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1.
BMC Gastroenterol ; 24(1): 156, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720257

ABSTRACT

BACKGROUND: Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. METHODS: Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. RESULTS: The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. CONCLUSIONS: MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.


Subject(s)
Adenocarcinoma , Carcinoma, Mucoepidermoid , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Male , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Carcinoma, Mucoepidermoid/pathology , Carcinoma, Mucoepidermoid/mortality , Carcinoma, Mucoepidermoid/surgery , Female , Middle Aged , Retrospective Studies , Aged , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/surgery , Survival Rate , Lymphatic Metastasis/pathology , Kaplan-Meier Estimate , Prognosis , Sex Factors , Neoplasm Staging
3.
Adv Mater ; : e2401693, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733317

ABSTRACT

Flexible metal-organic framework (MOF) adsorbents commonly encounter limitations in removing trace impurities below gate-opening threshold pressures. Topology reconfiguration can fundamentally eliminate intrinsic structural flexibility, yet remains a formidable challenge and is rarely achieved in practical applications. Herein, we present a solvent-mediated approach to regulate the flexible CuSnF6-dpds-sql (dpds = 4,4''-dipyridyldisulfide) with sql topology into rigid CuSnF6-dpds-cds with cds topology. Notably, the cds topology is unprecedented and firstly obtained in anion-pillared MOF materials. As a result, rigid CuSnF6-dpds-cds exhibits enhanced C2H2 adsorption capacity of 48.61 cm3 g-1 at 0.01 bar compared to flexible CuSnF6-dpds-sql (21.06 cm3 g-1). The topology transformation also facilitates the adsorption kinetics for C2H2, exhibiting a 6.5-fold enhanced diffusion time constant (D/r2) of 1.71 × 10-3 s-1 on CuSnF6-dpds-cds than that of CuSnF6-dpds-sql (2.64 × 10-4 s-1). Multiple computational simulations reveal the structural transformations and guest-host interactions in both adsorbents. Furthermore, dynamic breakthrough experiments demonstrate that high-purity C2H4 (>99.996%) effluent with a productivity of 93.9 mmol g-1 can be directly collected from C2H2/C2H4 (1/99, v/v) gas-mixture in a single CuSnF6-dpds-cds column. This article is protected by copyright. All rights reserved.

4.
Sci Rep ; 14(1): 10763, 2024 05 10.
Article in English | MEDLINE | ID: mdl-38730264

ABSTRACT

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.


Subject(s)
Cooking , Hearing Loss , Humans , Male , Hearing Loss/epidemiology , Hearing Loss/etiology , Hearing Loss/chemically induced , Female , Aged , China/epidemiology , Middle Aged , Longitudinal Studies , Cohort Studies , Aged, 80 and over , Adult , Risk Factors
5.
BMC Psychiatry ; 24(1): 352, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730288

ABSTRACT

BACKGROUND: To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . METHODS: The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. RESULTS: A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . CONCLUSION: The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.


Subject(s)
Bipolar Disorder , Comorbidity , Depressive Disorder, Major , Diagnostic Errors , Humans , Bipolar Disorder/diagnosis , Bipolar Disorder/epidemiology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Male , Female , Adult , Diagnostic Errors/statistics & numerical data , Middle Aged , China/epidemiology , Young Adult , Diagnostic and Statistical Manual of Mental Disorders
6.
Int J Mol Sci ; 25(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731886

