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Pseudomonas aeruginosa is a Gram-negative bacterium causing morbidity and mortality in immuno-compromised humans. It produces a lectin, LecB, that is considered a major virulence factor, however, its impact on the immune system remains incompletely understood. Here we show that LecB binds to endothelial cells in human skin and mice and disrupts the transendothelial passage of leukocytes in vitro. It impairs the migration of dendritic cells into the paracortex of lymph nodes leading to a reduced antigen-specific T cell response. Under the effect of the lectin, endothelial cells undergo profound cellular changes resulting in endocytosis and degradation of the junctional protein VE-cadherin, formation of an actin rim, and arrested cell motility. This likely negatively impacts the capacity of endothelial cells to respond to extracellular stimuli and to generate the intercellular gaps for allowing leukocyte diapedesis. A LecB inhibitor can restore dendritic cell migration and T cell activation, underlining the importance of LecB antagonism to reactivate the immune response against P. aeruginosa infection.
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Pseudomonas aeruginosa , Migración Transendotelial y Transepitelial , Humanos , Animales , Ratones , Células Endoteliales/metabolismo , Lectinas/metabolismo , Lectinas/farmacología , InmunidadRESUMEN
Dexmedetomidine (DEX) has been confirmed to exert neuroprotective effects in various nerve injury models by regulating ferroptosis, including spinal cord injury (SCI). Although it has been established that CDGSH iron sulfur domain 2 (CISD2) can regulate ferroptosis, whether DEX can regulate ferroptosis by CISD2 in SCI remains unclear. Lidocaine was used to induce PC12 cells and stimulate rats to establish SCI models in vitro and in vivo. MTT assays were performed to analyze cell viability. Ferroptosis was assessed by determining the levels of cellular reactive axygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+. Ferritinophagy was analyzed by LysoTracker staining, FerroOrange staining, and immunofluorescence. Western blotting was carried out to quantify the levels of several proteins. Fluorescence microscopy was also used to observe cell autophagy. The morphology of mitochondria within the tissue was observed under transmission electron microscopy (TEM). DEX treatment weakened lidocaine-induced elevation of ROS, Fe2+, and MDA and reduced GSH in PC12 cells, indicating that DEX treatment weakened lidocaine-induced ferroptosis in PC12 cells. Similarly, lidocaine promoted autophagy, Fe2+, and microtubule-associated protein 1 light chain 3 (LC3) in PC12 cells and suppressed ferritin and p62 protein levels, indicating that DEX could weaken lidocaine-induced ferritinophagy in PC12 cells. DEX treatment improved the BBB score, reduced tissue damage, increased the number of neurons, and alleviated mitochondrial damage by inhibiting ferroptosis and ferritinophagy in lidocaine-induced SCI rat models. The decreased CISD2, ferritin heavy chain 1 (FTH1), solute carrier family 7-member 11-glutathione (SLC7A11), and glutathione peroxidase 4 (GPX4) protein levels and the elevated nuclear receptor coactivator 4 (NCOA4) protein levels in rat models in the lidocaine group were weakened by DEX treatment. Moreover, CISD2 inhibition reversed the inhibitory effects of DEX treatment on lidocaine-induced ferroptosis and ferritinophagy in PC12 cells significantly. Taken together, DEX treatment could impair lidocaine-induced SCI by inhibiting ferroptosis and ferritinophagy by upregulating CISD2 in rat models.
