifying agent, which could be beneficial to remove the blood phospholipids. The C18@PS-DVB-GMA-Fe3O4 nanoparticles have been used and evaluated in the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) procedure for human plasma prior to the analysis of propofol by supercritical fluid chromatography (SFC). In the QuEChERS procedure, human plasma samples are directly mixed with extraction solvent and C18@PS-DVB-GMA-Fe3O4 nanoparticles, and the extraction and cleanup procedures have been accomplished simultaneously. The SFC separation was performed with a C18 column (Thermo Scientific™ Acclaim™ 120, 250 × 4. 6 mm, 5 µm) within 5 min, using thymol as the internal standard. Supercritical carbon dioxide was used as the mobile phase with methanol as the cosolvent at the flow rate of 1.0 mL/min. The column temperature was 38°C, and detection wavelength was 275 nm. A good linearity was obtained among the propofol concentration range of 0.5-10 mg/L (R2 = 0.9997) with the limit of detection of 0.17 mg/L. Recoveries were in the range of 76.5-91.9%, with RSD less than 7.9%. These results suggested that method is convenient, rapid with high accuracy and little matrix effect, and suitable for rapid determination of propofol plasma concentration.

Reactive Fluorescent and Colorimetric Probe for Highly Selective and Sensitive Detection of Hg2+ in Real Water Samples.

Construction of efficient chemosensors for highly specific and sensitive detection of mercury ions remains a great challenge. In this work a highly selective and sensitive probe CY was designed and synthesized by using coumarin fluorophore as the matrix and thioacetal moiety as the reactive recognition site for Hg2+. By virtue of the thiophilicity of Hg2+, probe CL could be hydrolyzed to deprotect and the thioacetal was transformed to the acyl group after the addition of Hg2+, the blue-green fluorescence was quenched and meanwhile the solution changed from light green to yellow. The detection limit of probe CY for Hg2+ was as low as 6.8 nM, and it could completely react with Hg2+ within 3 min. Moreover, probe CY exhibited good resistance against interference from competitive metal ions and biothiols, high stability in pH 1-11 and applicability for fluorogenic and chromogenic dual-modal detection of Hg2+ in real water samples over a broad range of pH 5-10.

Tuning Nanochannel Microenvironments of a Thermoresponsive MXene Membrane for Mixed Molecule Gradient Separation.

Drawing inspiration from dynamic biological ion channels, researchers have developed various artificial membranes featuring responsive nanochannels. Typically, these membranes modify mass transport behaviors by manipulating the responsive layer on the inner surfaces of the intrinsic layer. In this study, we build two-dimensional lamellar membranes composed of titanium carbide MXene and poly(N-isopropylacrylamide), endowed with dual-level regulatable nanochannels, achieved through adjustments of nanochannel microenvironments. The size of these two-dimensional nanochannels can be altered by both the thermoresponsive polymer layer and the intrinsic MXene layer that could undergo spontaneous oxidation. The multilevel regulation strategy substantially enhances the molecular selectivity of MXene separation membranes, which is further applied for precise gradient separation toward multiple molecules. This advancement showcases the versatility and transformative capabilities of responsive nanochannel technology, setting the stage for innovative developments in diverse fields.

Psychosocial profiles influencing healthy dietary behaviors among adolescents in Shandong Province, China: a cross-sectional study.

