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1.
Dent Mater ; 2024 May 30.
Article En | MEDLINE | ID: mdl-38821839

OBJECTIVE: Extrafibrillar demineralization is considered to be an ideal solution for addressing the durability of resin-dentin bonding interfaces. However, its theoretical basis is contradictory to ionization equilibrium of hydroxyapatite dissolution. In this study, various calcium chelators were selected as dentin conditioners to explore the essence of dentin demineralization with chelators and its effect on resin-dentin adhesion. METHODS: Polyethyleneimine grafted with EDTA and polyacrylic acid sodium (PAAN450k) larger than 40 kDa, as well as PAAN (PAAN3k) and EDTA smaller than 6 kDa, were prepared as dentin conditioners. The dentin powder was designed to characterize whether it would demineralize without contact with PAAN450k. Dentin demineralization effect with four conditioners was evaluated with field emission scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, atomic force microscopy and quantification of hydroxyproline concentration after enzymatic degradation. Micro-tensile bond strength (µTBS) test and failure mode analysis were employed to assess the bonding effect of the four chelators in both wet and dry bonding, with H3PO4 wet bonding serving as the control group. RESULTS: Demineralization occurs when PAAN450k was not in direct contact with the dentin powder. The extrafibrillar demineralization cannot be induced by any chelator regardless of its molecular weight. Complete demineralization including extrafibrillar and intrafibrillar demineralization would occur with sufficient interaction time. Moreover, chelators could not provide a reliable dentin bonding effect under a short interaction time. SIGNIFICANCE: From the perspective of theory and application, extrafibrillar demineralization is not a reliable strategy, which provides a reminder for exploring new strategies in the future.

2.
Mol Pharm ; 2024 May 31.
Article En | MEDLINE | ID: mdl-38819959

Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.

3.
Angew Chem Int Ed Engl ; : e202406417, 2024 May 07.
Article En | MEDLINE | ID: mdl-38712562

Responsive organic luminescent aggregates have a wide range of application fields, but currently there is still a lack of reasonable molecular design strategies. Introducing ion-π interactions into molecules can effectively alter their luminescent properties. However, current research typically focuses on ion localization at luminescent conjugated groups with the strong interaction forces. In this work, we introduce the flexible alkoxy chain spacers between fluorescent conjugated groups and ion-π interaction sites, and then adjust the fluorescence performance of the molecule by changing the strength of ion-π interactions. Bromine ion-based molecules with strong ion-π interactions exhibit high and stable fluorescence quantum yields in crystals and amorphous powders under the external stimuli. Hexafluorophosphate ion-based molecules with weak ion-π interactions have the high fluorescence quantum yield in crystals and very low fluorescence quantum yield in amorphous powders, showing variable fluorescence intensities under external stimuli. This demonstrates a new class of responsive organic luminescent solid-state materials.

4.
Cell Biochem Biophys ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38713402

Nonalcoholic fatty liver disease (NAFLD) become a main public health concern, and is characterized by lipid accumulation in the hepatocytes. We found that overexpression of lncRNA MEG3 significantly reduced the expression of FOXO1, ACC1, and FAS, and subsequently decreased the lipid accumulation in HepG2 cells. Moreover, inhibition of lncRNA MEG3 could increase the lipid accumulation and the mRNA and protein levels of FOXO1, ACC1, and FAS. Further study showed that lncRNA MEG3 regulates the lipogenesis process by inhibiting the entry of FOXO1 into the nucleus translocation. Our study demonstrated that lncRNA MEG3 regulates de novo lipogenesis by decreasing the expression and nucleus translocation of FOXO1 in HepG2 cells, suggesting that lncRNA MEG3 could be a promising therapeutic target in lipid metabolic disorders.