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Background: The aim of this work was to investigate left atrial electrophysiological properties for their ability to predict the recurrence of atrial fibrillation (AF) following pulmonary vein isolation (PVI). Methods: The study comprised 53 patients with AF [62 (interquartile range (IQR): 52-68) years old; 47.2% females]. High-density, three-dimensional electro-anatomic mapping using PentaRay was conducted during sinus rhythm in the left atrium (LA) immediately after PVI. LA conduction time, conduction velocity in predefined anterior and posterior routes, low voltage area percentage and distribution were assessed. Results: The AF recurrence group had longer LA conduction time compared to the non-recurrence group [11 (IQR: 10-12) ms vs. 9 (IQR: 8-10) ms, p = 0.001). The percent low voltage area was greater in the recurrence group than the non-recurrence group [31.2 (IRQ: 7.1-49.3)% vs. 7.7 (IQR: 4.3-15.2)%, p = 0.008]. Multivariate Cox regression revealed that LA conduction time independently predicted AF recurrence following ablation over a median follow-up of 235 days [IQR: 154-382 days; hazard ratio (HR): 2.37, 95% confidence interval (CI): 1.08-5.23, p = 0.031]. The optimal cut-off for LA conduction time was 98 ms [area under curve (AUC): 0.926, sensitivity: 0.833, specificity: 0.894, p < 0.01]. Kaplan-Meier analysis revealed that patients with a conduction time > 98 ms had a higher rate of AF recurrence following ablation (p < 0.001). Conclusions: Patients with longer LA conduction time after PVI had more frequent AF recurrence.
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We study the nematic-to-isotropic phase transitions in thin slabs of nematic liquid crystals with photopatterned director fields of topological defect arrays at constant heating rates and show that the transition kinetics is significantly impacted by both the heating rate and the topological strengths of these defects. Specifically, with ±1/2 defect arrays, the isotropic domains emerge from the defect cores when the heating rate is high, while from random places when the heating rate is low. With ±1 defect arrays, the isotropic domains always emerge from the defect cores regardless of the heating rate. Furthermore, the isotropic domains show significant movements at slow heating rates, and the total area of the isotropic domains grows with the temperature T following a simple power law (T - T')γ, where the exponent γ is approximately 1 in most cases and is 2/3 for the ±1 defect arrays at low heating rates when the isotropic domains are pinned on the defect cores. We attribute this phenomenon to an interplay between the surface tension and bulk free energy.
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Abnormal co-occurrence medical visit behavior is a form of medical insurance fraud. Specifically, an organized gang of fraudsters hold multiple medical insurance cards and purchase similar drugs frequently at the same time and the same location in order to siphon off medical insurance funds. Conventional identification methods to identify such behaviors rely mainly on manual auditing, making it difficult to satisfy the needs of identifying the small number of fraudulent behaviors in the large-scale medical data. On the other hand, the existing single-view bi-clustering algorithms only consider the features of the time-location dimension while neglecting the similarities in prescriptions and neglecting the fact that fraudsters may belong to multiple gangs. Therefore, in this paper, we present a multi-view bi-clustering method for identifying abnormal co-occurrence medical visit behavioral patterns, which performs cluster analysis simultaneously on the large-scale, complex and diverse visiting record dimension and prescription dimension to identify bi-clusters with similar time-location features. The proposed method constructs a matrix view of patients and visit records as well as a matrix view of patients and prescriptions, while decomposing multiple data matrices into sparse row and column vectors to obtain a consistent patient population across views. Subsequently the proposed method identifies the corresponding abnormal co-occurrence medical visit behavior and may greatly facilitate the safe operations and the sustainability of medical insurance funds. The experimental results show that our proposed method leads to more efficient and more accurate identifications of abnormal co-occurrence medical visit behavior, demonstrating its high efficiency and effectiveness.
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Algoritmos , Humanos , Análisis por ConglomeradosRESUMEN
Soft-bodied aquatic invertebrates, such as sea slugs and snails, are capable of diverse locomotion modes under water. Recapitulation of such multimodal aquatic locomotion in small-scale soft robots is challenging, due to difficulties in precise spatiotemporal control of deformations and inefficient underwater actuation of existing stimuli-responsive materials. Solving this challenge and devising efficient untethered manipulation of soft stimuli-responsive materials in the aquatic environment would significantly broaden their application potential in biomedical devices. We mimic locomotion modes common to sea invertebrates using monolithic liquid crystal gels (LCGs) with inherent light responsiveness and molecular anisotropy. We elicit diverse underwater locomotion modes, such as crawling, walking, jumping, and swimming, by local deformations induced by selective spatiotemporal light illumination. Our results underpin the pivotal role of the physicomechanical properties of LCGs in the realization of diverse modes of light-driven robotic underwater locomotion. We envisage that our results will introduce a toolbox for designing efficient untethered soft robots for fluidic environments.
