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1.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39000482

RESUMO

Plesiomonas shigelloides, a Gram-negative bacillus, is the only member of the Enterobacteriaceae family able to produce polar and lateral flagella and cause gastrointestinal and extraintestinal illnesses in humans. The flagellar transcriptional hierarchy of P. shigelloides is currently unknown. In this study, we identified FlaK, FlaM, FliA, and FliAL as the four regulators responsible for polar and lateral flagellar regulation in P. shigelloides. To determine the flagellar transcription hierarchy of P. shigelloides, the transcriptomes of the WT and ΔflaK, ΔflaM, ΔfliA, and ΔfliAL were carried out for comparison in this study. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and luminescence screening assays were used to validate the RNA-seq results, and the Electrophoretic Mobility Shift Assay (EMSA) results revealed that FlaK can directly bind to the promoters of fliK, fliE, flhA, and cheY, while the FlaM protein can bind directly to the promoters of flgO, flgT, and flgA. Meanwhile, we also observed type VI secretion system (T6SS) and type II secretion system 2 (T2SS-2) genes downregulated in the transcriptome profiles, and the killing assay revealed lower killing abilities for ΔflaK, ΔflaM, ΔfliA, and ΔfliAL compared to the WT, indicating that there was a cross-talk between the flagellar hierarchy system and bacterial secretion system. Invasion assays also showed that ΔflaK, ΔflaM, ΔfliA, and ΔfliAL were less effective in infecting Caco-2 cells than the WT. Additionally, we also found that the loss of flagellar regulators causes the differential expression of some of the physiological metabolic genes of P. shigelloides. Overall, this study aims to reveal the transcriptional hierarchy that controls flagellar gene expression in P. shigelloides, as well as the cross-talk between motility, virulence, and physiological and metabolic activity, laying the groundwork for future research into P. shigelloides' coordinated survival in the natural environment and the mechanisms that infect the host.


Assuntos
Proteínas de Bactérias , Flagelos , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Plesiomonas , Flagelos/metabolismo , Flagelos/genética , Plesiomonas/genética , Plesiomonas/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Transcriptoma , Regiões Promotoras Genéticas , Sistemas de Secreção Bacterianos/genética , Sistemas de Secreção Bacterianos/metabolismo , Transcrição Gênica , Humanos
2.
Appl Microbiol Biotechnol ; 108(1): 402, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951204

RESUMO

Delayed graft function (DGF) is a frequently observed complication following kidney transplantation (KT). Our prior research revealed dynamic shifts in salivary microbiota post-KT with immediate graft function (IGF), yet its behavior during DGF remains unexplored. Five recipients with DGF and 35 recipients with IGF were enrolled. Saliva samples were collected during the perioperative period, and 16S rRNA gene sequencing was performed. The salivary microbiota of IGFs changed significantly and gradually stabilized with the recovery of renal function. The salivary microbiota composition of DGFs was significantly different from that of IGFs, although the trend of variation appeared to be similar to that of IGFs. Salivary microbiota that differed significantly between patients with DGF and IGF at 1 day after transplantation were able to accurately distinguish the two groups in the randomForest algorithm (accuracy = 0.8333, sensitivity = 0.7778, specificity = 1, and area under curve = 0.85), with Selenomonas playing an important role. Bacteroidales (Spearman's r = - 0.4872 and p = 0.0293) and Veillonella (Spearmen's r = - 0.5474 and p = 0.0125) were significantly associated with the serum creatinine in DGF patients. Moreover, the significant differences in overall salivary microbiota structure between DGF and IGF patients disappeared upon long-term follow-up. This is the first study to investigate the dynamic changes in salivary microbiota in DGFs. Our findings suggested that salivary microbiota was able to predict DGF in the early stages after kidney transplantation, which might help the perioperative clinical management and early-stage intervention of kidney transplant recipients. KEY POINTS: • Salivary microbiota on the first day after KT could predict DGF. • Alterations in salivary taxa after KT are related to recovery of renal function.


Assuntos
Função Retardada do Enxerto , Transplante de Rim , Microbiota , RNA Ribossômico 16S , Saliva , Humanos , Transplante de Rim/efeitos adversos , Saliva/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Adulto , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética
3.
Sci Adv ; 10(26): eadk2913, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941455

RESUMO

The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of astrocytes in the regulation of BBB integrity. We showed that Dmp1-expressing astrocytes transfer mitochondria to endothelial cells via their endfeet for maintaining BBB integrity. Deletion of the Mitofusin 2 (Mfn2) gene in Dmp1-expressing astrocytes inhibited the mitochondrial transfer and caused BBB leakage. In addition, the decrease of MFN2 in astrocytes contributes to the age-associated reduction of mitochondrial transfer efficiency and thus compromises the integrity of BBB. Together, we describe a mechanism in which astrocytes regulate BBB integrity through mitochondrial transfer. Our findings provide innnovative insights into the cellular framework that underpins the progressive breakdown of BBB associated with aging and disease.