5.
Biomater Adv ; 161: 213899, 2024 May 18.
Article En | MEDLINE | ID: mdl-38772133

Large bone defects, particularly those exceeding the critical size, present a clinical challenge due to the limited regenerative capacity of bone tissue. Traditional treatments like autografts and allografts are constrained by donor availability, immune rejection, and mechanical performance. This study aimed to develop an effective solution by designing gradient gyroid scaffolds with titania (TiO2) surface modification for the repair of large segmental bone defects. The scaffolds were engineered to balance mechanical strength with the necessary internal space to promote new bone formation and nutrient exchange. A gradient design of the scaffold was optimized through Finite Element Analysis (FEA) and Computational Fluid Dynamics (CFD) simulations to enhance fluid flow and cell adhesion. In vivo studies in rabbits demonstrated that the G@TiO2 scaffold, featuring a gradient structure and TiO2 surface modification, exhibited superior healing capabilities compared to the homogeneous structure and TiO2 surface modification (H@TiO2) and gradient structure (G) scaffolds. At 12 weeks post-operation, in a bone defect representing nearly 30 % of the total length of the radius, the implantation of the G@TiO2 scaffold achieved a 27 % bone volume to tissue volume (BV/TV) ratio, demonstrating excellent osseointegration. The TiO2 surface modification provided photothermal antibacterial effects, enhancing the scaffold's biocompatibility and potential for infection prevention. These findings suggest that the gradient gyroid scaffold with TiO2 surface modification is a promising candidate for treating large segmental bone defects, offering a combination of mechanical strength, bioactivity, and infection resistance.

6.
Anal Chem ; 2024 May 20.
Article En | MEDLINE | ID: mdl-38768388

DNA biosynthesis, a focus of fundamental and applied research, typically involves DNA polymerases by using templates, primers, and dNTPs. Some polymerases can polymerize dNTPs for DNA de novo synthesis, although this is generally to occur randomly. This novel synthesis method has garnered our attention and practical use. Herein, we observed that the addition of endonuclease significantly enhances the efficiency of the de novo synthesis reaction catalyzed by the DNA polymerase. We further investigated the reaction conditions that influence this efficiency. Building on the optimal reaction conditions, we developed a rapid and efficient strategy for preparing DNA hydrogel. Further, coupled with the CRISPR-Cas system, we developed a nucleic acid signal amplification system characterized by versatility, sensitivity, specificity, and no risk of aerosol contamination. We successfully detected viral nucleic acids in clinical samples. In summary, our study demonstrates the significant potential of DNA polymerase- and endonuclease-catalyzed DNA de novo synthesis in diverse applications.

7.
Plant Cell Environ ; 2024 May 16.
Article En | MEDLINE | ID: mdl-38752443

Bamboo cultivation, particularly Moso bamboo (Phyllostachys edulis), holds significant economic importance in various regions worldwide. Bamboo shoot degradation (BSD) severely affects productivity and economic viability. However, despite its agricultural consequences, the molecular mechanisms underlying BSD remain unclear. Consequently, we explored the dynamic changes of BSD through anatomy, physiology and the transcriptome. Our findings reveal ruptured protoxylem cells, reduced cell wall thickness and the accumulation of sucrose and reactive oxygen species (ROS) during BSD. Transcriptomic analysis underscored the importance of genes related to plant hormone signal transduction, sugar metabolism and ROS homoeostasis in this process. Furthermore, BSD appears to be driven by the coexpression regulatory network of senescence-associated gene transcription factors (SAG-TFs), specifically PeSAG39, PeWRKY22 and PeWRKY75, primarily located in the protoxylem of vascular bundles. Yeast one-hybrid and dual-luciferase assays demonstrated that PeWRKY22 and PeWRKY75 activate PeSAG39 expression by binding to its promoter. This study advanced our understanding of the molecular regulatory mechanisms governing BSD, offering a valuable reference for enhancing Moso bamboo forest productivity.

8.
World J Stem Cells ; 16(4): 334-352, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38690516

Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

9.
Bioengineering (Basel) ; 11(5)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38790312

BACKGROUND AND AIMS: Accurate recognition of endoscopic instruments facilitates quantitative evaluation and quality control of endoscopic procedures. However, no relevant research has been reported. In this study, we aimed to develop a computer-assisted system, EndoAdd, for automated endoscopic surgical video analysis based on our dataset of endoscopic instrument images. METHODS: Large training and validation datasets containing 45,143 images of 10 different endoscopic instruments and a test dataset of 18,375 images collected from several medical centers were used in this research. Annotated image frames were used to train the state-of-the-art object detection model, YOLO-v5, to identify the instruments. Based on the frame-level prediction results, we further developed a hidden Markov model to perform video analysis and generate heatmaps to summarize the videos. RESULTS: EndoAdd achieved high accuracy (>97%) on the test dataset for all 10 endoscopic instrument types. The mean average accuracy, precision, recall, and F1-score were 99.1%, 92.0%, 88.8%, and 89.3%, respectively. The area under the curve values exceeded 0.94 for all instrument types. Heatmaps of endoscopic procedures were generated for both retrospective and real-time analyses. CONCLUSIONS: We successfully developed an automated endoscopic video analysis system, EndoAdd, which supports retrospective assessment and real-time monitoring. It can be used for data analysis and quality control of endoscopic procedures in clinical practice.