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Many natural materials possess built-in structural variation, endowing them with superior performance. However, it is challenging to realize programmable structural variation in self-assembled synthetic materials since self-assembly processes usually generate uniform and ordered structures. Here, we report the formation of asymmetric microribbons composed of directionally self-assembled two-dimensional nanoflakes in a polymeric matrix during three-dimensional direct-ink printing. The printed ribbons with embedded structural variations show site-specific variance in their mechanical properties. Remarkably, the ribbons can spontaneously transform into ultrastretchable springs with controllable helical architecture upon stimulation. Such springs also exhibit superior nanoscale transport behavior as nanofluidic ionic conductors under even ultralarge tensile strains (>1,000%). Furthermore, to show possible real-world uses of such materials, we demonstrate in vivo neural recording and stimulation using such springs in a bullfrog animal model. Thus, such springs can be used as neural electrodes compatible with soft and dynamic biological tissues.
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Neuroestimuladores Implantables , Microtecnología/instrumentación , Nanoestructuras , Impresión Tridimensional , Animales , Anuros , Elasticidad , Grafito/química , Iones/química , Nanoestructuras/química , Nanoestructuras/ultraestructura , Neurofisiología/instrumentación , Nervio Ciático/fisiologíaRESUMEN
PURPOSE: Microgravity is known to cause endothelium dysfunction in astronauts returning from spaceflight. We aimed to reveal the regulatory mechanism in alterations of human endothelial cells after simulated microgravity (SMG). METHODS: We utilized the rotary cell culture system (RCCS-1) to explore the subsequent effects of SMG on human umbilical vein endothelial cells (HUVECs). RESULTS: SMG-treated HUVECs appeared obvious growth inhibition after return to normal gravity, which might be attributed to a set of responses including alteration of cytoskeleton, decreased cell adhesion capacity and increased apoptosis. Expression levels of mTOR and its downstream Apaf-1 were increased during subsequent culturing after SMG. miR-22 was up-regulated and its target genes SRF and LAMC1 were down-regulated at mRNA levels. LAMC1 siRNAs reduced cell adhesion rate and inhibited stress fiber formation while SRF siRNAs caused apoptosis. CONCLUSION: SMG has the subsequent biological effects on HUVECs, resulting in growth inhibition through mTOR signaling and miR-22-mediated mechanism.
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Células Endoteliales de la Vena Umbilical Humana/fisiología , Simulación de Ingravidez , Apoptosis , Proliferación Celular , Células Cultivadas , Humanos , Laminina/genética , MicroARNs/fisiologíaRESUMEN
In this paper, we present experimental and numerical studies on the microstructures of a cholesteric liquid crystal (CLC) confined in rectangular micron-channels. By using a sequence of microfabrication techniques we fabricated the micro-sized channels with accurately controlled size, aspect ratio and homeotropic surface anchoring. Through optical microscopic studies we established a phase diagram for the liquid crystal defect textures as a function of the channel depth and width. For the channel width larger than â¼2 times the cholesteric pitch p, the LC molecules are oriented primarily vertical to the channel when the channel depth is below 0.75p, form bubble domain defects when the channel depth is around 0.75p, and form stripe textures when the cell depth is above the cholesteric pitch p. In addition, the bubble domain size and the stripe texture periodicity are found to grow with the increase of the channel width. For the channel width smaller than â¼2p and the channel depth between 0.6p to 1.1p, no textures can be observed in the channels. Numerical simulations based on a director tensor relaxation approach yield detailed molecular director fields, and show that the bubble domain defects are baby-skyrmions and that the stripes are the first type of cholesteric fingerprints. A comparison with previous experiments and numerical simulations indicates that the size of the microchannels also influences what type of soliton-like topological textures form in the CLCs confined in the channels.
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Correction for 'Cholesteric liquid crystals in rectangular microchannels: skyrmions and stripes' by Yubing Guo et al., Soft Matter, 2016, DOI: 10.1039/c6sm01190j.