ABSTRACT

The cerebrovascular endothelial cells with distinct characteristics line cerebrovascular blood vessels and are the fundamental structure of the blood-brain barrier, which is important for the development and homeostatic maintenance of the central nervous system. Cre-LoxP system-based spatial gene manipulation in mice is critical for investigating the physiological functions of key factors or signaling pathways in cerebrovascular endothelial cells. However, there is a lack of Cre recombinase mouse lines that specifically target cerebrovascular endothelial cells. Here, using a publicly available single-cell RNAseq database, we screened the solute carrier organic anion transporter family member 1a4 (Slco1a4) as a candidate marker of cerebrovascular endothelial cells. Then, we generated an inducible Cre mouse line in which a CreERT2-T2A-tdTomato cassette was placed after the initiation codon ATG of the Slco1a4 locus. We found that tdTomato, which can indicate the endogenous Slco1a4 expression, was expressed in almost all cerebrovascular endothelial cells but not in any other non-endothelial cell types in the brain, including neurons, astrocytes, oligodendrocytes, pericytes, smooth muscle cells, and microglial cells, as well as in other organs. Consistently, when crossing the ROSA26LSL-EYFP Cre reporter mouse, EYFP also specifically labeled almost all cerebrovascular endothelial cells upon tamoxifen induction. Overall, we generated a new inducible Cre line that specifically targets cerebrovascular endothelial cells.


Subject(s)
Brain , Endothelial Cells , Integrases , Animals , Mice , Endothelial Cells/metabolism , Integrases/metabolism , Integrases/genetics , Brain/metabolism , Gene Knock-In Techniques , Mice, Transgenic , Blood-Brain Barrier/metabolism , Organic Anion Transporters/genetics , Organic Anion Transporters/metabolism , Tamoxifen/pharmacology , Red Fluorescent Protein
7.
Cancer Lett ; : 216940, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38729554

ABSTRACT

Decreased levels of ß-hydroxybutyrate (BHB), a lipid metabolic intermediate known to slow the progression of colorectal cancer (CRC), have been observed in the colon mucosa of patients with inflammatory bowel diseases (IBD). In particular, patients with recurrent IBD present an increased risk of developing colitis-associated colorectal cancer (CAC). The role and molecular mechanism of BHB in the inflammatory and carcinogenic process of CAC remains unclear. Here, the anti-tumor effect of BHB was investigated in the (Azoxymethane) AOM /(Dextran Sulfate Sodium) DSS-induced CAC model and tumor organoids derivatives. The underlying mechanisms were studied using transcriptome and non-target metabolomic assay and further validated in colon tumor cell lineage CT26 in vitro. The tumor tissues and the nearby non-malignant tissues from colon cancer patients were collected to measure the expression levels of ketogenic enzymes. The exogenous BHB supplement lightened tumor burden and angiogenesis in the CAC model. Notably, transcriptome analysis revealed that BHB effectively decreased the expression of VEGFA in the CAC tumor mucosa. In vitro, BHB directly reduced VEGFA expression in hypoxic-treated CT26 cells by targeting transcriptional factor HIF-1α. Conversely, the deletion of HIF-1α largely reversed the inhibitory effect of BHB on CAC tumorigenesis. Additionally, decreased expression of ketogenesis-related enzymes in tumor tissues were associated with poor survival outcomes in patients with colon cancer. In summary, BHB carries out anti-angiogenic activity in CAC by regulating HIF-1α/VEGFA signaling. These findings emphasize the role of BHB in CAC and may provide novel perspectives for the prevention and treatment of colonic tumors.

8.
Sci Total Environ ; 932: 172864, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38697532

ABSTRACT

The increasing interfacial impacts of polystyrene nanoplastics (PS) and per- and polyfluoroalkyl substances (PFAS) complex aquatic environments are becoming more evident, drawing attention to the potential risks to aquatic animal health and human seafood safety. This study aims to investigate the relative impacts following exposure (7 days) of Crassostrea hongkongensis oysters to the traditional PFAS congener, perfluorooctanoic acid (PFOA) at 50 µg/L, and its novel alternative, hexafluoropropylene oxide dimer acid (HFPO-DA), also known as GenX at 50 µg/L, in conjunction with fluorescent polystyrene nanoplastics (PS, 80 nm) at 1 mg/L. The research focuses on assessing the effects of combined exposure on oxidative stress responses and gut microbiota in the C. hongkongensis. Comparing the final results of PS + GenX (PG) and PS + PFOA (PF) groups, we observed bioaccumulation of PS in both groups, with the former causing more pronounced histopathological damage to the gills and intestines. Furthermore, the content of antioxidant enzymes induced by PG was higher than that of PF, including Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR) and Glutathione Peroxidase (GSH). Additionally, in both PG and PF groups, the expression levels of several immune-related genes were significantly upregulated, including tnfα, cat, stat, tlr-4, sod, and ß-gbp, with no significant difference between these two groups (p > 0.05). Combined exposure induced significant changes in the gut microbiota of C. hongkongensis at its genus level, with a significant increase in Legionella and a notable decrease in Endozoicomonas and Lactococcus caused by PG. These shifts led to beneficial bacteria declining and pathogenic microbes increasing. Consequently, the microbial community structure might be disrupted. In summary, our findings contribute to a deeper understanding of the comparative toxicities of marine bivalves under combined exposure of traditional and alternative PFAS.

