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Developing multifunctional materials which could simultaneously possess anti-bacterial ability and electromagnetic (EM) absorption ability during medical care is quite essential since the EM waves radiation and antibiotic-resistant bacteria are threatening people's health. In this work, the multifunctional carbon fiber/Ti3C2Tx MXene (CM) were synthesized through repeated dip-coating and following in-situ growth method. The as-fabricated CF/MXene displayed outstanding EM wave absorption and highly efficient photothermal converting ability. The minimum reflection loss (RL) of -57.07 dB and ultra-broad absorption of 7.74 GHz could be achieved for CM composites. By growth of CoNi-layered double hydroxides (LDHs) sheets onto MXene, the absorption bandwidth for carbon fiber/Ti3C2Tx MXene layered double hydroxides (CML) could be reach 5.44 GHz, which could cover the whole Ku band. The excellent photothermal effect endow the CM composites with excellent antibacterial performance. The antibacterials tests indicated that nearly 100 % bactericidal efficiency against E. acoil and S. aureus was obtained for the CM composite after exposure to near-infrared region (NIR) irradiation. This work provides a promising candidate to combat medical device-related infections and EM pollution.
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Since gastric cancer shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence PCR. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ² test, and ROC was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation, infiltration depth of tumors, TNM stage, lymph node metastases, and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis.
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Purpose: To explore the influence of corneal higher-order aberrations (HOAs) on dynamic visual acuity (DVA) post cataract surgery. Methods: A total of 27 patients with 45 eyes following cataract surgery were included in this study. The postoperative monocular object-moving DVA at the velocity of 20, 40, and 80 degrees per second (dps) were examined at 1 month. The total corneal HOAs were measured with Scheimpflug-based corneal topography. The correlation between postoperative DVA and HOAs was analyzed. Results: Significant difference was shown among DVA at different velocities (P < 0.001). The 20 dps DVA was significantly better than 40 (P < 0.001) and 80 (P < 0.001) dps DVA. No significant difference was observed between 40 and 80 dps DVA (P = 0.420). The vertical coma and the root mean square (RMS) of coma (RMScoma) were statistically correlated with 80 dps DVA (P < 0.05). The vertical trefoil, RMStrefoil and total RMSHOA were statistically correlated with 40 and 80 dps DVA (P < 0.05). The spherical aberration was not significantly associated with postoperative DVA (P > 0.05 for all velocites). The multivariate linear regression model revealed that age was a significant influential factor for 20 dps DVA (P = 0.002), and RMStrefoil (4 mm) and age were significantly associated with 40 and 80 dps DVA (P ≤ 0.01). Conclusion: The research demonstrated that larger corneal HOAs, especially coma and trefoil aberrations were significantly associated with worse high-speed DVA, but not spherical aberration post cataract surgery.
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Chronic hepatitis (CH) encompasses a prevalent array of liver conditions that significantly contribute to global morbidity and mortality. Yiguanjian (YGJ) is a classical traditional Chinese medicine with a long history of medicinal as a treatment for CH. Although it has been reported that YGJ can reduce liver inflammation, the intricate mechanism requires further elucidation. We used network pharmacology approaches in this work, such as gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and network-based analysis of protein-protein interactions (PPIs), to clarify the pharmacological constituents, potential therapeutic targets, and YGJ signaling pathways associated with CH. Employing the random walk restart (RWR) algorithm, we identified GNAS, GNB1, CYP2E1, SFTPC, F2, MAPK3, PLG, SRC, HDAC1, and STAT3 as pivotal targets within the PPI network of YGJ-CH. YGJ attenuated liver inflammation and inhibited GNAS/STAT3 signaling in vivo. In vitro, we overexpressed the GNAS gene further to verify the critical role of GNAS in YGJ treatment. Our findings highlight GNAS/STAT3 as a promising therapeutic target for CH, providing a basis and direction for future investigations.