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Pyroptosis, an inflammatory Programmed cell death, has recently been found to play an important role in spinal cord injury (SCI). C-type lectin domain family 5 member A (CLEC5A), triggering receptor expressed on myeloid cells 1 (TREM1), and NLR-family CARD-containing protein 4 (NLRC4) have been reported to be associated with neuronal pyroptosis, but few studies have clarified their functions and regulatory mechanisms in SCI. In this study, CLEC5A, TREM1, and NLRC4 were highly expressed in lidocaine-induced SCI rat models, and their knockdown alleviated lidocaine-induced SCI. The elevation of proptosis related indicators LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1ß levels in SCI rats was attenuated after silencing of CLEC5A, TREM1, or NLRC4. Lidocaine-induced the decrease in cell viability and the elevation in cell death were partly reversed after CLEC5A, TREM1, or NLRC4 silencing. Lidocaine-mediated effects on the levels of LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1ß in lidocaine-induced PC-12 cells were weakened by downregulating CLEC5A, TREM1, or NLRC4. CLEC5A could interact with TREM1 to mediate NLRC4 expression, thus accelerating neuronal pyroptosis, ultimately leading to SCI exacerbation. In conclusions, CLEC5A interacted with TREM1 to increase NLRC4 expression, thus promoting neuronal pyroptosis in rat SCI models, providing new insights into the role of neuronal pyroptosis in SCI.Significance statement Pyroptosis has been reported to be involved in SCI. Higher levels of CLEC5A, TREM1, and NLRC4 associated with neuronal pyroptosis. However, the role and regulatory mechanism of CLEC5A, TREM1, and NLRC4 in SCI were not clear. Here, high expression of CLEC5A, TREM1, and NLRC4 was observed in lidocaine-induced SCI rat models. CLEC5A could interact with TREM1 to enhance the expression of NLRC4, thus accelerating neuronal pyroptosis in rat SCI models. These findings identify CLEC5A, TREM1, and NLRC4 as potential therapeutic targets for SCI.
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OBJECTIVE: Bacillus subtilis, a kind of probiotic with broad-spectrum antibacterial function, was commonly used in livestock and poultry production. Recent research suggested that Bacillus subtilis may have antioxidant properties and improve immune response. This study aimed to verify the probiotic function of Bacillus subtilis in the production of broiler chickens. METHODS: A total of 324 (1-day-old) Arbor Acres broilers were selected and randomly divided into three groups: basal diet group (Ctr Group), basal diet + antibiotic growth promoter group (Ctr + AGP) and basal diet + 0.5% Bacillus subtilis preparation group (Ctr + Bac). The experiment lasted for 42 days. Muscle, serum and liver samples were collected at 42 days for determination. RESULTS: The results showed that Bacillus subtilis could decrease malondialdehyde content in the serum and liver (p<0.05) and increase superoxide dismutase 1 mRNA expression (p<0.01) and total superoxide dismutase (p<0.05) in the liver. In addition, compared with AGP supplementation, Bacillus subtilis supplementation increased interleukin-10 (IL-10) and decreased tumor necrosis factor-α and IL-1ß level in the serum (p<0.05). At 45 minutes after slaughter Ctr + Bac presented a higher a* value of breast muscle than Ctr Group (p<0.05), while significant change in leg muscle was not identified. Moreover, there was no difference in weight, shear force, cooking loss and drip loss of breast and leg muscle between treatments. CONCLUSION: Our results demonstrate that Bacillus subtilis in diet can enhance antioxidant capacity and optimize immune response of broilers.
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Double-sided microlens arrays (DSMLAs) include combinations of two single-sided MLAs to overcome positioning errors and greatly improve light transmissivity compared to other types of lenses. Precision glass molding (PGM) is used to fabricate DSMLAs, but controlling alignment errors during this process is challenging. In this paper, a mold assembly was manufactured with a novel combination of materials to improve the alignment accuracy of mold cores during PGM by using the nonlinear thermal expansion characteristics of the various materials to improve the DSMLA alignment accuracy. By establishing a mathematical model of the DSMLA alignment error and a thermal expansion model of the mold-sleeve pair, the relationship between the maximum alignment error of the DSMLA and the mold-sleeve gap was determined. This research provides a method to optimize the mold-sleeve gap and minimize the alignment error of the DSMLA. The measured DSMLA alignment error was 10.56 µm, which is similar to the predicted maximum alignment error. Optical measurements showed that the uniformity of the homogenized beam spot was 97.81%, and the effective homogeneous area accounted for 91.66% of the total area. This proposed method provides a novel strategy to improve the performance of DSMLAs.