10.
Chemistry ; : e202400741, 2024 May 15.
Article En | MEDLINE | ID: mdl-38745544

To address key concerns on solid-state pyrene-based luminescent materials, we propose a novel and efficient mechanical bond strategy. This strategy results in a transformation from ACQ to AIE effect and a remarkable enhancement of pyrene emission in the solid state. Moreover, an unusual purification of emission is also achieved. Through computational calculation and experimental characterisation, finally determined by X-ray diffraction analysis, we prove that the excellent emissions result from mechanical bond induced refinement of molecular arrangements, including reduced π-π stacking, well-ordered packing and enhanced structural stability. This work demonstrates the potential of mechanical bond in the field of organic luminescent molecules, providing a new avenue for developing high-performance organic luminescent materials.

11.
Adv Healthc Mater ; : e2401095, 2024 May 24.
Article En | MEDLINE | ID: mdl-38794821

Enamel has good optical and mechanical properties because of its multiscale hierarchical structure. Biomimetic construction of enamel-like 3D bulk materials at nano-, micro-, mesh- and macro-levels is a challenge. We reported a novel facile, cost-effective, and easy large-scale bottom-up assembly strategy to align 1D hydroxyapatite (HA) nanowires bundles to 3D hierarchical enamel structure with the nanowires bundles layer-by-layer interweaving orientation. In the strategy, the surface of oleate templated ultralong HA nanowires with a large aspect ratio was functionalized with amphiphilic 10-methacryloyloxydecyl dihydrogen phosphate (MDP). Furtherly, the MDP functionalized HA nanowire bundles were assembled layer-by-layer with oriented fibers in a single layer and cross-locked between layers at a certain angle at mesoscale and macroscale in the viscous bisphenol A-glycidyl methacrylate (Bis-GMA) ethanol solution by shear force induced by simple agitation and high-speed centrifugation. Finally, the excessive Bis-GMA and ethanol were removed, and (Bis-GMA)-(MDP-HA nanowire bundle) matrix was densely packed under hot pressing and polymerized to form bulk enamel-like materials. The composite has superior optical properties and comparable comprehensive mechanic performances through a combination of strength, hardness, toughness, and friction. This method may open new avenues for precisely controlling the nanowires assembly to develop hierarchical nanomaterials with superior properties for many different applications. This article is protected by copyright. All rights reserved.

12.
Article En | MEDLINE | ID: mdl-38805325

The process of labeling medical text plays a crucial role in medical research. Nonetheless, creating accurately labeled medical texts of high quality is often a time-consuming task that requires specialized domain knowledge. Traditional methods for generating labeled data typically rely on rigid rule-based approaches, which may not adapt well to new tasks. While recent machine learning (ML) methodologies have mitigated the manual labeling efforts, configuring models to align with specific research requirements can be challenging for labelers without technical expertise. Moreover, automated labeling techniques, such as transfer learning, face difficulties in in directly incorporating expert input, whereas semi-automated methods, like data programming, allow knowledge integration through rules or knowledge bases but may lack continuous result refinement throughout the entire labeling process. In this study, we present a collaborative human-ML teaming workflow that seamlessly integrates visual cluster analysis and active learning to assist domain experts in labeling medical text with high efficiency. Additionally, we introduce an innovative neural network model called the embedding network, which incorporates expert insights to generate task-specific embeddings for medical texts. We integrate the workflow and embedding network into a visual analytics tool named KMTLabeler, equipped with coordinated multi-level views and interactions. Two illustrative case studies, along with a controlled user study, provide substantial evidence of the effectiveness of KMTLabeler in creating an efficient labeling environment for medical text classification.