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Chronic liver damage (CLD) encompasses a spectrum of conditions and poses a significant global health challenge, affecting millions of individuals. Currently, there is a deficiency of clinically validated therapeutics with minimal side effects. Emerging evidence underscores the significant potential of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) as a promising therapeutic method for CLD. This study aimed to evaluate the influence of BMSC-EVs containing microRNA-136-5p (BMSC-EVs-miR-136-5p) on macrophage polarization during chronic liver injury and elucidate the mechanisms associated with the GNAS/PI3K/ERK/STAT3 axis. Surface markers of BMSCs were detected via Immunofluorescent Staining. Subsequently, EVs were harvested from the BMSC culture medium. In vivo fluorescence imaging was employed to locate the BMSC-EVs. Additionally, fluorescence microscopy was used to visualize the uptake of DIR-labeled BMSC-EVs by RAW264.7 cells. Various methods were employed to assess the impact of BMSC-EVs on the expression levels of inflammatory factors (IL-1ß, IL-6, IL-10, and TNF-α), M1/M2 macrophage markers (iNOS and Arg-1), and members of inflammation-related signaling pathways (GNAS, PI3K, ERK, and STAT3) in RAW264.7 cells co-cultured with BMSC-EVs. Loss-of-function approaches targeting miR-136-5p in RAW264.7 cells were subsequently utilized to validate the role of BMSC-EVs-miR-136-5p. The Luciferase Reporter Assay indicates that GNAS was identified to be a target of miR-136-5p, and miR-136-5p demonstrating increased within BMSC-EVs compared to Raw264.7-EVs. BMSC-EVs-miR-136-5p mitigated CCl4-induced liver inflammation and improved liver function by Suppressing the GNAS/STAT3 Signaling. Notably, miR-136-5p suppressed lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. BMSC-EVs-miR-136-5p alleviates CLD by activating M2 polarization through the GNAS-mediated PI3K/ERK/STAT3 axis. Accordingly, the members of this axis may serve as therapeutic targets.
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Lactococcus garvieae (L. garvieae) is a pathogenic bacterium that is Gram-positive and catalase-negative (GPCN), and it is capable of growing in a wide range of environmental conditions. This bacterium is associated with significant mortality and losses in fisheries, and there are concerns regarding its potential as a zoonotic pathogen, given its presence in cattle and dairy products. While we have identified and characterized virulent strains of L. garvieae through phenotyping and molecular typing studies, their impact on mammary tissue remains unknown. This study aims to investigate the pathogenicity of strong and weak virulent strains of L. garvieae using in vivo mouse models. We aim to establish MAC-T cell model to examine potential injury caused by the strong virulent strain LG41 through the TLR2/NLRP3/NF-kB pathway. Furthermore, we assess the involvement of NLRP3 inflammasome-mediated pyroptosis in dairy mastitis by silencing NLRP3. The outcomes of this study will yield crucial theoretical insights into the potential mechanisms involved in mastitis in cows caused by the L. garvieae-induced inflammatory response in MAC-T cells.
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Inflamasomas , Mastitis , Humanos , Femenino , Animales , Bovinos , Ratones , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Linfocitos T/metabolismo , Lactococcus/metabolismo , Mastitis/microbiología , Mastitis/veterinaria , InflamaciónRESUMEN
Low temperature severely affects rice development and yield. Ethylene signal is essential for plant development and stress response. Here, we reported that the OsEIN2-OsEIL1/2 pathway reduced OsICE1-dependent chilling tolerance in rice. The overexpressing plants of OsEIN2, OsEIL1 and OsEIL2 exhibited severe stress symptoms with excessive reactive oxygen species (ROS) accumulation under chilling, while the mutants (osein2 and oseil1) and OsEIL2-RNA interference plants (OsEIL2-Ri) showed the enhanced chilling tolerance. We validated that OsEIL1 and OsEIL2 could form a heterxodimer and synergistically repressed OsICE1 expression by binding to its promoter. The expression of OsICE1 target genes, ROS scavenging- and photosynthesis-related genes were downregulated by OsEIN2 and OsEIL1/2, which were activated by OsICE1, suggesting that OsEIN2-OsEIL1/2 pathway might mediate ROS accumulation and photosynthetic capacity under chilling by attenuating OsICE1 function. Moreover, the association analysis of the seedling chilling tolerance with the haplotype showed that the lower expression of OsEIL1 and OsEIL2 caused by natural variation might confer chilling tolerance on rice seedlings. Finally, we generated OsEIL2-edited rice with an enhanced chilling tolerance. Taken together, our findings reveal a possible mechanism integrating OsEIN2-OsEIL1/2 pathway with OsICE1-dependent cascade in regulating chilling tolerance, providing a practical strategy for breeding chilling-tolerant rice.