Assuntos
Astrócitos , Barreira Hematoencefálica , Células Endoteliais , Mitocôndrias , Astrócitos/metabolismo , Barreira Hematoencefálica/metabolismo , Animais , Mitocôndrias/metabolismo , Camundongos , Células Endoteliais/metabolismo , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética
4.
Front Chem ; 12: 1402870, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841337

RESUMO

The healing of damaged skin is a complex and dynamic process, and the multi-functional hydrogel dressings could promote skin tissue healing. This study, therefore, explored the development of a composite multifunctional hydrogel (HDCP) by incorporating the dopamine modified hyaluronic acid (HA-DA) and phenylboronic acid modified chitosan (CS-PBA) crosslinked using boric acid ester bonds. The integration of HA-DA and CS-PBA could be confirmed using the Fourier transform infrared spectrometer and 1H nuclear magnetic resonance analyses. The fabricated HDCP hydrogels exhibited porous structure, elastic solid behavior, shear-thinning, and adhesion properties. Furthermore, the HDCP hydrogels exhibited antibacterial efficacy against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Subsequently, the cytocompatibility of the HDCP hydrogels was verified through CCK-8 assay and fluorescent image analysis following co-cultivation with NIH-3T3 cells. This research presents an innovative multifunctional hydrogel that holds promise as a wound dressing for various applications within the realm of wound healing.

5.
Front Pharmacol ; 15: 1393693, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855753

RESUMO

Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.

6.
Nat Commun ; 15(1): 5094, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877020

RESUMO

Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression.


Assuntos
Reabsorção Óssea , Ferroptose , Mitocôndrias , Células Mieloides , Osteoclastos , Osteoporose , Animais , Mitocôndrias/metabolismo , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osteoclastos/metabolismo , Células Mieloides/metabolismo , Osteoporose/metabolismo , Osteoporose/patologia , Camundongos , Glucocorticoides/metabolismo , Glutationa/metabolismo , Camundongos Endogâmicos C57BL , Diferenciação Celular , Camundongos Knockout , Humanos , Masculino
7.
Front Hum Neurosci ; 18: 1429130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903409

RESUMO

Although brain-computer interface (BCI) is considered a revolutionary advancement in human-computer interaction and has achieved significant progress, a considerable gap remains between the current technological capabilities and their practical applications. To promote the translation of BCI into practical applications, the gold standard for online evaluation for classification algorithms of BCI has been proposed in some studies. However, few studies have proposed a more comprehensive evaluation method for the entire online BCI system, and it has not yet received sufficient attention from the BCI research and development community. Therefore, the qualitative leap from analyzing and modeling for offline BCI data to the construction of online BCI systems and optimizing their performance is elaborated, and then user-centred is emphasized, and then the comprehensive evaluation methods for translating BCI into practical applications are detailed and reviewed in the article, including the evaluation of the usability (including effectiveness and efficiency of systems), the evaluation of the user satisfaction (including BCI-related aspects, etc.), and the evaluation of the usage (including the match between the system and user, etc.) of online BCI systems. Finally, the challenges faced in the evaluation of the usability and user satisfaction of online BCI systems, the efficacy of online BCI systems, and the integration of BCI and artificial intelligence (AI) and/or virtual reality (VR) and other technologies to enhance the intelligence and user experience of the system are discussed. It is expected that the evaluation methods for online BCI systems elaborated in this review will promote the translation of BCI into practical applications.

8.
Biomed Mater ; 19(4)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38815598

RESUMO

Bacterial infection can lead to various complications, such as inflammations on surrounding tissues, which can prolong wound healing and thus represent a significant clinical and public healthcare problem. Herein, a report on the fabrication of a novel genipin/quaternized chitosan (CS) hydrogel for wound dressing is presented. The hydrogel was prepared by mixing quaternized CS and genipin under 35 °C bath. The hydrogels showed porous structure (250-500 µm) and mechanical properties (3000-6000 Pa). In addition, the hydrogels displayed self-healing ability and adhesion performance on different substrates. Genipin crosslinked quaternized CS hydrogels showed antibacterial activities againstE. coliandS. aureus. The CCK-8 and fluorescent images confirmed the cytocompatibility of hydrogels by seeding with NIH-3T3 cells. The present study showed that the prepared hydrogel has the potential to be used as wound dressing.