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IMPORTANCE: HAdV-3, -7, and -55 are the predominant types causing acute respiratory disease outbreaks and can lead to severe and fatal pneumonia in children and adults. In recent years, emerging or re-emerging strains of HAdV-7 and HAdV-55 have caused multiple outbreaks globally in both civilian and military populations, drawing increased attention. Clinical studies have reported that HAdV-7 and HAdV-55 cause more severe pneumonia than HAdV-3. This study aimed to investigate the mechanisms explaining the higher severity of HAdV-7 and HAdV-55 infection compared to HAdV-3 infection. Our findings provided evidence linking the receptor-binding protein fiber to stronger infectivity of the strains mentioned above by comparing several fiber-chimeric or fiber-replaced adenoviruses. Our study improves our understanding of adenovirus infection and highlights potential implications, including in novel vector and vaccine development.
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Infecciones por Adenovirus Humanos , Adenovirus Humanos , Neumonía , Infecciones del Sistema Respiratorio , Niño , Adulto , Humanos , VirulenciaRESUMEN
OBJECTIVE: Intraoperative blood loss is a major challenge in pediatric brain tumor removal. Several clinical and surgical factors may influence the occurrence of intraoperative blood loss and blood transfusion. This study aimed to identify the risk factors of intraoperative blood loss and intraoperative red blood cell (RBC) transfusion for pediatric patients undergoing brain tumor removal. METHODS: A total of 297 pediatric patients undergoing brain tumor removal were selected in this retrospective, singlecenter study. Demographic data, laboratory data, imaging data, and surgical records were collected, and then independent risk factors for intraoperative blood loss and transfusion were identified using multivariate stepwise regression analysis. RESULTS: The median intraoperative blood loss in our cohort was 23.1 ml/kg (IQR 10.0-60.0 ml/kg). In total, 284 (95.6%) patients received intraoperative RBC transfusion, with a median amount of 0.2 U/kg (IQR 0.0-2.6 U/kg). Age (ß = -0.189; 95% CI [-1.359, -0.473]; p < 0.001); preoperative hemoglobin level (ß = -0.141; 95% CI [-1.528, -0.332]; p = 0.003); anesthesia time (ß = 0.189; 95% CI [0.098, 0.302]; p < 0.001); unclear tumor boundary (ß = 0.100; 95% CI [2.067, 41.053]; p = 0.031); tumor size (ß = 0.390; 95% CI [14.706, 24.342]; p < 0.001); and intraoperative continuous infusion of vasopressor (ß = 0.155; 95% CI [13.364, 52.400]; p = 0.001) were independent predictors of intraoperative blood loss. Independent predictors of the need for RBC transfusion included age (ß = -0.268; 95% CI [-0.007, -0.004]; p < 0.001); preoperative hemoglobin level (ß = -0.117; 95% CI [-0.005, -0.001]; p = 0.003); anesthesia time (ß = 0.221; 95% CI [0.001, 0.001]; p < 0.001); unclear tumor boundary (ß = 0.110; 95% CI [0.024, 0.167]; p = 0.010); tumor size (ß = 0.370; 95% CI [0.056, 0.092]; p < 0.001); intraoperative continuous infusion of vasopressor (ß = 0.157; 95% CI [0.062, 0.205]; p < 0.001); and tumor grade (ß = 0.107; 95% CI [0.007, 0.062]; p = 0.014). CONCLUSIONS: Overall, age, preoperative hemoglobin, tumor size, anesthesia time, continuous infusion of vasopressors, and unclear tumor boundary were the main determinants for intraoperative blood loss and RBC transfusion in pediatric patients undergoing brain tumor removal. Clinical trial registration no.: ChiCTR1900024803 (ChiCTR.org).