9.
Clin Chim Acta ; 559: 119716, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38710402

ABSTRACT

OBJECTIVE: To integrate an enhanced molecular diagnostic technique to develop and validate a machine-learning model for diagnosing sepsis. METHODS: We prospectively enrolled patients suspected of sepsis from August 2021 to August 2023. Various feature selection algorithms and machine learning models were used to develop the model. The best classifier was selected using 5-fold cross validation set and then was applied to assess the performance of the model in the testing set. Additionally, we employed the Shapley Additive exPlanations (SHAP) method to illustrate the effects of the features. RESULTS: We established an optimized mNGS assay and proposed using the copies of microbe-specific cell-free DNA per milliliter of plasma (CPM) as the detection signal to evaluate the real burden, with strong precision and high accuracy. In total, 237 patients were eligible for participation, which were randomly assigned to either the training set (70 %, n = 165) or the testing set (30 %, n = 72). The random forest classifier achieved accuracy, AUC and F1 scores of 0.830, 0.918 and 0.856, respectively, outperforming other machine learning models in the training set. Our model demonstrated clinical interpretability and achieved good prediction performance in differentiating between bacterial sepsis and non-sepsis, with an AUC value of 0.85 and an average precision of 0.91 in the testing set. Based on the SHAP value, the top nine features of the model were PCT, CPM, CRP, ALB, SBPmin, RRmax, CREA, PLT and HRmax. CONCLUSION: We demonstrated the potential of machine-learning approaches for predicting bacterial sepsis based on optimized mcfDNA sequencing assay accurately.

10.
Clinics (Sao Paulo) ; 79: 100376, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38733690

ABSTRACT

OBJECTIVE: This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). STUDY DESIGN: A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. RESULTS: General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). CONCLUSIONS: Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value.

11.
Heliyon ; 10(9): e30015, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707411

ABSTRACT

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

12.
Chemosphere ; : 142286, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38729439

ABSTRACT

Antibiotics are emerging organic pollutants that have attracted huge attention owing to their abundant use and associated ecological threats. The aim of this study is to develop and use photocatalysts to degrade antibiotics, including tetracycline (TC), ciprofloxacin (CIP), and amoxicillin (AMOX). Therefore, a novel Z-scheme heterojunction composite of g-C3N4 (gCN) and 3D flower-like Bi2WO6 (BW) perovskite structure was designed and developed, namely Bi2WO6/g-C3N4 (BW/gCN), which can degrade low-concentration of antibiotics in aquatic environments under visible light. According to the Density Functional Theory (DFT) calculation and the characterization results of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FITR), Scanning electron microscopy - energy spectroscopy (SEM-EDS) and X-ray photoelectron spectroscopy (XPS), this heterojunction was formed in the recombination process. Furthermore, the results of 15wt%-BW/gCN photocatalytic experiments showed that the photodegradation rates (Rp) of TC, CIP, and AMOX were 92.4%, 90.1% and 82.3%, respectively, with good stability in three-cycle photocatalytic experiments. Finally, the quenching experiment of free radicals showed that the holes (h+) and superoxide radicals (·O2-) play a more important role than the hydroxyl radicals (·OH) in photocatalysis. In addition, a possible antibiotic degradation pathway was hypothesized on the basis of High performance liquid chromatography (HPLC) analysis. In general, we have developed an effective catalyst for photocatalytic degradation of antibiotic pollutants and analyzed its photocatalytic degradation mechanism, which provides new ideas for follow-up research and expands its application in the field of antibiotic composite pollution prevention and control.