Assuntos
Antibacterianos , Bandagens , Quitosana , Reagentes de Ligações Cruzadas , Escherichia coli , Hidrogéis , Iridoides , Compostos de Amônio Quaternário , Staphylococcus aureus , Cicatrização , Quitosana/química , Iridoides/química , Animais , Camundongos , Hidrogéis/química , Cicatrização/efeitos dos fármacos , Células NIH 3T3 , Antibacterianos/química , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Compostos de Amônio Quaternário/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Porosidade
9.
ACS Macro Lett ; 13(6): 703-710, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38767665

RESUMO

Polymer vesicles are of profound interest for designing delivery vehicles and nanoreactors toward a variety of biomedical and catalytic applications, yet robust synthesis of stable and permeable vesicles remains challenging. Here, we propose an electrostatic-templated polymerization that enables fabrication of polyelectrolyte vesicles with simultaneously regulated stability and permeability. In our design, cationic monomers were copolymerized with cross-linkers in the presence of a polyanionic-neutral diblock copolymer as a template. By properly choosing the block length ratio of the template, we fabricated a type of polyion complex vesicle consisting of a cross-linked cationic membrane, electrostatically assembled with the template copolymer which can be removed by sequential dissociation and separation under concentrated salt. We finally obtained stable polyelectrolyte vesicles of regulated size, membrane permeability, and response properties by tuning the synthesis factors including ionic strength, cross-linker type, and fraction as well as different monomers and concentrations. As a proof-of-concept, lipase was loaded in the designed cationic vesicles, which exhibited enhanced enzyme stability and activity. Our study has developed a novel and robust strategy for controllable synthesis of a new class of stable and permeable polymer (polyelectrolyte) vesicles that feature great potential applications as functional delivery carriers and nanoreactors.

10.
Int J Biol Macromol ; 271(Pt 2): 132588, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38788878

RESUMO

Interface residues at sites of protein-protein interaction (PPI) are the focus for affinity optimisation. However, protein hydrophobic cores (HCs) play critical roles and shape the protein surface. We hypothesise that manipulating protein HCs can enhance PPI interaction affinities. A cell stress molecule, major histocompatibility complex class I chain-related protein A (MICA), binds to the natural killer group 2D (NKG2D) homodimer to form three molecule interactions. MICA was used as a study subject to support our hypothesis. We redesigned MICA HCs by directed mutagenesis and isolated high-affinity variants through a newly designed partial-denature panning (PDP) method. A few mutations in MICA HCs increased the NKG2D-MICA interaction affinity by 325-5613-fold. Crystal structures of the NKG2D-MICA variant complexes indicated that mutagenesis of MICA HCs stabilised helical elements for decreasing intermolecular interactive free energy (ΔG) of the NKG2D-MICA heterotrimer. The repacking of MICA HC mutants maintained overall surface residues and the authentic binding specificity of MICA. In conclusion, this study provides a new method for MICA redesign and affinity optimisation through HC manipulation without mutating PPI interface residues. Our study introduces a novel approach to protein manipulation, potentially expanding the toolkit for protein affinity optimisation.


Assuntos
Antígenos de Histocompatibilidade Classe I , Interações Hidrofóbicas e Hidrofílicas , Ligação Proteica , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/química , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Modelos Moleculares , Mutação
11.
Ann Vasc Surg ; 106: 162-167, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38821477

RESUMO

BACKGROUND: To evaluate the safety and effectiveness of a stepwise interventional strategy for the removal of adherent totally implanted central venous access port catheters, consisting of a guidewire support, antegrade coaxial separation, and retrograde coaxial separation with increasing technical complexity. METHODS: This study has a retrospective design. Thirty-two patients who had failed routine removal of the port catheter and were then transferred to interventional radiology between November 2017 and December 2023 were reviewed. The technical success and complication rates were recorded. RESULTS: All adherent catheters were successfully removed without catheter fragmentation, using guidewire support (n = 21), antegrade coaxial separation (n = 5), and retrograde coaxial separation (n = 6). The technical success rate was 100%, and no complications occurred. CONCLUSIONS: The proposed stepwise interventional strategy successfully removed adherent port catheters, with good safety and high effectiveness. It appeared to reduce the incidence of catheter fracture during the removal of adherent totally implantable central venous access port catheters.