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Frío , Regulación de la Expresión Génica de las Plantas , Oryza , Proteínas de Plantas , Especies Reactivas de Oxígeno , Oryza/genética , Oryza/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Plantas Modificadas Genéticamente , Fotosíntesis , Transducción de Señal , Etilenos/metabolismoRESUMEN
INTRODUCTION: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by inflammatory infiltration, and dysfunction of the salivary and lacrimal glands. This research aimed to explore the disease pathogenesis and improve the diagnosis and treatment of pSS by mining inflammation-associated biomarkers. METHODS: Five pSS-related datasets were retrieved from the Gene Expression Omnibus (GEO) database. Inflammation-associated biomarkers were determined by the least absolute shrinkage and selection operator (LASSO) and support vector machines recursive feature elimination (SVM-RFE). Single sample gene set enrichment analysis (ssGSEA) was implemented to profile the infiltration levels of immune cells. Real-time quantitative PCR (RT-qPCR) verified the expression of biomarkers in clinical samples. RESULTS: Four genes (LY6E, EIF2AK2, IL15, and CXCL10) were screened as inflammation-associated biomarkers in pSS, the predictive performance of which were determined among three pSS-related datasets (AUC > 0.7). Functional enrichment results suggested that the biomarkers were involved in immune and inflammation-related pathways. Immune infiltration analysis revealed that biomarkers were notably connected with type 2 T helper cells, regulatory T cells which were significantly expressed between pSS and control. TESTOSTERONE and CYCLOSPORINE were predicted to take effect by targeting CXCL10 and IL15 in pSS, respectively. CONCLUSION: Four inflammation-associated biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were explored, and the underlying regulatory mechanisms and targeted drugs associated with these biomarkers were preliminarily investigated according to a series of bioinformatics methods based on the online datasets of pSS, which provided a reference for understanding the pathogenesis of pSS. Key Points ⢠Inflammation-associated biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were firstly identified in Sjögren's syndrome based on LASSO and SVM-RFE analyses. ⢠CXCL10, EIF2AK2 and LY6E were prominently positively correlated with immature B cells, while IL15 were significantly negatively correlated with memory B cells in Sjögren's syndrome. ⢠LY6E, EIF2AK2, IL15, and CXCL10 were significantly more highly expressed in clinical Sjögren's syndrome samples compared to healthy control samples, which was consistent with the analysis results of the GEO database. â¢LY6E, EIF2AK2, IL15, and CXCL10 might be used as the biomarkers for the treatment and diagnosis of Sjögren's syndrome.