13.
ACS Infect Dis ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703116

ABSTRACT

In this study, we designed and synthesized a series of pleuromutilin derivatives containing thiazole. The in vitro antimicrobial efficacy of these synthesized compounds was examined by using four strains. Compared with tiamulin (MIC = 0.25 µg/mL), compound 14 exhibited potency in inhibiting MRSA growth (MIC = 0.0625 µg/mL) in these derivatives. Meanwhile, the time-killing kinetics further demonstrated that compound 14 could efficiently inhibit the MRSA growth. After exposure at 4 × MIC, the postantibiotic effect (PAE) of compound 14 was 1.29 h. Additionally, in thigh-infected mice, compound 14 exhibited a more potent antibacterial efficacy (-1.78 ± 0.28 log10 CFU/g) in reducing MRSA load compared to tiamulin (-1.21 ± 0.23 log10 CFU/g). Moreover, the MTT assay on RAW 264.7 cells demonstrated that compound 14 (8 µg/mL) had no significant cytotoxicity. Docking studies indicated the strong affinity of compound 14 toward the 50S ribosomal subunit, with a binding free energy of -9.63 kcal/mol. Taken together, it could be deduced that compound 14 was a promising candidate for treating MRSA infections.

14.
Perception ; : 3010066241253073, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725355

ABSTRACT

Observers can rapidly extract the mean emotion from a set of faces with remarkable precision, known as ensemble coding. Previous studies have demonstrated that matched physical backgrounds improve the precision of ongoing ensemble tasks. However, it remains unknown whether this facilitation effect still occurs when matched social information is perceived from the backgrounds. In two experiments, participants decided whether the test face in the retrieving phase appeared more disgusted or neutral than the mean emotion of the face set in the encoding phase. Both phases were paired with task-irrelevant animated backgrounds, which included either the forward movement trajectory carrying the "cooperatively chasing" information, or the backward movement trajectory conveying no such chasing information. The backgrounds in the encoding and retrieving phases were either mismatched (i.e., forward and backward replays of the same trajectory), or matched (i.e., two identical forward movement trajectories in Experiment 1, or two different forward movement trajectories in Experiment 2). Participants in both experiments showed higher ensemble precisions and better discrimination sensitivities when backgrounds matched. The findings suggest that consistent social information perceived from memory-related context exerts a context-matching facilitation effect on ensemble coding, and more importantly, this effect is independent of consistent physical information.

16.
Front Oncol ; 14: 1391835, 2024.
Article in English | MEDLINE | ID: mdl-38746671

ABSTRACT

Background: Lung segmentectomy has gained much more attention as an important surgical method for treating early-stage lung cancer. However, incomplete fissures increase the difficulty of lung segmentectomy. The aim of this study was to analyze the safety and efficacy of the fissure-first approach in precision resection of lung segments for patients with incomplete fissures. Methods: The clinical data of patients with incomplete fissures who underwent lung segmentectomy were retrospectively analyzed. Date was divided into fissure-first approach in lung segmentectomy group (group A) and fissure-last approach in lung segmentectomy group (group B). The general linear data, operation times, intraoperative adverse events, postoperative recovery dates and complications were compared. Results: A total of 122 patients with complete clinical data were included. Patients in group B had more COPD (p < 0.05), and the lesions in group A were more closely related to the hilum of the lung (p < 0.05). Compared to Group B, Group A achieved better surgical outcomes, such as operation time, postoperative hospital stays, intraoperative bleeding, number of intrapulmonary lymph nodes sampled, counts of resected subsegments (except the upper lobe of the right lung), and rate of conversion to thoracotomy (all p < 0.05). Conclusion: The fissure-first approach is a safe and effective surgical approach in lung segmentectomy for patients with incomplete fissures. This approach can reduce the counts of resected subsegments and improve techniques in lung segmentectomy for patients with lung incomplete fissures.