12.
Int J Paediatr Dent ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725105

RESUMO

BACKGROUND: Changes in healthy and inflamed pulp on periapical radiographs are traditionally so subtle that they may be imperceptible to human experts, limiting its potential use as an adjunct clinical diagnostic feature. AIM: This study aimed to investigate the feasibility of an image-analysis technique based on the convolutional neural network (CNN) to detect irreversible pulpitis in primary molars on periapical radiographs (PRs). DESIGN: This retrospective study was performed in two health centres. Patients who received indirect pulp therapy at Peking University Hospital for Stomatology were retrospectively identified and randomly divided into training and validation sets (8:2). Using PRs as input to an EfficientNet CNN, the model was trained to categorise cases into either the success or failure group and externally tested on patients who presented to our affiliate institution. Model performance was evaluated using sensitivity, specificity, accuracy and F1 score. RESULTS: A total of 348 PRs with deep caries were enrolled from the two centres. The deep learning model achieved the highest accuracy of 0.90 (95% confidence interval: 0.79-0.96) in the internal validation set, with an overall accuracy of 0.85 in the external test set. The mean greyscale value was higher in the failure group than in the success group (p = .013). CONCLUSION: The deep learning-based model could detect irreversible pulpitis in primary molars with deep caries on PRs. Moreover, this study provides a convenient and complementary method for assessing pulp status.

13.
Brain Behav ; 14(5): e3529, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747741

RESUMO

BACKGROUND AND AIMS: Stress ulcer (SU) is a common complication in patients with acute ischemic stroke. The relationship of infarction location and the incidence of SU was unclear. Herein, we aim to investigate the association between ischemic insular damage and the development of SU. METHODS: Data were retrieved from the SPARK study (Effect of Cardiac Function on Short-Term Functional Prognosis in Patients with Acute Ischemic Stroke). We included the patients who had experienced an ischemic stroke within 7 days. The diagnosis of SU was based on clinical manifestations, including hematemesis, bloody nasogastric tube aspirate, or hematochezia. Evaluation of ischemic insular damage was conducted through magnetic resonance imaging. Cyclo-oxygenase regression analysis and Kaplan-Meier survival curves were used to assess the relationship between ischemic insular damage and the occurrence of SU. RESULTS: Among the 1357 patients analyzed, 110 (8.1%) developed SUs during hospitalization, with 69 (6.7%) experiencing infarctions in the anterior circulation. After adjusting for potential confounders, patients with ischemic insular damage exhibited a 2.16-fold higher risk of developing SUs compared to those without insular damage (p = .0206). Notably, among patients with infarctions in the anterior circulation, those with insular damage had a 2.21-fold increased risk of SUs (p = .0387). Moreover, right insular damage was associated with a higher risk of SUs compared to left insular damage or no insular damage (p for trend = .0117). Kaplan-Meier curves demonstrated early separation among groups, persisting throughout the follow-up period (all p < .0001). CONCLUSIONS: This study identified a significant independent correlation between ischemic insular damage, particularly on the right side, and the development of SU during hospitalization, indicating the need to consider prophylactic acid-suppressive treatment for patients with ischemic insular damage.


Assuntos
AVC Isquêmico , Humanos , Masculino , Feminino , AVC Isquêmico/complicações , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico por imagem , Idoso , Pessoa de Meia-Idade , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Imageamento por Ressonância Magnética , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Úlcera/patologia
14.
Sci Rep ; 14(1): 11945, 2024 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-38789468

RESUMO

Understanding the mechanisms underlying dysphagia is crucial in devising effective, etiology-centered interventions. However, current clinical assessment and treatment of dysphagia are still more symptom-focused due to our limited understanding of the sophisticated symptom-etiology associations causing swallowing disorders. This study aimed to elucidate the mechanisms giving rise to penetration flows into the laryngeal vestibule that results in aspirations with varying symptoms. Methods: Anatomically accurate, transparent throat models were prepared with a 45° down flapped epiglottis to simulate the instant of laryngeal closure during swallowing. Fluid bolus dynamics were visualized with fluorescent dye from lateral, rear, front, and endoscopic directions to capture key hydrodynamic features leading to aspiration. Three influencing factors, fluid consistency, liquid dispensing site, and dispensing speed, were systemically evaluated on their roles in liquid aspirations. Results: Three aspiration mechanisms were identified, with liquid bolus entering the airway through (a) the interarytenoid notch (notch overflow), (b) cuneiform tubercle recesses (recess overflow), and (c) off-edge flow underneath the epiglottis (off-edge capillary flow). Of the three factors considered, liquid viscosity has the most significant impact on aspiration rate, followed by the liquid dispensing site and the dispensing speed. Water had one order of magnitude higher aspiration risks than 1% w/v methyl cellulose solution, a mildly thick liquid. Anterior dispensing had higher chances for aspiration than posterior oropharyngeal dispensing for both liquids and dispensing speeds considered. The effects of dispending speed varied. A lower speed increased aspiration for anterior-dispensed liquids due to increased off-edge capillary flows, while it significantly reduced aspiration for posterior-dispensed liquids due to reduced notch overflows. Visualizing swallowing hydrodynamics from multiple orientations facilitates detailed site-specific inspections of aspiration mechanisms.