Objectives: We aimed to assess the influence of psychosocial profiles on dietary behaviors among school-aged adolescents in China. Methods: A cross-sectional study was conducted involving 7,862 adolescents from 100 schools in Shandong, China. Psychosocial profiles and dietary behaviors were assessed using the Junior High School Students' Psychosocial Profiles Questionnaire (JPPQ) and the Chinese Diet Quality Questionnaire (DQQ), respectively. Linear regression models were used to investigate the association between adolescents' psychosocial profiles and dietary behaviors. Results: The mean age of the participants was 13.18 ± 1.15 years; 48.5% of them were boys. The majority of participants (97.90%) were Han Chinese, and approximately half of the participants (50.90%) resided in rural areas. After adjusting for sociodemographic characteristics and family computer and Internet ownership and usage, healthy dietary behavior was positively correlated with higher psychosocial profile scores (p < 0.05). The stratified analysis results revealed that the group with the highest psychosocial profile score was associated with an increased overall global dietary reference (GDR) score in "households without a family computer and Internet" ( ß : 5.357, 95% Cl: 4.931-5.784, p < 0.05). Conclusion: Good psychosocial profiles exhibit a positive influence on healthy dietary behaviors. Therefore, policymakers should focus on Internet usage to maximize the positive effects on global youth health behaviors.

Functionalized Quasi-Solid-State Electrolytes in Aqueous Zn-Ion Batteries for Flexible Devices: Challenges and Strategies.

The rapid development of wearable and intelligent flexible devices has posed strict requirements for power sources, including excellent mechanical strength, inherent safety, high energy density, and eco-friendliness. Zn-ion batteries with aqueous quasi-solid-state electrolytes (AQSSEs) with various functional groups that contain electronegative atoms (O/N/F) with tunable electron accumulation states are considered as a promising candidate to power the flexible devices and tremendous progress has been achieved in this prospering area. Herein, this review proposes a comprehensive summary of the recent achievements using the AQSSE in flexible devices by focusing on the significance of different functional groups. The fundamentals and challenges of the ZIBs are introduced from a chemical view in the first place. Then, the mechanism behind the stabilization of the flexible ZIBs with the functionalized AQSSE is summarized and explained in detail. Then the recent progress regarding the enhanced electrochemical stability of the ZIBs with the AQSSE is summarized and classified based on the functional groups on the polymer chain. The advanced characterization methods for the AQSSE are briefly introduced in the following sections. Last but not least, current challenges and future perspectives for this promising area are provided from the authors' point of view.

Retinol metabolism signaling participates in microbiota-regulated fat deposition in obese mice.

Obesity is a global pandemic threatening public health, excess fat accumulation and overweight are its characteristics. In this study, the interplay between gut microbiota and retinol metabolism in modulating fat accumulation was verified. We observed gut microbiota depletion reduced the body weight (P<0.05) and the ratios of white adipose tissues (WATs) to body weight (P<0.05) in high-fat diet (HFD) fed-mice. Both the hepatic metabolomics and transcriptomics analyses confirmed that gut microbiota modulated fat accumulation in obese mice. Besides, the kyoto encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network of RNA-seq results indicated that retinol metabolism signaling may be involved in the microbiota-regulated fat deposition. Furthermore, activated retinol metabolism signaling by all-trans retinoic acid (atRA) supplementation reduced body weight (P<0.05) and WAT accumulation in obese mice. On the other hand, 16S rRNA gene sequencing of the ileal microbiota suggested that atRA supplementation, in turn, increased the microbial diversity and induced the growth of beneficial bacteria including Parabacteroides, Bacteroides, Clostridium_XVIII, Bifidobacterium, Enterococcus, Bacillus, Leuconostoc, and Lactobacillus in obese mice. Spearman correlation showed that atRA decreased the bacteria (Parvibacter, Asaccharobacter, Romboutsia, and Clostridium_IV) that were positively associated with body and WAT weights, whereas increased the bacteria (Lactobacillus) that were negatively associated with body and WAT weights. Together, this study reveals the interaction between the gut microbiota and retinol metabolism signaling in regulating adipose accumulation and obesity. It is expected of this finding to provide new insights to prevent and develop therapeutic measures of obesity-related metabolic syndrome.

[Establishment of rabbit knee osteoarthritis model by simple anterior cruciate ligament disruption].