18.
Sci China Life Sci ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38748355

ABSTRACT

The COVID-19 pandemic has caused many fatalities worldwide and continues to affect the health of the recovered patients in the form of long-COVID. In this study, we compared the gut microbiome of uninfected infants and children before the pandemic began (BEFORE cohort, n=906) to that of after the pandemic (AFTER cohort, n=220) to examine the potential impact of social distancing and life habit changes on infant/children gut microbiome. Based on 16S rRNA sequencing, we found a significant change in microbiome composition after the pandemic, with Bacteroides enterotype increasing to 35.45% from 30.46% before the pandemic. qPCR quantification indicated that the bacterial loads of seven keystone taxa decreased by 91.69%-19.58%. Quantitative microbiome profiling, used to enhance the resolution in detecting microbiome differences, revealed a greater explained variance of pandemic on microbiome compared to gender, as well as a significant decrease in bacterial loads in 15 of the 20 major genera. The random forest age-predictor indicated the gut microbiomes were less mature in the after-pandemic cohort than in the before-pandemic cohort in the children group (3-12 years old) and had features of a significantly younger age (average of 1.86 years). Lastly, body weight and height were significantly lower in the after-pandemic cohort than in the before-pandemic cohort in infants (<1 year of age), which was associated with a decrease in bacterial loads in the fecal microbiome.

19.
Article in English | MEDLINE | ID: mdl-38743443

ABSTRACT

Strong precorneal clearance mechanisms including reflex blink, constant tear drainage, and rapid mucus turnover constitute great challenges for eye drops for effective drug delivery to the ocular epithelium. In this study, cyclosporine A (CsA) for the treatment of dry eye disease (DED) was selected as the model drug. Two strategies, PEGylation for mucus penetration and cationization for potent cellular uptake, were combined to construct a novel CsA nanosuspension (NS@lipid-PEG/CKC) by coating nanoscale drug particles with a mixture of lipids, DSPE-PEG2000, and a cationic surfactant, cetalkonium chloride (CKC). NS@lipid-PEG/CKC with the mean size ∼173 nm and positive zeta potential ∼+40 mV showed promoted mucus penetration, good cytocompatibility, more cellular uptake, and prolonged precorneal retention without obvious ocular irritation. More importantly, NS@lipid-PEG/CKC recovered tear production and goblet cell density more efficiently than the commercial cationic nanoemulsion on a dry eye disease rat model. All results indicated that a combination of PEGylation and cationization might provide a promising strategy to coordinate mucus penetration and cellular uptake for enhanced drug delivery to the ocular epithelium for nanomedicine-based eye drops.

20.
PLoS One ; 19(5): e0302729, 2024.
Article in English | MEDLINE | ID: mdl-38743667

ABSTRACT

The constitutive model and modulus parameter equivalence of shape memory alloy composites (SMAC) serve as the foundation for the structural dynamic modeling of composite materials, which has a direct impact on the dynamic characteristics and modeling accuracy of SMAC. This article proposes a homogenization method for SMA composites considering interfacial phases, models the interface stress transfer of three-phase cylinders physically, and derives the axial and shear stresses of SMA fiber phase, interfacial phase, and matrix phase mathematically. The homogenization method and stress expression were then used to determine the macroscopic effective modulus of SMAC as well as the stress characteristics of the fiber phase and interface phase of SMA. The findings demonstrate the significance of volume fraction and tensile pre-strain in stress transfer between the fiber phase and interface phase at high temperatures. The maximum axial stress in the fiber phase is 705.05 MPa when the SMA is fully austenitic and the pre-strain increases to 5%. At 10% volume fraction of SMA, the fiber phase's maximum axial stress can reach 1000 MPa. Ultimately, an experimental verification of the theoretical calculation method's accuracy for the effective modulus of SMAC lays the groundwork for the dynamic modeling of SMAC structures.


Subject(s)
Alloys , Stress, Mechanical , Tensile Strength , Alloys/chemistry , Materials Testing/methods , Elastic Modulus , Smart Materials/chemistry , Models, Theoretical
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