Assuntos
Transtornos de Deglutição , Deglutição , Epiglote , Hidrodinâmica , Deglutição/fisiologia , Humanos , Transtornos de Deglutição/fisiopatologia , Viscosidade , Faringe , Modelos Anatômicos , Orofaringe , Laringe/fisiopatologia
15.
Heliyon ; 10(8): e29352, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644837

RESUMO

Background and objective: The association between cardiac dysfunction and functional outcome in acute ischemic stroke (AIS) is not clear. We aimed to investigate the relationship between the routinely assessed left ventricular ejection fraction (LVEF) and functional outcomes in patients with AIS. Methods: Data came from a prospective, observational, single-center study (Effect of Cardiac Function on Short-term Functional Prognosis in Patients with Acute Ischemic Stroke, SPARK). The LVEF was assessed with transthoracic echocardiography within 7 days of stroke onset. The primary outcome was functional disability, defined as a modified Rankin Scale score of 3-6 at 90 days (range: 0-6, with higher scores indicating greater disability). We also investigated the association of the LVEF with mortality, early neurological deterioration, hospital stay, and costs. Multivariate logistic regression analysis and 2:1 propensity score matching (PSM) were performed to compare the differences in outcomes. Results: A total of 1181 patients were included in this analysis, of which 87 (7.4 %) patients were found to have LVEF of <60 %. In the entire study population, LVEF<60 % was significantly associated with functional disability at 90 days (odds ratio [OR]: 1.85, 95 % confidence intervals (CI): 1.01-3.40) after adjusting for all confounders. After PSM, the association was consistently significant (OR: 5.32, 95 % CI: 3.04-9.30). However, associations of the LVEF with mortality, early neurological deterioration, hospital stay, and costs were not consistently significant across all analyses. In the subgroup analysis, the association of LVEF of <60 % with functional disability was statistically significant in patients with non-cardioembolic stroke, but not in patients with cardioembolic stroke (P for interaction = 0.872). Conclusions: An LVEF of <60 % will likely increase the risk of functional disability in patients with AIS. Future strategies to prevent cardiac dysfunction in the acute phase are needed.

16.
J Exp Clin Cancer Res ; 43(1): 128, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685050

RESUMO

BACKGROUND: Brain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential strategy for improving radiation resistance. METHODS: We used databases to detect the expression of MIF in NSCLC and its relationship with prognosis. We analyzed the effects of targeted blockade of the MIF/CD74 axis on the polarization and function of microglia during radiotherapy using flow cytometry. The mouse model of brain metastasis was used to assess the effect of targeted blockade of MIF/CD74 axis on the growth of brain metastasis. RESULT: Our findings reveals that the macrophage migration inhibitory factor (MIF) was highly expressed in NSCLC and is associated with the prognosis of NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation in microglia and promoted the M1 polarization in combination of radiation. Additionally, blocking the MIF-CD74 interaction between NSCLC and microglia promoted microglia M1 polarization. Furthermore, radiation improved tumor hypoxia to decrease HIF-1α dependent MIF secretion by NSCLC. MIF inhibition enhanced radiosensitivity for brain metastasis via synergistically promoting microglia M1 polarization in vivo. CONCLUSIONS: Our study revealed that targeting the MIF-CD74 axis promoted microglia M1 polarization and synergized with radiotherapy for brain metastasis in NSCLC.