OBJECTIVE: The rabbit knee osteoarthritis(KOA) model was established by simple anterior cruciate ligament disruption. METHODS: The selected 40 adult white rabbits were randomly divided into two groups, blank group with 6 rabbits and model group with 34 rabbits. The rabbits in model group were given the disruption of anterior cruciate ligament of right knee joint. In the fourth, eighth and the twelfth weeks of modeling, different degrees of degenerative changes have been observed on the rabbits articular cartilages from both macroscopic and microscopic aspects. RESULTS: At 4, 8 and 12 weeks after modeling, the articular cartilage of the rabbits in the model group showed degenerative changes in different degrees. At 8 and 12 weeks, the typical pathological manifestations of KOA in the middle and late stages were found in the infrapatellar fat pad and synovium, respectively. There were no changes in articular cartilage, infrapatellar fat pad and synovial membrane in the blank group at the same time. There were significant differences in the gross score between the model group and the blank group at 4 weeks [(1.300±0.674) vs 0.000], 8 weeks [(2.400±0.516) vs 0.000] and 12 weeks [(3.583±0.668) vs 0.000] (P<0.05), the histopathological scores were significantly different, at 4 weeks [(2.900±0.567) vs 0.000], 8 weeks [(7.500±1.178) vs (0.500±0.707)], 12 weeks[(11.833±1.337) vs (1.500±0.707)], (P<0.05). CONCLUSION: The establishment of rabbit knee arthritis model by simply cutting the anterior cruciate ligament is simple and feasible, with good stability, high success rate, small trauma, short modeling cycle and less changes in animal physiological structure. The rabbit knee arthritis model established by simply cutting the anterior cruciate ligament has good modeling effect on different stages and grades of knee osteoarthritis, and the postoperative infection and trauma can be controlled, which can meet the test requirements.

Enhancing Drug Solubility, Bioavailability, and Targeted Therapeutic Applications through Magnetic Nanoparticles.

Biological variability poses significant challenges in the development of effective therapeutics, particularly when it comes to drug solubility and bioavailability. Poor solubility across varying physiological conditions often leads to reduced absorption and inconsistent therapeutic outcomes. This review examines how nanotechnology, especially through the use of nanomaterials and magnetic nanoparticles, offers innovative solutions to enhance drug solubility and bioavailability. This comprehensive review focuses on recent advancements and approaches in nanotechnology. We highlight both the successes and remaining challenges in this field, emphasizing the role of continued innovation. Future research should prioritize developing universal therapeutic solutions, conducting interdisciplinary research, and leveraging personalized nanomedicine to address biological variability.

Co3O4-Induced Na2CO3-Rich SEI Film on an FeNCN Electrode with Promoted Loading and High-Rate Na-Storage Performance.

Iron carbodiimide (FeNCN) often suffers from unstable interfacial structure with an unexpected failure of Na-ion storage performance. In this work, Co3O4 particles were deposited on the surface of FeNCN. This Co3O4 nanolayer led to the formation of a Na2CO3-rich inorganic component SEI film to enhance the stability of a promoted-loading FeNCN electrode interface with fast Na+ migration pathway. Benefitting from this strategy, the FeNCN electrode could present a capacity retention rate of 99.95% per cycle after 1500 cycles at 1 A g-1. The design of interfacial structure in a promoted-loading electrode could be a reference for stable and high-rate performance of carbodiimide-based materials.

Identifying modifiable factors associated with neuroimaging markers of brain health.

AIMS: Brain structural alterations begin long before the presentation of brain disorders; therefore, we aimed to systematically investigate a wide range of influencing factors on neuroimaging markers of brain health. METHODS: Utilizing data from 30,651 participants from the UK Biobank, we explored associations between 218 modifiable factors and neuroimaging markers of brain health. We conducted an exposome-wide association study using the least absolute shrinkage and selection operator (LASSO) technique. Restricted cubic splines (RCS) were further employed to estimate potential nonlinear correlations. Weighted standardized scores for neuroimaging markers were computed based on the estimates for individual factors. Finally, stratum-specific analyses were performed to examine differences in factors affecting brain health at different ages. RESULTS: The identified factors related to neuroimaging markers of brain health fell into six domains, including systematic diseases, lifestyle factors, personality traits, social support, anthropometric indicators, and biochemical markers. The explained variance percentage of neuroimaging markers by weighted standardized scores ranged from 0.5% to 7%. Notably, associations between systematic diseases and neuroimaging markers were stronger in older individuals than in younger ones. CONCLUSION: This study identified a series of factors related to neuroimaging markers of brain health. Targeting the identified factors might help in formulating effective strategies for maintaining brain health.