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Enfermedades Autoinmunes , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/patología , Interleucina-15 , Biomarcadores/metabolismo , InflamaciónRESUMEN
Objectives: To investigate the effect of 2% hydroxypropyl methylcellulose (HPMC) and bandage contact lens (BCL) on dry eye disease after cataract surgery. Methods: This prospective randomized controlled trial included 63 eyes which were divided into the balanced salt solution (BSS), HPMC, BCL, and combined HPMC and BCL (H&B) groups. The Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), and average tear break-up time were measured before cataract surgery and 30 days postoperatively. Differences in corneal nerve fiber (CNF) and dendritic cell (DC) density in various directions were evaluated and compared. The CNFs and DCs in central and infratemporal directions were observed using in vivo confocal microscopy. Data were evaluated using the Kruskal-Wallis rank-sum test and analysis of variance. Results: The differences in variations in OSDI and TMH after cataract surgery between the four groups were statistically significant (P < 0.05). The postoperative OSDI of the HPMC group decreased compared with their preoperative OSDI. A statistically significant difference in the variations of OSDI score was observed between the HPMC and other groups (P < 0.05). The postoperative variations in TMH in the HPMC group were significantly higher than those observed preoperatively and significantly differed between HPMC and BCL groups and between BCL and H&B groups (P < 0.05). Postoperatively, the density of corneal DCs decreased in BSS and HPMC groups and increased in BCL and H&B groups (P < 0.001). Conclusions: The application of 2% HPMC in cataract surgery has a certain effect on managing dry eye after cataract surgery. Although the use of BCLs after cataract surgery has some benefits, it may cause mild ocular surface inflammation. Nevertheless, using 2% HPMC with BCLs in the perioperative phase of cataract surgery can alleviate the subjective discomfort of patients and can safely and effectively replace eye patch after cataract surgery.
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BACKGROUND: Cellular response to pharmacological action of drugs is significant for drug development. Traditional detection method for cellular response to drugs normally rely on cell proliferation assay and metabolomics examination. In principle, these analytical methods often required cell labeling, invasion analysis, and hours of co-culture with drugs, which are relatively complex and time-consuming. Moreover, these methods can only indicate the drug effectiveness on cell colony rather than single cells. Thus, to meet the requirements of personal precision medicine, the development of drug response analysis on the high resolution of single cell is demanded. RESULTS: To provide precise result for drug response on single-cell level, a microfluidic platform coupled with the label-free hyperspectral imaging was developed. With the help of horizontal single-cell trapping sieves, hundreds of single cells were trapped independently in microfluidic channels for the purposes of real-time drug delivery and single-cell hyperspectral image recording. To significantly identify the cellular hyperspectral change after drug stimulation, the differenced single-cell spectrum was proposed. Compared with the deep learning classification method based on hyperspectral images, an optimal performance can be achieved by the classification strategy based on differenced spectra. And the cellular response to different reagents, for example, K+, Epidermal Growth Factor (EGF), and Gefitinib at different concentrations can be accurately characterized by the differenced single-cell spectra analysis. SIGNIFICANCE AND NOVELTY: The high-throughput, rapid analysis of cellular response to drugs at the single-cell level can be accurately performed by our platform. After systematically analyzing the materials and the structures of the single-cell microfluidic chip, the optimal single-cell trapping method was proposed to contribute to the further application of hyperspectral imaging on microfluidic single-cell analysis. And the hyperspectral characterization of single-cell with cancer drug stimulation proved the application potential of our method in personal cancer medication.
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Imágenes Hiperespectrales , Microfluídica , Microfluídica/métodos , Preparaciones Farmacéuticas , Técnicas de Cocultivo , Análisis de la Célula IndividualRESUMEN
Parkinson's disease (PD) is a debilitating neurodegenerative disorder. Its symptoms are typically treated with levodopa or dopamine receptor agonists, but its action lacks specificity due to the wide distribution of dopamine receptors in the central nervous system and periphery. Here, we report the development of a gene therapy strategy to selectively manipulate PD-affected circuitry. Targeting striatal D1 medium spiny neurons (MSNs), whose activity is chronically suppressed in PD, we engineered a therapeutic strategy comprised of a highly efficient retrograde adeno-associated virus (AAV), promoter elements with strong D1-MSN activity, and a chemogenetic effector to enable precise D1-MSN activation after systemic ligand administration. Application of this therapeutic approach rescues locomotion, tremor, and motor skill defects in both mouse and primate models of PD, supporting the feasibility of targeted circuit modulation tools for the treatment of PD in humans.