Assuntos
Antígenos de Diferenciação de Linfócitos B , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Antígenos de Histocompatibilidade Classe II , Neoplasias Pulmonares , Fatores Inibidores da Migração de Macrófagos , Microglia , Animais , Feminino , Humanos , Camundongos , Antígenos de Diferenciação de Linfócitos B/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Antígenos de Histocompatibilidade Classe II/metabolismo , Oxirredutases Intramoleculares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Microglia/metabolismo , Microglia/patologia
17.
Front Hum Neurosci ; 18: 1391550, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601800

RESUMO

Brain-computer interface (BCI) is a revolutionizing human-computer interaction, which has potential applications for specific individuals or groups in specific scenarios. Extensive research has been conducted on the principles and implementation methods of BCI, and efforts are currently being made to bridge the gap from research to real-world applications. However, there are inaccurate or erroneous conceptions about BCI among some members of the public, and certain media outlets, as well as some BCI researchers, developers, manufacturers, and regulators, propagate misleading or overhyped claims about BCI technology. Therefore, this article summarizes the several misconceptions and misleading propaganda about BCI, including BCI being capable of "mind-controlled," "controlling brain," "mind reading," and the ability to "download" or "upload" information from or to the brain using BCI, among others. Finally, the limitations (shortcomings) and limits (boundaries) of BCI, as well as the necessity of conducting research aimed at countering BCI systems are discussed, and several suggestions are offered to reduce misconceptions and misleading claims about BCI.

19.
J Dent ; 144: 104931, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38458378

RESUMO

OBJECTIVES: To develop a deep learning-based system for precise, robust, and fully automated segmentation of the mandibular canal on cone beam computed tomography (CBCT) images. METHODS: The system was developed on 536 CBCT scans (training set: 376, validation set: 80, testing set: 80) from one center and validated on an external dataset of 89 CBCT scans from 3 centers. Each scan was annotated using a multi-stage annotation method and refined by oral and maxillofacial radiologists. We proposed a three-step strategy for the mandibular canal segmentation: extraction of the region of interest based on 2D U-Net, global segmentation of the mandibular canal, and segmentation refinement based on 3D U-Net. RESULTS: The system consistently achieved accurate mandibular canal segmentation in the internal set (Dice similarity coefficient [DSC], 0.952; intersection over union [IoU], 0.912; average symmetric surface distance [ASSD], 0.046 mm; 95% Hausdorff distance [HD95], 0.325 mm) and the external set (DSC, 0.960; IoU, 0.924; ASSD, 0.040 mm; HD95, 0.288 mm). CONCLUSIONS: These results demonstrated the potential clinical application of this AI system in facilitating clinical workflows related to mandibular canal localization. CLINICAL SIGNIFICANCE: Accurate delineation of the mandibular canal on CBCT images is critical for implant placement, mandibular third molar extraction, and orthognathic surgery. This AI system enables accurate segmentation across different models, which could contribute to more efficient and precise dental automation systems.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Imageamento Tridimensional , Mandíbula , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Mandíbula/diagnóstico por imagem , Mandíbula/anatomia & histologia , Imageamento Tridimensional/métodos , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos
20.
ACS Appl Mater Interfaces ; 16(14): 17766-17777, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38534058

RESUMO

Serving as neuromorphic hardware accelerators, memristors play a crucial role in large-scale neuromorphic computing. Herein, two-terminal memristors utilizing amorphous indium-gallium-zinc oxide (a-IGZO) are fabricated through room-temperature sputtering. The electrical characteristics of these memristors are effectively modulated by varying the oxygen flow during the deposition process. The optimized a-IGZO memristor, fabricated under 3 sccm oxygen flow, presents a 5 × 103 ratio between its high- and low-resistance states, which can be maintained over 1 × 104 s with minimal degradation. Meanwhile, desirable properties such as electroforming-free and self-compliance, crucial for low-energy consumption, are also obtained in the a-IGZO memristor. Moreover, analog conductance switching is observed, demonstrating an interface-type behavior, as evidenced by its device-size-dependent performance. The coexistence of negative differential resistance with analog switching is attributed to the migration of oxygen vacancies and the trapping/detrapping of charges. Furthermore, the device demonstrates optical storage capabilities by exploiting the optical properties of a-IGZO, which can stably operate for up to 50 sweep cycles. Various synaptic functions have been demonstrated, including paired-pulse facilitation and spike-timing-dependent plasticity. These functionalities contribute to a simulated recognition accuracy of 90% for handwritten digits. Importantly, a one-selector one-memristor (1S1M) architecture is successfully constructed at room temperature by integrating a-IGZO memristor on a TaOx-based selector. This architecture exhibits a 107 on/off ratio, demonstrating its potential to suppress sneak currents among adjacent units in a memristor crossbar.

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