STASCAN deciphers fine-resolution cell distribution maps in spatial transcriptomics by deep learning.

Spatial transcriptomics technologies have been widely applied to decode cellular distribution by resolving gene expression profiles in tissue. However, sequencing techniques still limit the ability to create a fine-resolved spatial cell-type map. To this end, we develop a novel deep-learning-based approach, STASCAN, to predict the spatial cellular distribution of captured or uncharted areas where only histology images are available by cell feature learning integrating gene expression profiles and histology images. STASCAN is successfully applied across diverse datasets from different spatial transcriptomics technologies and displays significant advantages in deciphering higher-resolution cellular distribution and resolving enhanced organizational structures.

Genetic profiling and PVY resistance identification of potato germplasm resources.

Excellent germplasm resources are the foundation for cultivating high-quality, disease-resistant, and stress-tolerant varieties. In this study, simple sequence repeat (SSR) markers were used to identify 138 potato accessions collected from worldwide, and genetic cluster analysis was used to characterize the genetic diversity of the tested germplasm resources. The Potato virus Y (PVY) resistance of these potato accessions was identified by artificial friction inoculation combined with molecular marker detection, and potato accessions with different PVY resistance were screened based on disease index and incidence rate. Using SSR markers, 138 potato accessions were identified, and the results showed that the genetic distances between the tested potato germplasm resources ranged from 0.025 to 0.660, and the genetic similarity coefficients ranged from 0.489 to 0.975. The 138 accessions could be clustered into five subgroups using Unweighted Pair-Group Method with Arithmetic Mean (UPGMA). Among them, Z173, Biyin No. 4, Suyin No. 2, XN995, XN987, Biyin No 22, Bibiao104, Sarpo mira, XN996, XN979, Desiree, RUNSHI, Actrice, Jia 1219, Heyin No 12, and Moyin No.1 have relatively distant genetic relationship with another 122 accessions. Based on the disease index, the following different accessions were screened: five highly resistant, 11 resistant, 45 moderately resistant, 35 susceptible, and 42 highly susceptible. Fourteen resource materials with good resistance (disease index ≤ 33.74%, and a grading of high resistance (HR) or medium resistance (MR); incidence rate ≤ 67.58%) were identified. By combining genetic cluster analysis and PVY resistance identification, six accessions showed PVY resistance and had distant genetic relationships with other accessions selected which provided important materials for disease resistance breeding and quality improvement of potato. In this study, the genetic diversity and PVY resistance of global potato germplasm resources was explored, and potato germplasm materials with important utilization value were screened. The results obtained in this study could provide important references for the research and utilization of global potato germplasm resources.

Efficacy and safety of vancomycin for local application in the prevention of surgical site infection after joint arthroplasty: a systematic review and meta-analysis.