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Terapia Genética , Enfermedad de Parkinson , Animales , Humanos , Ratones , Cuerpo Estriado/metabolismo , Levodopa/uso terapéutico , Levodopa/genética , Neuronas/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia , Primates , Receptores de Dopamina D1/metabolismo , Modelos Animales de EnfermedadRESUMEN
Lactococcus lactis (L. lactis) is the primary organism for lactic acid bacteria (LAB) and is a globally recognized safe microorganism for the regulation of the intestinal micro-ecological balance of animals and improving the immune performance of the host. L. lactis is known to play a commercially important role in feed fortification, milk fermentation, and vaccine production, but pathogenic L. lactis has been isolated from many clinical cases in recent years, such as the brain of silver carp with Lactococcosis, the liver and spleen of diseased waterfowl, milk samples and padding materials with cow mastitis, and blood and urine from human patients with endocarditis. In dairy farming, where L. lactis has been used as a probiotic in the past, however, some studies have found that L. lactis can cause mastitis in cows, but the lack of understanding of the pathogenesis of mastitis in cows caused by L. lactis has become a new problem. The main objective of this review is to analyze the increasingly serious clinical mastitis caused by L. lactis and combined with the wide application of L. lactis as probiotics, to comprehensively discuss the characteristics and diversity of L. lactis.
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Lactococcus lactis , Mastitis , Probióticos , Femenino , Humanos , Bovinos , Animales , Virulencia , Leche/microbiologíaRESUMEN
PURPOSE: In this study, we determined the positive rates of allergen-specific immunoglobulin E (IgE) in the tear fluid of Chinese patients with common allergic conjunctivitis (AC) in autumn and winter, compared systemic and ocular allergen tests, and explored the correlation between the numbers and categories of allergens and clinical AC features. METHODS: This cross-sectional study recruited 44 patients with AC (86 eyes). Specific IgEs for allergens common in China (house dust mite, cat/dog dander, mugwort/ragweed pollen, cottonwood/willow/elm pollen, milk, egg whites, soybeans) were measured in collected tears using kits for allergen-specific IgE antibodies. AC signs and symptoms were graded according to severity. RESULTS: Specific IgE in tears was positive in 87.2% of eyes. House dust mite was the most common allergen (86.0%), followed by cat (24.4%) and dog (7.0%) dander; tree and grass pollen accounted for only 4.7% and 2.3%, respectively. Food allergens were not detected. The positive rates of the systemic allergen tests were lower than in tear fluid tests in both eyes, especially for house dust mites (P = 0.000). In patients with more allergens, itching was more severe (P = 0.035), while conjunctival hyperemia was milder (P = 0.002). CONCLUSION: In autumn and winter, the most common AC allergen in Chinese patients was house dust mites. Compared with systemic allergen tests, measuring specific IgE in tears may be a non-invasive method to diagnose and evaluate AC severity, which may be more suitable to reflect the local conditions of ocular surface inflammation due to its high positive rate and convenience.