13.
Cell Cycle ; : 1-10, 2024 May 31.
Article En | MEDLINE | ID: mdl-38819114

Surfeit locus protein 4 is a cargo receptor mediating cargo transport from the endoplasmic reticulum lumen to the Golgi apparatus. Loss of Surf4 gene led to embryonic lethality in mice. However, the role of Surf4 during oocyte development remains unknown. In this study, we generated the mouse model with oocyte-specific knockout of Surf4 gene. We found that adult mice with deletion of Surf4 showed normal folliculogenesis, ovulation and fertility. However, loss of Surf4 slightly impaired oocyte quality, thus led to partial oocyte meiotic arrest and reduced ratio of blastocyst formation. Consistent with this, the distribution of endoplasmic reticulum was disturbed in Surf4-deficient oocytes in mice. These results demonstrated that although Surf4 is dispensable for female mouse fertility, Surf4 modulates endoplasmic reticulum arrangement and participates in regulation of developmental competence of oocytes.

14.
J Ovarian Res ; 17(1): 99, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730385

With increasingly used assisted reproductive technology (ART), the acquisition of high-quality oocytes and early embryos has become the focus of much attention. Studies in mice have found that the transition of chromatin conformation from non-surrounded nucleolus (NSN) to surrounded nucleolus (SN) is essential for oocyte maturation and early embryo development, and similar chromatin transition also exists in human oocytes. In this study, we collected human NSN and SN oocytes and investigated their transcriptome. The analysis of differentially expressed genes showed that epigenetic functions, cyclin-dependent kinases and transposable elements may play important roles in chromatin transition during human oocyte maturation. Our findings provide new insights into the molecular mechanism of NSN-to-SN transition of human oocyte and obtained new clues for improvement of oocyte in vitro maturation technique.


Chromatin , Oocytes , Transcriptome , Humans , Oocytes/metabolism , Chromatin/metabolism , Chromatin/genetics , Female , Gene Expression Profiling , Cell Nucleolus/metabolism , Cell Nucleolus/genetics
15.
Menopause ; 2024 May 28.
Article En | MEDLINE | ID: mdl-38814194

OBJECTIVE: To determine the potential association between the triglyceride-glucose (TyG) index and bone mineral density (BMD) in community-dwelling adults without diabetes using a nationally representative database from the United States (US). METHODS: Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, 2013-2014, and 2017-2018. Men and postmenopausal women aged ≥50 years with complete data on femoral neck BMD, triglycerides, and fasting plasma glucose levels were eligible for inclusion. Participants with diabetes, history of malignancy, thyroid disease, underweight status, end-stage kidney disease, rheumatoid arthritis, estrogen/selective estrogen receptor modulators, bisphosphonate or bone resorption inhibitors, or missing dataset weight values were excluded. Univariate and multivariable logistic regression analyses were performed to determine the associations between low BMD, TyG index, and other study variables. RESULTS: A total of 1,844 participants (1,161 men and 683 women) were included, representing 31,517,106 community-dwelling individuals in the US. The mean age of the study population was 60.7 years old, and 26.7% of the men and 60.4% of the women had low bone density. In both males and females, the mean TyG index was 8.6. After adjusting for demographic, lifestyle, and clinical factors, no significant association was observed between TyG and femoral neck BMD among men (adjusted odds ratio [aOR] = -0.0002, 95% confidence interval [CI]: -0.02 to 0.02) and women (aBeta = 0.005, 95% CI: -0.02 to 0.04). Similarly, no significant association was observed between TyG index and the odds for low bone density among men (aOR = 1.09, 95% CI: 0.73-1.63) and women (aOR = 0.99, 95% CI: 0.49-2.01). CONCLUSIONS: Based on data from a large sample in the US, this study did not find an association between the TyG index and femoral neck BMD or the occurrence of low bone density in community-dwelling males and females without diabetes.