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Pérdida de Sangre Quirúrgica , Neoplasias Encefálicas , Humanos , Niño , Estudios Retrospectivos , Transfusión Sanguínea , Neoplasias Encefálicas/cirugía , Factores de Riesgo , Hemoglobinas/análisisRESUMEN
Endosulfan belongs to persistent organic pollutants (POPs), closely related to an increased risk of prostate cancer (PCa). The existing evidence shows that lncRNAs compete with miRNAs for binding sites and contribute to the onset and progression of human malignancies. In this study we investigate how endosulfan promotes cell migration and invasion in DU145 and PC3 prostate cancer cells through epigenetic mechanism of lncRNA-miRNA regulation. Based on our past research we focused on PTP4A3 and constructed wild-type (WT) and mutant PTP4A3 plasmids for further analysis. Our results revealed that transfection of PTP4A3-WT can lead to changes in the expression of epithelial-mesenchymal transition (EMT) biomarkers and critical proteins in the TGF-ß signaling pathway, and promote cell migration and invasion in PCa cells. Bioinformatics analysis shows that there were complementary sequences in PTP4A3 3'-UTR and KCNQ1OT1 3'-UTR to the seed sequence of hsa-miR-137-3p, and dual luciferase reporter assay indicates the potential binding capacity of miR-137-3p to 3'-UTR of PTP4A3 and KCNQ1OT1. We found that miR-137-3p mimic inhibited cell migration and invasion, as well as repressed alterations of EMT biomarkers and critical proteins in the TGF-ß signaling pathway. Rescue experiment results revealed that co-transfection of miR-137-3p mimic and PTP4A3-WT plasmid reversed these changes following transfection with miR-137-3p mimic alone. We found that KCNQ1OT1 was predominantly distributed in the cytoplasm from a subcellular fractionation assay. Functionally, silencing of KCNQ1OT1 repressed cell migration and invasion, and caused alterations of EMT biomarkers and critical proteins in the TGF-ß signaling pathway, which were all restored by co-transfection with anti-miR-137-3p or PTP4A3-WT plasmid. Furthermore, overexpression of miR-137-3p or silencing of KCNQ1OT1 dramatically rescued the effects of endosulfan on promoting cell migration and invasion. These findings suggest that endosulfan can indeed promote cell migration and invasion via the KCNQ1OT1/miR-137-3p/PTP4A3 axis in PCa cells.
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MicroARNs , Neoplasias de la Próstata , Proteínas Tirosina Fosfatasas , ARN Largo no Codificante , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Endosulfano/toxicidad , Humanos , Masculino , MicroARNs/genética , Proteínas de Neoplasias/genética , Canales de Potasio con Entrada de Voltaje , Proteínas Tirosina Fosfatasas/genética , ARN Largo no Codificante/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Air purifiers should pay much attention to hospital-associated infections, but the role of a single air purifier is limited. The goal of this study was to evaluate the effectiveness of the combined application of the nonequilibrium positive and negative oxygen ion purifier (PNOI) and the high-efficiency particulate air filter (HEPA) on a complex, polluted environment. Two of the better performing purifiers were selected before the study. The efficacy of their use alone and in combination for purification of cigarette particulate matter (PM), Staphylococcus albicans, and influenza virus were then evaluated under a simulated contaminated ward. PNAI and HEPA alone are deficient. However, when they were combined, they achieved 98.44%, 99.75%, and 100% 30 min purification rates for cigarette PM, S. albus, and influenza virus, respectively. The purification of pollution of various particle sizes and positions was optimized and reduced differentials, and a subset of airborne influenza viruses is inactivated. Furthermore, they were superior to ultraviolet disinfection for microbial purification in air. This work demonstrates the strong purification capability of the combined application of these two air purifiers for complex air pollution, which provides a new idea for infection control in medical institutions.