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Conjuntivitis Alérgica , Humanos , Animales , Perros , Conjuntivitis Alérgica/diagnóstico , Estudios Transversales , Alérgenos , Polen , Inmunoglobulina ERESUMEN
Cerebral ischemia is a serious disease characterized by brain tissue ischemia and hypoxic necrosis caused by the blockage of blood vessels within the central nervous system. Although stem cell therapy is a promising approach for treating ischemic stroke, the inflammatory, oxidative, and hypoxic environment generated by cerebral ischemia greatly reduces the survival and therapeutic effects of transplanted stem cells. Endothelial colony-forming cells (ECFCs) are a class of precursor cells with strong proliferative potential that can migrate and differentiate directly into mature vascular endothelial cells. Consequently, ECFCs can exert significant therapeutic and reparative effects in diseases associated with vascular injury. Monocyte chemoattractant protein-induced protein 1 (MCPIP-1) exerts multiple biological effects; however, no studies have yet reported its role in the angiogenic function of ECFCs. In this study, we performed Proteome Profiler™ Human Angiogenesis Antibody arrays and tandem mass tag protein profiling to investigate the effect of MCPIP-1 on ECFCs. We demonstrated that MCPIP-1 knockdown enhanced the proliferation, migration, and in vivo and in vitro angiogenic capacity of ECFCs by upregulating the transferrin receptor-activated AKT/m-TOR signaling pathway to promote cellular trophic factor secretion. Furthermore, we found that the lateral ventricular transplantation of ECFCs with lentiviral MCPIP-1 knockdown into mice with middle cerebral artery occlusion increased serum vacular endothelial growth factor(VEGF), angiopoietin-1, and HIF-1a levels, enhanced neovascularization and neurogenesis in the ischemic penumbra, reduced the size of cerebral infarcts, and promoted neurological recovery. Together, these findings suggest new avenues for enhancing the therapeutic efficacy of ECFCs.
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Isquemia Encefálica , Células Endoteliales , Neovascularización Fisiológica , Animales , Humanos , Ratones , Isquemia Encefálica/metabolismo , Células Cultivadas , Células Endoteliales/metabolismo , Isquemia/metabolismo , Isquemia/terapia , Neovascularización Fisiológica/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: The coexistence of MRCS (microcornea, retinal dystrophy, cataract, and posterior staphyloma) syndrome and extremely long axis is rare since microcornea frequently accompanies with diminution of entire anterior segment and occasionally the whole globe. In the case presented here, combination of these two elements were identified, together with XFS (exfoliation syndrome). CASE PRESENTATION: A 66-year-old Han Chinese woman presented for consultation due to impaired vision which accompanied throughout her entire life span and worsened during the last 2 years. Combination of MRCS syndrome and extremely long axial length was evidently diagnosed in both eyes, with XFS confirmed in her right eye, but mutation screening failed to identify disease-causing sequence variants in some specific genes reported previously, including BEST1 and ARL2. However, likely pathogenic mutations in FBN2 gene were identified. Bilateral cataract phacoemulsification without intraocular lens implantation was performed using scleral tunnel incision and under general anesthesia. At 3-month follow-up, ocular recovery of the patient was satisfactory. CONCLUSIONS: The case presented here exhibited rare coexistence of MRCS syndrome, extremely long axis and XFS. The complexity of her ocular abnormalities brought challenges to surgical management, in which multidisciplinary collaboration is often required. Furthermore, the genetic analysis in this case yielded a possible novel candidate gene for MRCS syndrome and provided evidence in support of genetic heterogeneity in this phenotype.
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Extracción de Catarata , Catarata , Síndrome de Exfoliación , Facoemulsificación , Distrofias Retinianas , Femenino , Humanos , Síndrome de Exfoliación/complicaciones , Síndrome de Exfoliación/diagnóstico , Síndrome de Exfoliación/genética , Catarata/complicaciones , Catarata/diagnóstico , Catarata/genética , Proteínas de Unión al GTP , BestrofinasRESUMEN
Multi-object tracking (MOT) is a topic of great interest in the field of computer vision, which is essential in smart behavior-analysis systems for healthcare, such as human-flow monitoring, crime analysis, and behavior warnings. Most MOT methods achieve stability by combining object-detection and re-identification networks. However, MOT requires high efficiency and accuracy in complex environments with occlusions and interference. This often increases the algorithm's complexity, affects the speed of tracking calculations, and reduces real-time performance. In this paper, we present an improved MOT method combining an attention mechanism and occlusion sensing as a solution. A convolutional block attention module (CBAM) calculates the weights of space and channel attention from the feature map. The attention weights are used to fuse the feature maps to extract adaptively robust object representations. An occlusion-sensing module detects an object's occlusion, and the appearance characteristics of an occluded object are not updated. This can enhance the model's ability to extract object features and improve appearance feature pollution caused by the short-term occlusion of an object. Experiments on public datasets demonstrate the competitive performance of the proposed method compared with the state-of-the-art MOT methods. The experimental results show that our method has powerful data association capability, e.g., 73.2% MOTA and 73.9% IDF1 on the MOT17 dataset.