16.
Phytomedicine ; 129: 155627, 2024 Jul.
Article En | MEDLINE | ID: mdl-38696924

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by an exaggerated response to infection. In the lungs, one of the most susceptible organs, this can manifest as acute respiratory distress syndrome (ARDS). Shenfu (SF) injection is a prominent traditional Chinese medicine used to treat sepsis. However, the exact mechanism of its action has rarely been reported in the literature. PURPOSE: In the present study, we detected the protective effect of SF injection on sepsis-induced ARDS and explored its underlying mechanism. METHODS: We investigated the potential targets and regulatory mechanisms of SF injections using a combination of network pharmacology and RNA sequencing. This study was conducted both in vivo and in vitro using a mouse model of ARDS and lipopolysaccharide (LPS)-stimulated MLE-12 cells, respectively. RESULTS: The results showed that SF injection could effectively inhibit inflammation, oxidative stress, and apoptosis to alleviate LPS-induced ARDS. SF inhibited the PI3K-AKT pathway, which controls autophagy and apoptosis. Subsequently, MLE-12 cells were treated with 3-methyladenine to assess its effects on autophagy and apoptosis. Additional experiments were conducted by adding rapamycin, an mTOR antagonist, or SC79, an AKT agonist, to investigate the effects of SF injection on autophagy, apoptosis, and the PI3K-AKT pathway. CONCLUSION: Overall, we found that SF administration could enhance autophagic activity, reduce apoptosis, suppress inflammatory responses and oxidative stress, and inhibit the PI3K-AKT pathway, thus ameliorating sepsis-induced ARDS.


Apoptosis , Autophagy , Drugs, Chinese Herbal , Lipopolysaccharides , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Respiratory Distress Syndrome , Sepsis , Signal Transduction , Animals , Drugs, Chinese Herbal/pharmacology , Autophagy/drug effects , Sepsis/complications , Sepsis/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , Apoptosis/drug effects , Respiratory Distress Syndrome/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Mice , Male , Signal Transduction/drug effects , Disease Models, Animal , Oxidative Stress/drug effects , Cell Line , Mice, Inbred C57BL , TOR Serine-Threonine Kinases/metabolism , Network Pharmacology
17.
IEEE Comput Graph Appl ; PP2024 May 03.
Article En | MEDLINE | ID: mdl-38700972

Promoting the development of electric vehicles requires the widespread deployment of charging infrastructure, which poses numerous technical and financial constraints. Despite extensive research focusing on optimizing charging station locations, few studies have accounted for charging station utilization and the factors that influence it. This study aims to evaluate charging station operations and explore charging station utilization to inform planning and facilitate better utilization of funds for expanding charging infrastructure. We present EVCSeer, a visual analytics system that utilizes representative predictive models and well-designed visualizations to analyze factors affecting charging station utilization, compare deployment strategies, and optimize utilization. The system also enables "what-if" analysis of charging station deployments. Two case studies, expert interviews, and a qualitative user study support the validity and usefulness of EVCSeer.

18.
Front Oncol ; 14: 1309681, 2024.
Article En | MEDLINE | ID: mdl-38746684

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

19.
Vet Microbiol ; 294: 110131, 2024 May 23.
Article En | MEDLINE | ID: mdl-38805917

Outer membrane vesicles (OMVs) are membranous structures frequently observed in Gram-negative bacteria that contain bioactive substances. These vesicles are rich in bacterial antigens that can activate the host's immune system, making them a promising candidate vaccine to prevent and manage bacterial infections. The aim of this study was to assess the immunogenicity and protective efficacy of OMVs derived from Salmonella enterica serovar Typhimurium and S. Choleraesuis, while also focusing on enhancing OMV production. Initial experiments showed that OMVs from wild-type strains did not provide complete protection against homologous Salmonella challenge, possible due to the presence of flagella in the purified OMVs samples, which may elicit an unnecessary immune response. To address this, flagellin-deficient mutants of S. Typhimurium and S. Choleraesuis were constructed, designated rSC0196 and rSC0199, respectively. These mutants exhibited reduced cell motility and their OMVs were found to be flagellin-free. Immunization with non-flagellin OMVs derived from rSC0196 induced robust antibody responses and improved survival rates in mice, as compared to the OMVs derived from the wild-type UK-1. In order to enhance OMV production, deletions of ompA or tolR were introduced into rSC0196. The deletion of tolR not only increase the yield of OMVs, but also conferred complete protection against homologous S. Typhimurium challenge in mice. Collectively, these findings indicate that the flagellin-deficient OMVs with a tolR mutation have the potential to serve as a versatile vaccine platform, capable of inducing broad-spectrum protection against significant pathogens.

20.
Article En | MEDLINE | ID: mdl-38561861

BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.

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