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Filtros de Aire , Contaminantes Atmosféricos , Contaminación del Aire Interior , Orthomyxoviridae , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Bacterias , Polvo , Hospitales , Material Particulado/análisisRESUMEN
The opportunistic bacterium Pseudomonas aeruginosa can infect mucosal tissues of the human body. To persist at the mucosal barrier, this highly adaptable pathogen has evolved many strategies, including invasion of host cells. Here, we show that the P. aeruginosa lectin LecB binds and cross-links fucosylated receptors at the apical plasma membrane of epithelial cells. This triggers a signaling cascade via Src kinases and phosphoinositide 3-kinase (PI3K), leading to the formation of patches enriched with the basolateral marker phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the apical plasma membrane. This identifies LecB as a causative bacterial factor for activating this well-known host cell response that is elicited upon apical binding of P. aeruginosa. Downstream from PI3K, Rac1 is activated to cause actin rearrangement and the outgrowth of protrusions at the apical plasma membrane. LecB-triggered PI3K activation also results in aberrant recruitment of caveolin-1 to the apical domain. In addition, we reveal a positive feedback loop between PI3K activation and apical caveolin-1 recruitment, which provides a mechanistic explanation for the previously observed implication of caveolin-1 in P. aeruginosa host cell invasion. Interestingly, LecB treatment also reversibly removes primary cilia. To directly prove the role of LecB for bacterial uptake, we coated bacterium-sized beads with LecB, which drastically enhanced their endocytosis. Furthermore, LecB deletion and LecB inhibition with l-fucose diminished the invasion efficiency of P. aeruginosa bacteria. Taken together, the results of our study identify LecB as a missing link that can explain how PI3K signaling and caveolin-1 recruitment are triggered to facilitate invasion of epithelial cells from the apical side by P. aeruginosa. IMPORTANCE An intriguing feature of the bacterium P. aeruginosa is its ability to colonize highly diverse niches. P. aeruginosa can, besides forming biofilms, also enter and proliferate within epithelial host cells. Moreover, research during recent years has shown that P. aeruginosa possesses many different mechanisms to invade host cells. In this study, we identify LecB as a novel invasion factor. In particular, we show that LecB activates PI3K signaling, which is connected via a positive feedback loop to apical caveolin-1 recruitment and leads to actin rearrangement at the apical plasma membrane. This provides a unifying explanation for the previously reported implication of PI3K and caveolin-1 in host cell invasion by P. aeruginosa. In addition, our study adds a further function to the remarkable repertoire of the lectin LecB, which is all brought about by the capability of LecB to recognize fucosylated glycans on many different niche-specific host cell receptors.
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Lectinas , Pseudomonas aeruginosa , Actinas/metabolismo , Caveolina 1/metabolismo , Membrana Celular/metabolismo , Humanos , Lectinas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Pseudomonas aeruginosa/metabolismoRESUMEN
In a forced light scattering experiment, after the diffraction efficiency arrives to a stable state, both direct current (DC) voltage and two writing beams are turned off, and then by reapplication of the DC voltage we observed a peak. We provide an explanation based on periodically changed anchoring energy and also discuss the evolution of diffraction efficiency under different grating constants, laser polarization, and the direction of the optical axis of a liquid crystal cell. Experiment results show that photo-introduced charge density is nearly in proportion to the intensity of writing beams.
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Soft materials that respond to wireless external stimuli are referred to as "smart" materials due to their promising potential in real-world actuation and sensing applications in robotics, microfluidics, and bioengineering. Recent years have witnessed a burst of these stimuli-responsive materials and their preliminary applications. However, their further advancement demands more versatility, configurability, and adaptability to deliver their promised benefits. Here, a dual-stimuli-responsive soft bimorph material with three configurations that enable complex programmable 3D shape-morphing is presented. The material consists of liquid crystal elastomers (LCEs) and magnetic-responsive elastomers (MREs) via facile fabrication that orthogonally integrates their respective stimuli-responsiveness without detrimentally altering their properties. The material offers an unprecedented wide design space and abundant degree-of-freedoms (DoFs) due to the LCE's programmable director field, the MRE's programmable magnetization profile, and diverse geometric configurations. It responds to wireless stimuli of the controlled magnetic field and environmental temperature. Its dual-responsiveness allows the independent control of different DoFs for complex shape-morphing behaviors with anisotropic material properties. A diverse set of in situ reconfigurable shape-morphing and an environment-aware untethered miniature 12-legged robot capable of locomotion and self-gripping are demonstrated. Such material can provide solutions for the development of future soft robotic and other functional devices.