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ETHNOPHARMACOLOGICAL RELEVANCE: Hydroxysafflor yellow A (HSYA) is the principal bioactive compound isolated from the plant Carthamus tinctorius L. and has been reported to exert neuroprotective effects against various neurological diseases, including traumatic brain injury (TBI). However, the specific molecular and cellular mechanisms underlying HSYA-mediated neuroprotection against TBI are unclear. AIM OF THE STUDY: This study explored the effects of HSYA on autophagy and the NLRP3 inflammasome in mice with TBI and the related mechanisms. MATERIALS AND METHODS: Mice were subjected to TBI and treated with or without HSYA. Neurological severity scoring, LDH assays and apoptosis detection were first performed to assess the effects of HSYA in mice with TBI. RNA-seq was then conducted to explore the mechanisms that contributed to HSYA-mediated neuroprotection. ELISA, western blotting, and immunofluorescence were performed to further investigate the mechanisms of neuroinflammation and autophagy. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, was applied to determine the connection between autophagy and the NLRP3 inflammasome. RESULTS: HSYA significantly decreased the neurological severity score, serum LDH levels and apoptosis in mice with TBI. A total of 921 differentially expressed genes were identified in the cortices of HSYA-treated mice with TBI and were significantly enriched in the inflammatory response and autophagy. Furthermore, HSYA treatment markedly reduced inflammatory cytokine levels and astrocyte activation. Importantly, HSYA suppressed neuronal NLRP3 inflammasome activation, as indicated by decreased levels of NLRP3, ASC and cleaved caspase-1 and a reduced NLRP3+ neuron number. It increased autophagy and ameliorated autophagic flux dysfunction, as evidenced by increased LC3 II/LC3 I levels and decreased P62 levels. The effects of HSYA on the NLRP3 inflammasome were abolished by 3-MA. Mechanistically, HSYA may enhance autophagy through AMPK/mTOR signalling. CONCLUSION: HSYA enhanced neuronal autophagy by triggering the AMPK/mTOR signalling pathway, leading to inhibition of the NLRP3 inflammasome to improve neurological recovery after TBI.
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Lesiones Traumáticas del Encéfalo , Inflamasomas , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neuroprotección , Proteínas Quinasas Activadas por AMP , Lesiones Traumáticas del Encéfalo/metabolismo , Autofagia , Serina-Treonina Quinasas TORRESUMEN
Due to its excellent bone conductivity and drug adsorption as well as pH-responsive drug release property, hydroxyapatite (HAp) is widely used as a drug carrier in bone repair field. Here, we report for the first time a novel multi-functional polydopamine (PDA) coated Cu/F-codoped HAp (Cu/F-HAp-PDA) hollow microspheres. Both Cu2+ and F- were successfully doped into the lattice of HAp and uniformly distributed in the shell of hollow microspheres through a one-step hydrothermal synthesis. Then PDA was coated homogeneously on the outer layer of Cu/F-HAp hollow microspheres. Both Cu/F-HAp and Cu/F-HAp-PDA samples displayed high drug loading efficiency and pH responsive drug release behavior. Moreover, the obtained Cu/F-HAp-PDA hollow microspheres exhibited excellent photothermal conversion efficiency and photothermal stability. The molecular dynamics simulations showed that PDA and HAp can form mutual binding mainly through Ca-O bonding, while doxorubicin (DOX) is mainly bound to PDA molecules through hydrogen bonding and π-π stacking interaction.