Purpose: The aim of this systematic review and meta-analysis is to explore the effect of topical vancomycin powder (VP) in surgical site infection (SSI) prevention and adverse events after joint arthroplasty and to provide a specific theoretical basis for clinical treatment. Methods: The review process was conducted according to the PRISMA guidelines. Two independent researchers meticulously screened the literature based on predefined inclusion and exclusion criteria, evaluated the quality of the selected studies, and extracted relevant data. Data analysis was conducted using RevMan 5.4 software. Results: This meta-analysis included 24 studies encompassing a total of 34 811 patients. The pooled analysis showed that the topical administration of VP significantly reduced the incidence of SSI. Subgroup analyses by doses, type of joint (hip and knee), and type of surgery (primary and revision) confirmed that vancomycin consistently lowered SSI rates. Moreover, the incidence of SSI caused by gram-negative germs and gram-positive germs decreased following the use of VP, although the reduction was not significant for infections caused by MRSA. However, the use of VP was associated with a significant increase in sterile complications at the incision site and delayed incision healing. Conclusion: The topical application of VP is effective in reducing the incidence of infections following joint arthroplasty. Despite an increased risk of complications such as delayed healing of incisions, the pros and cons should be weighed in clinical decision-making. However, it should not be discarded due to side effects.

Clinical outcomes of endoscopic balloon dilation for refractory esophageal strictures after esophageal atresia repair.

BACKGROUND: Managing refractory esophageal strictures (RES) presents formidable challenges. Although endoscopic balloon dilation (EBD) is the first step for esophageal stricture, the clinical outcomes of EBD for RES after esophageal atresia (EA) repair are not established. METHODS: All EA patients with esophageal balloon strictures (EBS) from October 2016 to October 2022 treated by EBD in our institution were retrospectively reviewed. The primary endpoint was to evaluate the clinical outcomes and the risk factors for poor outcomes of EBD for RES. The secondary endpoint was to evaluate the risk factors for pathological weight in RES patients. RESULTS: 87 patients with RES were included in our study. After the first session of EBDs, 40.2 % experienced a recurrence of esophageal strictures. The median number (IQR) of the first session of EBD was 13.0 (8.0, 16.0), and the median number (IQR) of total dilations of achieving long-term clinical success was 14.0 (10.0, 19.0) with 81.6 % achieving long-term clinical success with less than 20 EBDs. In follow-up, all patients achieved a total oral diet. On multivariable analysis, the presence of GERD (OR 4.17, 95%Cl 1.29-13.51, p = 0.017), LGEA (long-gap esophageal atresia) (OR 5.19, 95 % Cl 1.15-23.52, p = 0.033), eccentric stricture shape (OR 3.34, 95%Cl 1.06-10.53, p = 0.040), and longer stricture length (OR 10.22, 95%Cl 1.14-92.01, p = 0.038) were statistically significant associated with increased endoscopic dilations. The presence of LGEA (OR 3.25, 95%Cl 1.03-10.20, p = 0.044) was significantly associated with recurrence after short-term clinical success. Additionally, Older age at first dilation after LEAP, stricture level at 1/3 upper (ref = 1/3 middle), and LGEA were identified as risk factors for developing pathological weight. CONCLUSION: Endoscopic balloon dilation is an effective method for treating RES after EA repair. GERD, LGEA, eccentric stricture shape, and longer stricture length are the risk factors for increased dilation times. Older age at first dilation after LEAP, stricture level at 1/3 upper, and LGEA were identified as risk factors for developing pathological weight.

Differentiation of CD166-positive hPSC-derived lung progenitors into airway epithelial cells.

The generation of lung epithelial cells through the directed differentiation of human pluripotent stem cells (hPSCs) in vitro provides a platform to model both embryonic lung development and adult airway disease. Here, we describe a robust differentiation protocol that closely recapitulates human embryonic lung development. Differentiating cells progress through obligate intermediate stages, beginning with definitive endoderm formation and then patterning into anterior foregut endoderm that yields lung progenitors (LPs) with extended culture. These LPs can be purified using the cell surface marker CD166 (also known as ALCAM), and further matured into proximal airway epithelial cells including basal cells, secretory cells and multiciliated cells using either an organoid platform or culture at the air-liquid interface (ALI). We additionally demonstrate that these hPSC-derived airway epithelial cells can be used to model Influenza A infection. Collectively, our results underscore the utility of CD166 expression for the efficient enrichment of LPs from heterogenous differentiation cultures and the ability of these isolated cells to mature into more specialized, physiologically relevant proximal lung cell types.