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Portadores de Fármacos , Durapatita , Portadores de Fármacos/química , Durapatita/química , Microesferas , Polímeros/química , Doxorrubicina/química , Liberación de FármacosRESUMEN
Purpose: To investigate the dynamic visual acuity (DVA) after implantation of toric bifocal or trifocal intraocular lens in age-related cataract patients. Methods: This was a prospective randomized controlled trial. Of one hundred and twenty-four patients enrolled and randomized to receive unilateral phacoemulsification and toric trifocal (939 M/MP, Carl Zeiss Meditec AG, Jena, Germany) or toric bifocal (909 M, Carl Zeiss Meditec AG, Jena, Germany) intraocular lenses (IOL) implantation, ninety-nine patients completed the follow-up and were included in final analysis. Postoperatively, uncorrected and corrected distance (UDVA and CDVA), intermediate (UIVA and DCIVA) and near (UNVA and DCNVA) static visual acuity, manifest refraction and uncorrected and corrected distance DVA (UDDVA and CDDVA) at 20, 40 and 80 degrees per second (dps) were evaluated at one week, one month and three months. Results: Three months postoperatively, the UDVA were 0.13 ± 0.11 and 0.14 ± 0.13 in the toric trifocal and bifocal IOL group, respectively. Significant better UIVA (trifocal, 0.17 ± 0.13 vs. bifocal, 0.23 ± 0.13, p = 0.037) and DCIVA (trifocal, 0.16 ± 0.11 vs. bifocal, 0.20 ± 0.12, p = 0.048) were observed in patients implanting toric trifocal than bifocal IOL at three months postoperatively. Patients implanted with toric bifocal IOL obtained better CDDVA at 80 dps (0.5607 ± 0.2032) than the trifocal group (0.6573 ± 0.2450, p = 0.039) at three months. Postoperative UDDVA and CDDVA at 20, 40 and 80 dps were significantly associated with age (p < 0.05, respectively) and postoperative static visual acuity (p < 0.05, respectively). Conclusion: Toric trifocal IOL provides better static intermediate visual acuity, and toric bifocal IOL implantation provides better distance dynamic visual acuity at high speed.
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We evaluated how different degrees of air pollution affect the ocular surface of a cohort of human subjects in Beijing by correlating in-patient test outcomes with tear cytokines. A cross-sectional study involving 221 volunteers was carried out in different districts of Beijing. Air pollution indices were recorded for 7 d (including the visit day). The indices recorded were the air quality index (AQI), which is a dimensionless measure that quantitatively describes the state of air quality, concentrations of particulate matter smaller than 2.5 µm (PM2.5) and 10 µm (PM10), sulfur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2). The Ocular Symptom Disease Index (OSDI) questionnaire provided. Subsequently, subjects underwent slit-lamp examination, which included meibomian gland examination, conjunctival congestion score, conjunctivochalasis grade, tear meniscus height (TMH), tear breakup time (TBUT), corneal fluorescein staining (CFS), Schirmer I test, and conjunctival impression cytology. The concentrations of vascular endothelial growth factor (VEGF), interleukins (IL)-1ß, IL-6 and IL-8 in tears were measured by microsphere-based immunoassay analysis. According to the value of the AQI, participants are divided into a slightly polluted (SP) group (n = 103) which the AQI value is less than or equal to 100 and a heavily polluted (HP) group (n = 118) whose AQI value is more than 100. Air pollution is related to ocular discomfort based on tear cytokine concentrations. PM2.5, PM10 and NO2 were positively correlated with OSDI, MG expressibility, meibum score, meiboscore, conjunctival congestion score, Schirmer I test value, TMH, goblet-cell density, concentrations of IL-6, and VEGF were negatively correlated with TBUT. PM2.5 and PM10 appear to be the major risk factors to the ocular surface, with NO2 being another important risk factor based on this study. The symptoms and signs of eye discomfort in the SP group were significantly less severe than those in the HP group, and tear cytokine concentrations (IL-6 and VEGF) were lower. Air pollution degrees were significantly correlated with tear cytokine concentrations, indicating an alteration of cytokine balance at the ocular surface under different degrees of air pollution.